Screening of Poria cocos polysaccharide with immunomodulatory activity and its activation effects on TLR4/MD2/NF-κB pathway.

PCP-W1, the Poria cocos polysaccharide with the strong immunomodulatory activity, was isolated through column chromatography and screened for in vitro immune activity in RAW 264.7 cells in this study. The structure analysis results revealed that the PCP-W1 were composed of galactose, glucose, fucose and mannose in a molar percentage of 35.87: 28.56: 21.77: 13.64. And it exhibited a random coil and branched conformational features with a molecular weight of 18.38 kDa. The main chain consisted of residues→3)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Glcp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ 2,6)-α-D-Galp-(1→6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ , while branching occurred at ß-D-Glcp-(1→, α-D-Manp-(1→, and α-L-Fucp-(1 â†’ 3)- α-L-Fucp-(1→. The pharmacodynamic studies demonstrated that PCP-W1 activated the release of NO, IL-6, IL-ß, TNF-α, CD86, and ROS to induce polarization of RAW 264.7 murine macrophages towards M1-type through modulation of the TLR4/MD2/NF-κB pathway. The molecular docking results showed that PCP-W1 could primarily dock onto the hydrophobic binding site of TLR4/MD2 complex via its galactose chain. Furthermore, molecular dynamics simulation displayed stable modeling for TLR4-MD2-PCP-W1 complex. Overall, we screened the most immunoactive components of the polysaccharide, analyzed its structure, demonstrated its impact on TLR4/MD2/NF-kB pathway, and studied the interaction between TLR4/MD2 and the polysaccharide fragments. These results provide further support for the structure-activity relationship study of the immunomodulatory effects of Poria cocos polysaccharide.

Enhancing trabecular CT scans based on deep learning with multi-strategy fusion.

Trabecular bone analysis plays a crucial role in understanding bone health and disease, with applications like osteoporosis diagnosis. This paper presents a comprehensive study on 3D trabecular computed tomography (CT) image restoration, addressing significant challenges in this domain. The research introduces a backbone model, Cascade-SwinUNETR, for single-view 3D CT image restoration. This model leverages deep layer aggregation with supervision and capabilities of Swin-Transformer to excel in feature extraction. Additionally, this study also brings DVSR3D, a dual-view restoration model, achieving good performance through deep feature fusion with attention mechanisms and Autoencoders. Furthermore, an Unsupervised Domain Adaptation (UDA) method is introduced, allowing models to adapt to input data distributions without additional labels, holding significant potential for real-world medical applications, and eliminating the need for invasive data collection procedures. The study also includes the curation of a new dual-view dataset for CT image restoration, addressing the scarcity of real human bone data in Micro-CT. Finally, the dual-view approach is validated through downstream medical bone microstructure measurements. Our contributions open several paths for trabecular bone analysis, promising improved clinical outcomes in bone health assessment and diagnosis.

Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain. OBJECTIVES: To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis. DATA SOURCES: Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023. STUDY ELIGIBILITY CRITERIA: RCTs. PARTICIPANTS: Adults with clinical suspicion of HAP. INTERVENTIONS: Any empiric antibiotic regimen vs. another, placebo, or no treatment. ASSESSMENT OF RISK OF BIAS: Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials. METHODS OF DATA SYNTHESIS: Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis. CONCLUSIONS: For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality. REGISTRATION: PROSPERO (CRD 42022297224).

CRF08_BC subtype is more prone to ART failure and new-generation NNRTI-resistance under long-term first-line ART.

OBJECTIVE: To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. METHODS: Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. RESULTS: Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. CONCLUSIONS: The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

High certainty evidence is stable and trustworthy, whereas evidence of moderate or lower certainty may be equally prone to being unstable.

OBJECTIVES: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available. METHODS: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSION: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

Electron transfer mediated photo-Fenton-like synergistic catalysis of Fe,Cu-doped MIL-101 coupled with Ag3PO4: Quantitative evaluation and DFT calculations.

Widespread use of tetracycline (TC) results in its persistent residue and bioaccumulation in aquatic environments, posing a high toxicity to non-target organisms. In this study, a bimetal-doped composite material Ag3PO4/MIL-101(Fe,Cu) has been designed for the treatment of TC in aqueous solutions. As the molar ratio of Fe/Cu in composite is 1:1, the obtained material AP/MFe1Cu1 is placed in an aqueous environment under visible light irradiation in the presence of 3 mM peroxydisulfate (PDS), which forms a photo-Fenton-like catalytic system that can completely degrade TC (10 mg/L) within 60 min. Further, the degradation rate constant (0.0668 min-1) is 5.66 and 7.34 times higher than that of AP/MFe and AP/MCu, respectively, demonstrating a significant advantage over single metal-doped catalysts. DFT calculations confirm the strong adsorption capacity and activation advantage of PDS on the composite surface. Therefore, the continuous photogenerated electrons (e-) accelerate the activation of PDS and the production of SO4•-, resulting in the stripping of abundant photogenerated h + for TC oxidation. Meanwhile, the internal circulation of FeⅢ/FeⅡ and CuⅡ/CuⅢ in composite also greatly enhances the photo-Fenton-like catalytic stability. According to the competitive dynamic experiments, SO4•- have the greatest contribution to TC degradation (58.93%), followed by 1O2 (23.80%). The degradation intermediates (products) identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) technique indicate the involvement of various processes in TC degradation, such as dehydroxylation, deamination, N-demethylation, and ring opening. Furthermore, as the reaction proceeds, the toxicity of the intermediates produced during TC degradation gradually decreases, which can ensure the safety of the aquatic ecosystem. Overall, this work reveals the synergy mechanism of PDS catalysis and photocatalysis, as well as provides technical support for removal of TC-contaminated wastewater.

Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.

White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis.

BACKGROUND: Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. METHODS: Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. RESULTS: The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aß42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). CONCLUSION: Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aß42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body's immune system recognition and attack through various mechanisms, including the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation in specific TNBC subtypes. Consequently, targeting the JAK2/STAT3 signaling pathway emerges as a promising and precise therapeutic strategy for TNBC. The signal transduction cascade of the JAK2/STAT3 pathway predominantly involves receptor tyrosine kinases, the tyrosine kinase JAK2, and the transcription factor STAT3. Ongoing preclinical studies and clinical research are actively investigating this pathway as a potential therapeutic target for TNBC treatment. This article comprehensively reviews preclinical and clinical investigations into TNBC treatment by targeting the JAK2/STAT3 signaling pathway using small molecule compounds. The review explores the role of the JAK2/STAT3 pathway in TNBC therapeutics, evaluating the benefits and limitations of active inhibitors and proteolysis-targeting chimeras in TNBC treatment. The aim is to facilitate the development of novel small-molecule compounds that target TNBC effectively. Ultimately, this work seeks to contribute to enhancing therapeutic efficacy for patients with TNBC.

Structural characterization and improves cognitive disorder in ageing mice of a glucomannan from Dendrobium huoshanense.

In the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)-ß-D-Manp-(1 and 4)-ß-D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the BCL2/BAX/CASP3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and BCL2/BAX/CASP3, resulting in protective effects against cognitive disorder.

A Systematic Review and Quality Assessment of Cardiovascular Disease-Specific Health-Related Quality-of-Life Instruments Part I: Instrument Development and Content Validity.

OBJECTIVES: Health-related quality-of-life (HRQoL) instruments for cardiovascular diseases (CVD) have been commonly used to measure important patient-reported outcomes (PROs) in clinical trials and practices. This study aimed at systematically identifying and assessing the content validity of CVD-specific HRQoL instruments in clinical studies. METHODS: The research team searched Cumulative Index to Nursing and Allied Health Literature, Embase, and PubMed from inception to January 20, 2022. The research team included studies that reported the development and content validity for CVD-specific instruments. Two reviewers independently assessed the methodological quality using the Consensus-based Standards for the Selection of Health Measurement Instruments methods on evaluating content validity of PROs. Content analysis was used to categorize the items included in the instruments. RESULTS: The research team found 69 studies reporting the content validity of 40 instruments specifically developed for CVD. Fourteen (35.0%) were rated "sufficient" with very low to moderate quality of evidence. For PRO development, all instruments were rated "doubtful" or "inadequate." Twenty-eight (70.0%) instruments cover the core concepts of HRQoL. CONCLUSIONS: The quality of development and content validity vary among existing CVD-specific instruments. The evidence on the content validity should be considered when choosing a HRQoL instrument in CVD clinical studies and health economic evaluations.

Extended culture of 2D gastruloids to model human mesoderm development.

Micropatterned human pluripotent stem cells (hPSCs) treated with BMP4 (2D gastruloids) are among the most widely used stem cell models for human gastrulation. Due to its simplicity and reproducibility, this system is ideal for high throughput quantitative studies of tissue patterning and has led to many insights into the mechanisms of mammalian gastrulation. However, 2D gastruloids have only been studied up to 48h. Here we extended this system to 96h. We discovered a phase of highly reproducible morphogenesis during which directed migration from the primitive streak-like region gives rise to a mesodermal layer beneath an epiblast-like layer. Multiple types of mesoderm arise with striking spatial organization including lateral mesoderm-like cells on the colony border and paraxial mesoderm-like further inside the colony. Single cell transcriptomics showed strong similarity of these cells to mesoderm in human and non-human primate embryos. However, our data suggest that the annotation of the reference human embryo may need to be revised. This illustrates that extended culture of 2D gastruloids provides a powerful model for human mesoderm differentiation and morphogenesis.

Covalent Organic Frameworks as Single-Site Photocatalysts for Solar-to-Fuel Conversion.

Single-site photocatalysts (SSPCs) are well-established as potent platforms for designing innovative materials to accomplish direct solar-to-fuel conversion. Compared to classical inorganic porous materials, such as zeolites and silica, covalent organic frameworks (COFs)─an emerging class of porous polymers that combine high surface areas, structural diversity, and chemical stability─are attractive candidates for SSPCs due to their molecular-level precision and intrinsic light harvesting ability, both amenable to structural engineering. In this Perspective, we summarize the design concepts and state-of-the-art strategies for the construction of COF SSPCs, and we review the development of COF SSPCs and their applications in solar-to-fuel conversion from their inception. Underlying pitfalls concerning photocatalytic characterization are discussed, and perspectives for the future development of this burgeoning field are given.

Associations of depression and perceived physical fatigability with white matter integrity in older adults.

BACKGROUNDS: Fatigability is prevalent in older adults. However, it is often associated with depressed mood. We aim to investigate these two psychobehavioral constructs by examining their underpinning of white matter structures in the brain and their associations with different medical conditions. METHODS: Twenty-seven older adults with late-life depression (LLD) and 34 cognitively normal controls (CN) underwent multi-shell diffusion MRI. Fatigability was measured with the Pittsburgh Fatigability Scale. We examined white matter integrity by measuring the quantitative anisotropy (QA), a fiber tracking parameter with better accuracy than the traditional imaging technique. RESULTS: We found those with LLD had lower QA in the 2nd branch of the left superior longitudinal fasciculus (SLF-II), and those with more physical fatigability had lower QA in more widespread brain regions. In tracts associated with more physical fatigability, the lower QA in left acoustic radiation and left superior thalamic radiation correlated with higher blood glucose (r = - 0.46 and - 0.49). In tracts associated with depression, lower QA in left SLF-II correlated with higher bilirubin level (r = - 0.58). DISCUSSION: Depression and fatigability were associated with various white matter integrity changes, which correlated with biochemistry biomarkers all related to inflammation.

Time-integrated BMP signaling determines fate in a stem cell model for early human development.

How paracrine signals are interpreted to yield multiple cell fate decisions in a dynamic context during human development in vivo and in vitro remains poorly understood. Here we report an automated tracking method to follow signaling histories linked to cell fate in large numbers of human pluripotent stem cells (hPSCs). Using an unbiased statistical approach, we discover that measured BMP signaling history correlates strongly with fate in individual cells. We find that BMP response in hPSCs varies more strongly in the duration of signaling than the level. However, both the level and duration of signaling activity control cell fate choices only by changing the time integral. Therefore, signaling duration and level are interchangeable in this context. In a stem cell model for patterning of the human embryo, we show that signaling histories predict the fate pattern and that the integral model correctly predicts changes in cell fate domains when signaling is perturbed. Our data suggest that mechanistically, BMP signaling is integrated by SOX2.

Downsizing Porphyrin Covalent Organic Framework Particles Using Protected Precursors for Electrocatalytic CO2 Reduction.

Covalent organic frameworks (COFs) are promising electrocatalyst platforms owing to their designability, porosity, and stability. Recently, COFs with various chemical structures are developed as efficient electrochemical CO2 reduction catalysts. However, controlling the morphology of COF catalysts remains a challenge, which can limit their electrocatalytic performance. Especially, while porphyrin COFs show promising catalytic properties, their particle size is mostly large and uncontrolled because of the severe aggregation of crystallites. In this work, a new synthetic methodology for rationally downsized COF catalyst particles is reported, where a tritylated amine is employed as a novel protected precursor for COF synthesis. Trityl protection provides high solubility to a porphyrin precursor, while its deprotection proceeds in situ under typical COF synthesis conditions. Subsequent homogeneous nucleation and colloidal growth yield smaller COF particles than a conventional synthesis, owing to suppressed crystallite aggregation. The downsized COF particles exhibit superior catalytic performance in electrochemical CO2 reduction, with higher CO production rate and faradaic efficiency compared to conventional COF particles. The improved performance is attributed to the higher contact area with a conductive agent. This study reveals particle size as an important factor for the evaluation of COF electrocatalysts and provides a strategy to control it.

Age-Related Macular Degeneration Choroidal Vascular Distribution Characteristics Based on Indocyanine Green Angiography.

Purpose: The purpose of this study was to present our findings of the distribution pattern of choroidal arteries and large veins in patients with age-related macular degeneration (AMD) using indocyanine green angiography (ICGA). Methods: A retrospective analysis was conducted on 980 patients who underwent ICGA at The Second Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2023, including 240 patients with AMD. Secondary image processing was applied to the angiographic videos to obtain posterior distribution maps of choroidal arteries and large veins. Differences between different distribution patterns regarding age, gender, eye laterality, and circulation time were compared. We also conducted a comparison of choroidal vascular distribution characteristics between patients with AMD and patients with diabetic retinopathy (DR) and provided a summary of choroidal vascular distribution patterns in AMD. Results: The filling patterns of choroidal arteries can be classified into the invisible trunk arteries type, the partially masked trunk arteries type, and the exposed trunk arteries type. The vascular topography of the large choroidal vein can be classified into the watershed type, the non-watershed type, and the unknown type, further divided into six subtypes. The distribution patterns of choroidal arteries and veins were significantly correlated with age (P < 0.001). Left eye, older age, and the exposed trunk arteries type were independent risk factors for non-watershed large choroidal vein (P < 0.05). The non-watershed type was the main characteristic of the venous phase in AMD. Conclusions: The distribution characteristics of the arterial and venous patterns in AMD suggest atrophy of the small blood vessels in the choroid and insufficient perfusion pressure of the blood flow.

Dendrobium huoshanense in the treatment of ulcerative colitis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use. DH has been recorded as protecting the gastrointestinal function. Modern pharmacology research shows that DH regulates intestinal flora, intestinal mucosal immunity, gastrointestinal peristalsis and secretion of digestive juices. At the same time, some studies have shown that DH has a good therapeutic effect on ulcerative colitis, but its mechanism of action has not been fully elucidated. AIMS OF THIS STUDY: To investigate the mechanism and effect of Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) in the treatment of ulcerative colitis (UC) by combining network pharmacology and in vivo experimental validation. METHODS: A network pharmacology approach was used to perform component screening, target prediction, PPI network interaction analysis, GO and KEGG enrichment analysis to initially predict the mechanism of DH treatment for UC. Then, the mechanism was validated with the UC mouse model induced by 3% DSS. RESULTS: Based on the network pharmacological analysis, a comprehensive of 101 active components were identified, with 19 of them potentially serving as the crucial elements in DH's effectiveness against UC treatment. Additionally, the study revealed 314 potential core therapeutic targets along with the top 5 key targets: SRC, STAT3, AKT1, HSP90AA1, and PIK3CA. In experiments conducted on live mice with UC, DH was found to decrease the levels of IL-6 and TNF-α in the blood, while increasing the levels of IL-10 and TGF-ß. This led to notable improvements in colon length, injury severity, and an up-regulation of SRC, STAT3, HSP90AA1, PIK3CA, p-AKT1 and PI3K/AKT signaling pathway expression in the colon tissue. CONCLUSIONS: In this study, the active components and main targets of DH for UC treatment were initially forecasted, and the potential mechanism was investigated through network pharmacology. These findings offer an experimental foundation for the clinical utilization of DH.

Comparative outcomes of catheter-directed thrombolysis versus AngioJet pharmacomechanical catheter-directed thrombolysis for treatment of acute iliofemoral deep vein thrombosis.

OBJECTIVE: The objective of this study was to compare the outcomes of pharmacomechanical thrombolysis and thrombectomy (PCDT) plus catheter-directed thrombolysis (CDT) vs CDT alone for the treatment of acute iliofemoral deep vein thrombosis (DVT) and summarize the clinical experience, safety outcomes, and short- and long-term efficacy. METHODS: We performed a 4-year retrospective, case-control study. A total of 95 consecutive patients with acute symptomatic iliofemoral deep vein thrombosis (DVT) with a symptom duration of ≤7 days involving the iliac and/or common femoral veins underwent endovascular interventions. The patients were divided into two groups according to their clinical indications: PCDT plus CDT vs CDT alone. Statistical analyses were used to compare the clinical characteristics and outcomes between the two groups. Additionally, the patients were followed up for 3 to 36 months after treatment, and the proportions of post-thrombotic syndrome (PTS) and moderate to severe PTS were analyzed using the Kaplan-Meier survival method. RESULTS: A total of 95 consecutive patients were analyzed in this retrospective study, of whom, 51 underwent CDT alone and 44 underwent PCDT plus CDT. Between the two groups, in terms of immediate-term efficacy and safety, significant differences were found in the catheter retention time (60.64 ± 12.04 hours vs 19.42 ± 4.04 hours; P < .001), dosages of urokinase required (5.82 ± 0.81 million units vs 1.80 ± 0.64 million units; P < .001), the detumescence rate at 24 hours postoperatively (48.46% ± 8.62% vs 76.79% ± 7.98%; P = .026), the descent velocity of D-dimer per day (2266.28 ± 1358.26 µg/L/D vs 3842.34 ± 2048.02 µg/L/D; P = .018), total hospitalization stay (6.2 ± 1.40 days vs 3.8 ± 0.70 days; P = .024), number of postoperative angiograms (2.4 ± 0.80 vs 1.2 ± 0.30; P = .042), and grade III venous patency (>95% lysis: 54.5% vs 68.6%; P = .047). Furthermore, during the follow-up period, significant differences were found in the incidence of PTS (Villalta scale ≥5 or a venous ulcer: 47.0% vs 27.7%; P = .037), and the incidence proportion of moderate to severe PTS at 12 months (15.7% vs 4.5%; P = .024) and 24 months (35.3% vs 11.4%; P = .016). CONCLUSIONS: Compared with CDT alone, in the iliofemoral DVT subgroup with a symptom duration of ≤7 days, PCDT plus CDT could significantly relieve early leg symptoms, shorten the hospitalization stay, reduce bleeding complications, promote long-term venous patency, and decrease the occurrence of PTS and the incidence proportion of moderate to severe PTS. Thus, the short- and long-term outcomes both support the superiority of PCDT plus CDT vs CDT in this subgroup.