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The poxvirus-derived protein vCCI (viral CC chemokine inhibitor) binds almost all members of the CC chemokine family with nanomolar affinity, inhibiting their pro-inflammatory actions. Understanding the affinity and specificity of vCCI could lead to new anti-inflammatory therapeutics. CCL17, also known as TARC, is unusual among CC chemokines by having only micromolar binding to vCCI. We have used sequence analysis and molecular simulations to determine the cause of this weak binding, which identified several locations in CCL17 where mutations seemed likely to improve binding to vCCI. Based on the aforementioned analysis, we expressed and tested multiple mutants of CCL17. We found two single point mutants V44K and Q45R that increased binding affinity to vCCI by 2-3-fold and, in combination, further improved affinity by 7-fold. The CCL17 triple mutant G17R/V44K/Q45R yielded a Kd of 0.25 ± 0.13 μM, a 68-fold improvement in affinity compared to the complex with wild-type CCL17. A quadruple mutant G17R/V44K/Q45R/R57W showed high affinity (0.59 ± 0.09 μM) compared to the wild type but lower affinity than the triple mutant. This work demonstrates that sequence comparisons and molecular simulations can predict chemokine mutations that increase the level of binding to vCCI, an important first step in developing engineered chemokine inhibitors useful for anti-inflammatory therapy.

Copyright of African Journal of Reproductive Health is the property of Women's Health & Action Research Centre and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans, the severity of which depends on multiple factors, including intrinsic characteristics of the affected individuals and the pathogen itself. Additionally, emerging evidence suggests that epigenetic modifications may also modulate host susceptibility to infection. Therefore, different clinical outcomes can be expected, ranging from self-limiting gastroenteritis to severe central nervous system and maternal-neonatal infections, and bacteremia. Furthermore, L. monocytogenes is a genetically and phenotypically diverse species, resulting in a large variation in virulence potential between strains. Multilocus sequence typing (MLST) has been widely used to categorize the clonal structure of bacterial species and to define clonal complexes (CCs) of genetically related isolates. The combination of MLST and epidemiological data allows to distinguish hypervirulent CCs, which are notably more prevalent in clinical cases and typically associated with severe forms of the disease. Conversely, other CCs, termed hypovirulent, are predominantly isolated from food and food processing environments and are associated with the occurrence of listeriosis in immunosuppressed individuals. Reports of genetic traits associated with this diversity have been described. The Food and Agriculture Organization (FAO) is encouraging the search for virulence biomarkers to rapidly identify the main strains of concern to reduce food waste and economical losses. The aim of this review is to comprehensively collect, describe and discuss the methodologies used to discriminate the virulence potential of L. monocytogenes CCs. From the exploration of in vitro and in vivo models to the study of expression of virulence genes, each approach is critically explored to better understand its applicability and efficiency in distinguishing the virulence potential of the pathogen. [ABSTRACT FROM AUTHOR]

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28-/- mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

Sarath S Nair,1 Jyothi Nagesh,1 Shambhavi C,2 Anshul Singh,1 Shirley Lewis,1 Umesh Velu,1 Deepika Chenna3 1Department of Radiation Oncology, Kasturba Medical College Manipal MAHE, Manipal, Karnataka, India; 2Department of Medical Radiation Physics Program, MCHP Manipal, MAHE, Manipal, Karanataka, India; 3Department of Immunohematology and Blood Transfusion, Kasturba Medical College Manipal MAHE, Manipal, Karnataka, IndiaCorrespondence: Jyothi Nagesh, Email jyothi.nagesh@manipal.eduObjective: To identify a suitable approach for blood irradiation other than the commonly used water medium and to study the impact of different algorithm dose computations.Methods: Water is the commonly used medium for blood irradiation. In this study computed tomography scans were taken with locally made blood irradiation phantoms other than water, by using air, rice powder and thermocole using parallel beam for 25 Gy. Plans were recalculated for different algorithms such as collapsed cone (CC), Monte Carlo (MC) and pencil beam (PB). The dose–volume parameters and measured doses were collected and analyzed for each medium and algorithm.Findings: The monitor unit (MU) for rice powder and water are close (2461± 57 and 2469± 61, respectively), with a maximum dose of 28.0± 1.8 and 28.0± 1.9 Gy. The PB algorithm resulted in lower monitor unit values regardless of the medium used, generating values of 2418, 2406, 2382, and 2362 for water, rice powder, air, and Thermocol, respectively. A significant increase in dose was observed irrespective of the medium used when the MC algorithm was employed, with a maximum of 30.26 Gy in rice powder; a smaller dose was used when the CC algorithm was employed, with 26.3 Gy in water medium. The average maximum doses of all groups were equal using the one-way Anova statistical test. Regarding the impact of field size, rice powder appears to have consistent doses across various field sizes, with slight increases as field size grows, which is similar to water.Novelty/Applications: While water is the conventional medium, this study highlights the potential benefits of rice powder, such as eliminating the risks associated with bubble formation and water spillage, which can lead to equipment malfunction and safety hazards. Although previous studies have explored rice powder as a bolus and tissue-equivalent material, this study uniquely applies this knowledge to blood irradiation, an area where rice powder has not been thoroughly investigated.Keywords: computed tomography, collapsed cone, Monte Carlo, pencil beam, monitor units, MU, treatment planning station.

Copyright of Romanian Journal of Information Technology & Automatic Control / Revista Română de Informatică și Automatică is the property of National Institute for Research & Development in Informatics - ICI Bucharest and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

[Display omitted] In this study, a flexible, free-standing Fe-doped CoP nanoarrays electrode for superior lithium-ion storage has been successfully fabricated. The electrode combines the advantages of a Fe-doping and a flexible carbon cloth (CC) support, resulting in a high specific capacity (1356 mAh/g at 0.2 A/g) and excellent cycling stability (1138 mAh/g after 100 cycles). The cyclic voltammetry (CV) curves at different scan rates investigate the outstanding lithium storage behavior of Fe-CoP-NAs/CC which indicates a combined influence of diffusion behavior and capacitance behavior on the electrochemical process. The galvanostatic intermittent titration technique (GITT) analyzes the diffusion kinetics of Li+ which indicates the fast diffusion kinetics in the Fe-CoP/NAs/CC anode. The assembled Fe-CoP-NAs/CC//LiFePO 4 battery exhibits a remarkable capacity of 325.2 mAh/g even at 5 A/g. And the battery also has good cycle stability, and still provides 498.1 mAh/g specific capacity after 200 cycles. Moreover, the Fe-CoP-NAs/CC//LiFePO 4 soft-pack battery can continuously power the LEDs when it is bent at various angles which demonstrates its potential for use in wearable devices. [ABSTRACT FROM AUTHOR]

Colon cancer (CC) is a malignant disease of the digestive tract, and its rising prevalence poses a grave threat to people's health. N6-methyladenosine (m6A) modification is essential for various crucial life processes through modulating gene expression. Methyltransferase-like 14 (METTL14), the m6A methylation transferase core protein, and its aberrant expression is intimately correlated to tumor development. This study was conducted to probe the impacts and specific mechanisms of METTL14 on the biological process of CC. Bioinformatics data disclosed that METTL14 was significantly attenuated in CC. Functional assays were executed to ascertain how METTL14 affected CC tumorigenicity, and METTL14 overexpression caused a notable decline in viability, migration, invasion, and stemness phenotype of CC cells. Then, in-depth mechanistic studies displayed that stearoyl-CoA desaturase 1 (SCD1) was a downstream target gene of METTL14-mediated m6A modification. METTL14 overexpression substantially augmented the m6A modification of SCD1 mRNA and diminished the SCD1 mRNA level. In addition, we revealed that YTHDF2 was the m6A reader to recognize METTL14 m6A-modified SCD1 mRNA and abolish its stability. Finally, we also validated that METTL14 might impede the tumorigenic process of CC through SCD1 mediated Wnt/β-catenin signaling. Taken together, this study presented that METTL14 performed as a potential therapeutic target in CC with important implications for the prognosis amelioration of CC patients. [ABSTRACT FROM AUTHOR]

LncRNA ZNF667-AS1 plays an important role in the carcinogenesis and progression of various cancers. However, their role in colon cancer (CC) remains unclear. The expression of ZNF667-AS1, KIF5C, and miR-523-3p in CC cells and tissues was analyzed using RT-qPCR and western blotting. CCK-8 scratch-wound assay, western blotting, and flow cytometry were conducted to investigate the malignant activity of CC in vitro. Luciferase reporter, RNA pull-down, and Ago2 immunoprecipitation (RIP) experiments were conducted to ascertain the association of miR-523-3p with ZNF667-AS1 and KIF5C 3ʹUTR. Xenograft tumor experiments were also performed. CC cells and tissues showed low expression of NF667-AS1 and KIF5C and elevated expression of miR-523-3p. ZNF667-AS1 overexpression attenuates proliferation and migration of CC cells, restores inactivated apoptosis in vitro, and inhibits tumor growth in vivo. MiR-523-3p targets both ZNF667-AS1 and the KIF5C 3ʹUTR. ZNF667-AS1 overexpression in SW480 and SW620 cells attenuated the oncogenic effect of miR-523-3p in CC. However, this attenuating effect was counteracted by KIF5C overexpression. ZNF667-AS1 sequestered miR-523–3, reducing miR-523-3p-mediated inhibition of KIF5C expression, thereby repressing colon carcinogenesis in vitro. Our findings shed light on a novel anticancer strategy that could potentially combat CC. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans, the severity of which depends on multiple factors, including intrinsic characteristics of the affected individuals and the pathogen itself. Additionally, emerging evidence suggests that epigenetic modifications may also modulate host susceptibility to infection. Therefore, different clinical outcomes can be expected, ranging from self-limiting gastroenteritis to severe central nervous system and maternal-neonatal infections, and bacteremia. Furthermore, L. monocytogenes is a genetically and phenotypically diverse species, resulting in a large variation in virulence potential between strains. Multilocus sequence typing (MLST) has been widely used to categorize the clonal structure of bacterial species and to define clonal complexes (CCs) of genetically related isolates. The combination of MLST and epidemiological data allows to distinguish hypervirulent CCs, which are notably more prevalent in clinical cases and typically associated with severe forms of the disease. Conversely, other CCs, termed hypovirulent, are predominantly isolated from food and food processing environments and are associated with the occurrence of listeriosis in immunosuppressed individuals. Reports of genetic traits associated with this diversity have been described. The Food and Agriculture Organization (FAO) is encouraging the search for virulence biomarkers to rapidly identify the main strains of concern to reduce food waste and economical losses. The aim of this review is to comprehensively collect, describe and discuss the methodologies used to discriminate the virulence potential of L. monocytogenes CCs. From the exploration of in vitro and in vivo models to the study of expression of virulence genes, each approach is critically explored to better understand its applicability and efficiency in distinguishing the virulence potential of the pathogen.

Nodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition.

CC (CC) remains a significant global health concern, imposing a substantial health burden on women worldwide due to its high incidence and mortality rates. To address this issue, there is a need for ongoing research to uncover the underlying molecular mechanisms of CC and to discover novel diagnostic and therapeutic strategies. Recent progress in non-coding RNAs (ncRNAs) has opened new avenues for investigation, and circular RNAs (circRNAs) have emerged as molecules with diverse roles in various cellular processes. These circRNAs are distinct in structure, forming a closed loop, setting them apart from their linear counterparts. They are intricately involved in regulating different aspects of cellular functions, particularly in cell growth and development. Remarkably, circRNAs can have varying functions, either promoting or inhibiting oncogenic processes, depending on the specific cellular context. Recent studies have identified abnormal circRNAs expression patterns associated with CC, indicating their significant involvement in disease development. The differing circRNAs profiles linked to CC present promising opportunities for early detection, precise prognosis evaluation, and personalized treatment strategies. In this comprehensive review, we embark on a detailed exploration of CC-related circRNAs, elucidating their distinct roles and providing insights into the intricate molecular mechanisms governing CC's onset and progression. A growing body of evidence strongly suggests that circRNAs can serve as valuable biomarkers for early CC detection and hold potential as therapeutic targets for intervention. By delving into the complex interplay between circRNAs and CC, we are paving the way for innovative, individualized approaches to combat this serious disease, with the goal of reducing its impact on women's health globally and improving patient outcomes. As our understanding of circRNAs in the context of CC continues to deepen, the outlook for breakthroughs in diagnosis and treatment becomes increasingly promising.

In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab. Clinical Trials Registration. NCT04678830.

In last few years, chaotic maps are being used extensively by the researchers to build image cryptosystems. This paper proposes a novel Hybrid chaotic map, and discusses the implementation of an image encryption method that uses an existing Sine–Cosine (SC) chaotic map, and the proposed novel Hybrid chaotic map. The proposed image encryption method uses these two maps in pairs, but dynamically, in both permutation and diffusion phases, where if one map is used for permutation of one-pixel block based on dynamic selection, then the other map will be used for diffusion of the same pixel block. This encryption mechanism uses 128-bit shared key along with the 128-bit Initial vector. The initialization phase of this encryption scheme consists of the initialization of the intermediate key, seeds and the control parameters for the chaotic maps. After that, the two different chaotic initial sequences are created using the SC and Hybrid chaotic map, respectively, where sequence from one map will be used for permutation, and sequence from other map will be used for diffusion. The chaotic range of proposed Hybrid map lies between 5.5 to 15, and its chaotic properties have been validated using Lyapunov exponent, Bifurcation diagram, and Shannon Entropy. The results show that the Bifurcation diagram of the Hybrid map is uniform in entire range. Also, the Lyapunov Exponent of the Hybrid map is greater than 0, and the value of the Shannon entropy of the Hybrid map is close to 10. Also, the proposed image encryption scheme is capable of resisting different types of security attacks. [ABSTRACT FROM AUTHOR]

Cloud computing is characterized as a shared computing and communication infrastructure. It encourages the efficient and effective developmental processes that are carried out in various organizations. Cloud computing offers both possibilities and solutions of problems for outsourcing and management of software developmental operations across distinct geography. Cloud computing is adopted by organizations and application developers for developing quality software. The cloud has the significant impact on utilizing the artificial complexity required in developing and designing quality software. Software developmental organization prefers cloud computing for outsourcing tasks because of its available and scalable nature. Cloud computing is the ideal choice utilized for development modern software as they have provided a completely new way of developing real‐time cost‐effective, efficient, and quality software. Tenants (providers, developers, and consumers) are provided with platforms, software services, and infrastructure based on pay per use phenomenon. Cloud‐based software services are becoming increasingly popular, as observed by their widespread use. Cloud computing approach has drawn the interest of researchers and business because of its ability to provide a flexible and resourceful platform for development and deployment. To determine a cohesive understanding of the analyzed problems and solutions to improve the quality of software, the existing literature resources on cloud‐based software development should be analyzed and synthesized systematically. Keyword strings were formulated for analyzing relevant research articles from journals, book chapters, and conference papers. The research articles published in (2011–2021) various scientific databases were extracted and analyzed for retrieval of relevant research articles. A total of 97 research publications are examined in this SLR and are evaluated to be appropriate studies in explaining and discussing the proposed topic. The major emphasis of the presented systematic literature review (SLR) is to identify the participating entities of cloud‐based software development, challenges associated with adopting cloud for software developmental processes, and its significance to software industries and developers. This SLR will assist organizations, designers, and developers to develop and deploy user‐friendly, efficient, effective, and real time software applications. [ABSTRACT FROM AUTHOR]

Radical surgical intervention, chemoradiotherapy and immune therapy implicated for patients with cervical cancer (CC) can result in significant morphofunctional, psychological, sexual disorders and social maladjustment. To optimize treatment and rehabilitation for CC patients, a routing approach has been established. This approach involves the patient's journey during diagnosis and treatment with well-defined timed stages. Additionally, a rehabilitation program with lifelong follow-up has been implemented. Prior to commencing therapy, undertaking rehabilitation after oncogynecological treatment during the stage spanning from diagnosis to therapy initiation contributes to enhancing the quality of life (QoL) for CC patients.

Technology for Cloud Computing (CC) has advanced, so Cloud Computing creates a variety of cloud services. Users may receive storage space from the provider as Cloud storage services are quite practical; many users and businesses save their data in cloud storage. Data confidentiality becomes a larger risk for service providers when more information is outsourced to Cloud storage. Hence in this work, a Ciphertext and Elliptic Curve Cryptography (ECC) with Identity-based encryption (CP-IBE) approaches are used in the cloud environment to ensure data security for a healthcare environment. The revocation problem becomes complicated since characteristics are used to create cipher texts and secret keys; therefore, a User revocation algorithm is introduced for which a secret token key is uniquely produced for each level ensuring security. The initial operation, including signature, public audits, and dynamic data, are sensible to Sybil attacks; hence, to overcome that, a Sybil Attack Check Algorithm is introduced, effectively securing the system. Moreover, the conditions for public auditing using shared data and providing typical strategies, including the analytical function, security, and performance conditions, are analyzed in terms of accuracy, sensitivity, and similarity.

Background: The aim of this study is to evaluate comparative biomechanical fixation provided with the BDSF method with the conventional CC screw fixation for treatment of femoral neck fractures with three parallel cannulated screws. Methods: This is a prospective cohort study. There were two teams of surgeons out of which one team operated the patients with BDSF technique and second with conventional CC screw fixation technique; thus, the patients were randomly distributed into two groups. Patients were included in the study as per the following inclusion and exclusion criteria. Results: Union was achieved in 15 (83.33%) patients managed by conventional CC screw technique, while union was achieved in 11 (91.67%) patients managed by BDSF technique in the present study. The average Harris hip score in present study was 90 score in patients managed by BDSF technique, while the average Harris hip score in present study was 80 score in patients managed by BDSF technique. Conclusion: Both BDSF and conventional CC screw fixation are good fixation methods for fracture neck of femur. But functional outcome and fracture union rates are better with BDSF Technique. Although, there are some minor problems noted in BDSF technique such as outer cortical fracture at the entry point of beam screw and opening up of anterior cortex of oblique fracture patterns. Thus, BDSF method provides reliable fixation in which early mobilization and partial weight bearing of the patient may be allowed. [ABSTRACT FROM AUTHOR]

Abstract Objective Classical Cox proportional hazard models tend to overestimate the event probability in a competing risk setup. Due to the lack of quantitative evaluation of competitive risk data for colon cancer (CC), the present study aims to evaluate the probability of CC-specific death and construct a nomogram to quantify survival differences among CC patients. Methods Data on patients diagnosed with CC between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database. Patients were divided into a training dataset for the establishment of the model and a validation dataset to evaluate the performance the model at a ratio of 7:3. To evaluate the ability of multiple variables to predict cause-specific death in CC patients, univariate and multivariate analyses with Fine-Gray models were performed to screen the predictors of cause-specific death, and a nomogram for predicting cause-specific mortality was constructed. Then, the receiver operating characteristic (ROC) curve and the calibration curve were plotted to evaluate the prognostic performance of the nomogram. Results The dataset was randomly divided into a training (n = 16,655) dataset and a validation (n = 7,139) dataset at a ratio of 7:3. In the training dataset, variables including pathological subtypes of tumors, pathological grading (degree of differentiation), AJCC staging, T-staging, surgical type, lymph node surgery, chemotherapy, tumor deposits, lymph node metastasis, liver metastasis, and lung metastasis were identified as independent risk factors for cause-specific death of CC patients. Among these factors, the AJCC stage had the strongest predictive ability, and these features were used to construct the final model. In the training dataset, the consistency index (C-index) of the model was 0.848, and the areas under the receiver operating characteristic curve (AUC) at 1, 3, and 5 years was 0.852, 0.861, and 0.856, respectively. In the validation dataset, the C-index of the model was 0.847, and the AUC at 1 year, 3 years, and 5 years was 0.841, 0.862, and 0.852, respectively, indicating that this nomogram had an excellent and robust predictive performance. Conclusion This study can help clinical doctors make better clinical decisions and provide better support for patients with CC.

Despite the well-accepted view that chronic inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), the function and regulation of eosinophils remain an unclear facet of type II innate immunity in dystrophic muscle. We report the observation that group 2 innate lymphoid cells (ILC2s) are present in skeletal muscle and are the principal regulators of muscle eosinophils during muscular dystrophy. Eosinophils were elevated in DMD patients and dystrophic mice along with interleukin (IL)-5, a major eosinophil survival factor that was predominantly expressed by muscle ILC2s. We also find that IL-33 was upregulated in dystrophic muscle and was predominantly produced by fibrogenic/adipogenic progenitors (FAPs). Exogenous IL-33 and IL-2 complex (IL-2c) expanded muscle ILC2s and eosinophils, decreased the cross-sectional area (CSA) of regenerating myofibers, and increased the expression of genes associated with muscle fibrosis. The deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia and impaired the induction of IL-5 and fibrosis-associated genes. Our findings highlight a FAP/ILC2/eosinophil axis that promotes type II innate immunity, which influences the balance between regenerative and fibrotic responses during muscular dystrophy.

Purpose: Colon cancer (CC) is a cancer of the large intestine with high prevalence and poor prognosis. enhancer RNAs. Therefore, valuable tools or biomarkers for predicting patient status, directing clinical practice, and reducing overtreatment are needed. Enhancer RNAs (eRNAs), a class of noncoding RNAs transcribed from enhancers, have been shown to function as regulators of oncogene or tumor suppressor gene expression. The aim of our study was to explore the potential roles of eRNAs and their target enhancer-related genes (ERGs) in the prognosis of CC. Methods: Selected CC cases (stage I–III) from The Cancer Genome Atlas database were used as a training set, and cases from the Gene Expression Omnibus were used as the validation set. ERGs associated with prognosis were screened through three steps: potential, candidate, and prognosis ERGs. Multivariate Cox proportional hazards analysis was used to identify independent prognostic factors, and a nomogram was created. Calibration curves were drawn by comparing predicted and observed survival probability. For validation, the calibration curves and ROC analysis were also applied to two external validation sets. The biological significance and clinical application of the genes obtained were investigated. Results: Based on the multiple tiers of strict screening, 11 prognostic ERGs were obtained, which were combined to obtain a prognosis signature. A compound nomogram integrating age, TNM classification, and the prognostic signature was constructed. The model was reliable in distinguishing the risk of patients with stage I–III CC, with AUCs of 0.78 and 0.70 at 5 and 7 years, respectively. There was good reproducibility in calibration curves. The prognostic model also yielded good prediction capability in the validation sets. Conclusion: In this study, the usefulness and specificity of the ERGs in prognosis were described, which should be considered a key feature in the clinical guidance of CC patients with early stage. We concluded that the major implications of the eRNAs and ERGs should be valued, which would be an emerging hallmark in the prognosis of cancer. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the role of circ_0000119 on CC progression and its molecular mechanism. The expression levels of circ_0000119, miR-433-3p, and p21-activated kinase 2 (PAK2) in CC tissues and cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Cell cycle and apoptosis were assessed by flow cytometry. Cell migration and invasive ability were examined by Transwell assays. Downstream binding targets of circ_0000119 were predicted by online bioinformatics tools and confirmed by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. The role of circ_0000119/miR-433-3p/PAK2 axis in regulating the CC process was explored by rescue experiments. A xenograft model was constructed to further determine the effect of circ_0000119 on CC tumor growth in vivo. Immunohistochemistry (IHC) assay was conducted for Ki67 expression. Circ_0000119 was aberrantly upregulated in CC tissues and cell lines. Knockdown of circ_0000119 inhibited CC cell proliferation, cell cycle progress, migration, invasion, and promoted apoptosis of CC cells. MiR-433-3p was a binding target of circ_0000119, and PAK2 was a downstream gene of miR-433-3p. MiR-433-3p inhibition reversed the inhibitory effect of silencing circ_0000119 on CC progression. In addition, PAK2 overexpression reversed the effect of miR-433-3p on CC progression. PAK2 expression was regulated by circ_0000119 and miR-433-3p. Moreover, circ_0000119 knockdown reduced tumor growth of CC in vivo. Circ_0000119 was upregulated in CC, and circ_0000119 knockdown suppressed CC malignant development through the miR-433-3p/PAK2 axis. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a common cancer in women and a serious threat to women's lives. TRIM11 has been confirmed as a carcinogen in multiple cancers. Here, we will excavate the detailed mechanism of TRIM11 in CC. CC cell lines and nude mice were experimental subjects in this study. The abundance of genes and proteins was detected using qRT-PCR, western blot, and IHC. Cell proliferation, migration, and invasion were determined by CCK-8 assay, wound healing assay, and Transwell, respectively. The interactions among METTL14, TRIM11, and PHLPP1 were confirmed using RIP and co-IP, respectively. The stability of TRIM11 mRNA was examined by qRT-PCR with actinomycin D treatment. The m6A level of TRIM11 was detected by MeRIP assay. Results showed that TRIM11 levels were elevated in CC cells. TRIM11 depletion attenuated the proliferation, migration, and invasion of Hela and SiHa cells. Additionally, TRIM11 was modified with m6A, which was mediated by METTL14, and the stability of TRIM11 mRNA was enhanced by IGF2BP1 depending on the level of m6A modification. TRIM11 ubiquitinated PHLPP1 and led to reduced PHLPP1 expression at the protein level. PHLPP1 could further result in the dephosphorylation of AKT and inhibit AKT signaling. PHLPP1 knockdown neutralized TRIM11 silencing-mediated repression of malignant phenotypes of CC cells. TRIM11 mediated by the METTL14-IGF2BP1 axis promotes the AKT pathway to accelerate CC progression by mediating the ubiquitination of PHLPP, which might provide novel therapeutic targets for CC treatment. [ABSTRACT FROM AUTHOR]

This study offers the most recent network architecture employing the CWDM/DWDM/5G millimeter wave system over the Free-Space Optical Communication (or FSOC) channel with performance analysis of the Refractive Index Structural Parameter (or RISP), from weak turbulence 10 - 20 m−2/3 to strong turbulence 10 - 10 m−2/3. The hybrid CWDM/DWDM system and the 5G millimeter Wave (or mm Wave) transmission technology are the two major components that the proposed system would unite under a single FSOC channel. To assess the effectiveness of the proposed system at 500 m transmission data distance, the Min Bit Error Rate (or BER), the Max Q-factor, the Received Electrical Signal Power (or RESP), the Received signal-to-noise ratio (or RSNR), the Communication Capacity (or CC), and the Total Communication Capacity (or TCC) are investigated. The effectiveness analysis of the proposed system indicates that the FSOC transmission channel may be impacted by the RISP variance, which may lead to a decline in system performance. To get around this, the receiver side of the proposed system performs better thanks to the usage of the SQuare RooT (or SQRT) and Electrical Rescale (or ER) blocks. However, to correct the photodiode's square law characteristics and enhance the received signal quality, the SQRT block has been used. Moreover, the ER block has been included to scale the electrical signal input's minimum and maximum values to those previously set in the electrical pulse generator. The results of the simulation are successful, particularly when the SQRT and ER blocks are incorporated into the suggested system. For each result, the predicted RISP value and the estimated RESP, RSNR, CC, and TCC values have been achieved for the tolerable Min BER and Max Q-factor values of approximately 1e-09 and 6, respectively. [ABSTRACT FROM AUTHOR]

Progressive lung fibrosis is a major cause of mortality in systemic sclerosis (SSc) patients, but the underlying mechanisms remain unclear. We demonstrate that immune complexes (ICs) activate human monocytes to promote lung fibroblast migration partly via osteopontin (OPN) secretion, which is amplified by autocrine monocyte colony stimulating factor (MCSF) and interleukin-6 (IL-6) activity. Bulk and single-cell RNA sequencing demonstrate that elevated OPN expression in SSc lung tissue is enriched in macrophages, partially overlapping with CCL18 expression. Serum OPN is elevated in SSc patients with interstitial lung disease (ILD) and prognosticates future lung function deterioration in SSc cohorts. Serum OPN levels decrease following tocilizumab (monoclonal anti-IL-6 receptor) treatment, confirming the connection between IL-6 and OPN in SSc patients. Collectively, these data suggest a plausible link between autoantibodies and lung fibrosis progression, where circulating OPN serves as a systemic proxy for IC-driven profibrotic macrophage activity, highlighting its potential as a promising biomarker in SSc ILD.

Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs in a mouse model of pancreatic cancer. Contrary to our expectations, Treg depletion failed to relieve immunosuppression and led to accelerated tumor progression. We show that Tregs are a key source of TGFβ ligands and, accordingly, their depletion reprogramed the fibroblast population, with loss of tumor-restraining, smooth muscle actin-expressing fibroblasts. Conversely, we observed an increase in chemokines Ccl3, Ccl6, and Ccl8 leading to increased myeloid cell recruitment, restoration of immune suppression, and promotion of carcinogenesis, an effect that was inhibited by blockade of the common CCL3/6/8 receptor CCR1. Further, Treg depletion unleashed pathologic CD4+ T-cell responses. Our data point to new mechanisms regulating fibroblast differentiation in pancreatic cancer and support the notion that fibroblasts are a heterogeneous population with different and opposing functions in pancreatic carcinogenesis. SIGNIFICANCE: Here, we describe an unexpected cross-talk between Tregs and fibroblasts in pancreatic cancer. Treg depletion resulted in differentiation of inflammatory fibroblast subsets, in turn driving infiltration of myeloid cells through CCR1, thus uncovering a potentially new therapeutic approach to relieve immunosuppression in pancreatic cancer.See related commentary by Aykut et al., p. 345.This article is highlighted in the In This Issue feature, p. 327.

The fourth most prevalent gynaecological malignancy affecting females globally is cervical cancer (CC). HPV (high-risk) infection has been related to the majority of CC cases. Owing to efficient screening through Pap smear and vaccination delivery, the commonness and death rate of CC have significantly decreased. Nevertheless, not all societies have access to this equally. A better therapeutic outcome may be achieved by targeting CSCs, which might play a significant impact in carcinogenesis, metastasis, recurrence, and radio / chemo –resistance of CC. The majority of tumours are made up of a tiny subset of tumour cells called CSCs that have the capability to self-renew and develop into a variety of tumour cell types. Cervical CSCs (CCSC) are challenging to recognise, which has prompted the hunt for other markers. The potential indicators of CSCs in CC are described in the current review. These CCSC indicators might be used as molecular goals to improve the effectiveness and lessen the negative effects of chemotherapy in HR-HPV-positive CC. [ABSTRACT FROM AUTHOR]

Technology for Cloud Computing (CC) has advanced, so Cloud Computing creates a variety of cloud services. Users may receive storage space from the provider as Cloud storage services are quite practical; many users and businesses save their data in cloud storage. Data confidentiality becomes a larger risk for service providers when more information is outsourced to Cloud storage. Hence in this work, a Ciphertext and Elliptic Curve Cryptography (ECC) with Identity-based encryption (CP-IBE) approaches are used in the cloud environment to ensure data security for a healthcare environment. The revocation problem becomes complicated since characteristics are used to create cipher texts and secret keys; therefore, a User revocation algorithm is introduced for which a secret token key is uniquely produced for each level ensuring security. The initial operation, including signature, public audits, and dynamic data, are sensible to Sybil attacks; hence, to overcome that, a Sybil Attack Check Algorithm is introduced, effectively securing the system. Moreover, the conditions for public auditing using shared data and providing typical strategies, including the analytical function, security, and performance conditions, are analyzed in terms of accuracy, sensitivity, and similarity. [ABSTRACT FROM AUTHOR]

This research paper presents a novel digital color image encryption approach that ensures high-level security while remaining simple and efficient. The proposed method utilizes a composite key r and x of 128-bits to create a small in-dimension private key (a chaotic map), which is then resized to match the color matrix dimension. The proposed method is uncomplicated and can be applied to any image without any modification. Image quality, sensitivity analysis, security analysis, correlation analysis, quality analysis, speed analysis, and attack robustness analysis are conducted to prove the efficiency and security aspects of the proposed method. The speed analysis shows that the proposed method improves the performance of image cryptography by minimizing encryption–decryption time and maximizing the throughput of the process of color cryptography. The results demonstrate that the proposed method provides better throughput than existing methods. Overall, this research paper provides a new approach to digital color image encryption that is highly secure, efficient, and applicable to various images. [ABSTRACT FROM AUTHOR]

Objective: Classical Cox proportional hazard models tend to overestimate the event probability in a competing risk setup. Due to the lack of quantitative evaluation of competitive risk data for colon cancer (CC), the present study aims to evaluate the probability of CC-specific death and construct a nomogram to quantify survival differences among CC patients. Methods: Data on patients diagnosed with CC between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database. Patients were divided into a training dataset for the establishment of the model and a validation dataset to evaluate the performance the model at a ratio of 7:3. To evaluate the ability of multiple variables to predict cause-specific death in CC patients, univariate and multivariate analyses with Fine-Gray models were performed to screen the predictors of cause-specific death, and a nomogram for predicting cause-specific mortality was constructed. Then, the receiver operating characteristic (ROC) curve and the calibration curve were plotted to evaluate the prognostic performance of the nomogram. Results: The dataset was randomly divided into a training (n = 16,655) dataset and a validation (n = 7,139) dataset at a ratio of 7:3. In the training dataset, variables including pathological subtypes of tumors, pathological grading (degree of differentiation), AJCC staging, T-staging, surgical type, lymph node surgery, chemotherapy, tumor deposits, lymph node metastasis, liver metastasis, and lung metastasis were identified as independent risk factors for cause-specific death of CC patients. Among these factors, the AJCC stage had the strongest predictive ability, and these features were used to construct the final model. In the training dataset, the consistency index (C-index) of the model was 0.848, and the areas under the receiver operating characteristic curve (AUC) at 1, 3, and 5 years was 0.852, 0.861, and 0.856, respectively. In the validation dataset, the C-index of the model was 0.847, and the AUC at 1 year, 3 years, and 5 years was 0.841, 0.862, and 0.852, respectively, indicating that this nomogram had an excellent and robust predictive performance. Conclusion: This study can help clinical doctors make better clinical decisions and provide better support for patients with CC. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD).MethodsPatients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.ResultsBaseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only).ConclusionIn a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.

With almost 2 million new HIV infections worldwide each year, the prevention of HIV infection is critical for stopping the pandemic. The only approved form of pre-exposure prophylaxis is a costly daily pill, and it is recognized that several options will be needed to provide protection to the various affected communities around the world. In particular, many at-risk people would benefit from a prevention method that is simple to use and does not require medical intervention or a strict daily regimen. We show that silk fibroin protein can be formulated into insertable discs that encapsulate either an antibody (IgG) or the potent HIV inhibitor 5P12-RANTES. Several formulations were studied, including silk layering, water vapor annealing and methanol treatment to stabilize the protein cargo and impact the release kinetics over weeks. In the case of IgG, high concentrations were released over a short time using methanol treatment, with more sustained results with the use of water vapor annealing and layering during device fabrication. For 5P12-RANTES, sustained release was obtained for 31 days using water vapor annealing. Further, we show that the released inhibitor 5P12-RANTES was functional both in vitro and in ex vivo colorectal tissue. This work shows that silk fibroin discs can be developed into formidable tools to prevent HIV infection.

CCL28 is a mucosal chemokine that has been involved in various responses, including IgA production. We have analyzed its production in human tissues using a comprehensive microarray database. Its highest expression is in the salivary gland, indicating that it is an important component of saliva. It is also expressed in the trachea, bronchus, and in the mammary gland upon onset of lactation. We have also characterized a Ccl28-/- mouse that exhibits very low IgA levels in milk, and the IgA levels in feces are also reduced. These observations confirm a role for the CCL28/CCR10 chemokine axis in the recruitment of IgA plasmablasts to the lactating mammary gland. CCL28 is also expressed in the vomeronasal organ. We also detected olfactory defects (anosmia) in a Ccl28-/- mouse suggesting that CCL28 is involved in the function/development of olfaction. Importantly, Ccl28-/- mice are highly susceptible to Salmonella enterica serovar Typhimurium in an acute model of infection, indicating that CCL28 plays a major role in innate immunity against Salmonella in the gut. Finally, microbiome studies revealed modest differences in the gut microbiota between Ccl28-/- mice and their cohoused wild-type littermates. The latter observation suggests that under homeostatic conditions, CCL28 plays a limited role in shaping the gut microbiome.

Multiparental populations (MPPs) encompass greater genetic diversity than traditional experimental crosses of two inbred strains, enabling broader surveys of genetic variation underlying complex traits. Two such mouse MPPs are the Collaborative Cross (CC) inbred panel and the Diversity Outbred (DO) population, which are descended from the same eight inbred strains. Additionally, the F1 intercrosses of CC strains (CC-RIX) have been used and enable study designs with replicate outbred mice. Genetic analyses commonly used by researchers to investigate complex traits in these populations include characterizing how heritable a trait is, i.e. its heritability, and mapping its underlying genetic loci, i.e. its quantitative trait loci (QTLs). Here we evaluate the relative merits of these populations for these tasks through simulation, as well as provide recommendations for performing the quantitative genetic analyses. We find that sample populations that include replicate animals, as possible with the CC and CC-RIX, provide more efficient and precise estimates of heritability. We report QTL mapping power curves for the CC, CC-RIX, and DO across a range of QTL effect sizes and polygenic backgrounds for samples of 174 and 500 mice. The utility of replicate animals in the CC and CC-RIX for mapping QTLs rapidly decreased as traits became more polygenic. Only large sample populations of 500 DO mice were well-powered to detect smaller effect loci (7.5-10%) for highly complex traits (80% polygenic background). All results were generated with our R package musppr, which we developed to simulate data from these MPPs and evaluate genetic analyses from user-provided genotypes. [ABSTRACT FROM AUTHOR]

Background: Chylous Ascites is a rare condition. It develops as a result of iatrogenic injury to the cisterna chyli, thoracic duct, or their major tributaries. It leads to an increase in chyle release. Subsequently, obstruction of lymphatic return from abdomen. It is more prevalent after major abdominal procedures involving retro-peritoneum. Case Presentation: A 65 years old female patient was admitted with a history of pain at epigastric and left upper abdominal quadrant via the emergency department at King Hussein Medical Centre. She was planned for elective Whipple's procedure for cancer head of pancreas. This case report considers the impact of intraoperative injury to major lymphatic system leading to chylous ascites and death following her pancreatic resection. Retrospective evaluation of her records revealed an intraoperative iatrogenic injury to the cisterna chyli had occurred during Whipple's Procedure. The injured lymphatic duct was discovered and repaired intraoperatively. The chyle drainage was resolved temporarily after 3 weeks of conservative management. Despite its resolution, it recurred after massive upper GI bleeding, which was managed operatively after failed endoscopic and embolization. The patient failed to recover and died as a direct result of her poor general condition due to the effects of an iatrogenic injury of Cisterna Chyli. We report this case of intraoperative injury to the cisterna chyli, subsequent development of chylous ascites, and its post-operative sequelae. This article considers, even if discovered and repaired intraoperatively, the impact of such injury on development of postoperative chylous ascites, nutritional insufficiency, poor prognosis, and subsequent death. Conclusion: Chylous ascites is a rare complication of Whipple's Procedure. It usually progresses due to iatrogenic operational trauma to a significant lymphatic channel. Even if such injury to cisterna chyli is discovered and managed intraoperatively, it carries a poor prognosis and subsequent death. [ABSTRACT FROM AUTHOR]

An Ultra-Wide Band (UWB) MIMO antenna working at millimeter-wave is proposed in this research. It is composed of eight radiating elements with various shapes. It is designed with a rectangular structure and various carved slots. The carved slots are used to increase the antenna's bandwidth. The antenna's radiating elements are placed near one another, and thus, isolation is widespread. In order to improve the isolation of the MIMO antenna, parasitic elements and a defective ground structure are used. Antenna parameters such as Correlation Coefficient (CC), Envelope Correlation Coefficient (ECC), Diversity Gain (DG), and Total Active Reflection Coefficient (TARC) depend on the isolation. Parasitic elements with a rectangular form are positioned between the radiating patches. Rectangular-shaped ground structures with defects comprise the ground plane. An FR-4 substrate is used to fabricate the antenna. The analysis of the antenna shows that there is less than -14dB return loss, less than -40dB isolation, less than 0.0010 crosscorrelation, less than 0.10 TARC, and higher than 500MHz bandwidth. The antenna uses a fractional bandwidth higher than 35% (UWB) for the 6GHz frequency and operates on a variety of bands. This antenna is suitable for many different wireless system applications. [ABSTRACT FROM AUTHOR]

Abstract Purpose Cholecystectomy (XGB) is widely recognized as a risk factor for colon cancer (CC). Continuous exposure of the colonic epithelium to deoxycholic acid (DCA) post-XGB may exert cytotoxic effects and be involved in the progression of CC. However, the functions of the XGB-induced DCA increase and the underlying mechanism remain unclear. Methods Colitis-associated CC (CAC) mouse models constructed by AOM-DSS inducement were used to confirm the effect of XGB on the CC progression. Hematoxylin & eosin staining was performed to assess the tumor morphology of CAC mouse models tissues. Various cell biological assays including EdU, live-cell imaging, wound-healing assays, and flow cytometry for cell cycle and apoptosis were used to evaluate the effect of DCA on CC progression. The correlation among XGB, DCA, and CC and their underlying mechanisms were detected with immunohistochemistry, mass spectrometry, transcriptome sequencing, qRT-PCR, and western blotting. Results Here we proved that XGB increased the plasma DCA level and promoted colon carcinogenesis in a colitis-associated CC mouse model. Additionally, we revealed that DCA promoted the proliferation and migration of CC cells. Further RNA sequencing showed that 120 mRNAs were upregulated, and 118 downregulated in DCA-treated CC cells versus control cells. The upregulated mRNAs were positively correlated with Wnt signaling and cell cycle-associated pathways. Moreover, DCA treatment could reduced the expression of the farnesoid X receptor (FXR) and subsequently increased the levels of β-Catenin and c-Myc in vitro and in vivo. Moreover, the FXR agonist GW4064 decreased the proliferation of CC cells by repressing the expression of β-catenin. Conclusion We concluded that XGB-induced DCA exposure could promote the progression of CC by inhibiting FXR expression and enhancing the Wnt-β-catenin pathway. Video Abstract