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In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota imbalance can lead to the development of many diseases, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome, endometriosis, and cancer. Short-chain fatty acids are metabolites of specific intestinal bacteria and are crucial for maintaining intestinal homeostasis and regulating metabolism and immunity. Endometriosis is the result of cell proliferation, escape from immune surveillance, and invasive metastasis. There is a strong correlation between the anti-proliferative and anti-inflammatory effects of short-chain fatty acids produced by gut microbes and the development of endometriosis. Given that the mechanism of action of gut microbiota and Short-chain fatty acids in endometriosis remain unclear, this paper aims to provide a comprehensive review of the complex interactions between intestinal flora, short-chain fatty acids and endometriosis. In addition, we explored potential microbial-based treatment strategies for endometriosis, providing new insights into the future development of diagnostic tests and prevention and treatment methods for endometriosis.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan–Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse events for ICIs. Stevens-Johnson syndrome (SJS) is one of the serious cutaneous reactions threatening the life. Here, we reported a case of 76-year-old male patient with poorly differentiated metastatic lung adenocarcinoma, after 9 weeks exposure of sintilimab (3 doses) combined with paclitaxel liposome after concurrent chemotherapy/radiotherapy, experienced Stevens-Johnson syndrome involving limbs, trunk, lip and the oral mucosa. Biopsy of the skin tissue showed infiltration of CD4 and CD8 positive T lymphocytes. We also found PD-L1 expression in the glands and the basal layer of the skin. This finding is distinct from the previously reported expression of PD-L1 on the surface of epidermal keratinocytes in patients with SJS due to immunotherapy.

Background EDIL3, which contains epidermal growth factor-like repeats and discoidin I-like domains, is a secretory protein that plays an important role in embryonic development and various illnesses. However, the biological function of EDIL3 in gastric cancer (GC) is still unclear. The objective of this research was to explore the role and potential mechanism of EDIL3 in GC. Methods In this study, we used the GEPIA, HPA, MethSurv, SMART, STRING, GeneMANIA, LinkedOmics TIMER, TIMER2.0, TISIDB, and RNAactDrug databases to comprehensively analyze the roles of EDIL3 in GC. To validate the in silico findings, EDIL3 expression was measured in our collected GC tissues. Meanwhile, several in vitro experiments were performed to test the function of EDIL3 in GC. Results We found that EDIL3 was highly expressed in GC and associated with adverse clinical features. In vitro assays revealed that EDIL3 promoted the proliferation, migration, and invasion of GC cells. The functions of EDIL3 and co-expression genes were significantly associated with extracellular structure organization and matrix receptor interaction. EDIL3 expression was positively associated with numerous tumor-infiltrating immune cells and their biomarkers. Conclusion This study determined that EDIL3 may function as an oncogene and is associated with immune infiltration in GC. EDIL3 could be used as a potential therapeutic target for GC.

Objective To explore the intrinsic mechanism of the mammalian target of rapamycin (mTOR) pathway activation and promotion of neuronal axon growth. Methods Human neuroblastoma cells, SH-SY5Y, were induced with all-trans retinoic acid (ATRA; 10 μM for three days) which differentiated the cell line into a neuronal-like state. Immunohistochemical staining was used to detect the differentiation status of the neuronal-like cells. Phosphatase and tensin homolog (PTEN) RNA interference (RNAi) experiments were performed on the differentiated cells; reverse transcription-polymerase chain reaction (RT-PCR) detected transcriptional levels of PTEN following 24 h of interference. After 36 h, western blot assay was used to detect expression levels of ribosomal protein S6 kinase (pS6k) and mTOR. To downregulate the expression of PTEN and cluster of differentiation 44 (CD44), a cell-surface glycoprotein, simultaneously, PTEN siRNA and CD44 siRNA sequences were mixed in equal proportions in co-interference experiments. RT-PCR detected the transcription level of CD44, and the relationship between the CD44 and axonal growth was observed after 48 h of interference. Results Microtubule-associated protein 2 (MAP2) expression was enhanced after three days of induction in SH-SY5Y cells. RT-PCR showed the transcription level of PTEN was significantly downregulated after 24 h of PTEN knockdown. mTOR and pS6k protein expression levels were significantly upregulated after 36 h of interference. CD44 transcription levels were upregulated after PTEN gene interference. The neurite length of the cells in the experimental interference group was significantly longer than that in the control group, and the expression level of CD44 was positively correlated with neurite growth. The neurite length of the PTEN-only interference group was significantly greater than that of the co-interference and ATRA groups. Conclusion Activation of the mTOR pathway promoted neurite growth through upregulation of CD44 expression, thus promoting neuronal regeneration.

This study mitigated the challenge of head and neck CT angiography by IPA-based time-resolved imaging of contrast kinetics. To this end, 627 cerebral hemorrhage patients with dizziness, brain aneurysm, stroke, or hemorrhagic stroke diagnosis were randomly categorized into three groups, namely, the original dataset (450), verification group (112), and in vivo testified group (65), in the Affiliated BenQ Hospital of Nanjing Medical University. In the first stage, seven risk factors were assigned: age, CTA tube voltage, body surface area, heart rate per minute, cardiac output blood per minute, the actual injected amount of contrast media, and CTA delayed trigger timing. The expectation value of the semi-empirical formula was the CTA number of the patient’s left artery (LA). Accordingly, 29 items of the first-order nonlinear equation were calculated via the inverse problem analysis (IPA) technique run in the STATISTICA 7.0 program, yielding a loss function and variance of 3.1837 and 0.8892, respectively. A dimensionless AT was proposed to imply the coincidence, with a lower AT indicating a smaller deviation between theoretical and practical values. The derived formula was confirmed for the verification group of 112 patients, reaching high coincidence, with average ATavg and standard deviation values of 3.57% and 3.06%, respectively. In the second stage, the formula was refined to find the optimal amount of contrast media for the CTA number of LA approaching 400. Finally, the above procedure was applied to head and neck CTA images of the third group of 65 patients, reaching an average CTA number of LA of 407.8 ± 16.2 and finding no significant fluctuations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.

Purpose: The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown. Patients and Methods: This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments. Results: In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells. Conclusion: Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a common pulmonary complication observed in preterm infants that is composed of multifactorial pathogenesis. Current strategies, albeit successful in moderately reducing morbidity and mortality of BPD, failed to draw overall satisfactory conclusion. Here, using a typical mouse model mimicking hallmarks of BPD, we revealed that both cord blood-derived mononuclear cells (CB-MNCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) are efficient in alleviating BPD. Notably, infusion of CB-MNCs has more prominent effects in preventing alveolar simplification and pulmonary vessel loss, restoring pulmonary respiratory functions and balancing inflammatory responses. To further elucidate the underlying mechanisms within the divergent therapeutic effects of UC-MSC and CB-MNC, we systematically investigated the long noncoding RNA (lncRNA)–microRNA (miRNA)–messenger RNA (mRNA) and circular RNA (circRNA)–miRNA–mRNA networks by whole-transcriptome sequencing. Importantly, pathway analysis integrating Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/gene set enrichment analysis (GSEA) method indicates that the competing endogenous RNA (ceRNA) network is mainly related to the regulation of GTPase activity (GO: 0043087), extracellular signal-regulated kinase 1 (ERK1) and ERK2 signal cascade (GO: 0070371), chromosome regulation (GO: 0007059), and cell cycle control (GO: 0044770). Through rigorous selection of the lncRNA/circRNA-based ceRNA network, we demonstrated that the hub genes reside in UC-MSC- and CB-MNC-infused networks directed to the function of cell adhesion, motor transportation (Cdk13, Lrrn2), immune homeostasis balance, and autophagy (Homer3, Prkcd) relatively. Our studies illustrate the first comprehensive mRNA–miRNA–lncRNA and mRNA–miRNA–circRNA networks in stem cell-infused BPD model, which will be valuable in identifying reliable biomarkers or therapeutic targets for BPD pathogenesis and shed new light in the priming and conditioning of UC-MSCs or CB-MNCs in the treatment of neonatal lung injury.

This study optimized the ultrasound image of carotid artery stenosis using Taguchi dynamic analysis and an indigenous water phantom. Eighteen combinations of seven essential factors of the ultrasound scan facility were organized according to Taguchi’s L18 orthogonal array. The seven factors were assigned as follows: (1) angle of probe; (2) signal gain; (3) resolution vs. speed; (4) dynamic range; (5) XRES; (6) zoom; (7) time gain compensation. An indigenous water phantom was customized to satisfy the quantified need in Taguchi’s analysis. Unlike the conventional dynamic Taguchi analysis, an innovative quantified index, the figure of merit (FOM), was proposed to integrate four specific quality characteristics, namely (i) average difference between the practical scan and theoretically preset area (78.5, 50.2 and 12.6 mm2) of stenosis, (ii) standard deviation of the average, (iii) practical scan’s sensitivity β to various stenosis diameters (10, 8, and 4 mm), and (iv) correlation coefficient r2 of the linear regressed sensitivity curve. The highest value (FOM = 0.413) was furnished by the optimal combination of factors on 18 groups under study, yielding high r2 and low β or standard deviation values and the best quality of ultrasound images for the further clinical diagnosis. The comparison between FOM and the conventional signal-to-noise (S/N) ratio in Taguchi’s analysis revealed that FOM compiled more quality characteristics that were superior by nature to fulfill the practical need in clinical diagnosis. The alternative choice in ultrasound scan optimization can be based on stenosis diameter variation from a different perspective to be explored in the follow-up study.

The deployment of a client–server-based distributed intelligent system involves application development in both the network domain and the device domain. In the network domain, an application server (typically in the cloud) is deployed to execute the network applications. In the device domain, several Internet of Things (IoT) devices may be configured as, for example, wireless sensor networks (WSNs), and interact with each other through the application server. Developing the network and the device applications are tedious tasks that are the major costs for building a distributed intelligent system. To resolve this issue, a low-code or no-code (LCNC) approach has been purposed to automate code generation. As traditional LCNC solutions are highly generic, they tend to generate excess code and instructions, which will lack efficiency in terms of storage and processing. Fortunately, optimization of automated code generation can be achieved for IoT by taking advantage of the IoT characteristics. An IoT-based distributed intelligent system consists of the device domain (IoT devices) and the network domain (IoT server). The software of an IoT device in the device domain consists of the Device Application (DA) and the Sensor Application (SA). Most IoT LCNC approaches provide code generation in the network domain. Very few approaches automatically generate the DA code. To our knowledge, no approach supports the SA code generation. In this paper, we propose DeviceTalk, an LCNC environment for the DA and the SA code development. DeviceTalk automatically generates the code for IoT devices to speed up the software development in the device domain for a distributed intelligent system. We propose the DeviceTalk architecture, design and implementation of the code generation mechanism for the IoT devices. Then, we show how a developer can use the DeviceTalk Graphical User Interface (GUI) to exercise LCNC development of the device software.

The thyroid biokinetic model of radioactive I-131 was re-evaluated using a refined nine-compartmental model and applied to twelve thyroid cancer patients. In contrast to the simplified four-compartmental model regulated by the ICRP-56 report, the revised model included nine compartments specified in the ICRP-128 report, namely, oral, stomach, body fluid, thyroid, whole body, liver, kidney, bladder, and remainder (i.e., the whole body minus kidney and bladder). A self-developed program run in MATLAB was designed to solve the nine first-order simultaneous linear differential equations. The model was realized in standard and simplified versions. The latter neglected two feedback paths (body fluid to oral, i31, and kidney to the whole body, i87) to reduce computations. Accordingly, the biological half-lives for the major compartments (thyroid and body fluid + whole body) were 36.00 ± 15.01, 15.04 ± 5.63, 34.33 ± 15.42, and 14.83 ± 5.91 of standard and simplified version. The correlations between theoretical and empirical data for each patient were quantified by the dimensionless AT (agreement) index and, the ATtot index integrated each individual AT of a specific organ of one patient. Since small AT values indicated a closer correlation, the obtained range of ATtot (0.048 ± 0.019) proved the standard model’s reliability and high accuracy, while the simplified one yielded slightly higher ATtot (0.058 ± 0.023). The detailed outcomes among various compartments of twelve patients were calculated and compared with other researchers’ work. The correlation results on radioactive I-131 evolution in thyroid cancer patients’ bodies are instrumental in viewpoint of radioactive protection of patients and radiological personnel.

This study tried to propose an innovated idea of solidifying the resolution of gamma camera in routine quality control and recommended a quantified index as minimum detectable difference (MDD) of gamma camera SPECT images using the Taguchi analysis and an indigenous V-shaped slit gauge. The gauge was customized to fulfill the quantitative requirement of the Taguchi analysis. The MDD among slit gauge of derived SPECT image was calculated from two overlapped peak profiles collected from a tangent slice of the V-shaped slit gauge with two nearby peaks. In particular, MDD was evaluated as minimum distance between two peak centers through the Student’s t-test with a constant, 1.96, which indicates that two peak centers separated distant enough to create a 95% confidence level of separation. Eighteen combinations of six gamma camera scanned factors were organized according to Taguchi analysis. Accordingly, (A) collimator, (B) detector to targe distance, (C) total counts, (D) acquired energy width, (E) Matrix size, and (F) zoom of collected ROI with each of two or three levels were organized into 18 groups to collect the slit gauge images according to Taguchi L18 orthogonal array. Then, three well-trained radiologists were ranked the scanned gauge images to derive the fish-bone-plot of signal-to-noise ratio (S/N, dB) and correlated ANOVA. Furthermore, the quantified MDD was proposed to verify the optimal suggestion of gamma camera scanned protocol, and obtained the MDD as 8.4, 7.9, and 7.1 mm for the second group of original L18 preset, conventional, and the optimal preset, respectively. Thus, the optimal preset of gamma camera was achieved in this study. The MDD proved to be a successful index in quantifying the imaging resolution of a gamma camera.