Metagenomic next-generation sequencing promotes diagnosis and treatment of Pneumocystis jirovecii pneumonia in non-HIV infected children: a retrospective study.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children. METHODS: Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-ß-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed. RESULTS: Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26-100%). The sensitivity of BDG was 57.58% (95% CI: 39.22-74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts. CONCLUSIONS: The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.

Serum C-reactive protein to albumin ratio as a potential risk indicator of pneumonia caused by Chlamydia psittaci: a multicenter retrospective study.

Introduction: The aim of the study was to describe psittacosis pneumonia and to assess the predictive value of the C-reactive protein/albumin ratio in psittacosis pneumonia for severity. Methods: Data on psittacosis pneumonia cases diagnosed using metagenomic sequencing were collected from three hospitals in Shanghai, China from Oct. 2019 to Oct. 2022. Serum levels of C-reactive protein and albumin were measured and the C-reactive protein to albumin ratio (CAR) was calculated. Spearman's correlation analysis, ordered logistic regression analysis, and receiver operating characteristic curve analysis were conducted to examine the correlation and predictive ability of the three indicators on the severity of the disease. Results: A total of 27 patients with psittacosis pneumonia were enrolled, with an average age of 62 years and 70.4% being male. 44.4% of patients had a clear history of contact with poultry or birds. The predominant symptom was fever (100%). Patients treated in the respiratory intensive care unit (RICU) had a higher likelihood of experiencing wheezing (88.9% versus 33.3%, P=0.013) and chest tightness (88.9% vs. 33.3%, P=0.013) than those in the general ward (Non-RICU). The proportion of patients with pleural effusion was significantly higher in the RICU compared to the Non-RICU (88.9% vs. 38.9%, P=0.019). The RICU group had a significantly higher CAR than the Non-RICU group (9.41 vs. 4.05, P=0.017). This result was accompanied by higher intubation and ventilator support (33.3% vs. 0.0%, P=0.029), higher PCT and CRP levels and lower albumin and PaCO2 levels in the RICU than in the Non-RICU. Logistic regression analysis indicated that CAR (OR 1.49; 95% CI 1.07-2.06, P=0.017) was risk factor for prolonged hospitalization (> 14 days). Discussion: Elevated serum CAR levels were found to be associated with a greater risk of severe psittacosis pneumonia. Consequently, it may serve as an uncomplicated and useful diagnostic tool for clinicians to promptly and precisely ascertain the severity of psittacosis pneumonia, ultimately aiding them in devising the most optimal therapeutic plan.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research.

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Epigallocatechin-3-Gallate attenuates lipopolysacharide-induced pneumonia via modification of inflammation, oxidative stress, apoptosis, and autophagy.

BACKGROUND: Pneumonia, the acute inflammation of lung tissue, is multi-factorial in etiology. Hence, continuous studies are conducted to determine the mechanisms involved in the progression of the disease and subsequently suggest effective treatment. The present study attempted to evaluate the effects of Epigallocatechin-3-Gallate (EGCG), an herbal antioxidant, on inflammation, oxidative stress, apoptosis, and autophagy in a rat pneumonia model. METHODS: Forty male Wistar rats, 5 months old and 250-290 g were divided into four groups including control, EGCG, experimental pneumonia (i/p LPS injection, 1 mg/kg), and experimental pneumonia treated with EGCG (i/p, 15 mg/kg, 1 h before and 3 h after LPS instillation). Total cell number in the bronchoalveolar lavage fluid, inflammation (TNF-a, Il-6, IL-1ß, and NO), oxidative stress (Nrf2, HO-1, SOD, CAT, GSH, GPX, MDA, and TAC), apoptosis (BCL-2, BAX, CASP-3 and CASP-9), and autophagy (mTOR, LC3, BECN1) were evaluated. RESULTS: The findings demonstrated that EGCG suppresses the LPS-induced activation of inflammatory pathways by a significant reduction of inflammatory markers (p-value < 0.001). In addition, the upregulation of BCL-2 and downregulation of BAX and caspases revealed that EGCG suppressed LPS-induced apoptosis. Furthermore, ECGC suppressed oxidative injury while promoting autophagy in rats with pneumonia (p-value < 0.05). CONCLUSION: The current study revealed that EGCG could suppress inflammation, oxidative stress, apoptosis, and promote autophagy in experimental pneumonia models of rats suggesting promising therapeutical properties of this compound to be used in pneumonia management.

Granulysin-mediated reduction of PDZRN3 induces Cx43 gap junctions activity exacerbating skin damage in trichloroethylene hypersensitivity syndrome.

Trichloroethylene (TCE)-induced hypersensitivity syndrome (THS) has been a concern for many researchers in the field of environmental and occupational health. Currently, there is no specific treatment for THS, leaving patients to contend with severe infections arising from extensive skin lesions, consequently leading to serious adverse effects. However, the pathogenesis of severe skin damage in THS remains unclear. This study aims to investigate the specific danger signals and mechanisms underlying skin damage in THS through in vivo and in vitro experiments. We identified that cell supernatant containing 15 kDa granulysin (GNLY), released from activated CD3-CD56+NK cells or CD3+CD56+NKT cells in PBMC induced by TCE or its metabolite, promoted apoptosis in HaCaT cells. The apoptosis level decreased upon neutralization of GNLY in the supernatant by a GNLY-neutralizing antibody in HaCaT cells. Subcutaneous injection of recombinant 15 kDa GNLY exacerbated skin damage in the THS mouse model and better mimicked patients' disease states. Recombinant 15 kDa GNLY could directly induce cellular communication disorders, inflammation, and apoptosis in HaCaT cells. In addition to its cytotoxic effects, GNLY released from TCE-activated NK cells and NKT cells or synthesized GNLY alone could induce aberrant expression of the E3 ubiquitin ligase PDZRN3, causing dysregulation of the ubiquitination of the cell itself. Consequently, this resulted in the persistent opening of gap junctions composed of connexin43, thereby intensifying cellular inflammation and apoptosis through the "bystander effect". This study provides experimental evidence elucidating the mechanisms of THS skin damage and offers a novel theoretical foundation for the development of effective therapies targeting severe dermatitis induced by chemicals or drugs.

Unveiling the mechanisms of trichloroethylene hypersensitivity syndrome: Exploring the role of connexin 43 gap junctions in severe skin damage.

Trichloroethylene (TCE), extensively used as an organic solvent in various industrial applications, has been identified as a causative factor in inducing hypersensitivity syndrome (THS). Currently, there is no specific treatment for THS, and most patients experience serious adverse outcomes due to extensive skin damage leading to severe infection. However, the pathogenesis of THS-associated skin damage remains unclear. This study aims to elucidate the mechanism underlying skin damage from the perspective of intercellular communication and gap junctions in THS. Our results verified that hyperactivation of connexin43 gap junctions, caused by the aberrantly elevated expression of connexin43, triggers a bystander effect that promotes apoptosis and inflammation in THS via the TNF-TNFRSF1B and mitochondria-associated pathways. Additionally, we identified the gap junction inhibitor Carbenoxolone disodium (CBX) as a promising agent for the treatment of skin damage in THS. CBX protects against inflammatory cell infiltration in the skin and decreases immune cell imbalance in the peripheral blood of THS mice. Furthermore, CBX reduces connexin43 expression, apoptosis and inflammation in THS mice. The study reveals new insights into the mechanisms underlying TCE-induced skin damage, offering a potential treatment strategy for the development of effective therapies targeting severe dermatitis induced by chemical exposure.

Pillararene-Based Stimuli-Responsive Supramolecular Delivery Systems for Cancer Therapy.

Cancer poses a significant challenge to global public health, seriously threatening human health and life. Although various therapeutic strategies, such as chemotherapy (CT), radiotherapy, phototherapy, and starvation therapy, are applied to cancer treatment, their limited therapeutic effect, severe side effects, and unsatisfactory drug release behavior need to be carefully considered. Thus, there is an urgent need to develop efficient drug delivery strategies for improving cancer treatment efficacy and realizing on-demand drug delivery. Notably, pillararenes, as an emerging class of supramolecular macrocycles, possess unique properties of highly tunable structures, superior host-guest chemistry, facile modification, and good biocompatibility, which are widely used in cancer therapy to achieve controllable drug release and reduce the toxic side effects on normal tissues under various internal/external stimuli conditions. This review summarizes the recent advance of stimuli-responsive supramolecular delivery systems (SDSs) based on pillararenes for tumor therapy from the perspectives of different assembly methods and hybrid materials, including molecular-scale SDSs, supramolecular nano self-assembly delivery systems, and nanohybrid SDSs. Moreover, the prospects and critical challenges of stimuli-responsive SDSs based on pillararenes for cancer therapy are also discussed.

Dual-modality probe nanodrug delivery systems with ROS-sensitivity for atherosclerosis diagnosis and therapy.

Most acute cardiovascular and cerebrovascular diseases are caused by atherosclerotic plaque rupture leading to blocked arteries. Targeted nanodelivery systems deliver imaging agents or drugs to target sites for diagnostic imaging or the treatment of various diseases, providing new insights for the detection and treatment of atherosclerosis. Based on the pathological characteristics of atherosclerosis, a hydrogen peroxide-sensitive bimodal probe PPIS@FC with integrated diagnosis and treatment function was designed. Bimodal probes Fe3O4@SiO2-CDs (FC) were prepared by coupling superparamagnetic iron oxide and carbon quantum dots synthesized with citric acid, and self-assembled with hydrogen peroxide stimulus-responsive amphiphilic block polymer PGMA-PEG modified with simvastatin (Sim) and target molecule ISO-1 to obtain drug-loaded micelles PGMA-PEG-ISO-1-Sim@FC (PPIS@FC). PPIS@FC could release Sim and FC in an H2O2-triggered manner, achieving the goal of releasing drugs using the special microenvironment at the plaque. At the same time, in vivo magnetic resonance and fluorescence imaging results proved that PPIS@FC possessed targeting ability, magnetic resonance imaging and fluorescence imaging effects. The results of the FeCl3 and ApoE-/- model showed that PPIS@FC had an excellent therapeutic effect and in vivo safety. Therefore, dual-modality imaging drug delivery systems with ROS response will become a promising strategy for the diagnosis and treatment of atherosclerosis.

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.

Shear Stress and ROS Dual-Responsive RBC-Hitchhiking Nanoparticles for Atherosclerosis Therapy.

Atherosclerosis (AS), a leading cause of death worldwide, is a chronic inflammatory disease rich in lipids and reactive oxygen species (ROS) within plaques. Therefore, lowering lipid and ROS levels is effective in treating AS and reducing AS-induced mortality. In this study, an intelligent biomimetic drug delivery system that specifically responded to both shear stress and ROS microenvironment was developed, consisting of red blood cells (RBCs) and cross-linked polyethyleneimine nanoparticles (SA PEI) loaded with a lipid-lowering drug simvastatin acid (SA), and RBCs were self-assembled with SA PEI to obtain biresponsive SA PEI@RBCs for the treatment of AS. SA PEI could achieve sustained release of SA in response to ROS and reduce ROS and lipid levels to achieve the purpose of treating AS. Shear stress model experiments showed that SA PEI@RBCs could respond to the high shear stress level (100 dynes/cm2) at plaques, realizing the desorption and enrichment of SA PEI and improving the therapeutic efficiency of SA PEI@RBCs. In vitro and in vivo experiments have confirmed that SA PEI@RBCs exhibits better in vivo safety and therapeutic efficacy than SA PEI and free SA. Therefore, shaping SA PEI@RBCs into a biomimetic drug delivery system with dual sensitivity to ROS and shear stress is an effective strategy and treatment to facilitate their delivery into plaques.

Utilizing metagenomic next-generation sequencing for diagnosis and lung microbiome probing of pediatric pneumonia through bronchoalveolar lavage fluid in pediatric intensive care unit: results from a large real-world cohort.

Background: Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples. Methods: A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients' lung BALF microbiomes were explored using the mNGS data. Results: Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%). Conclusions: mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.

Case report: The clinical utility of metagenomic next-generation sequencing in mucormycosis diagnosis caused by fatal Lichtheimia ramosa infection in pediatric neuroblastoma.

Lichtheimia ramosa (L. ramosa) is an opportunistic fungal pathogen of the order Mucorales that may result in a rare but serious mucormycosis infection. Mucormycosis could be angioinvasive, causing thrombosis and necrosis in the nose, brain, digestive tract, and respiratory tract. The infection is highly lethal, especially in immunocompromised hosts, and the incidence has been on the rise. However, due to its relatively low incidence in pediatric population and the challenges with diagnosis, the awareness and management experience for pediatric mucormycosis are extremely limited, which might lead to poor outcomes. In this study, we comprehensively reviewed the course of a fatal rhinocerebral mucormycosis case in a pediatric neuroblastoma patient receiving chemotherapy. Due to a lack of awareness of the infection, the standard care of amphotericin B treatment was delayed and not administered until the identification of L. ramosa by metagenomic next-generation sequencing (mNGS)-based pan-pathogen detection of the patient's peripheral blood sample. We also reviewed the literature on L. ramosa infection cases reported worldwide between 2010 and 2022, with an analysis of clinical manifestation, prognosis, and epidemiological data. Our study not only highlighted the clinical value of comprehensive mNGS in rapid pathogen detection but also raised awareness of recognizing lethal fungal infection early in immunocompromised hosts including pediatric cancer patients.

Effect of trichloroethanol on TLR2 and TLR4/NF-κB-mediated antigen processing and presentation in HLA-B* 13:01-transfected antigen-presenting cells.

Trichloroethanol (TCOH), as a metabolite of trichloroethylene, has sensitization in the pathogenesis of trichloroethylene-induced hypersensitivity dermatitis (TIHD) which the human leukocyte antigen (HLA)-B∗13:01 gene is strongly associated with it. However, it is still obscure how TCOH participates in the pathogenesis of TIHD. Here, we demonstrate that TLR2 and TLR4 signaling through MyD88 and TRAF6-dependent pathway could activate NF-κB by promoting degradation of the inhibitor IκB-α to stimulate the process of NF-κB nuclear translocation. Besides, the crucial molecules of antigen processing and presentation, including TAP1, LMP2, LMP7, and HLA-B* 13:01, were all enhanced and the abundance of HLA-B* 13:01 on the surface of CIR-B* 13:01 cells was also up-regulated with the TCOH concentration increasing. Notably, we used 50 µM pyrrolidinedithiocarbamate (ammonium) to effectively inhibit the activation of NF-κB, which could effectively reverse the stimulation of antigen processing and presentation in TCOH-treated CIR-B* 13:01 cells. Taken together, we speculated that TCOH could promote the abundance of HLA complex on the antigen-presenting cells via TLR2 and TLR4/NF-κB to induce the severe reactivation of T lymphocytes, leading to the extreme immune response.

Optical frequency comb assisted reconfigurable broadband spread spectrum signal generation.

A photonic-assisted scheme for spread spectrum communication signals generation is proposed and demonstrated in this article. The spreading sequence and the baseband data codes are modulated on the photonic link by electro-optic modulators, and the spread spectrum process is completed through stream processing on the analog microwave photonic link. By combining optical frequency comb and injection locking technologies, the carrier frequency of the communication signals can be tuned over an ultra-broadband range of 3-39 GHz. In the proof-of-concept experiments, spread spectrum signals at 3 GHz and 6 GHz are obtained with a spread factor of 31. The analysis results indicate that the generated signals possess excellent reconfiguration, anti-interference, and anti-interception properties. Overall, our proposed scheme offers a flexible photonic architecture with significant potential in the application of ultra-broadband covert communication systems.

The application of metagenomic next-generation sequencing for Angiostrongylus eosinophilic meningitis in a pediatric patient: A case report.

Background: Angiostrongylus eosinophilic meningitis (AEM) is a rare yet emerging disease caused by Angiostrongylus cantonensis infection. Its atypical symptoms may delay the diagnosis and cause fatal outcomes, especially in the early stages of infection and among children. Case presentation: Here we reported the use of metagenomic next-generation sequencing (mNGS) to facilitate the diagnosis and treatment of an 8-year-old boy with severe A. cantonensis infection. The mNGS tests consistently identified the infection of A. cantonensis prior to the detection by the immunologic method and confirmed it as AEM. Owing to the multidisciplinary team (MDT)-administrated treatments and close disease monitoring based on regular clinical tests and sequential mNGS tests, the patients eventually fully recovered from severe infectious conditions. Conclusion: This case demonstrated the advantages of mNGS for early diagnosis of AEM in pediatric patients, highlighting its application for pan-pathogen detection, as well as disease monitoring for severe A. cantonensis infection.

Occupational health effect of TCE exposure: Experiment evidence of gene-environment interaction in hypersensitivity reaction.

BACKGROUND: Recently, Trichloroethylene (TCE) induced TCE hypersensitivity syndrome (THS) has attracted the attention of many researchers in the field of environmental and occupational health. Studies have revealed that Human leukocyte antigen (HLA) polymorphisms were the important genetic determinants of the diseases, but the potential molecular mechanism remains unclear. OBJECTIVE: This study aimed to investigate the association between THS and HLA at the molecular level. METHOD: We chose the human B-lymphoblastoid cell line Hmy2.C1R transfected with cDNA of HLA-B*13:01 and HLA-B*13:02 to analyze the characteristics of HLA-B-binding peptides and investigate the effect of TCE on the binding affinity of peptides to the HLA-B molecules. Further, the mathematical model was used to identify the possible interaction between TCE and HLA-B*13:01 or HLA-B*13:02 molecule. RESULTS: 54 HLA-B*13:01-binding peptides and 85 HLA-B*13:02-binding peptides were identified. Comparing the protein sequences of HLA-B*13:01 and HLA-B*13:02, amino acids were different at positions 94, 95 and 97. The results of the binding affinity of self-peptides to HLA molecules in the presence of TCE showed that TCE significantly decreased the binding affinity of peptides to HLA-B*13:01 only, but did not affect that of HLA-B*13:02. Molecular docking model showed that there was a unique high-affinity binding mode between TCE and HLA-B*13:01 (but not HLA-B*13:02), and the binding site located in the region of F pocket, suggesting that the unique structure of the F pocket of HLA-B*13:01 might provide the possibility of binding TCE. The pathogenesis of interaction between HLA-B*13:01 and TCE might belong to the model of the alteration of the HLA-presented self-peptide repertoire. DISCUSSION: This study explored the molecular mechanism of the association between THS and HLA-B*13:01, and had important implications for understanding the role of gene-environment interaction in the development of complex environment-related diseases.

Therapeutic strategies for gastric cancer targeting immune cells: Future directions.

Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell-based therapeutic methods will be developed and applied.

Trend Analysis of Occupational Lung Cancer from Coke Oven Emission Exposure - China, 2008-2019.

What is already known about this topic?: Coke oven emissions are a complex mixture of particulate matter and gases, some with carcinogenicity, released during coke production. Lung cancer caused by coke oven emissions has been listed as a statutory occupational cancer in China and many countries. What is added by this report?: In this study, coke oven emissions-induced lung cancer was mainly found in the manufacturing industries. Coke oven workers exposed to higher levels of polycyclic aromatic hydrocarbons in different workplaces had a high risk of occupational lung cancer. What are the implications for public health practice?: It is necessary to take efforts to greatly reduce emissions from coke production and effectively monitor the health of workers.

Hyaluronic acid targeted and pH-responsive multifunctional nanoparticles for chemo-photothermal synergistic therapy of atherosclerosis.

Atherosclerosis is a global disease with an extremely high morbidity and fatality rate, so it is necessary to develop effective treatments to reduce its impact. In this work, we successfully prepared a multifunctional drug-loaded nano-delivery system with pH-responsive, CD44-targeted, and chemical-photothermal synergistic treatment. Dendritic mesoporous silica nanoparticles capped with copper sulfide (CuS) were synthesized via an oil-water biphase stratification reaction system; these served as the carrier material and encapsulated the anticoagulant drug heparin (Hep). The pH-sensitive Schiff base bond was used as a gatekeeper and targeting agent to modify hyaluronic acid (HA) on the surface of the nanocarrier. HA coating endowed the nanocomposite with the ability to respond to pH and target CD44-positive inflammatory macrophages. Based on this multifunctional nanocomposite, we achieved precise drug delivery, controlled drug release, and chemical-photothermal synergistic treatment of atherosclerosis. The in vitro drug release results showed that the nanocarriers exhibited excellent drug-controlled release properties, and could release drugs in the weakly acidic microenvironment of atherosclerotic inflammation. Cytotoxicity and cell uptake experiments indicated that nanocarriers had low cytotoxicity against RAW 264.7 cells. Modification of HA to nanocarriers can be effectively internalized by RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Combining CuS photothermal treatment with anti-atherosclerosis chemotherapy showed better effects than single treatment in vitro and in vivo. In summary, our research proved that H-CuS@DMSN-NC-HA has broad application prospects in anti-atherosclerosis.

Deep-learning-assisted linearization for the broadband photonic scanning channelized receiver.

An autoencoder-residual (AE-Res) network is designated to assist the linearization of the wideband photonic scanning channelized receiver. It is capable of adaptively suppressing spurious distortions over multiple octaves of signal bandwidth, obviating the need for calculating the multifactorial nonlinear transfer functions. Proof-of-concept experiments indicate that the improvement of the third-order spur-free dynamic range (SFDR2/3) is 17.44 dB. Moreover, the results for real wireless communication signals demonstrate that the improvement of the spurious suppression ratio (SSR) is 39.69 dB and the reduction of the noise floor is ∼10 dB.