Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Direct and specific detection of methyl-paraoxon using a highly sensitive fluorescence strategy combined with phosphatase-like nanozyme and molecularly imprinted polymer.

Methyl paraoxon (MP) is a highly toxic, efficient and broad-spectrum organophosphorus pesticide, which poses significant risks to ecological environment and human health. Many detection methods for MP are based on the enzyme catalytic or inhibition effect. But natural biological enzymes are relatively expensive and easy to be inactivated with a short service life. As a unique tool of nanotechnology with enzyme-like characteristics, nanozyme has attracted increasing concern. However, a large proportion of nanozymes lack the intrinsic specificity, becoming a main barrier of constraining their use in biochemical analysis. Here, we use a one-pot reverse microemulsion polymerization combine the gold nanoclusters (AuNCs) with molecularly imprinted polymers (MIPs), polydopamine (PDA) and hollow CeO2 nanospheres to synthesize the bright red-orange fluorescence probe (CeO2@PDA@AuNCs-MIPs) with high phosphatase-like activity for selective detection of MP. The hollow structure possesses a specific surface area and porous matrix, which not only increases the exposure of active sites but also enhances the efficiency of mass and electron transport. Consequently, this structure significantly enhances the catalytic activity by reducing transport distances. The introduced MIPs provide the specific recognition sites for MP. And Ce (III) can excite aggregation induced emission of AuNCs and enhance the fluorescent signal. The absolute fluorescence quantum yield (FLQY) of CeO2@PDA@AuNCs-MIPs (1.41 %) was 12.8-fold higher than that of the GSH-AuNCs (0.11 %). With the presence of MP, Ce (IV)/Ce (III) species serve as the active sites to polarize and hydrolyze phosphate bonds to generate p-nitrophenol (p-NP), which can quench the fluorescent signal through the inner-filter effect. The as-prepared CeO2@PDA@AuNCs-MIPs nanozyme-based fluorescence method for MP detection displayed superior analytical performances with wide linearities range of 0.45-125 nM and the detection limit of 0.15 nM. Furthermore, the designed method offers satisfactory practical application ability. The developed method is simple and effective for the in-field detection.

Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice.

Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

Universal relation between the conditional auto-correlation function and the cross-correlation function of biphotons.

We systematically studied the relation between the conditional auto-correlation function (CACF) and cross-correlation function (CCF) of biphotons or pairs of single photons. The biphotons were generated from a heated atomic vapor via the spontaneous four-wave mixing (SFWM) process. In practical usage, one single photon of a pair is utilized as the heralding photon, and another is employed as the heralded photon. Motivated by the data of CACF of the heralded photons versus CCF, we proposed a universal formula to predict the CACF. The derived formula was based on general theory and is also valid for the biphoton generation process of spontaneous parametric down-conversion (SPDC). With the formula, we utilized the experimentally determined parameters to predict CACFs, which can well agree with the measured CACFs. The proposed formula enables one to quantitatively know the CACF of heralded single photons without the measurement of Hanbury-Brown-Twiss-type three-fold coincidence count. This study provides a better understanding of biphoton generation using the SFWM or SPDC process. Our work demonstrates a valuable tool for analyzing a vital property of how the heralded photons are close to Fock-state single photons.

Comprehensive assessment of combined inorganic and organic fertilization strategies on cotton cultivation: implications for sustainable agriculture.

BACKGROUND: The integration of inorganic and organic fertilizers is increasingly being recommended to address the demand for sustainable cotton cultivation and to mitigate the ecological impacts of reliance on inorganic fertilizers. However, the nuanced effects of this combined fertilization approach on soil quality, cotton growth, yield, and their interaction mechanisms, remain unclear. METHOD: To elucidate this, a 2-year field trial (2022-2023) was conducted, incorporating five fertilization treatments: low inorganic fertilizer (BI1), high inorganic fertilizer (BI2), organic fertilizer (BO), combined low inorganic and organic fertilizer (BIO1), and combined high inorganic and organic fertilizer (BIO2). This study aimed to evaluate the influence of these treatments on soil quality, cotton growth, and yield. RESULTS: The results indicate that the BO treatment significantly enhanced plant height growth rate, and BIO1 treatment increased leaf area index and dry matter accumulation growth rate. Critical soil parameters such as alkali-hydrolyzed nitrogen and available potassium emerged as pivotal determinants of soil quality over the trial period, corresponding to soil quality index (SQI) values of 0.482 and 0.478, and yields of 7506.19 kg ha-1 and 6788.02 kg ha-1, respectively. Water productivity reached optimum levels at SQI values of 0.461 and 0.462, with corresponding efficiencies of 13.31 kg (ha mm)-1 and 12.16 kg (ha mm)-1. Partial least squares path modeling revealed that integrating organic fertilizer with reduced inorganic fertilizer usage significantly boosts cotton yield by enhancing soil quality (path coefficient: 0.842). CONCLUSION: In conclusion, this integrated fertilization strategy not only improves soil health but also increases agricultural productivity. It presents a promising approach for optimizing crop yields while fostering sustainable agricultural practices. © 2024 Society of Chemical Industry.

Deep self-reconstruction driven joint nonnegative matrix factorization model for identifying multiple genomic imaging associations in complex diseases.

OBJECTIVE: Comprehensive analysis of histopathology images and transcriptomics data enables the identification of candidate biomarkers and multimodal association patterns. Most existing multimodal data association studies are derived from extensions of the joint nonnegative matrix factorization model for identifying complex data associations, which can make full use of clinical prior information. However, the raw data were usually taken as the input without considering the underlying complex multi-subspace structure, influencing the subsequent integration analysis results. METHODS: This study proposed a deep-self reconstructed joint nonnegative matrix factorization (DSRJNMF) model to use self-expressive properties to reconstruct the raw data to characterize the similarity structure associated with clinical labels. Then, the sparsity, orthogonality, and regularization constraints constructed from prior information are added to the DSRJNMF model to determine the sparse set of biologically relevant features across modalities. RESULTS: The algorithm has been applied to identify the imaging genetic association of triple negative breast cancer (TNBC). Multilevel experimental results demonstrate that the proposed algorithm better estimates potential associations between pathological image features and miRNA-gene and identifies consistent multimodal imaging genetic biomarkers to guide the interpretation of TNBC. CONCLUSION: The propose method provides a novel idea of data association analysis oriented to complex diseases.

Assessment of the herpes zoster risk among renal transplant recipients administered the influenza vaccine.

BACKGROUND: Reactivation of the latent varicella-zoster virus can cause herpes zoster (HZ) infection, and renal transplant recipients undergoing immunosuppressive therapy are particularly susceptible to this condition. This study aims to evaluate the potential increase in HZ incidence following influenza vaccination among this specific patient population. METHODS: This study was a population-based, retrospective, self-controlled case series. Data were retrieved from Taiwan's National Health Insurance Research Database spanning the years 2008 to 2017. Patients diagnosed with HZ within a 6-month period before and after receiving the influenza vaccine were eligible for inclusion. Two distinct time intervals were defined for analysis: the initial 15 days and 30 days following vaccination were categorized as risk intervals, while all other periods served as control intervals. Incidence rate ratios (IRRs) were computed to compare HZ incidence during the risk intervals with that during the control intervals. RESULTS: This study encompassed a cohort of 4,222 renal transplant recipients who had received the influenza vaccine. Among this group, 67 recipients were subsequently diagnosed with HZ. The IRR during both the initial 15 days (IRR = 0.63; 95 % CI, 0.23-1.89) and the first 30 days (IRR = 1.50; 95 % CI, 0.71-3.16) following influenza vaccination did not demonstrate a statistically significant increase when compared to the post-exposure observation times. Comparable results were also observed when comparing these IRR values to the pre-exposure observation times. The subgroup analysis, stratified by age, sex, and underlying medical conditions (including cancer and autoimmune diseases), revealed that the IRRs did not exhibit statistically significant differences. CONCLUSIONS: No significant association between the influenza vaccine and an elevated risk of HZ was detected. The administration of annual influenza vaccines appears to be a reasonable practice for renal transplant recipients.

The mechanism of using magnetized-ionized water in combination with organic fertilizer to enhance soil health and cotton yield.

Addressing critical challenges in sustainable agriculture, notably water scarcity and soil degradation, necessitates innovative irrigation and fertilization methods. This investigation thoroughly assessed the effects of combining inorganic and organic fertilizers under brackish water irrigation, particularly focusing on magnetized-ionized brackish water-a promising solution for these challenges. The study shows that the integration of inorganic and organic fertilizers notably enhances soil water retention and salt leaching when applied with magnetized-ionized brackish water irrigation (MIBIO treatment), with water storage rate and salt accumulation rate observed at -0.454 and -0.075, respectively. Additionally, soil microbial diversity and uniformity witnessed significant improvement, positively influencing cotton growth rates, particularly noting a dry matter accumulation rate of 9.3262 kg·(ha·°C)-1. Transcriptomic analysis revealed that the MIBIO treatment elevated gene expression during the boll period, with notable enrichment in pathways such as the MAPK signaling pathway-plant and amino sugar and nucleotide sugar metabolism. Furthermore, the partial least squares path modeling indicated that soil alkali-hydrolyzed nitrogen (AN) and available potassium (AK) positively impact cotton leaf transcription and yield, with path coefficients of 0.613 and 0.428, respectively. Specifically, AN and AK contribute to enhancing cotton growth and affect the expression of metabolism genes in cotton leaves, thereby increasing cotton yield. Our study highlights the crucial role of irrigation and fertilization in influencing the soil environment and cotton growth. We recommend the use of magnetized-ionized water irrigation in combination with organic fertilizers as a strategy to boost agricultural productivity. Through the development of these strategies, our goal is to offer farmers practical guidance that can be readily implemented to enhance crop production efficiency, reduce environmental impact, and adhere to the principles of sustainable agriculture.

Advancing precision rheumatology: applications of machine learning for rheumatoid arthritis management.

Rheumatoid arthritis (RA) is an autoimmune disease causing progressive joint damage. Early diagnosis and treatment is critical, but remains challenging due to RA complexity and heterogeneity. Machine learning (ML) techniques may enhance RA management by identifying patterns within multidimensional biomedical data to improve classification, diagnosis, and treatment predictions. In this review, we summarize the applications of ML for RA management. Emerging studies or applications have developed diagnostic and predictive models for RA that utilize a variety of data modalities, including electronic health records, imaging, and multi-omics data. High-performance supervised learning models have demonstrated an Area Under the Curve (AUC) exceeding 0.85, which is used for identifying RA patients and predicting treatment responses. Unsupervised learning has revealed potential RA subtypes. Ongoing research is integrating multimodal data with deep learning to further improve performance. However, key challenges remain regarding model overfitting, generalizability, validation in clinical settings, and interpretability. Small sample sizes and lack of diverse population testing risks overestimating model performance. Prospective studies evaluating real-world clinical utility are lacking. Enhancing model interpretability is critical for clinician acceptance. In summary, while ML shows promise for transforming RA management through earlier diagnosis and optimized treatment, larger scale multisite data, prospective clinical validation of interpretable models, and testing across diverse populations is still needed. As these gaps are addressed, ML may pave the way towards precision medicine in RA.

Molecular characterization, expression analysis and function identification of Pf_IL-12p35, Pf_IL-23p19 and Pf_IL-12p40 genes in yellow catfish (Pelteobagrus fulvidraco).

The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf_IL-12p35a/b, Pf_IL-23p19 and Pf_IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf_IL-12p35a/b and Pf_IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf_IL-12p35a/b and Pf_IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf_IL-12p40a mRNA was induced in gill, and Pf_IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf_IL-12p35a and Pf_IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf_IL-12 and rPf_IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf_IL-12 and Pf_IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development.

Hematoporphyrin derivative-mediated photodynamic techniques for the diagnosis and treatment of chordoma.

BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

Wolbachia symbionts control sex in a parasitoid wasp using a horizontally acquired gene.

Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.

Three undescribed dihydrostilbene glycosides from leaves of Camellia oleifera Abel. And their anti-inflammatory activity.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4-12) were also identified. The undescribed secondary metabolites 1-3 were elucidated as 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4'-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1-4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

Identification of DNA methylation characteristics associated with metastasis and prognosis in colorectal cancer.

Colorectal cancer (CRC) is prone to metastasis and recurrence after surgery, which is one of the main causes for its poor treatment and prognosis. Therefore, it is essential to identify biomarkers associated with metastasis and recurrence in CRC. DNA methylation has a regulatory role in cancer metastasis, tumor immune microenvironment (TME), and prognosis and may be one of the most valuable biomarkers for predicting CRC metastasis and prognosis. We constructed a diagnostic model and nomogram that can effectively predict CRC metastasis based on the differential methylation CpG sites (DMCs) between metastatic and non-metastatic CRC patients. Then, we identified 17 DMCs associated with progression free survival (PFS) of CRC and constructed a prognostic model. The prognosis model based on 17 DMCs can predict the PFS of CRC with medium to high accuracy. The results of immunohistochemical analysis indicated that the protein expression levels of the genes involved in prognostic DMCs were different between normal and colorectal cancer tissues. According to the results of immune-related analysis, we found that the low-risk patients had better immunotherapy response. In addition, high risk scores were negatively correlated with high tumor mutation burden (TMB) levels, and patients with low TMB levels in the high-risk group had the worst PFS. Our work shows the clinical value of DNA methylation in predicting CRC metastasis and PFS, as well as their correlation with TME, immunotherapy, and TMB, which helps understand the changes of DNA methylation in CRC metastasis and improving the treatment and prognosis of CRC.

Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments.

Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2), apoptosis (Interferon Alpha Inducible Protein 6, G1P3), differentiation (Grainyhead Like Transcription Factor 2, GRHL2), and angiogenesis (Vascular Endothelial Growth Factor, VEGF); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, TNF-α; Interleukin-17, IL-17); and signaling pathways (JAK-STAT, Nuclear Factor Kappa B, NF-κB) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.

Effects of Organic Fertilizer on Photosynthesis, Yield, and Quality of Pakchoi under Different Irrigation Conditions.

Water scarcity and the overuse of chemical fertilizers present significant challenges to modern agriculture, critically affecting crop photosynthesis, yield, quality, and productivity sustainability. This research assesses the impact of organic fertilizer on the photosynthetic attributes, yield, and quality of pakchoi under varying irrigation water conditions, including fresh water and brackish water. Findings reveal that the modified rectangular hyperbolic model most accurately captures the photosynthetic reaction to organic fertilization, outperforming other evaluated models. The maximum net photosynthesis rate (Pnmax), yield, soluble sugar (SS), and soluble protein content (SP) all exhibited a downward-opening quadratic parabolic trend with increasing amounts of organic fertilizer application. Specifically, under fresh-water irrigation, the optimal Pnmax, yield, SS, and SP were obtained at organic fertilizer rates of 65.77, 74.63, 45.33, and 40.79 kg/ha, respectively, achieving peak values of 20.71 µmol/(m2·s), 50,832 kg/ha, 35.63 g/kg, and 6.25 g/kg. This investigation provides a foundational basis for further research into the intricate relationship between water salinity stress and nutrient management, with the goal of crafting more sophisticated and sustainable farming methodologies. The insights gained could significantly influence organic fertilizer practices, promoting not only higher yields but also superior quality in agricultural outputs.

Macrophage polarization in rheumatoid arthritis: signaling pathways, metabolic reprogramming, and crosstalk with synovial fibroblasts.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Macrophages are key effector cells that play a central role in RA pathogenesis through their ability to polarize into distinct functional phenotypes. An imbalance favoring pro-inflammatory M1 macrophages over anti-inflammatory M2 macrophages disrupts immune homeostasis and exacerbates joint inflammation. Multiple signaling pathways, including Notch, JAK/STAT, NF-κb, and MAPK, regulate macrophage polarization towards the M1 phenotype in RA. Metabolic reprogramming also contributes to this process, with M1 macrophages prioritizing glycolysis while M2 macrophages utilize oxidative phosphorylation. Redressing this imbalance by modulating macrophage polarization and metabolic state represents a promising therapeutic strategy. Furthermore, complex bidirectional interactions exist between synovial macrophages and fibroblast-like synoviocytes (FLS), forming a self-perpetuating inflammatory loop. Macrophage-derived factors promote aggressive phenotypes in FLS, while FLS-secreted mediators contribute to aberrant macrophage activation. Elucidating the signaling networks governing macrophage polarization, metabolic adaptations, and crosstalk with FLS is crucial to developing targeted therapies that can restore immune homeostasis and mitigate joint pathology in RA.

Stacking architecture for collimated backlight using cylindrical lens sheet with linear light sources or edge-lit/direct-lit BLU.

Highly collimated and directional backlights are essential for realizing advanced display technologies such as autostereoscopic 3D displays. Previously reported collimated backlights, either edge-lit or direct-lit, in general still suffer unsatisfactory form factors, directivity, uniformity, or crosstalk etc. In this work, we report a simple stacking architecture for the highly collimated and uniform backlights, by combining linear light source arrays and carefully designed cylindrical lens arrays. Experiments were conducted to validate the design and simulation, using the conventional edge-lit backlight or the direct-lit mini-LED (mLED) arrays as light sources, the NiFe (stainless steel) barrier sheets, and cylindrical lens arrays fabricated by molding. Highly collimated backlights with small angular divergence of ±1.45°âˆ¼±2.61°, decent uniformity of 93-96%, and minimal larger-angle sidelobes in emission patterns were achieved with controlled divergence of the light source and optimization of lens designs. The architecture reported here provides a convenient way to convert available backlight sources into a highly collimated backlight, and the use of optically reflective barrier also helps recycle light energy and enhance the luminance. The results of this work are believed to provide a facile approach for display technologies requiring highly collimated backlights.

Hyperacute Radiation Pneumonitis after Severe irAE.

A 54-year-old woman presented to an outpatient clinic with a recurrence of triple-negative breast cancer and multiple bone metastases. The patient had a large mass lesion of 10 cm on the sternum. She received the immune checkpoint inhibitors pembrolizumab and taxane. Initially, the patient responded excellently to treatment, but stopped pembrolizumab for grade IV skin toxicity with multiple ulcerative wounds over the bilateral leg and trunk. The lesions abated following administration of antibiotics and oral prednisolone for two months. After that, she was referred to the radiation oncology department for further treatment. She received radiotherapy for the sternum mass but stopped radiation at 42Gy/21 fractions for severe dyspnea and fever. Blood sampling found leukocytosis with neutrophil predominance. Chest radiography showed bilateral lung infiltration. Pulmonary CT scan yielded bilateral lung patchy consolidation compatible with radiation isodose-line. Bronchial lavage showed positive Pneumocystis jiroveci PCR. Dyspnea improved after titrating methylprednisolone within two days. The patient recovered well with TMP-SMX and glucocorticoids after the initiation of therapy.

Syphilis and cardiovascular risk: a Taiwanese registry.

BACKGROUND AND AIMS: Studies on the impact of syphilis on the cardiovascular system in large populations are limited. This study investigated the effects of syphilis on cardiovascular outcomes. METHODS: Medical records from 2010 to 2015 were retrieved from the Taiwan National Health Insurance Research Database, linked to the Notifiable Infectious Diseases database from the Taiwan Centers for Disease Control. Patients with syphilis were identified, excluding those with missing information, under 20 years of age, or with a history of human immunodeficiency virus infection, acute myocardial infarction, heart failure, aortic regurgitation, replacement of the aortic valve, aneurysm and/or dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, and venous thromboembolism. Primary outcomes included new-onset acute myocardial infarction, heart failure, aortic regurgitation, aneurysm and dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, cardiovascular death, and all-cause mortality. RESULTS: A total of 28 796 patients with syphilis were identified from 2010 to 2015. After exclusions and frequency matching, 20 601 syphilis patients and 20 601 non-syphilis patients were analysed. The relative rate (RR) was utilized in the analysis, as the competing risk of death was not considered. Compared with patients without syphilis, patients with syphilis had increased risks of acute myocardial infarction (RR 38%, 95% confidence interval [CI] 1.19-1.60, P < .001), heart failure (RR 88%, 95% CI 1.64-2.14, P < .001), aortic regurgitation (RR 81%, 95% CI 1.18-2.75, P = .006), atrial fibrillation (RR 45%, 95% CI 1.20-1.76, P < .001), ischaemic stroke (RR 68%, 95% CI 1.52-1.87, P < .001), haemorrhagic stroke (RR 114%, 95% CI 1.74-2.64, P < .001), venous thromboembolism (RR 67%, 95% CI 1.23-2.26, P = .001), cardiovascular death (RR 155%, 95% CI 2.11-3.08, P < .001), and all-cause death (RR 196%, 95% CI 2.74-3.19, P < .001) but not for aneurysm and dissection of the aorta. CONCLUSIONS: This study demonstrates that patients with syphilis have a higher risk of cardiovascular events and all-cause mortality compared with those without syphilis.