Important role of DNA methylation hints at significant potential in tuberculosis.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, has persisted as a major global public health threat for millennia. Until now, TB continues to challenge efforts aimed at controlling it, with drug resistance and latent infections being the two main factors hindering treatment efficacy. The scientific community is still striving to understand the underlying mechanisms behind Mtb's drug resistance and latent infection. DNA methylation, a critical epigenetic modification occurring throughout an individual's growth and development, has gained attention following advances in high-throughput sequencing technologies. Researchers have observed abnormal DNA methylation patterns in the host genome during Mtb infection. Given the escalating issue of drug-resistant Mtb, delving into the role of DNA methylation in TB's development is crucial. This review article explores DNA methylation's significance in human growth, development and disease, and its role in regulating Mtb's evolution and infection processes. Additionally, it discusses potential applications of DNA methylation research in tuberculosis.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure.

BACKGROUND: A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown. PATIENTS AND METHODS: This retrospective, single-centre-based cohort study included 1531 hospitalized patients with ADHF from September 2010 to January 2020. The HGI is calculated from the difference between the observed and predicted HbA1c values [predicted HbA1c = 0.024 × fasting plasma glucose (FPG) (mg/dL)+3.1]. The endpoints examined in the study included all-cause death, cardiovascular (CV) death, and major adverse cardiac events (MACE). We fitted multivariable-adjusted Cox proportional hazard models to investigate the association between the HGI and clinical outcomes. RESULTS: During the five-year follow-up, 427 (27.9%) patients died from all causes, 232 (15.6%) from CV death, and 848 (55.4%) from MACE. The restricted cubic spline analysis also showed that the cumulative risk of all-cause and CV deaths decreased linearly with increasing HGI. According to multivariate Cox proportional hazard models, the highest tertile of the HGI was associated with a lower incidence of all-cause and cardiovascular deaths [all-cause death, adjusted hazard ratio (HR): 0.720, 95% confidence interval (CI): 0.563-0.921, p = 0.009; CV death, adjusted HR: 0.619, 95% CI: 0.445-0.861, p = 0.004]. A 1% increase in the HGI was associated with a 12.5% reduction in the risk of all-cause death and a 20.8% reduction in the risk of CV death. CONCLUSIONS: A high HGI was directly associated with a reduction in all-cause and CV deaths but was not associated with MACE. These findings may be helpful in the management of patients with ADHF.

Recent studies have demonstrated that significant discrepancies between HbA1c and actual blood glucose levels may lead to clinical decision-making errors.The inconsistency of previous research results suggests that the HGI may have different predictive ability in populations with different diseases.

Noninvasive Assessment of HER2 Expression Status in Gastric Cancer Using 18F-FDG Positron Emission Tomography/Computed Tomography-Based Radiomics: A Pilot Study.

Purpose: Immunohistochemistry (IHC) is the main method to detect human epidermal growth factor receptor 2 (HER2) expression levels. However, IHC is invasive and cannot reflect HER2 expression status in real time. The aim of this study was to construct and verify three types of radiomics models based on 18F-fuorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging and to evaluate the predictive ability of these radiomics models for the expression status of HER2 in patients with gastric cancer (GC). Patients and Methods: A total of 118 patients with GC were enrolled in this study. 18F-FDG PET/CT imaging was performed prior to surgery. The LIFEx software package was applied to extract PET and CT radiomics features. The minimum absolute contraction and selection operator (least absolute shrinkage and selection operator [LASSO]) algorithm was used to select the best radiomics features. Three machine learning methods, logistic regression (LR), support vector machine (SVM), and random forest (RF) models, were constructed and verified. The Synthetic Minority Oversampling Technique (SMOTE) was applied to address data imbalance. Results: In the training and test sets, the area under the curve (AUC) values of the LR, SVM, and RF models were 0.809, 0.761, 0.861 and 0.628, 0.993, 0.717, respectively, and the Brier scores were 0.118, 0.214, and 0.143, respectively. Among the three models, the LR and RF models exhibited extremely good prediction performance. The AUC values of the three models significantly improved after SMOTE balanced the data. Conclusions: 18F-FDG PET/CT-based radiomics models, especially LR and RF models, demonstrate good performance in predicting HER2 expression status in patients with GC and can be used to preselect patients who may benefit from HER2-targeted therapy.

Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.

BACKGROUND: The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast-immunocyte interaction network have not yet been fully elucidated. MAIN BODY AND CONCLUSION: Therefore, we systematically reviewed the molecular mechanisms of fibroblast-immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast-immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.

Multiple Intrahepatic Inflammatory Myofibroblastic Tumor on 68 Ga-FAPI and 18 F-FDG PET/CT.

ABSTRACT: A 31-year-old man with multiple intrahepatic inflammatory myofibroblastoma tumor was referred to nuclear medicine department to assess its malignant potential. Multiple lesions in the liver exhibited 68 Ga-FAPI uptake at different degrees. Instead, there was no abnormal 18 F-FDG activity in the other hepatic lesions under the normal liver background except for the puncture site. This case reflects tumor heterogeneity of the disease and shows the potential value of 68 Ga-FAPI PET/CT for the evaluation of hepatic inflammatory myofibroblastoma tumor.

Reversible lateral optical force on phase-gradient metasurfaces for full control of metavehicles.

Photonics is currently undergoing an era of miniaturization thanks in part to two-dimensional (2D) optical metasurfaces. Their ability to sculpt and redirect optical momentum can give rise to an optical force, which acts orthogonally to the direction of light propagation. Powered by a single unfocused light beam, these lateral optical forces (LOFs) can be used to drive advanced metavehicles and are controlled via the incident beam's polarization. However, the full control of a metavehicle on a 2D plane (i.e. forward, backward, left, and right) with a sign-switchable LOF remains a challenge. Here we present a phase-gradient metasurface route for achieving such full control while also increasing efficiency. The proposed metasurface is able to deflect a normally incident plane wave in a traverse direction by modulating the plane wave's polarization, and results in a sign-switchable recoil LOF. When applied to a metavehicle, this LOF enables a level of motion control that was previously unobtainable.

Enhancing progestin therapy via HDAC inhibitors in endometrial cancer.

Uterine endometrial cancer (EC) incidence and deaths are on the rise. Hormone therapy, a traditional treatment regimen for this disease, uses progesterone and its synthetic analogue, progestin, to induce cell differentiation, apoptosis, and inhibition of invasion. This therapy is highly effective for progesterone receptor (PR) positive tumors in the short term. However, responsiveness decreases over time due to loss of PR expression; acquired resistance leads to treatment failure and poor prognosis. Primary resistance occurs in advanced, PR-negative tumors. Regardless, progestin therapy can be effective if the PR downregulation mechanism is reversed and if functional PR expression is restored. Using histone deacetylase inhibitors (HDACi), we inhibited cell proliferation in three EC cell lines and restored functional PR expression at the mRNA and protein levels. Two HDACi were tested using an endometrial xenograft tumor model: entinostat, an oral drug, and romidepsin, an IV drug. In vitro and in vivo studies support that entinostat decreased EC tumor growth, induced differentiation, and increased expression of the PR-targeted gene, PAEP. These findings supported the approval of a new NIH NCTN clinical trial, NRG-GY011, which concluded that dual treatment of MPA and entinostat, decreased expression of the proliferation marker, Ki67, but did not increase PR expression relative to single treatment with MPA in this short-term study. Therefore, a more potent HDACi, romidepsin, was investigated. Romidepsin treatment inhibited tumor growth and enhanced progestin treatment efficacy. More importantly, PR, PAEP, and KIAA1324 expressions were upregulated. Using a chromatin immunoprecipitation assay, we verified that HDACi can reverse PR downregulation mechanisms in mice models. Other potential drug efficacy markers, such as CD52, DLK1, GALNT9, and GNG2, were identified by transcriptome analysis and verified by q-PCR. Many of the upregulated drug efficacy markers predict favorable patient outcomes, while downregulated genes predict worse survival. Here, our current data suggests that romidepsin is a more potent HDACi that has the potential to achieve more robust upregulation of PR expression and may be a more promising candidate for future clinical trials.

Manganese enhances macrophage defense against Mycobacterium tuberculosis via the STING-TNF signaling pathway.

The host cell antiviral response pathway depends heavily on manganese (Mn), but its role in defense against Mycobacterium tuberculosis (M. tuberculosis) infection is rarely reported. In this study, we found that, in H37Ra-infected macrophages, Mn2+ increases the phosphorylation of stimulator of interferon genes (STING) and P65, as well as triggers the phosphorylation cascade of tumor necrosis factor (TNF) signaling pathway proteins, signal-regulated kinase (ERK), P38, and c-Jun N-terminal kinase (JNK). The activation of the TNF signaling pathway stimulated the expression of downstream inflammatory factors TNF-α, C-X-C Motif Chemokine Ligand 10(CXCL10), CC Motif Chemokine Ligand 20(CCL20), Colony Stimulating Factor 1(CSF1), Colony Stimulating Factor 2(CSF2), and Jagged Canonical Notch Ligand 1(JAG1), thereby triggering a strong inflammatory response in the cells. The excessive accumulation of TNF-α in macrophages induces necroptosis and inhibits the survival of M. tuberculosis in macrophages. When we treated macrophages with the STING inhibitor H-151, the phosphorylation of P38 was reduced, and the secretion of downstream inflammatory factors TNF-α and CXCL10, CCL20, CSF1, and CSF2 were also inhibited. Overall, this study reveals that Mn2+ plays a crucial role in host cell defense against M. tuberculosis infection, contributes to a deeper understanding of pathogen-host interactions, and offers theoretical support for the use of Mn2+ as a drug cofactor for the treatment of tuberculosis and the development of a new generation of drugs and vaccine adjuvants.

Case Report: 68Ga-FAPI PET/CT, a more advantageous detection mean of gastric, peritoneal, and ovarian metastases from breast cancer.

Breast cancer is the most common malignant tumor in adult women. Its common metastatic sites are lymph nodes, bones, lungs, the liver, and the brain. It is so rare for a patient with breast cancer to have metastases of the gastrointestinal tract, peritoneum, and ovary at the same time that the clinical reporting rate is low. We present a case of a 61-year-old woman who underwent right mastectomy and chemoradiotherapy 3 years ago because of mixed invasive ductal-lobular breast cancer. This time, she came to the hospital due to the symptom of stomach discomfort for 2 weeks. The gastroscopy biopsy result showed gastric metastasis from breast cancer. Then, 18F-FDG imaging and 68Ga-FAPI PET/CT imaging were performed for further diagnosis; 68Ga-FAPI PET/CT demonstrated a significantly elevated FAPI activity in the thickened gastric wall, peritoneum, and bilateral adnexal areas, which was superior to that of 18F-FDG. Finally, a biopsy of suspicious lesions was taken for pathological and histochemical examination, which confirmed that, in addition to the gastric metastasis, the peritoneum and bilateral ovaries were all consistent with metastatic breast cancer.

Sulforaphane kills Mycobacterium tuberculosis H37Ra and Mycobacterium smegmatis mc2155 through a reactive oxygen species dependent mechanism.

Mycobacterium tuberculosis (M. tuberculosis) is a highly pathogenic intracellular pathogen that causes tuberculosis (TB), the leading cause of mortality from single infections. Redox homeostasis plays a very important role in the resistance of M. tuberculosis to antibiotic damage and various environmental stresses. The antioxidant sulforaphane (SFN) has been reported to exhibit anticancer activity and inhibit the growth of a variety of bacteria and fungi. Nonetheless, it remains unclear whether SFN exhibits anti-mycobacterial activity. Our results showed that the SFN against M. tuberculosis H37Ra exhibited bactericidal activity in a time and dose-dependent manner. The anti-tubercular activity of SFN was significantly correlated with bacterial reactive oxygen species (ROS) levels. In addition, SFN promoted the bactericidal effect of macrophages on intracellular bacteria in a dose-dependent manner, mediated by increasing intracellular mitochondrial ROS levels and decreasing cytoplasmic ROS levels. Taken together, our data revealed the previously unrecognized antimicrobial functions of SFN. Future studies focusing on the mechanism of SFN in macrophages against M. tuberculosis are essential for developing new host-directed therapeutic approaches against TB.

The role of neoantigens in tumor immunotherapy.

Tumor neoantigens are aberrant polypeptides produced by tumor cells as a result of genomic mutations. They are also tumor-specific antigens (TSA). Neoantigens are more immunogenic than tumor-related antigens and do not induce autoimmunity. Based on the rapid development of bioinformatics and the continuous update of sequencing technology, cancer immunotherapy with tumor neoantigens has made promising breakthroughs and progress. In this review, the generation, prediction, and identification of novel antigens, as well as the individualized treatments of neoantigens, were first introduced. Secondly, the mechanism of Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) therapy and immune checkpoint blockade therapy in the treatment of tumors were outlined, and the three treatment methods were compared. Thirdly, the application of neoantigens in CAR-T therapy and PD-1/PD-L1 blockade therapy was briefly described. The benefits of the neoantigen vaccines over common vaccines were summarized as well. Finally, the prospect of neoantigen therapy was presented.

Semaphorin 3F Serves as a Tumor Suppressor in Esophageal Squamous Cell Carcinoma and is Associated With Lymph Node Metastasis in Disease Progression.

BACKGROUND: Esophageal squamous cell carcinoma is one of the leading aggressive malignancies with high mortality. Semaphorin 3F has been reported to be involved in lymphangiogenesis by interacting the vascular endothelial growth factor C/neuropilin 2 axis. This study aimed to assess the clinical and functional role of semaphorin 3F and preliminarily evaluate the relationship between semaphorin 3F and lymph node metastasis in esophageal squamous cell carcinoma. METHODS: The messenger RNA expression of semaphorin 3F was analyzed using quantitative real-time polymerase chain reaction. The expression differences of semaphorin 3F between patients having esophageal squamous cell carcinoma with and without lymph node metastasis were assessed, and the correlation of semaphorin 3F with vascular endothelial growth factor C and neuropilin 2 was estimated. The prognostic value of semaphorin 3F was evaluated using Kaplan-Meier survival curves and Cox regression analysis. Gain- and loss-functional cell experiments were performed to explore the biological function of semaphorin 3F, vascular endothelial growth factor C, and neuropilin 2. RESULTS: The messenger RNA expression of semaphorin 3F was reduced in esophageal squamous cell carcinoma tissues compared with normal tissues, and lower semaphorin 3F expression was observed in patients having esophageal squamous cell carcinoma with positive lymph node metastasis. Semaphorin 3F expression was associated with lymph node metastasis and negatively correlated with vascular endothelial growth factor C and neuropilin 2. Lower semaphorin 3F expression was related to a poor overall survival of esophageal squamous cell carcinoma and served as an independent prognostic indicator. In esophageal squamous cell carcinoma cells, semaphorin 3F messenger RNA expression was also decreased compared with normal cells, and the overexpression of semaphorin 3F could significantly inhibit cell proliferation, migration, and invasion. The downregulation of vascular endothelial growth factor C and neuropilin 2 could inhibit cell proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. CONCLUSION: All data indicate that semaphorin 3F serves as a potential prognostic biomarker and tumor suppressor of esophageal squamous cell carcinoma and may be involved in the lymph node metastasis development through regulating neuropilin 2.

Numerical Simulation of the Gas-Solid Two-Phase Flow-Reaction Process in a Maximizing Isoparaffin Process Reactor.

The process of the fluid catalytic cracking (FCC) is accompanied by complex physical and chemical reactions and phase transition processes. For the FCC process-maximizing isoparaffin process (MIP), coupled simulation and optimization of flow reaction can meet the requirements for the design and operation of high efficiency, low energy consumption, low pollution, and low cost in the catalytic device. A combination of Eulerian-Eulerian model and 11-lump kinetic model is adopted to simulate the flow-reaction process of gas-solid two-phase of an industrial MIP riser reactor. A drag model based on the energy-minimization multiscale model established by Yang is incorporated into FLUENT through a user-defined function (UDF). The temperature distribution of the catalyst and the concentration of each product component at the outlet are in good agreement with the industrial measured data, which indicates that the established coupling model of flow reaction and drag model are reliable and effective. The two operating variables of the catalyst-to-oil ratio and catalyst inlet temperature are explored their effects on the flow-reaction process of FCC gas-solid two-phase. In the prelifting zone, the velocity of catalyst particles presents parabolic distribution. In the first reaction zone, the maximum velocity of catalyst particles is about 1/2 of the radius of the riser. In the second reaction zone, the maximum particle velocity of catalyst is located in the central region, with a slight increase in about 1/2 of the radius of the riser. The increase in catalyst-to-oil ratio leads to the decrease in the yield of diesel oil and the increase in yields of gasoline, liquefied petroleum gas, propylene, and dry gas. The changes in the catalyst inlet temperature affect the product distribution of the outlet component, which can provide an important guiding significance.

Chromatic Dispersion Manipulation Based on Metalenses.

Metasurfaces are 2D metamaterials composed of subwavelength nanoantennas according to specific design. They have been utilized to precisely manipulate various parameters of light fields, such as phase, polarization, amplitude, etc., showing promising functionalities. Among all meta-devices, the metalens can be considered as the most basic and important application, given its significant advantage in integration and miniaturization compared with traditional lenses. However, the resonant dispersion of each nanoantenna in a metalens and the intrinsic chromatic dispersion of planar devices and optical materials result in a large chromatic aberration in metalenses that severely reduces the quality of their focusing and imaging. Consequently, how to effectively suppress or manipulate the chromatic aberration of metalenses has attracted worldwide attention in the last few years, leading to variety of excellent achievements promoting the development of this field. Herein, recent progress in chromatic dispersion control based on metalenses is reviewed.

Extending lead-free hybrid photovoltaic materials to new structures: thiazolium, aminothiazolium and imidazolium iodobismuthates.

We report on the synthesis, crystal structures, optoelectronic properties and solar cell device studies of three novel organic-inorganic iodobismuthates - [C3H4NS]3[Bi2I9] ([TH]3[Bi2I9]), [C3H4N2]3[Bi2I9] ([IM]3[Bi2I9]) and [C3H5N2S][BiI4] ([AT][BiI4]) as lead-free light harvesters. [TH]3[Bi2I9] and [IM]3[Bi2I9] show zero-dimensional structures, whereas a one-dimensional edge-sharing chain structure of BiI6-octahedra was observed in [AT][BiI4], with interchain short II contacts also giving rise to the possibility of three-dimensional charge transport ability. Accordingly, greater energy dispersion in the band structure of [AT][BiI4] can be observed, and less contribution from the organic moities at the conduction band minimum in [AT][BiI4] than [TH]3[Bi2I9] have been confirmed by density functional theory calculations. Moreover, bandgap values are redshifted from 2.08 eV for [TH]3[Bi2I9] and 2.00 eV for [IM]3[Bi2I9] to 1.78 eV for [AT][BiI4], determined by UV-Vis reflectance spectroscopy. Power conversion efficiency of 0.47% has been achieved by using ([AT][BiI4]) as the light absorber in a hole-conductor-free, fully printable solar cell, with relatively good reproducibility. We also note the observation of a capacitance effect for the first time in a photovoltaic device with bismuth-based solar absorber, which may be related to the mesoporous carbon counter-electrode.

High-Performance Porphyrin-Based Dye-Sensitized Solar Cells with Iodine and Cobalt Redox Shuttles.

Recently, enormous research passion has been devoted to enhance the power conversion efficiency (PCE) of porphyrin sensitizers for dye-sensitized solar cells (DSSCs), but the major stumbling block is the absorption defect in the visible-light region. To address this challenge, high-performance DSSCs are reported based on a new donor-π-acceptor sensitizer FW-1, 7H-dibenzo[c,g]carbazole-substituted and fused zinc porphyrin, co-sensitized with a benzotriazole-containing dye (WS-5) in iodine and cobalt redox systems, and high PCEs of 10.21 and 10.42 %, respectively, were obtained. An unprecedented breakthrough was obtained by making one sensitizer suitable for several electrolyte systems because of its appropriate molecular orbitals and co-sensitizer.

D-A-π-A Motif Quinoxaline-Based Sensitizers with High Molar Extinction Coefficient for Quasi-Solid-State Dye-Sensitized Solar Cells.

To meet the requirement of high molar extinction coefficient, broad absorption spectrum, and photo/thermal stability for sensitizers of quasi-solid-state dye-sensitized solar cells (Qs-DSSCs) with reduced film thickness, a novel D-A-π-A configuration organic sensitizer IQ22 was specifically designed, in which the conjugation bridge of cyclopentadithiophene (CPDT) unit was incorporated to widen the light response and enhance molar coefficients for increasing the short-circuit current density (JSC), and the octane chain on CPDT was targeted for suppressing the charge recombination and improving the open-circuit voltage (VOC). As a result, the Qs-DSSC based on IQ22 exhibits very promising conversion efficiency as high as 8.76%, with a JSC of 18.19 mA cm-2, a VOC of 715 mV, and a fill factor (FF) of 0.67 under AM 1.5 illumination (100 mW cm-2), standing out in the Qs-DSSCs utilizing metal-free organic sensitizers.

Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis.

Hepatocellular carcinoma (HCC) is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rate. Identifying novel prognostic biomarkers and therapeutic targets would be vital for HCC management. Long noncoding RNA (lncRNA) is a class of RNA with various roles in tumorigenesis. The aim of this study was to investigate the clinical significance and functions of lncRNA-small nucleolar RNA host gene 1 (SNHG1) in HCC. In this study, we found SNHG1 was upregulated in HCC tissues in comparison with adjacent liver tissues in both publicly available microarray data and our own cohort. High SNHG1 expression was correlated with large tumor size, poor differentiation, and aggressive BCLC stage. Kaplan-Meier survival analysis demonstrated that high SNHG1 expression predicts poor prognosis of HCC patients. Gain-of-function and loss-of function experiments showed that SNHG1 promotes HCC cells proliferation, cell cycle progression, and inhibits HCC cells apoptosis. Further experiments revealed that SNHG1 promotes HCC cells proliferation through inhibiting p53 and p53-target genes expression. Collectively, our results demonstrated the clinical prognostic significance and roles of SNHG1 in HCC, and suggested that SNHG1 may be considered as a prognostic biomarker and therapeutic target for HCC.