Optimizing immunofluorescence with high-dynamic-range imaging to enhance PD-L1 expression evaluation for 3D pathology assessment from NSCLC tumor tissue.

Assessing programmed death ligand 1 (PD-L1) expression through immunohistochemistry (IHC) is the golden standard in predicting immunotherapy response of non-small cell lung cancer (NSCLC). However, observation of heterogeneous PD-L1 distribution in tumor space is a challenge using IHC only. Meanwhile, immunofluorescence (IF) could support both planar and three-dimensional (3D) histological analyses by combining tissue optical clearing with confocal microscopy. We optimized clinical tissue preparation for the IF assay focusing on staining, imaging, and post-processing to achieve quality identical to traditional IHC assay. To overcome limited dynamic range of the fluorescence microscope's detection system, we incorporated a high dynamic range (HDR) algorithm to restore the post imaging IF expression pattern and further 3D IF images. Following HDR processing, a noticeable improvement in the accuracy of diagnosis (85.7%) was achieved using IF images by pathologists. Moreover, 3D IF images revealed a 25% change in tumor proportion score for PD-L1 expression at various depths within tumors. We have established an optimal and reproducible process for PD-L1 IF images in NSCLC, yielding high quality data comparable to traditional IHC assays. The ability to discern accurate spatial PD-L1 distribution through 3D pathology analysis could provide more precise evaluation and prediction for immunotherapy targeting advanced NSCLC.

Single Atom Ag Bonding Between PF3T Nanocluster and TiO2 Leads the Ultra-Stable Visible-Light-Driven Photocatalytic H2 Production.

Atomic Ag cluster bonding is employed to reinforce the interface between PF3T nano-cluster and TiO2 nanoparticle. With an optimized Ag loading (Ag/TiO2 = 0.5 wt%), the Ag atoms will uniformly disperse on TiO2 thus generating a high density of intermediate states in the band gap to form the electron channel between the terthiophene group of PF3T and the TiO2 in the hybrid composite (denoted as T@Ag05-P). The former expands the photon absorption band width and the latter facilitates the core-hole splitting by injecting the photon excited electron (from the excitons in PF3T) into the conduction band (CB) of TiO2. These characteristics enable the high efficiency of H2 production to 16 580 µmol h-1 g-1 and photocatalysis stability without degradation under visible light exposure for 96 h. Compared to that of hybrid material without Ag bonding (TiO2@PF3T), the H2 production yield and stability are improved by 4.1 and 18.2-fold which shows the best performance among existing materials in similar component combination and interfacial reinforcement. The unique bonding method offers a new prospect to accelerate the development of photocatalytic hydrogen production technologies.

Intramedullary Screw versus Locking Plate Fixation for Traumatic Displaced Proximal Fifth Metatarsal Fractures: A Systematic Review.

Background/Objectives: Intramedullary screw fixation (IMS) and locking plate fixation (LPF) are currently recommended treatments for proximal fifth metatarsal fractures (PFMF). However, treating comminuted or small displaced avulsion PFMF with IMS poses challenges due to complications. A novel alternative fixation method, the locking compression plate for distal ulna hook plate fixation (LPF), has been introduced recently for distal ulna fractures and has shown improved clinical results. This scoping review aims to assess whether LPF yields superior outcomes, such as postoperative AOFAS scores and rate of postoperative complications, compared to IMS in PFMF treatment. Methods: This review included randomized controlled trials (RCTs), prospective cohort studies, retrospective cohort studies, or case series involving patients with PFMF who underwent plate fixation or screw fixation. The primary outcome was the postoperative American Orthopedic Foot and Ankle Society (AOFAS) score. Studies were sourced from databases including PubMed, Embase, and Scopus, with the search conducted up to February 2024. The Systematic Review protocol was registered in the CRD PROSPERO database (CRD42024532593). Results: Ten studies were included, comprising 3 cohort studies, 1 case-control study, and 6 case series, with a total of 309 patients (158 with LPF and 142 with IMS). The postoperative AOFAS scores showed no significant difference between LPF and IMS in treating PFMF. However, LPF demonstrated efficient surgical procedures and enhanced functional outcomes. Complications were minimal in both groups, with no significant difference in the rate of postoperative complications. Conclusions: Although there was no significant difference in AOFAS scores between LPF and IMS, LPF demonstrated efficient surgical procedures and enhanced functional outcomes, making it a reasonable alternative method for PFMF. Effective shared decision-making (SDM) with patients becomes paramount in choosing the optimal surgical approach. In the surgical landscape, thoughtful deliberation, patient engagement, and adherence to biomechanical principles are crucial for achieving successful outcomes in the treatment of PFMF.

Oral mucosal lesions triage via YOLOv7 models.

BACKGROUND/PURPOSE: The global incidence of lip and oral cavity cancer continues to rise, necessitating improved early detection methods. This study leverages the capabilities of computer vision and deep learning to enhance the early detection and classification of oral mucosal lesions. METHODS: A dataset initially consisting of 6903 white-light macroscopic images collected from 2006 to 2013 was expanded to over 50,000 images to train the YOLOv7 deep learning model. Lesions were categorized into three referral grades: benign (green), potentially malignant (yellow), and malignant (red), facilitating efficient triage. RESULTS: The YOLOv7 models, particularly the YOLOv7-E6, demonstrated high precision and recall across all lesion categories. The YOLOv7-D6 model excelled at identifying malignant lesions with notable precision, recall, and F1 scores. Enhancements, including the integration of coordinate attention in the YOLOv7-D6-CA model, significantly improved the accuracy of lesion classification. CONCLUSION: The study underscores the robust comparison of various YOLOv7 model configurations in the classification to triage oral lesions. The overall results highlight the potential of deep learning models to contribute to the early detection of oral cancers, offering valuable tools for both clinical settings and remote screening applications.

Automatic wild bird repellent system that is based on deep-learning-based wild bird detection and integrated with a laser rotation mechanism.

Wild bird repulsion is critical in agriculture because it helps avoid agricultural food losses and mitigates the risk of avian influenza. Wild birds transmit avian influenza in poultry farms and thus cause large economic losses. In this study, we developed an automatic wild bird repellent system that is based on deep-learning-based wild bird detection and integrated with a laser rotation mechanism. When a wild bird appears at a farm, the proposed system detects the bird's position in an image captured by its detection unit and then uses a laser beam to repel the bird. The wild bird detection model of the proposed system was optimized for detecting small pixel targets, and trained through a deep learning method by using wild bird images captured at different farms. Various wild bird repulsion experiments were conducted using the proposed system at an outdoor duck farm in Yunlin, Taiwan. The statistical test results of our experimental data indicated that the proposed automatic wild bird repellent system effectively reduced the number of wild birds in the farm. The experimental results indicated that the developed system effectively repelled wild birds, with a high repulsion rate of 40.3% each day.

Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.

Irritability, a state of excessive reactivity to negative emotional stimuli, is common in individuals with autism spectrum disorder (ASD). Although it has a significant negative impact of patients' disease severity and quality of life, the neural mechanisms underlying irritability in ASD remain largely unclear. We have previously demonstrated that male mice lacking the Coiled-coil and C2 domain containing 1a (Cc2d1a) in forebrain excitatory neurons recapitulate numerous ASD-like behavioral phenotypes, including impaired social behaviors and pronounced repetitive behaviors. Here, using the bottle-brush test (BBT) to trigger and evaluate aggressive and defensive responses, we show that Cc2d1a deletion increases irritability-like behavior in male but not female mice, which is correlated with reduced number of oxytocin (OXT)-expressing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Intranasal OXT administration or chemogenetic activation of OXT neurons in the PVN rescues irritability-like behavior in Cc2d1a conditional knockout (cKO) mice. Administration of a selective melanocortin receptor 4 agonist, RO27-3225, which potentiates endogenous OXT release, also alleviates irritability-like behavior in Cc2d1a cKO mice, an effect blocked by a specific OXT receptor antagonist, L-368,899. We additionally identify a projection connecting the posterior ventral segment of the medial amygdala (MeApv) and ventromedial nucleus of the ventromedial hypothalamus (VMHvl) for governing irritability-like behavior during the BBT. Chemogenetic suppression of the MeApv-VMHvl pathway alleviates irritability-like behavior in Cc2d1a cKO mice. Together, our study uncovers dysregulation of OXT system in irritability-like behavior in Cc2d1a cKO mice during the BBT and provide translatable insights into the development of OXT-based therapeutics for clinical interventions.

Efficacy of Lactococcus lactis subsp. lactis LY-66 and Lactobacillus plantarum PL-02 in Enhancing Explosive Strength and Endurance: A Randomized, Double-Blinded Clinical Trial.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

Insect Cell-Based Quadrivalent Seasonal Influenza Virus-like Particles Vaccine Elicits Potent Immune Responses in Mice.

Influenza viruses can cause highly infectious respiratory diseases, posing noteworthy epidemic and pandemic threats. Vaccination is the most cost-effective intervention to prevent influenza and its complications. However, reliance on embryonic chicken eggs for commercial influenza vaccine production presents potential risks, including reductions in efficacy due to HA gene mutations and supply delays due to scalability challenges. Thus, alternative platforms are needed urgently to replace egg-based methods and efficiently meet the increasing demand for vaccines. In this study, we employed a baculovirus expression vector system to engineer HA, NA, and M1 genes from seasonal influenza strains A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, generating virus-like particle (VLP) vaccine antigens, H1N1-VLP, H3N2-VLP, Yamagata-VLP, and Victoria-VLP. We then assessed their functional and antigenic characteristics, including hemagglutination assay, protein composition, morphology, stability, and immunogenicity. We found that recombinant VLPs displayed functional activity, resembling influenza virions in morphology and size while maintaining structural integrity. Comparative immunogenicity assessments in mice showed that our quadrivalent VLPs were consistent in inducing hemagglutination inhibition and neutralizing antibody titers against homologous viruses compared to both commercial recombinant HA and egg-based vaccines (Vaxigrip). The findings highlight insect cell-based VLP vaccines as promising candidates for quadrivalent seasonal influenza vaccines. Further studies are worth conducting.

Blinatumomab in Children with MRD-Positive B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 11 Cases.

Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15-52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation.

Vascular Damage and Repair - Are Small-Diameter Vascular Grafts Still the "Holy Grail" of Tissue Engineering?

Cardiovascular diseases are the most important cause of morbidity and mortality in the civilized world. Stenosis or occlusion of blood vessels leads not only to events that are directly life-threatening, such as myocardial infarction or stroke, but also to a significant reduction in quality of life, for example in lower limb ischemia as a consequence of metabolic diseases. The first synthetic polymeric vascular replacements were used clinically in the early 1950s. However, they proved to be suitable only for larger-diameter vessels, where the blood flow prevents the attachment of platelets, pro-inflammatory cells and smooth muscle cells on their inner surface, whereas in smaller-diameter grafts (6 mm or less), these phenomena lead to stenosis and failure of the graft. Moreover, these polymeric vascular replacements, like biological grafts (decellularized or devitalized), are cell-free, i.e. there are no reconstructed physiological layers of the blood vessel wall, i.e. an inner layer of endothelial cells to prevent thrombosis, a middle layer of smooth muscle cells to perform the contractile function, and an outer layer to provide innervation and vascularization of the vessel wall. Vascular substitutes with these cellular components can be constructed by tissue engineering methods. However, it has to be admitted that even about 70 years after the first polymeric vascular prostheses were implanted into human patients, there are still no functional small-diameter vascular grafts on the market. The damage to small-diameter blood vessels has to be addressed by endovascular approaches or by autologous vascular substitutes, which leads to some skepticism about the potential of tissue engineering. However, new possibilities of this approach lie in the use of modern technologies such as 3D bioprinting and/or electrospinning in combination with stem cells and pre-vascularization of tissue-engineered vascular grafts. In this endeavor, sex-related differences in the removal of degradable biomaterials by the cells and in the behavior of stem cells and pre-differentiated vascular cells need to be taken into account. Key words: Blood vessel prosthesis, Regenerative medicine, Stem cells, Footprint-free iPSCs, sr-RNA, Dynamic bioreactor, Sex-related differences.

Effects of chain-chain interaction on the configuration of short-chain alkanethiol self-assembled monolayers on a metal surface.

Surface-specific sum frequency generation vibrational spectroscopy is applied to study the molecular configuration of short-chain n-alkanethiol self-assembled monolayers (SAMs with n = 2-6) on the Au surface. For monolayers with n≥ 3, the alkanethiols are upright-oriented, with the CH3 tilt angle varying between ∼33° and ∼46° in clear even-odd dependency. The ethanethiol monolayer (n = 2) is, however, found to exhibit a distinct lying-down configuration with a larger methyl tilt angle (67°-79°) and a smaller CH2 tilt angle (56°-68°). Such a unique configurational transition from n = 2 to n≥ 3 discloses the steric effect owing to chain-chain interaction among neighboring molecules. Through density functional theory calculations, the transition is further confirmed to be energetically favorable for thiols on a defective reconstructed Au(111) surface but not on the pristine one. Our study highlights the roles of the chain-chain interaction and the substrate surface atomic structure when organizing SAMs, offering a strategic pathway for exploiting their applications.

Performance of Baveno VII criteria for the screening of varices needing treatment in patients with biliary atresia.

OBJECTIVE: Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VI and Baveno VII criteria for the screening of varices need treatment (VNT) and the need for liver transplantation in BA patients. METHODS: This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design. RESULTS: The sensitivity and negative predictive value of Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p = 0.009, 0.03, and 0.007, respectively). CONCLUSION: The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non-necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation.

Anti-biofilm activities and antibiotic synergy of naturally occurring compounds against drug-resistant rapidly growing mycobacteria.

Some naturally occurring compounds, known for their antimicrobial activities, have been employed as food additives. However, their efficacy in treating infections caused by antibiotic-resistant bacteria is yet to be fully explored. Rapidly growing mycobacteria (RGM), a category within nontuberculous mycobacteria (NTM), are prevalent in various environments and can lead to infections in humans. The rise of antimicrobial resistance within RGM is a documented concern. In this study, we reported that four specific natural compounds effectively inhibited the growth and biofilm formation of three key RGM pathogens M. abscessus, M. fortuitum, and M. chelonae. We screened 12 natural compounds for their effectiveness against antibiotic-resistant clinical strains of RGM. Four compounds showed significant inhibitory effects from the most effective to least: trans-cinnamaldehyde, carvacrol, gentisaldehyde, and phloroglucinaldehyde. In the analysis of time-killing kinetics, gentisaldehyde and phloroglucinaldehyde displayed bactericidal activity while trans-cinnamaldehyde and carvacrol exhibited bacteriostatic effects. At 1× minimal inhibition concentrations, these compounds significantly reduced biofilm formation in all three RGM species to levels between 2.9% and 20.5% relative to controls. Checkerboard assays indicated synergistic interactions between these four compounds and antibiotics such as amikacin, clarithromycin, and linezolid. Of these 12 compound-antibiotic combinations, the pairs of carvacrol-linezolid, carvacrol-amikacin, and gentisaldehyde-clarithromycin demonstrated the most synergy against multiple RGM strains. Moreover, two other compounds citral and geraniol showed synergism with all three test antibiotics. Time-killing assays further confirmed most of synergistic combinations identified in the checkerboard tests. Our research suggests the potential of these essential oils and phenolic aldehydes, both individually and in combination with antibiotics, in treating RGM infections. In addition, this work illuminates applications of these natural compounds in environmental remediation to mitigate bacterial persistence for the control of infectious diseases. IMPORTANCE: The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus, M. fortuitum, and M. chelonae. We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.

Comparative transcriptomic and proteomic kinetic analysis of adeno-associated virus production systems.

Recombinant adeno-associated virus (rAAV) is a major gene delivery vehicle. We have constructed a stable rAAV producer cell line by integrating essential rAAV genome, viral and helper genes into the genome of HEK293 cell under the control of inducible promoters. Upon induction, the cell line produces transducing rAAV. To gain insight into enhancing rAAV productivity and vector quality, we performed a comparative transcriptomic and proteomic analysis of our synthetic cell line GX2 and two wild-type AAV (wtAAV) production systems, one by virus co-infection and the other by multi-plasmid transfection. The three systems had different kinetics in viral component synthesis but generated comparable copies of AAV genomes; however, the capsid titer of GX2 was an order of magnitude lower compared to those two wtAAV systems, indicating that its capsid production may be insufficient. The genome packaging efficiency was also lower in GX2 despite it produced higher levels of Rep52 proteins than either wtAAV systems, suggesting that Rep52 protein expression may not limit genome packaging. In the two wtAAV systems, VP were the most abundant AAV proteins and their levels continued to increase, while GX2 had high level of wasteful cargo gene expression. Furthermore, upregulated inflammation, innate immune responses, and MAPK signaling, as well as downregulated mitochondrial functions, were commonly observed in either rAAV or wtAAV systems. Overall, this comparative multi-omics study provided rich insights into host cell and viral factors that are potential targets for genetic and process intervention to enhance the productivity of synthetic rAAV producer cell lines. KEY POINTS: • wtAAV infection was more efficient in producing full viral particles than the synthetic cell GX2. • Capsid protein synthesis, genome replication, and packaging may limit rAAV production in GX2. • wtAAV infection and rAAV production in GX2 elicited similar host cell responses.

Three-Month Excessive Body Weight Loss < 37.7% as a Predictor of Mid-term Suboptimal Outcomes Postlaparoscopic Sleeve Gastrectomy: Risk Factors and the Impact of Neutrophil-to-Lymphocyte Ratio on Adipocyte Function.

INTRODUCTION: This study aimed to evaluate the impact of achieving < 37.7% excess body-weight loss (EBWL) within 3 months of postlaparoscopic sleeve gastrectomy (LSG) on clinical outcomes and its correlation with adipocyte function. METHODS: Patients (n = 176) who underwent LSG between January 2019 and January 2023 were included. Weight loss and status of health markers were monitored postoperatively. The cohort was stratified based on EBWL < 37.7% at 3 months or not. Variables including neutrophil-to-lymphocyte ratio (NLR), insulin resistance, and comorbidities were analyzed. Omental visceral and subcutaneous adipose tissue samples were used to analyze the differences in adipocyte function by western blot. RESULTS: Patients with EBWL < 37.7% at 3 months post-LSG (suboptimal group) comprised less likelihood of achieving ≥ 50% EBWL than those who achieved ≥ 37.7% EBWL (optimal group) at 6 months (42.55% vs. 95.52% in optimal group, p < 0.001), 12 months (85.11% vs. 99.25% in optimal group, p < 0.001) and 24 months (77.14% vs. 94.74% in optimal group, p = 0.009) post-LSG. High BMI (OR = 1.222, 95% CI 1.138-1.312, p < 0.001), NLR ≥ 2.36 (OR = 2.915, 95% CI 1.257-6.670, p = 0.013), and female sex (OR = 3.243, 95% CI 1.306-8.051, p = 0.011) significantly predicted EBWL < 37.7% at 3 months post-LSG. Patients with NLR ≥ 2.36 had significantly lower adipose triglyceride lipase in omental fat (p = 0.025). CONCLUSION: EBWL < 37.7% at 3 months post-LSG is a strong predictor of subsequent suboptimal weight loss. High BMI, NLR ≥ 2.36, and female sex are risk factors in predicting EBWL < 37.7% at 3 months post-LSG. These findings may offer a reference to apply adjuvant weight loss medications to patients who are predisposed to suboptimal outcomes.

Chemical characteristics and formation mechanism of secondary inorganic aerosols: The decisive role of aerosol acidity and meteorological conditions.

In recent years, there has been a growing concern about air pollution and its impact on the air quality and human health, especially for fine particulate matter (PM2.5) and its associated secondary aerosols in urban areas. This study conducted a year-long field campaign to collect PM2.5 samples day and night in an urban area of central Taiwan. Higher PM2.5 mass concentrations were observed in winter (27.7 ± 9.7 µg/m3), followed by autumn (22.5 ± 8.3 µg/m3), spring (19.2 ± 6.4 µg/m3), and summer (11.0 ± 3.1 µg/m3). The dominant formation mechanism of secondary inorganic aerosols was heterogeneous reactions of NO3- at night and homogeneous reactions of SO42- during the day. Additionally, significant correlations were observed between aerosol liquid water content (ALWC) and NO3- during nighttime, indicating the importance of aqueous-phase NO3- formation. The role of aerosol acidity was explored and a unique alkaline condition was found in spring and summer, which showed lower PM2.5 concentrations than the neutralized condition. Under the neutralized condition, higher PM2.5 concentrations were commonly found when combining the ammonium-rich regime with molar ratios of [NO3-]/[SO42-] exceeding 1.6, suggesting the importance of reducing both NH3 and NOx. Furthermore, the results showed that reducing NH3 should be prioritized under high temperature conditions, while reducing NOx became important under low temperature conditions. Clustering of backward trajectories showed that long-range transport could enhance the formation of secondary aerosols, but local emissions emerged as the main factor driving high PM2.5 concentrations. This study provides insights for policymakers to improve air quality, suggesting that different mitigation strategies should be formulated based on meteorological variables and that using clean energy for vehicles and electricity generation is important to alleviate air pollution.

Engineering of Aromatic Naphthalene and Solvent Molecules to Optimize Chemical Prelithiation for Lithium-Ion Batteries.

A cost-effective chemical prelithiation solution, which consists of Li+, polyaromatic hydrocarbon (PAH), and solvent, is developed for a model hard carbon (HC) electrode. Naphthalene and methyl-substituted naphthalene PAHs, namely 2-methylnaphthalene and 1-methylnaphthalene, are first compared. Grafting an electron-donating methyl group onto the benzene ring can decrease electron affinity and thus reduce the redox potential, which is validated by density functional theory calculations. Ethylene glycol dimethyl ether (G1), diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether solvents are then compared. The G1 solution has the highest conductivity and least steric hindrance, and thus the 1-methylnaphthalene/G1 solution shows superior prelithiation capability. In addition, the effects of the interaction time between Li+ and 1-methylnaphthalene in G1 solvent on the electrochemical properties of a prelithiated HC electrode are investigated. Nuclear magnetic resonance data confirm that 10-h aging is needed to achieve a stable solution coordination state and thus optimal prelithiation efficacy. It is also found that appropriate prelithiation creates a more Li+-conducing and robust solid-electrolyte interphase, improving the rate capability and cycling stability of the HC electrode.

Hydrogen-treated CoCrMo alloy: a novel approach to enhance biocompatibility and mitigate inflammation in orthopedic implants.

In recent decades, orthopedic implants have been widely used as materials to replace human bone tissue functions. Among these, metal implants play a crucial role. Metals with better chemical stability, such as stainless steel, titanium alloys, and cobalt-chromium-molybdenum (CoCrMo) alloy, are commonly used for long-term applications. However, good chemical stability can result in poor tissue integration between the tissue and the implant, leading to potential inflammation risks. This study creates hydrogenated CoCrMo (H-CoCrMo) surfaces, which have shown promise as anti-inflammatory orthopedic implants. Using the electrochemical cathodic hydrogen-charging method, the surface of the CoCrMo alloy was hydrogenated, resulting in improved biocompatibility, reduced free radicals, and an anti-inflammatory response. Hydrogen diffusion to a depth of approximately 106 ± 27 nm on the surface facilitated these effects. This hydrogen-rich surface demonstrated a reduction of 85.2% in free radicals, enhanced hydrophilicity as evidenced by a decrease in a contact angle from 83.5 ± 1.9° to 52.4 ± 2.2°, and an increase of 11.4% in hydroxyapatite deposition surface coverage. The cell study results revealed a suppression of osteosarcoma cell activity to 50.8 ± 2.9%. Finally, the in vivo test suggested the promotion of new bone formation and a reduced inflammatory response. These findings suggest that electrochemical hydrogen charging can effectively modify CoCrMo surfaces, offering a potential solution for improving orthopedic implant outcomes through anti-inflammatory mechanisms.

Tracing the footprints of MPXV in Asia: phylogenetic insights and lineage dynamics.

OBJECTIVES: The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive genomic surveillance to understand the virus's evolution and spread is needed, particularly in Asia. METHODS: Genomic data from 169 MPXV genome sequences in Asia were analysed. Through advanced genomic sequencing of clinical samples, we analysed the distribution and mutations of MPXV lineages in Asia. RESULTS: Phylogenetic analysis revealed a distinct clustering of C.1 strains rise in Northeast Asia in 2023, while genomic examination identified specific consensus mutations like R84K, R665C and L16F in C.1 strains. The mutations, coupled with an increased rate of apolipoprotein B mRNA-editing catalytic polypeptide-like 3 motif G-to-A mutations in C.1 (OR 24.87±8.81), indicate a potential adaptation mechanism. CONCLUSIONS: Our findings underscore the need for ongoing surveillance and provide vital insights into MPXV's evolving dynamics, aiding in public health strategy formulation against this emerging infectious threat.

N-Benzylated 5-Hydroxybenzothiophene-2-carboxamides as Multi-Targeted Clk/Dyrk Inhibitors and Potential Anticancer Agents.

Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective Clk1 inhibitors, which were based on the 5-methoxybenzothiophene-2-carboxamide scaffold. By incorporating a 5-hydroxy group, we increased the potential for additional hydrogen bond interactions that broadened the inhibitory effect to include Dyrk1A and Dyrk1B kinases. Within this series, compounds 12 and 17 emerged as the most potent multi-kinase inhibitors against Dyrk1A, Dyrk1B, and Clk1. Furthermore, when assessed against the most closely related kinases also implicated in cancer, the frontrunner compounds revealed additional inhibitory activity against Haspin and Clk2. Compounds 12 and 17 displayed high potency across various cancer cell lines with minimal effect on non-tumor cells. By examining the effect of these inhibitors on cell cycle distribution, compound 17 retained cells in the G2/M phase and induced apoptosis. Compounds 12 and 17 could also increase levels of cleaved caspase-3 and Bax, while decreasing the expression of the antiapoptotic Bcl-2 protein. These findings support the further study and development of these compounds as novel anticancer therapeutics.