Scutellaria baicalensis water decoction ameliorates lower respiratory tract infection by modulating respiratory microbiota.

BACKGROUND: The pathogenesis of lower respiratory tract infections (LRTIs) has been demonstrated to be strongly associated with dysbiosis of respiratory microbiota. Scutellaria baicalensis, a traditional Chinese medicine, is widely used to treat respiratory infections. However, whether the therapeutic effect of S. baicalensis on LRTIs depends upon respiratory microbiota regulation is largely unclear. PURPOSE: To investigate the potential effect and mechanism of S. baicalensis on the respiratory microbiota of LRTI mice. METHODS: A mouse model of LRTI was established using Klebsiella pneumoniae or Streptococcus pneumoniae. Antibiotic treatment was administered, and transplantation of respiratory microbiota was performed to deplete the respiratory microbiota of mice and recover the destroyed microbial community, respectively. High-performance liquid chromatography (HPLC) was used to determine and quantify the chemical components of S. baicalensis water decoction (SBWD). Pathological changes in lung tissues and the expressions of serum inflammatory cytokines, including interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were determined by hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA), respectively. Quantitative real-time PCR (qRT-PCR) analysis was performed to detect the mRNA expression of GM-CSF. Metagenomic sequencing was performed to evaluate the effect of SBWD on the composition and function of the respiratory microbiota in LRTI mice. RESULTS: Seven main components, including scutellarin, baicalin, oroxylin A-7-O-ß-d-glucuronide, wogonoside, baicalein, wogonin, and oroxylin A, were identified and their levels in SBWD were quantified. SBWD ameliorated pulmonary pathological injury and inflammatory responses in K. pneumoniae and S. pneumoniae-induced LRTI mice, as evidenced by the dose-dependent reductions in the levels of serum inflammatory cytokines, IL-6 and TNF-α. SBWD may exert a bidirectional regulatory effect on the host innate immune responses in LRTI mice and regulate the expressions of IL-17A and GM-CSF in a microbiota-dependent manner. K. pneumoniae infection but not S. pneumoniae infection led to dysbiosis in the respiratory microbiota, evident through disturbances in the taxonomic composition characterized by bacterial enrichment, including Proteobacteria, Enterobacteriaceae, and Klebsiella. K. pneumoniae and S. pneumoniae infection altered the bacterial functional profile of the respiratory microbiota, as indicated by increases in lipopolysaccharide biosynthesis, metabolic pathways, and carbohydrate metabolism. SBWD had a certain trend on the regulation of compositional disorders in the respiratory flora and modulated partial microbial functions embracing carbohydrate metabolism in K. pneumoniae-induced LRTI mice. CONCLUSION: SBWD may exert an anti-infection effect on LRTI by targeting IL-17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation.

Mechanical shear flow regulates the malignancy of colorectal cancer cells.

Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Synthesis of 2-(Trifluoromethyl)-[1,2,4]triazolo[5,1-a]isoquinoline via Cycloaddition of C,N-Cyclic Azomethine Imine with CF3CN.

A [3 + 2] cycloaddition of C,N-cyclic azomethine imine with in situ-generated CF3CN for the construction of 2-(trifluoromethyl)-[1,2,4]triazolo[5,1-a]isoquinoline is reported. Remarkably, this process shows a broad substrate scope with excellent functional group tolerance, which is scalable and enables a practical route to a library of 2-(trifluoromethyl)-[1,2,4]triazolo[5,1-a]isoquinoline derivatives in moderate to good yields.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Monomer-Recyclable Polyester from CO2 and 1,3-Butadiene.

Synthesis of monomer-recyclable polyesters solely from CO2 and bulk olefins holds great potential in significantly reducing CO2 emissions and addressing the issue of plastic pollution. Due to the kinetic disadvantage of direct copolymerization of CO2 and bulk olefins compared to homopolymerization of bulk olefins, considerable research attention has been devoted to synthesis of polyester via the ring-opening polymerization (ROP) of a six-membered disubstituted lactone intermediate, 1,2-ethylidene-6-vinyl-tetrahydro-2H-pyran-2-one (𝜹-L), obtained from telomerization of CO2 and 1,3-butadiene. However, the conjugate olefin on the six-membered ring of 𝜹-L leads to serious Michael addition side reactions. Thus, the selective ROP of 𝜹-L, which can precisely control the repeating unit for the production of polyesters potentially amenable to efficient monomer recycling, remains an unresolved challenge. Herein, the first example of selective ROP of 𝜹-L is reported using a combination of organobase and N,N'-Bis[3,5-bis(trifluoromethyl)phenyl]urea as the catalytic system. Systematic modifications of the substituent of the urea show that the presence of electron-deficient 3,5-bis(trifluoromethyl)-phenyl groups is the key to the extraordinary selectivity of ring opening over Michael addition. Efficient monomer recovery of oligo(𝜹-L) is also achieved under mild catalytic conditions.

Identifying lncRNAs and mRNAs related to survival of NSCLC based on bioinformatic analysis and machine learning.

Non-small cell lung cancer (NSCLC) is the most common histopathological type, and it is purposeful for screening potential prognostic biomarkers for NSCLC. This study aims to identify the lncRNAs and mRNAs related to survival of non-small cell lung cancer (NSCLC). The expression profile data of lung adenocarcinoma and lung squamous cell carcinoma were downloaded in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. A total of eight survival related long non-coding RNAs (lncRNAs) and 262 survival related mRNAs were filtered. By gene set enrichment analysis, 17 significantly correlated Gene Ontology signal pathways and 14 Kyoto Encyclopedia of Genes and Genomes signal pathways were screened. Based on the clinical survival and prognosis information of the samples, we screened eight lncRNAs and 193 mRNAs by single factor Cox regression analysis. Further single and multifactor Cox regression analysis were performed, 30 independent prognostication-related mRNAs were obtained. The PPI network was further constructed. We then performed the machine learning algorithms (Least absolute shrinkage and selection operator, Recursive feature elimination, and Random forest) to screen the optimized DEGs combination, and a total of 17 overlapping mRNAs were obtained. Based on the 17 characteristic mRNAs obtained, we firstly built a Nomogram prediction model, and the ROC values of training set and testing set were 0.835 and 0.767, respectively. By overlapping the 17 characteristic mRNAs and PPI network hub genes, three genes were obtained: CDC6, CEP55, TYMS, which were considered as key factors associated with survival of NSCLC. The in vitro experiments were performed to examine the effect of CDC6, CEP55, and TYMS on NSCLC cells. Finally, the lncRNAs-mRNAs networks were constructed.

Effect of commercial fibrolytic enzymes application to normal- and slightly lower energy diets on lactational performance, digestibility and plasma nutrients in high-producing dairy cows.

The inclusion of fibrolytic enzymes in the diet is believed to have positive effects on animal production. Hence, the objective of this study was to investigate the impact of supplementing diets with a commercial fibrolytic enzyme preparation (Vistamax; mixture of xylanase and cellulase) derived from Trichoderma reesei on lactational performance, digestibility, and plasma nutrient levels in high-producing dairy cows. Two dietary energy levels were considered: a normal energy diet (metabolizable energy = 2.68 Mcal/kg) and a slightly lower energy diet (metabolizable energy = 2.55 Mcal/kg). A total of 120 lactating Holstein cows (parity = 2; Days in Milk = 113 ± 23) were randomly assigned to four treatment groups using a 2 * 2 factorial arrangement. The dietary treatments consisted of: (1) normal energy diet without enzyme supplementation (NL); (2) normal energy diet with enzyme supplementation (NLE); (3) slightly lower energy diet without enzyme supplementation (SL); and (4) slightly lower energy diet with enzyme supplementation (SLE). The amount of enzyme added to the diets was determined based on previous in vitro studies and supplier recommendations. The enzyme and premix were mixed prior to the preparation of the total mixed ration, and the trial lasted for a duration of 42 days. The results indicated that the application of the fibrolytic enzyme did not have a significant effect on dry matter intake (DMI), but it did enhance the digestibility of dry matter (DM), neutral detergent fiber (NDF), potentially digestible NDF (pdNDF), organic matter (OM), milk production, milk urea nitrogen (MUN), and blood urea nitrogen (BUN). On the other hand, the slightly lower energy diet resulted in a decrease in DMI, milk production, milk protein yield, plasma free amino acids (FAA), and an increase in plasma B-hydroxybutyrate (BHBA). In conclusion, the inclusion of the fibrolytic enzyme in the diets of dairy cows led to improvements in the digestibility of DM, NDF, pdNDF, OM, milk production, and feed efficiency. Furthermore, the application of the enzyme to the slightly lower energy diet resulted in milk production levels comparable to those observed in cows fed the untreated normal energy diet.

Hydroxyl-Bonded Co Single Atom Site on Boroncarbonitride Surface Realizes Nonsacrificial H2O2 Synthesis in the Near-Infrared Region.

Photocatalytic synthesis of hydrogen peroxide (H2O2) from O2 and H2O under near-infrared light is a sustainable renewable energy production strategy, but challenging reaction. The bottleneck of this reaction lies in the regulation of O2 reduction path by photocatalyst. Herein, the center of the one-step two-electron reduction (OSR) pathway of O2 for H2O2 evolution via the formation of the hydroxyl-bonded Co single-atom sites on boroncarbonitride surface (BCN-OH2/Co1) is constructed. The experimental and theoretical prediction results confirm that the hydroxyl group on the surface and the electronic band structure of BCN-OH2/Co1 are the key factor in regulating the O2 reduction pathway. In addition, the hydroxyl-bonded Co single-atom sites can further enrich O2 molecules with more electrons, which can avoid the one-electron reduction of O2 to •O2 -, thus promoting the direct two-electron activation hydrogenation of O2. Consequently, BCN-OH2/Co1 exhibits a high H2O2 evolution apparent quantum efficiency of 0.8% at 850 nm, better than most of the previously reported photocatalysts. This study reveals an important reaction pathway for the generation of H2O2, emphasizing that precise control of the active site structure of the photocatalyst is essential for achieving efficient conversion of solar-to-chemical.

Advances in uremic toxin detection and monitoring in the management of chronic kidney disease progression to end-stage renal disease.

Patients with end-stage kidney disease (ESKD) rely on dialysis to remove toxins and stay alive. However, hemodialysis alone is insufficient to completely remove all/major uremic toxins, resulting in the accumulation of specific toxins over time. The complexity of uremic toxins and their varying clearance rates across different dialysis modalities poses significant challenges, and innovative approaches such as microfluidics, biomarker discovery, and point-of-care testing are being investigated. This review explores recent advances in the qualitative and quantitative analysis of uremic toxins and highlights the use of innovative methods, particularly label-mediated and label-free surface-enhanced Raman spectroscopy, primarily for qualitative detection. The ability to analyze uremic toxins can optimize hemodialysis settings for more efficient toxin removal. Integration of multiple omics disciplines will also help identify biomarkers and understand the pathogenesis of ESKD, provide deeper understanding of uremic toxin profiling, and offer insights for improving hemodialysis programs. This review also highlights the importance of early detection and improved understanding of chronic kidney disease to improve patient outcomes.

Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas.

Background: Hyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences. Methods: We consecutively enrolled all eligible Tibetan participants aged 18-60 who were undergoing routine medical examinations at the People's Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia. Results: Among the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu). Conclusion: This study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights.

Structural characteristics of alpha-fetoprotein, including N-glycosylation, metal ion and fatty acid binding sites.

Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as a clinical tumor marker, function as a carcinogen, immune suppressor, and transport vehicle; but the detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze the structure of the recombinant AFP obtained a 3.31 Å cryo-EM structure and built an atomic model of AFP. We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280. Furthermore, we compared the structural similarities and differences between AFP and human serum albumin. The elucidation of AFP's structural characteristics not only contributes to a deeper understanding of its functional mechanisms, but also provides a structural basis for developing AFP-based drug vehicles.

Isolation of undescribed cladosporols and spirobisnaphthalenes from a plant pathogen Cladosporium cladosporioides F-10-2-A.

Two undescribed cladosporol derivatives, cladosporols J-K (1-2), and three previously unreported spirobisnaphthalenes, urnucratins D-F (3-5), as well as eleven known cladosporols (6-16), were characterized from Cladosporium cladosporioides (Cladosporiaceae), a common plant pathogen isolated from the skin of Chinese toad. Cladosporols J-K (1-2) with a single double bond have been rarely reported, while urnucratins D-F (3-5) featured an unusual benzoquinone bisnaphthospiroether skeleton, contributing to an expanding category of undiscovered natural products. Their structures and absolute configurations were determined using extensive spectroscopic methods, including NMR, HRESIMS analyses, X-ray single crystal diffraction, as well as through experimental ECD analyses. Biological assays revealed that compounds 1 and 2 exhibited inhibitory activity against A549 cells, with IC50 values of 30.11 ± 3.29 and 34.32 ± 2.66 µM, respectively.

What Metals Should Be Used to Mediate Electrosynthesis of Ammonia from Nitrogen and Hydrogen from a Thermodynamic Standpoint?

Recently, metal-mediated electrochemical conversion of nitrogen and hydrogen to ammonia (M-eNRRs) has been attracting intense research attention as a potential route for ammonia synthesis under ambient conditions. However, which metals should be used to mediate M-eNRRs remains unanswered. This work provides an extensive comparison of the energy consumption in the classical Haber Bosch (H-B) process and the M-eNRRs. The results indicate that when employing lithium and calcium, metals popularly used to mediate the M-eNRRs, the energy consumption is more than 10 times greater than that of the H-B process even assuming a 100% Faradaic efficiency and zero overpotentials. Only electrosynthesis with a cell voltage not exceeding 0.38 V might have the potential to rival the H-B process from an energetic perspective. A further analysis of other metals in the periodic table reveals that only some heavy metals, including In, Tl, Co, Ni, Ga, Mo, Sn, Pb, Fe, W, Ge, Re, Bi, Cu, Po, Tc, Ru, Rh, Ag, Hg, Pd, Ir, Pt, and Au, can potentially consume less energy than that of the H-B process purely from a thermodynamic standpoint, but whether they can activate N2 under ambient conditions is yet to be explored. This work shows the importance of performing thermodynamic analysis for the development of an innovative strategy to synthesize ammonia with the ultimate goal of replacing the H-B process on a large scale.

Solvothermal Preparation of Microporous Polyureas for Au(III) Adsorption.

The enrichment and recovery of gold from wastewater are an alternative method to obtain this noble metal, which benefits reducing hazardous emissions from the conventional ore mining process and reserving natural gold for sustainable development. Inspired by our previous work (Lei et al., Macromol. Rapid Comm. 2022, 2200712), four families of microporous polyureas (mPPUs) with a large surface area (690 m2 g-1) and abundant heteroatom sites have been prepared via the factor-optimized solvothermal protocol. The resultant sample NPU-A starting from 1,5-naphthalene diisocyanate (NDI) and tri(4-aminophenyl) amine (TAPA) exhibits the maximum Au(III) adsorption capacity of 1300 mg g-1 and high selectivity even when the Au(III) concentration is as low as 0.1 mg L-1. This study not only demonstrates the robustness of the high-throughput synthetic strategy but also promotes the investigation of the structure-activity correlation between the mPPU chemical structure and Au(III) adsorption performance.

Perovskite Oxides Toward Oxygen Evolution Reaction: Intellectual Design Strategies, Properties and Perspectives.

Developing electrochemical energy storage and conversion devices (e.g., water splitting, regenerative fuel cells and rechargeable metal-air batteries) driven by intermittent renewable energy sources holds a great potential to facilitate global energy transition and alleviate the associated environmental issues. However, the involved kinetically sluggish oxygen evolution reaction (OER) severely limits the entire reaction efficiency, thus designing high-performance materials toward efficient OER is of prime significance to remove this obstacle. Among various materials, cost-effective perovskite oxides have drawn particular attention due to their desirable catalytic activity, excellent stability and large reserves. To date, substantial efforts have been dedicated with varying degrees of success to promoting OER on perovskite oxides, which have generated multiple reviews from various perspectives, e.g., electronic structure modulation and heteroatom doping and various applications. Nonetheless, the reviews that comprehensively and systematically focus on the latest intellectual design strategies of perovskite oxides toward efficient OER are quite limited. To bridge the gap, this review thus emphatically concentrates on this very topic with broader coverages, more comparative discussions and deeper insights into the synthetic modulation, doping, surface engineering, structure mutation and hybrids. More specifically, this review elucidates, in details, the underlying causality between the being-tuned physiochemical properties [e.g., electronic structure, metal-oxygen (M-O) bonding configuration, adsorption capacity of oxygenated species and electrical conductivity] of the intellectually designed perovskite oxides and the resulting OER performances, coupled with perspectives and potential challenges on future research. It is our sincere hope for this review to provide the scientific community with more insights for developing advanced perovskite oxides with high OER catalytic efficiency and further stimulate more exciting applications.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Na3V2(PO4)3-decorated Na3V2(PO4)2F3 as a high-rate and cycle-stable cathode material for sodium ion batteries.

Since Na3V2(PO4)3 (NVP) possesses modest volume deformation and three-dimensional ion diffusion channels, it is a potential sodium-ion battery cathode material that has been extensively researched. Nonetheless, NVP still endures the consequences of poor electronic conductivity and low voltage platforms, which need to be further improved. On this basis, a high voltage platform Na3V2(PO4)2F3 was introduced to form a composite with NVP to increase the energy density. In this study, the sol-gel technique was successfully used to synthesize a Na3V2(PO4)2.75F0.75/C (NVPF·3NVP/C) composite cathode material. The citric acid-derived carbon layer was utilized to construct three-dimensional conducting networks to effectively promote ion and electron diffusion. Furthermore, the composites' synergistic effect accelerates the quick ionic migration and improves the kinetic reaction. In particular, NVP as the dominant phase enhanced the structural stability and significantly increased the capacitive contribution. Therefore, at 0.1C, the discharge capacity of the modified NVPF·3NVP/C composite is 120.7 mA h g-1, which is greater than the theoretical discharge capacity of pure NVP (118 mA h g-1). It discharged 110.9 mA h g-1 of reversible capacity even at an elevated multiplicity of 10C, and after 200 cycles, it retained 64.1% of its capacity. Thus, the effort produced an optimized NVPF·3NVP/C composite cathode material that may be used in the sodium ion cathode.

Deep learning model for pleural effusion detection via active learning and pseudo-labeling: a multisite study.

BACKGROUND: The study aimed to develop and validate a deep learning-based Computer Aided Triage (CADt) algorithm for detecting pleural effusion in chest radiographs using an active learning (AL) framework. This is aimed at addressing the critical need for a clinical grade algorithm that can timely diagnose pleural effusion, which affects approximately 1.5 million people annually in the United States. METHODS: In this multisite study, 10,599 chest radiographs from 2006 to 2018 were retrospectively collected from an institution in Taiwan to train the deep learning algorithm. The AL framework utilized significantly reduced the need for expert annotations. For external validation, the algorithm was tested on a multisite dataset of 600 chest radiographs from 22 clinical sites in the United States and Taiwan, which were annotated by three U.S. board-certified radiologists. RESULTS: The CADt algorithm demonstrated high effectiveness in identifying pleural effusion, achieving a sensitivity of 0.95 (95% CI: [0.92, 0.97]) and a specificity of 0.97 (95% CI: [0.95, 0.99]). The area under the receiver operating characteristic curve (AUC) was 0.97 (95% DeLong's CI: [0.95, 0.99]). Subgroup analyses showed that the algorithm maintained robust performance across various demographics and clinical settings. CONCLUSION: This study presents a novel approach in developing clinical grade CADt solutions for the diagnosis of pleural effusion. The AL-based CADt algorithm not only achieved high accuracy in detecting pleural effusion but also significantly reduced the workload required for clinical experts in annotating medical data. This method enhances the feasibility of employing advanced technological solutions for prompt and accurate diagnosis in medical settings.

Clinical trajectories preceding incident dementia up to 15 years before diagnosis: a large prospective cohort study.

BACKGROUND: Dementia has a long prodromal stage with various pathophysiological manifestations; however, the progression of pre-diagnostic changes remains unclear. We aimed to determine the evolutional trajectories of multiple-domain clinical assessments and health conditions up to 15 years before the diagnosis of dementia. METHODS: Data was extracted from the UK-Biobank, a longitudinal cohort that recruited over 500,000 participants from March 2006 to October 2010. Each demented subject was matched with 10 healthy controls. We performed logistic regressions on 400 predictors covering a comprehensive range of clinical assessments or health conditions. Their evolutional trajectories were quantified using adjusted odds ratios (ORs) and FDR-corrected p-values under consecutive timeframes preceding the diagnosis of dementia. FINDINGS: During a median follow-up of 13.7 [Interquartile range, IQR 12.9-14.2] years until July 2022, 7620 subjects were diagnosed with dementia. In general, upon approaching the diagnosis, demented subjects witnessed worse functional assessments and a higher prevalence of health conditions. Associations up to 15 years preceding the diagnosis comprised declined physical strength (hand grip strength, OR 0.65 [0.63-0.67]), lung dysfunction (peak expiratory flow, OR 0.78 [0.76-0.81]) and kidney dysfunction (cystatin C, OR 1.13 [1.11-1.16]), comorbidities of coronary heart disease (OR 1.78 [1.67-1.91]), stroke (OR 2.34 [2.1-1.37]), diabetes (OR 2.03 [1.89-2.18]) and a series of mental disorders. Cognitive functions in multiple tests also demonstrate decline over a decade before the diagnosis. Inadequate activity (3-5 year, overall time of activity, OR 0.82 [0.73-0.92]), drowsiness (3-5 year, sleep duration, OR 1.13 [1.04-1.24]) and weight loss (0-5 year, weight, OR 0.9 [0.83-0.98]) only exhibited associations within five years before the diagnosis. In addition, serum biomarkers of enriched endocrine, dysregulations of ketones, deficiency of brand-chain amino acids and polyunsaturated fatty acids were found in a similar prodromal time window and can be witnessed as the last pre-symptomatic conditions before the diagnosis. INTERPRETATION: Our findings present a comprehensive temporal-diagnostic landscape preceding incident dementia, which could improve selection for preventive and early disease-modifying treatment trials.