Research on the wear trend analysis model and application method of diffraction grating ruling tools.

Tool wear is one of the main causes of failure during diffraction grating ruling. However, no theoretical model for tool wear analysis has been available to date. A mathematical model is established here to solve for the friction coefficient at the tool contact position for the first time. Based on the ruling principles for diffraction gratings, four parameters comprising the tool cutting edge radius, knife angle, pitch angle, and tool ruling depth, are introduced into the model. The positive pressure and shear stress acting on the tool contact surface element during plastic deformation of the metal film layer are given, and an integral is performed over the area where the tool meets the metal film layer. Equations describing the friction coefficients at different positions on the tip point and the main edge are derived. The friction coefficients at the tip point and main edge positions are then calculated using the model. The cutting edge radius, tool tip angle, and pitch angle are used as variables. The maximum value distribution of the friction coefficients of the anti-wear ruling tool is analyzed, and the principle that parameter selection for the anti-wear ruling tool should meet requirements for a large cutting edge radius, small pitch angle, and large tool tip angle is proposed for the first time. This principle provides the key to solving the technical problem where tool wear occurs easily during ruling of large-area echelle gratings, which has puzzled researchers for many years. Finally, a ruling experiment is performed using a 79 gr/mm echelle grating. Under the large pitch angle condition, the tool jumping phenomenon occurs because of excessive friction force, which results in ruling failure. The numerical analysis results are verified. The research results in this paper can provide a theoretical basis for anti-wear tool design and ruling process optimization.

Probiotic-Induced Modulation of Microbiota Composition and Antibiotic Resistance Genes Load, an In Vitro Assessment.

The imbalance of the gut microbiota (GM) is known as dysbiosis and is associated with disorders such as obesity. The increasing prevalence of microorganisms harboring antibiotic resistance genes (ARG) in the GM has been reported as a potential risk for spreading multi-drug-resistant pathogens. The objective of this work was the evaluation, in a fecal culture model, of different probiotics for their ability to modulate GM composition and ARG levels on two population groups, extremely obese (OB) and normal-weight (NW) subjects. Clear differences in the basal microbiota composition were observed between NW and OB donors. The microbial profile assessed by metataxonomics revealed the broader impact of probiotics on the OB microbiota composition. Also, supplementation with probiotics promoted significant reductions in the absolute levels of tetM and tetO genes. Regarding the blaTEM gene, a minor but significant decrease in both donor groups was detected after probiotic addition. A negative association between the abundance of Bifidobacteriaceae and the tetM gene was observed. Our results show the ability of some of the tested strains to modulate GM. Moreover, the results suggest the potential application of probiotics for reducing the levels of ARG, which constitutes an interesting target for the future development of probiotics.

A new scheme of PM2.5 and O3 control strategies with the integration of SOM, GA and WRF-CAMx.

Previous air pollution control strategies didn't pay enough attention to regional collaboration and the spatial response sensitivities, resulting in limited control effects in China. This study proposed an effective PM2.5 and O3 control strategy scheme with the integration of Self-Organizing Map (SOM), Genetic Algorithm (GA) and WRF-CAMx, emphasizing regional collaborative control and the strengthening of control in sensitive areas. This scheme embodies the idea of hierarchical management and spatial-temporally differentiated management, with SOM identifying the collaborative subregions, GA providing the optimized subregion-level priority of precursor emission reductions, and WRF-CAMx providing response sensitivities for grid-level priority of precursor emission reductions. With Beijing-Tianjin-Hebei and the surrounding area (BTHSA, "2 + 26" cities) as the case study area, the optimized strategy required that regions along Taihang Mountains strengthen the emission reductions of all precursors in PM2.5-dominant seasons, and strengthen VOCs reductions but moderate NOx reductions in O3-dominant season. The spatiotemporally differentiated control strategy, without additional emission reduction burdens than the 14th Five-Year Plan proposed, reduced the average annual PM2.5 and MDA8 O3 concentrations in 28 cities by 3.2%-8.2% and 3.9%-9.7% respectively in comparison with non-differential control strategies, with the most prominent optimization effects occurring in the heavily polluted seasons (6.9%-18.0% for PM2.5 and 3.3%-14.2% for MDA8 O3, respectively). This study proposed an effective scheme for the collaborative control of PM2.5 and O3 in BTHSA, and shows important methodological implications for other regions suffering from similar air quality problems.

High-fat/high-sucrose diet worsens metabolic outcomes and widespread hypersensitivity following early-life stress exposure in female mice.

Exposure to stress early in life has been associated with adult-onset comorbidities such as chronic pain, metabolic dysregulation, obesity, and inactivity. We have established an early-life stress model using neonatal maternal separation (NMS) in mice, which displays evidence of increased body weight and adiposity, widespread mechanical allodynia, and hypothalamic-pituitary-adrenal axis dysregulation in male mice. Early-life stress and consumption of a Western-style diet contribute to the development of obesity; however, relatively few preclinical studies have been performed in female rodents, which are known to be protected against diet-induced obesity and metabolic dysfunction. In this study, we gave naïve and NMS female mice access to a high-fat/high-sucrose (HFS) diet beginning at 4 wk of age. Robust increases in body weight and fat were observed in HFS-fed NMS mice during the first 10 wk on the diet, driven partly by increased food intake. Female NMS mice on an HFS diet showed widespread mechanical hypersensitivity compared with either naïve mice on an HFS diet or NMS mice on a control diet. HFS diet-fed NMS mice also had impaired glucose tolerance and fasting hyperinsulinemia. Strikingly, female NMS mice on an HFS diet showed evidence of hepatic steatosis with increased triglyceride levels and altered glucocorticoid receptor levels and phosphorylation state. They also exhibited increased energy expenditure as observed via indirect calorimetry and expression of proinflammatory markers in perigonadal adipose. Altogether, our data suggest that early-life stress exposure increased the susceptibility of female mice to develop diet-induced metabolic dysfunction and pain-like behaviors.

Absorption characteristics and solar absorption capacity of Au core NR coated with various shell material.

Au nanorods (NRs) can be used to improve the performance of direct absorption solar collectors (DASCs), however, the solar absorption of Au NRs should be further improved because the absorption of Au NRs in near-infrared range is strong while the absorption in visible range is relatively weak where the solar spectrum intensity is the strongest. Based on this tissue, a composite nanostructure composed of Au core NR and Mg shell is proposed to improve the solar absorption capacity. The choice of Mg material as the shell composition is explained. By optimizing the composition structure, the enhancement effect on the absorption properties of Au@Mg NR from visible range to near-infrared range is proven by the finite element method. Furthermore, the effect of imperfect shell on absorption capacity of Au@Mg NR is discussed. Finally, the DASCs performance based on optimal Au@Mg NR nanofluids is evaluated. The results show that when the volume fraction is lower than 2 ppm and the collector depth is 2 cm, the highest solar energy harvesting capacity (>92%) using Au@Mg NRs nanofluids can be obtained, showing an excellent Au-based material for DASCs application.

Effect of various metallic nanoparticles on plasmon-enhanced solar absorption efficiency.

Solar thermal conversion technology has attracted significant attention because it ensures sustainable and modern clean energy generation. The usage of plasmonic nanofluids as the working media is a useful strategy to collect solar energy. In this study, the optical properties of various individual nanospheres (NPs) and nanorods (NRs)--Au, Ag, Cu, Fe, Mg, Mn, Mo, Pb, Ti, Li, and Al--and their effect on the solar absorption efficiency factor (SAEF) with a solar wavelength between 300 nm and 1100 nm are determined using COMSOL Multiphysics software. For NPs, the SAEF is divided into three parts. In the first part with a radius lower than 35 nm, an Li NP has the highest SAEF of 1.3992. In the second part, with a radius between 35 nm and 50 nm, the Au and Cu NPs have the highest SAEFs of 1.1963 and 1.2469, respectively. In the third part, with a radius between 50 nm and 90 nm, the maximum SAEFs of Fe (1.5682 at radius of 75 nm), Pt (1.4914 at radius of 90 nm), Ti (1.4348 at radius of 75 nm), and Mn (1.4614 at radius of 75 nm) can be obtained. Compared to NPs, the SAEF of an NR greatly depends on the aspect ratio (AR) and the effective radius (r e f f ). We observe that the SAEFs of Ag, Al, Au, Cu, Fe Mg, Mn, Mo, and Ti NRs are much stronger than that of corresponding NPs with the same r e f f . The results obtained from the present study provide fundamental information and guidelines to choose optimal NPs for enhancements in solar energy harvesting.

Effect of morphological evolution and aggregation of plasmonic core-shell nanostructures on solar thermal conversion.

Achieving high solar energy absorption based on nanofluids (NFs) needs further study in solar photothermal conversion technology. In this work, we performed COMSOL simulations to investigate the solar energy absorption using a core-shell nanostructure composed of the Au core and shell with different materials. The influence of the radius of the Au core, the materials of the shell, and the shell thickness on the solar absorption efficiency factor (SAEF) are systematically studied. The results show that the SAEF of the Au@Li nanoparticle with ratio of 0.5 has the highest SAEF of 1.4779, increasing 1.99 times compared to that of the bare Au nanoparticle of 0.74326 with the same radius. Moreover, the optical properties, electric field distribution, and SAEF of the Au@Li dimer are further evaluated to demonstrate the aggregation effects on SAEF. We find that the SAEF of the Au@Li dimer reaches the maximum of 4.34 with a distance around 1 nm, where the LSPR coupling effect in the nanogap is sharply enhanced 700 times irradiated by light with wavelength of 760 nm. Finally, the direct absorber solar collector performance demonstrates that Au@Li dimer NFs can collect 93% of solar energy compared to 54% for Au@Li NFs and 51% for Au NFs. This work provides the possibility to achieve more efficient solar thermal conversion, and may have potential applications in efficient solar energy harvesting and utilization.

Exploring the mechanisms of Gui Zhi Fu Ling Wan on varicocele via network pharmacology and molecular docking.

Varicocele (VC) is a common urogenital disease that leads to a high risk of testicular pain or male infertility. The purpose of this research was to explore the molecular mechanism of the Gui Zhi Fu Ling Wan (GFW) in the treatment of VC. The main active ingredients and targets information of GFW were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the targets related to VC were determined by GeneCards, Online Mendelian Inheritance in Man (OMIM), and Disease Gene Network (DisGeNET) databases. The intersection of active ingredient targets and disease targets was selected to construct a protein-protein interaction (PPI) network through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Based on the use of CytoNCA plug-in to find the main targets, a 'component-target-disease' network was constructed by Cytoscape 3.8.2. Metascape was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of drug and disease targets. Molecular docking was employed to investigate the binding interaction between the main active components and core targets. A total of 76 active components of GFW were screened out. The main targets of the active components on VC were tumour protein p53 (TP53), tumour necrosis factor (TNF), hypoxia inducible factor 1 subunit alpha (HIF1A), interleukin-6 (IL-6), caspase 3 (CASP3), catalase (CAT), prostaglandin-endoperoxide synthase 2 (PTGS2), vascular endothelial growth factor A (VEGFA). The PI3K-Akt signalling pathway, HIF-1 signalling pathway, and apoptosis signalling pathway were mainly involved in the regulation of VC. The results of molecular docking showed that the binding potential and activity of the main active components and the core targets of GFW were good. We found that GFW could alleviate apoptosis, participate in venous vessel morphogenesis, and reduce oxidative stress in the treatment of VC. This study can provide a reference for subsequent clinical and scientific research experiments, which can be used to design new drugs and develop new therapeutic instructions to treat VC.

High level stable expression of recombinant HIV gp120 in glutamine synthetase gene deficient HEK293T cells.

Due to the important pathological roles of the HIV-1 gp120, the protein has been intensively used in the research of HIV. However, recombinant gp120 preparation has proven to be difficult because of extremely low expression levels. In order to facilitate gp120 expression, previous methods predominantly involved the replacement of native signal peptide with a heterologous one, resulting in very limited improvement. Currently, preparation of recombinant gp120 with native glycans relies solely on transient expression systems, which are not amendable for large scale production. In this work, we employed a different approach for gp120 expression. Besides replacing the native gp120 signal peptide with that of rat serum albumin and optimizing its codon usage, we generated a stable gp120-expressing cell line in a glutamine synthetase knockout HEK293T cell line that we established for the purpose of amplification of recombinant gene expressions. The combined usage of these techniques dramatically increased gp120 expression levels and yielded a functional product with human cell derived glycan. This method may be applicable to large scale preparation of other viral envelope proteins, such as that of the emerging SARS-CoV-2, or other glycoproteins which require the presence of authentic human glycans.

[Extracellular vesicles: Their physiological functions related to sperm maturation, sperm motility and fertilization].

Extracellular vesicles are cell-to-cell communication tools that play important roles in sperm maturation, motility, and fertilization. Epididymosomes provide proteins, lipids, and genetic materials to sperm as the latter go through the epididymis, not only promoting sperm maturation, but also influencing sperm and offspring phenotypes at the epigenetic level. After ejaculation, prostasomes fuse with sperm, leading to changes in the composition of the sperm plasma membrane and the contents of sperm, which maintains the stability of the sperm plasma membrane and increases sperm motility as well. Uterosomes can enhance sperm capacitation and acrosome reaction. Oviductosomes participate in sperm capacitation and motility, provide non-coding RNA to sperm, and influence the development of embryos. However, studies on extracellular vesicles and spermatozoa are mostly based on animal experiments, and their applicability to humans remains to be further explored.

AIM Platform: A Novel Nano Artificial Antigen-Presenting Cell-Based Clinical System Designed to Consistently Produce Multi-Antigen-Specific T-Cell Products with Potent and Durable Anti-Tumor Properties.

Over the last decade, tremendous progress has been made in the field of adoptive cell therapy. The two prevailing modalities include endogenous non-engineered approaches and genetically engineered T-cell approaches. Endogenous non-engineered approaches include dendritic cell-based systems and tumor-infiltrating lymphocytes (TIL) that are used to produce multi-antigen-specific T-cell products. Genetically engineered approaches, such as T-cell receptor engineered cells and chimeric antigen receptor T cells are used to produce single antigen-specific T-cell products. It is noted by the authors that there are alternative methods to sort for antigen-specific T cells such as peptide multimer sorting or cytokine secretion assay-based sorting, both of which are potentially challenging for broad development and commercialization. In this review, we are focusing on a novel nanoparticle technology that generates a non-engineered product from the endogenous T-cell repertoire. The most common approaches for ex vivo activation and expansion of endogenous, non-genetically engineered cell therapy products rely on dendritic cell-based systems or IL-2 expanded TIL. Hurdles remain in developing efficient, consistent, controlled processes; thus, these processes still have limited access to broad patient populations. Here, we describe a novel approach to produce cellular therapies at clinical scale, using proprietary nanoparticles combined with a proprietary manufacturing process to enrich and expand antigen-specific CD8+ T-cell products with consistent purity, identity, and composition required for effective and durable anti-tumor response.

Over-expression of a human CD62L ecto-domain and a potential role of RNA pseudoknot structures in recombinant protein expression.

L-selectin (CD62L) is an extracellular protein with a lectin-like domain that mediates rolling adhesion of leukocytes to vascular endothelial cell surfaces. Currently, there are no solved structures for the ectodomain of CD62L, nor of CD62L in complex with its ligand. We have developed a rapid mammalian recombinant protein expression system using an amplifiable glutamine synthase based vector. Here, we further developed and applied this method to express and purify the entire extracellular region of CD62L. This resulted in excess of 20 mg/L yield of recombinant CD62L. In an attempt to understand the different expression levels among four similar CD62L constructs that differ primarily in signal sequences, we calculated the presence of potential RNA pseudoknots in their signal sequences. The results showed the presence of pseudoknots involving the start codon and between the signal sequence and gene in the mRNA of the non-expressing constructs, suggesting a potential inhibitory role of RNA pseudoknots in recombinant protein expression.

Arthroscopic single-bundle anterior cruciate ligament reconstruction with six-strand hamstring tendon allograft versus bone-patellar tendon-bone allograft.

PURPOSE: The aim of this study was to compare the clinical outcomes of arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction with six-strand hamstring tendon (HT) allograft versus bone-patellar tendon-bone (BPTB) allograft. METHODS: The prospective randomized controlled trial was included 129 patients. Sixty-nine patients received reconstruction with six-strand HT allografts (HT group), whereas 60 patients with BPTB allografts (BPTB group). Outcome assessment included re-rupture findings, International Knee Documentation Committee (IKDC) scores, Lysholm scores, KT-1000 arthrometer, Lachman test, pivot-shift test, range of motion (ROM) and single-leg hop test. RESULTS: At a mean follow-up of 52 months, 113 patients (HT group, 61 patients; BPTB group, 52 patients) completed a minimum 4-year follow-up. Four patients in HT group and six in BPTB group experienced ACL re-rupture (6.2 vs. 10.3 %) and received revision surgery. Significant between-group differences were observed in KT-1000 outcomes and pivot-shift test 1 (1.2 ± 1.5 vs. 1.8 ± 1.3, p = 0.025; positive rate 6.5 vs. 18.9 %, p = 0.036), 2 (1.1 ± 1.4 vs. 1.6 ± 1.2, p = 0.044; 8.1 vs. 20.7 %, p = 0.039), 4 (1.1 ± 1.5 vs. 1.7 ± 1.4, p = 0.031; 9.7 vs. 25 %, p = 0.012) years postoperatively. The outcomes between the two groups were comparable in terms of IKDC scores, Lysholm scores, Lachman test, ROM and single-leg hop test. CONCLUSIONS: Six-strand HT allograft achieved superior anteroposterior and rotational stability after single-bundle ACL reconstruction. It is a reasonable graft substitute for ACL reconstruction. LEVEL OF EVIDENCE: II.

Femoral trochlear groove development after patellar subluxation and early reduction in growing rabbits.

PURPOSE: This animal study aimed to investigate whether early reduction in patellar subluxation could minimize femoral trochlear dysplasia in growing rabbits. METHODS: Sixty rabbits were divided into four groups (N = 30 knees/group). The control group underwent no surgical procedures. The rabbits in the three experimental groups underwent surgical patellar subluxation. Those in the early-reduced group underwent reduction surgery 1 month after patellar subluxation. The late-reduced group underwent reduction surgery 2 months after patellar subluxation. The rabbits in the non-reduced group underwent no reduction surgery. CT scans were performed monthly to measure the sulcus angle and trochlear width and depth. Gross specimen examination and histological observation were performed to investigate anatomical configuration and changes in the trochlear groove cartilage. RESULTS: CT scans demonstrated significant differences in the sulcus angle, trochlear width and trochlear depth by 6 months after subluxation surgery in the late-reduced and non-reduced groups. No obvious differences in these parameters were seen in the early-reduced group compared with the control group. Gross specimen examination and histological investigations showed degenerative changes in the femoral trochlear groove and cartilage by 6 months after subluxation surgery in the late-reduced and non-reduced groups. No degenerative changes were found in the early-reduced group, compared with the control group. CONCLUSION: Our results indicate that patellar subluxation or dislocation early in an animal's development can lead to femoral trochlear dysplasia or flattening and that early relocation of the patella can prevent femoral trochlear dysplasia in growing rabbits.

Recognition and functional activation of the human IgA receptor (FcalphaRI) by C-reactive protein.

C-reactive protein (CRP) is an important biomarker for inflammatory diseases. However, its role in inflammation beyond complement-mediated pathogen clearance remains poorly defined. We identified the major IgA receptor, FcαRI, as a ligand for pentraxins. CRP recognized FcαRI both in solution and on cells, and the pentraxin binding site on the receptor appears distinct from that recognized by IgA. Further competitive binding and mutational analysis showed that FcαRI bound to the effector face of CRP in a region overlapping with complement C1q and Fcγ receptor (FcγR) binding sites. CRP cross-linking of FcαRI resulted in extracellular signal-regulated kinase (ERK) phosphorylation, cytokine production, and degranulation in FcαRI-transfected RBL cells. In neutrophils, CRP induced FcαRI surface expression, phagocytosis, and TNF-α secretion. The ability of CRP to activate FcαRI defines a function for pentraxins in inflammatory responses involving neutrophils and macrophages. It also highlights the innate aspect of otherwise humoral immunity-associated antibody receptors.

Adaptive temporal compression for reduction of computational complexity in human behavior recognition.

The research on video analytics especially in the area of human behavior recognition has become increasingly popular recently. It is widely applied in virtual reality, video surveillance, and video retrieval. With the advancement of deep learning algorithms and computer hardware, the conventional two-dimensional convolution technique for training video models has been replaced by three-dimensional convolution, which enables the extraction of spatio-temporal features. Specifically, the use of 3D convolution in human behavior recognition has been the subject of growing interest. However, the increased dimensionality has led to challenges such as the dramatic increase in the number of parameters, increased time complexity, and a strong dependence on GPUs for effective spatio-temporal feature extraction. The training speed can be considerably slow without the support of powerful GPU hardware. To address these issues, this study proposes an Adaptive Time Compression (ATC) module. Functioning as an independent component, ATC can be seamlessly integrated into existing architectures and achieves data compression by eliminating redundant frames within video data. The ATC module effectively reduces GPU computing load and time complexity with negligible loss of accuracy, thereby facilitating real-time human behavior recognition.

Protocol for near-infrared optogenetics manipulation of neurons and motor behavior in C. elegans using emissive upconversion nanoparticles.

In deep tissue, optogenetics faces limitations with visible light. Here, we present a protocol for near-infrared (NIR) optogenetics manipulation of neurons and motor behavior in Caenorhabditis elegans using emissive upconversion nanoparticles (UCNPs). We describe steps for synthesizing and modifying UCNPs. We then detail procedures for regulating neurons using these UCNPs in the model organism C. elegans. Using NIR light allows for superior tissue penetration to manipulate neuronal activities and locomotion behavior. For complete details on the use and execution of this protocol, please refer to Guo et al.,1 Ao et al.,2 and Zhang et al.3.

High-quality Gossypium hirsutum and Gossypium barbadense genome assemblies reveal the landscape and evolution of centromeres.

Centromere positioning and organization are crucial for genome evolution; however, research on centromere biology is largely influenced by the quality of available genome assemblies. Here, we combined Oxford Nanopore and Pacific Biosciences technologies to de novo assemble two high-quality reference genomes for Gossypium hirsutum (TM-1) and Gossypium barbadense (3-79). Compared with previously published reference genomes, our assemblies show substantial improvements, with the contig N50 improved by 4.6-fold and 5.6-fold, respectively, and thus represent the most complete cotton genomes to date. These high-quality reference genomes enable us to characterize 14 and 5 complete centromeric regions for G. hirsutum and G. barbadense, respectively. Our data revealed that the centromeres of allotetraploid cotton are occupied by members of the centromeric repeat for maize (CRM) and Tekay long terminal repeat families, and the CRM family reshapes the centromere structure of the At subgenome after polyploidization. These two intertwined families have driven the convergent evolution of centromeres between the two subgenomes, ensuring centromere function and genome stability. In addition, the repositioning and high sequence divergence of centromeres between G. hirsutum and G. barbadense have contributed to speciation and centromere diversity. This study sheds light on centromere evolution in a significant crop and provides an alternative approach for exploring the evolution of polyploid plants.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

CRP, IL-1α, IL-1ß, and IL-6 levels and the risk of breast cancer: a two-sample Mendelian randomization study.

Epidemiological studies have reported a positive association between chronic inflammation and cancer risk. However, the causal association between chronic inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of chronic inflammation in BC risk. We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1a, IL-1b, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies and the Breast Cancer Association Consortium). Next, we conducted the two-sample Mendelian randomization study to investigate the relationship of the abovementioned inflammatory factors with the incidence of BC. We found that genetically predicted CRP, IL-6, and IL-1a levels did not increase BC incidence (odds ratio (OR)CRP 1.06, 95% confidence interval (CI) 0.98-1.12, P = 0.2059, ORIL-6 1.05, 95% CI 0.95-1.16, P = 0.3297 and ORIL-1a 1.01, 95% CI 0.99-1.03, P = 0.2167). However, in subgroup analysis, genetically predicted IL-1b levels increased ER + BC incidence (OR 1.15, 95% CI 1.03-1.27, P = 0.0088). Our study suggested that genetically predicted IL-1b levels were found to increase ER + BC susceptibility. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, which deserves further research.