KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of ß-amyloid (Aß) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding of the extent and role of adaptive immune responses in AD has been quite limited. T cells, as essential members of the adaptive immune system, exhibit quantitative and functional abnormalities in the brains of AD patients. Dysfunction of the blood-brain barrier (BBB) in AD is considered one of the factors leading to T cell infiltration. Moreover, the degree of neuronal loss in AD is correlated with the quantity of T cells. We first describe the differentiation and subset functions of peripheral T cells in AD patients and provide an overview of the key findings related to BBB dysfunction and how T cells infiltrate the brain parenchyma through the BBB. Furthermore, we emphasize the risk factors associated with AD, including Aß, Tau protein, microglial cells, apolipoprotein E (ApoE), and neuroinflammation. We discuss their regulation of T cell activation and proliferation, as well as the connection between T cells, neurodegeneration, and cognitive decline. Understanding the innate immune response is crucial for providing comprehensive personalized therapeutic strategies for AD.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Arginine vasopressin induces ferroptosis to promote heart failure via activation of the V1aR/CaN/NFATC3 pathway.

Arginine vasopressin (AVP) is a key contributor to heart failure (HF), but the underlying mechanisms remain unclear. In the present study, a mouse model of HF and human cardiomyocyte (HCM) cells treated with dDAVP are generated in vivo and in vitro, respectively. Hematoxylin and eosin (HE) staining is used to evaluate the morphological changes in the myocardial tissues. A colorimetric method is used to measure the iron concentration, Fe 2+ concentration and malondialdehyde (MDA) level. Western blot analysis is used to examine the protein levels of the V1a receptor (V1aR), calcineurin (CaN), nuclear factor of activated T cells isoform C3 (NFATC3), glutathione peroxidase 4 (GPX4) and acyl-CoA synthase long chain family member 4 (ACSL4). Immunoprecipitation (IP) and luciferase reporter assays are performed to determine the interaction between NFATC3 and ACSL4. Both in vivo and in vitro experiments reveal that the V1aR-CaN-NFATC3 signaling pathway and ferroptosis are upregulated in HFs, which are verified by the elevated protein levels of V1aR, CaN, NFATC3 and ACSL4; reduced GPX4 protein level; and enhanced Fe 2+ and MDA levels. We further find that inhibiting NFATC3 by suppressing the V1aR/CaN/NFATC3 pathway via V1aR/CaN inhibitors or sh-NFATC3 not only alleviates HF but also inhibits AVP-induced ferroptosis. Mechanistically, sh-NFATC3 significantly reverses the increase in AVP-induced ACSL4 protein level, Fe 2+ concentration, and MDA level by directly interacting with ACSL4. Our results demonstrate that AVP enhances ACSL4 expression by activating the V1aR/CaN/NFATC3 pathway to induce ferroptosis, thus contributing to HF. This study may lead to the proposal of a novel therapeutic strategy for HF.

Wogonin preconditioning of MSCs improved their therapeutic efficiency for colitis through promoting glycolysis.

Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and further explore the underlying mechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.

From Research to Roach Traps: Practical Considerations for a Home-Based Asthma Program.

CONTEXT: Home-based asthma interventions have a significant evidence base as an effective means to address moderate and severe breathing concerns triggered by home conditions. However, the literature lacks logistical and staffing considerations necessary to successfully implement such a program at a governmental level. This practice report and process evaluation outlines practical details and lessons learned during a healthy homes pilot, and how they were addressed in the design of a permanent program. OBJECTIVE: To inform the creation of a permanent home-based asthma intervention at the Alexandria Health Department (AHD) (City of Alexandria, Virginia) and understand the tools and resources necessary for success. INTERVENTION: Participating households received a health and environmental assessment, followed by cleaning supplies, relevant education, and referrals to partners for services. AHD staff tracked challenges and insights at each step of the intervention. At the end of the pilot, staff worked with the community to identify solutions and design a permanent program. CONCLUSIONS: Although the pilot model was constructed based on existing case studies, technical assistance from national experts, and guidance documents, the team still experienced challenges around recruitment, staff support, home visit implementation, and impact evaluation. While pilots and existing literature can be instructive for identifying issues, work with residents and partners to develop a uniquely tailored community program was essential for practical success. IMPLICATIONS ON POLICY AND PRACTICE: Health departments developing new initiatives should consider both the staff and participant experience throughout the creation of administrative and programmatic processes. Testing out draft versions of these processes and materials using internal and external focus groups can identify potential bottlenecks and solutions upfront.

Clinical Efficacy of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Coronary Heart Disease Patients with SYNTAX Score ≥33 and Euro Score ≥6: A Single-Center Retrospective Analysis.

OBJECTIVE: To observe clinical efficacy of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary heart disease patients with SYNTAX scores (SS) ≥33 and Euro Scores (ES) ≥6 who are unsuitable for or have declined coronary artery bypass graft (CABG). METHODS: A total of 117 patients with SS ≥33 and Euro Score (ES) ≥6 who were unsuitable for and/or who had declined CABG between Jan 2021 and June 2022 were enrolled in this retrospective analysis. All patients accepted optimal medical therapy and some accepted an FFR-guided PCI procedure. Patients who only underwent optimal medical therapy were divided into the optimal medical therapy group (OMT group) and patients who simultaneously underwent FFR-guided PCI procedure were divided into the PCI group in this retrospective analysis. All patients accepted follow-up for at least 12 months after discharge. RESULTS: SS and ES in the two groups were not statistically different (p > 0.05). Patients with chronic total occlusion accounted for a greater proportion in the PCI subgroup (31.3%, 5/16) than in other subgroups. Eighteen (18.6%, 18/97) cases in the PCI group developed major adverse cardiac and cerebrovascular events (MACCEs). There were 12 (60%, 12/20) cases of MACCEs in the OMT group, which was statistically different from the PCI group (p < 0.05). CONCLUSIONS: Based on optimal medical therapy, FFR-guided PCI can still have clinical benefit to coronary artery disease patients with SS ≥33 who were not suitable for CABG.

WTAP-MEDIATED M6A MODIFICATION OF KLF6 AGGRAVATES HYPOXIA/REOXYGENATION-INDUCED HUMAN CARDIOMYOCYTE INJURY.

ABSTRACT: Background: Myocardial infarction (MI) is a severe condition that typically results from the ischemia and necrosis of heart muscle. Kruppel-like factor 6 (KLF6) can aggravate myocardial ischemia/reperfusion injury. This work aims to reveal its role and mechanism in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. Methods: Human cardiomyocyte (AC16) was exposed to hypoxic treatment to mimic MI-like cell injury. mRNA expression levels of KLF6 and WT1-associated protein (WTAP) were detected by quantitative real-time polymerase chain reaction. Protein expression was detected by western blotting assay. Cell viability was assessed by CCK-8 assay. Cell apoptosis and cell cycle were investigated by flow cytometry. Enzyme-linked immunosorbent assays were conducted to detect IL-1ß, TNF-α and IL-6 levels. Fe 2+ colorimetric assay kit was used to detect Fe 2+ level. MDA Content Assay Kit was used to detect MDA level. Cellular ROS Assay kit was applied to assess ROS level. The association of KLF6 and WTAP was identified by RNA immunoprecipitation assay and dual-luciferase reporter assay. Results: KLF6 and WTAP expression at mRNA and protein levels were significantly upregulated in serum samples of MI patients and H/R-induced AC16 cells when compared with control groups. KLF6 silencing attenuated H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis. Additionally, WTAP stabilized KLF6 mRNA by regulating its m6A modification. Furthermore, WTAP knockdown rescued H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis by decreasing KLF6 expression. Conclusion: WTAP-mediated m6A modification of KLF6 aggravated hypoxia/reoxygenation-induced apoptosis, inflammatory response, oxidative stress, and ferroptosis of human cardiomyocytes, providing a therapeutic strategy for MI.

Research on prediction and evaluation algorithm of sports athletes performance based on neural network.

BACKGROUND: The Ultimate Fighting Championship (UFC) stands as a prominent global platform for professional mixed martial arts, captivating audiences worldwide. With its continuous growth and globalization efforts, UFC events have garnered significant attention and achieved commendable results. However, as the scale of development expands, the operational demands on UFC events intensify. At its core, UFC thrives on the exceptional performances of its athletes, which serve as the primary allure for audiences. OBJECTIVE: This study aims to enhance the allure of UFC matches and cultivate exceptional athletes by predicting athlete performance on the field. To achieve this, a recurrent neural network prediction model based on Bidirectional Long Short-Term Memory (BiLSTM) is proposed. The model seeks to leverage athlete portraits and characteristics for performance prediction. METHODS: The proposed methodology involves constructing athlete portraits and analyzing athlete characteristics to develop the prediction model. The BiLSTM-based recurrent neural network is utilized for its ability to capture temporal dependencies in sequential data. The model's performance is assessed through experimental analysis. RESULTS: Experimental results demonstrate that the athlete performance prediction model achieved an overall accuracy of 0.7524. Comparative analysis reveals that the proposed BiLSTM model outperforms traditional methods such as Linear Regression and Multilayer Perceptron (MLP), showcasing superior prediction accuracy. CONCLUSION: This study introduces a novel approach to predicting athlete performance in UFC matches using a BiLSTM-based recurrent neural network. By leveraging athlete portraits and characteristics, the proposed model offers improved accuracy compared to classical methods. Enhancing the predictive capabilities in UFC not only enriches the viewing experience but also contributes to the development of exceptional athletes in the sport.

Effect of dietary supplementation with sanguinarine on meat quality and lipid metabolism of broilers.

Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.

Enzymatic synthesis of pyridine heterocyclic compounds and their thermal stability.

An efficient method was discovered for catalyzing the esterification under air using Novozym 435 to obtain pyridine esters. The following conditions were found to be optimal: 60 mg of Novozyme 435, 5.0 mL of n-hexane, a molar ratio of 2:1 for nicotinic acids (0.4 mmol) to alcohols (0.2 mmol), 0.25 g of molecular sieve 3A, a revolution speed of 150 rpm, a reaction temperature of 50 °C, and reaction time of 48 h. Under nine cycles of Novozym 435, the 80 % yield was consistently obtained. Optimum conditions were used to synthesize 23 pyridine esters, including five novel compounds. Among them, gas chromatography-mass spectrometry-olfactometry (GC-MS-O) showed phenethyl nicotinate (3g), (E)-hex-4-en-1-yl nicotinate (3m), and octyl nicotinate (3n) possessed strong aromas. Thermogravimetric analysis (TG) revealed that the compounds 3g, 3m and 3n exhibited stability at the specified temperature. This finding provides theoretical support for adding pyridine esters fragrance to high-temperature processed food.

Traditional Chinese herbal medicine retention enema combined with perineal massage (THREM): a promising therapeutic strategy for refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized by lower urinary tract symptoms and persistent pelvic pain or discomfort lasting for more than three months. Currently available oral drug therapies exhibit limited efficacy in the treatment of CP/CPPS. Therefore, personalized and combination therapies are recommended by Chinese CP/CPPS guidelines, which primarily include traditional Chinese medicine, radiofrequency therapy, urethral lavage, transrectal prostate massage, extracorporeal shock wave therapy. However, a significant number of patients do not respond well to all types of these therapeutic methods. Among those who have sequentially or simultaneously undergone at least three different treatment modalities, in addition to oral medications, for more than 1 year, they are defined as patients with refractory CP/CPPS. This retrospective study aims to evaluate the clinical effect of traditional Chinese herbal medicine retention enema combined with perineal massage (THREM) in managing refractory CP/CPPS. Methods: A total of 20 patients with refractory CP/CPPS, who did not show significant improvement despite receiving multiple conventional treatments, including oral medications, were included in this study. Following THREM therapy, the International Prostate Symptom Score (IPSS), visual analogue scale (VAS), and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life (QoL) score were used to assess treatment efficacy. Results: Six months after THREM therapy, a significant decrease in IPSS, VAS, and QoL scores was observed (P<0.01). Importantly, 85% of the patients experienced a reduction in symptoms of ≥60%, with an average degree of alleviation reaching 70.25%±24.20%. Conclusions: THREM treatment demonstrated excellent efficacy in managing refractory CP/CPPS at least for 6 months. It has promising clinical application prospects. Further research is warranted to validate these results and explore the underlying mechanisms of THREM therapy.

Bifonazole caffeate: The first molecular salt of bifonazole with enhanced biopharmaceutical property based on experiments and quantum chemistry research.

In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.

Focused solar annealing for block copolymer fast self-assembly.

Block copolymer (BCP) self-assembly has tremendous potential applications in next-generation nanolithography. It offers significant advantages, including high resolution and cost-effectiveness, effectively overcoming the limitations associated with conventional optical lithography. In this work, we demonstrate a focused solar annealing (FSA) technique that is facile, eco-friendly, and energy-efficient for fast self-assembly of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) thin films. The FSA principle involves utilizing a common biconvex lens to converge incident solar radiation into a high-temperature spot, which is directly used to drive the microphase separation of PS-b-PMMA thin films. As a result, PS-b-PMMA undergoes self-assembly, forming ordered nanostructures in a vertical orientation at seconds timescales on silicon substrates with a neutral layer. In addition, the FSA technique can be employed for grafting neutral polymer brushes onto the silicon substrate. Furthermore, the FSA's compatibility with graphoepitaxy-directed self-assembly (DSA) of BCP is also demonstrated in the patterning of contact holes. The results of contact hole shrinking show that contact hole prepatterns of ∼60.4 nm could be uniformly shrunk to ∼20.5 nm DSA hole patterns with a hole open yield (HOY) of 100 %. For contact hole multiplication, doublet DSA holes were successfully generated on elliptical templates, revealing an average DSA hole size of ∼21.3 nm. Most importantly, due to the direct use of solar energy, the FSA technique provides many significant advantages such as simplicity, environmental friendliness, solvent-free, low cost, and net-zero carbon emissions, and will open up a new direction for BCP lithography that is sustainable, pollution-free, and carbon-neutral.

Fast and sensitive smartphone colorimetric detection of whole blood samples on a paper-based analytical device.

BACKGROUND: Methods based on paper-based analytical devices (PAD) and smartphone photographic colorimetric detection have become representative instrument-independent point-of-care testing (POCT) platforms due to their low cost and simplicity. However, the detection of target components from whole blood sample still presents challenges in terms of field preparation of small amounts of blood sample and detection sensitivity. This paper presents a rapid online processing method for whole blood samples on PAD based on plasma separation membrane (PSM), and combined with electrokinetic stacking and selective chromatic reaction. Real-time smartphone-based colorimetric detection of free hemoglobin (FHb) and human serum albumin (HSA) was successfully demonstrated. RESULTS: With the proposed method, both detections for low and high concentration analytes could be implemented. The limits of detection of 16.6 mg L-1 for FHb and 0.67 g L-1 for HSA were obtained, respectively, with RSD below 8 %. The reliability of the method was verified by the recovery test and desktop spectrophotometric method. The detection results for real blood samples were in agreement with that by clinical methods. SIGNIFICANCE AND NOVELTY: The PAD method is inexpensive, simple and fast, and detection of a whole blood sample of 5 µL can be finished in 5 min. This work shows that POCT of biomarkers from whole blood with PAD is possible without using any desktop facilities.

Revealing the mechanism: the influence of Baicalin on M1/M2 and Th1/Th2 imbalances in mycoplasma gallisepticum infection.

Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.

Manipulating the processing window of directed self-assembly in contact hole shrinking with binary block copolymer/homopolymer blending.

Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

Genomic surveillance and evolutionary dynamics of type 2 porcine reproductive and respiratory syndrome virus in China spanning the African swine fever outbreak.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China's pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China's pig industry in the post-epidemic era of ASF.