Digital health for sexually transmitted infection and HIV services: a global scoping review.

PURPOSE OF REVIEW: The current study aimed to review how digital health has been used for sexually transmitted infection (STI)/HIV prevention, testing, and treatment. RECENT FINDINGS: A scoping review was conducted by searching five databases for peer-reviewed literature published between March 2018 to August 2019. 23 out of 258 studies met the inclusion criteria and were assessed. Six studies used digital platform to enhance STI/HIV prevention messaging; four studies found that digital health can provide vivid promotional information and has been instrumental in increasing the accessibility and acceptability of STI/HIV testing; three studies reported digital health provides a channel to understand and interpret the discourses on preexposure prophylaxis (PrEP) and increase PrEP uptake; three studies focused on refining big data algorithms for surveillance; four studies reported on how digital interventions could be used to optimize clinical interventions; and four studies found digital interventions can be used to assist mental health services. SUMMARY: Digital health is a powerful and versatile tool that can be utilized in the production of high-quality, innovative strategies on STIs and HIV services. Future studies should consider focusing on strategies and implementations that leverage digital platforms for network-based interventions, in addition to recognizing the norms of individual digital intervention platforms.

IRGS: an immune-related gene classifier for lung adenocarcinoma prognosis.

BACKGROUND: Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for tumours has been widely studied, but a practical prognostic model based on immune-related genes in lung adenocarcinoma comparable to existing model has not been established and reported. METHODS: We first obtained publicly accessible lung adenocarcinoma RNA expression data from The Cancer Genome Atlas (TCGA) for differential gene expression analysis and then filtered immune-related genes based on the ImmPort database. By using the lasso algorithm and multivariate Cox Proportional-Hazards (CoxPH) regression analysis, we identified candidate genes for model development and validation. The robustness of the model was further examined by comparing the model with three established gene models. RESULTS: Gene expression data from a total of 524 lung adenocarcinoma patients from TCGA were used for model development. We identified four biomarkers (MAP3K8, CCL20, VEGFC, and ANGPTL4) that could predict overall survival in lung adenocarcinoma (HR = 1.98, 95% CI 1.48 to 2.64, P = 4.19e-06) and this model could be used as a classifier for the evaluation of low-risk and high-risk groups. This model was validated with independent microarray data and was highly comparable with previously reported gene expression signatures for lung adenocarcinoma prognosis. CONCLUSIONS: In this study, we identified a practical and robust four-gene prognostic model based on an immune gene dataset with cross-platform compatibility. This model has potential value in improving TNM staging for survival predictions in patients with lung adenocarcinoma. IMPACT: The study provides a method of immune relevant gene prognosis model and the identification of immune gene classifier for the prediction of lung adenocarcinoma prognosis with RNA sequencing and microarray compatibility.

TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells.

Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3.

Spatial distance between tumor and lymphocyte can predict the survival of patients with resectable lung adenocarcinoma.

Background and objective: Spatial interaction between tumor-infiltrating lymphocytes (TILs) and tumor cells is valuable in predicting the effectiveness of immune response and prognosis amongst patients with lung adenocarcinoma (LUAD). Recent evidence suggests that the spatial distance between tumor cells and lymphocytes also influences the immune responses, but the distance analysis based on Hematoxylin and Eosin (H&E) -stained whole-slide images (WSIs) remains insufficient. To address this issue, we aim to explore the relationship between distance and prognosis prediction of patients with LUAD in this study. Methods: We recruited patients with resectable LUAD from three independent cohorts in this multi-center study. We proposed a simple but effective deep learning-driven workflow to automatically segment different cell types in the tumor region using the HoVer-Net model, and quantified the spatial distance (DIST) between tumor cells and lymphocytes based on H&E-stained WSIs. The association of DIST with disease-free survival (DFS) was explored in the discovery set (D1, n = 276) and the two validation sets (V1, n = 139; V2, n = 115). Results: In multivariable analysis, the low DIST group was associated with significantly better DFS in the discovery set (D1, HR, 0.61; 95 % CI, 0.40-0.94; p = 0.027) and the two validation sets (V1, HR, 0.54; 95 % CI, 0.32-0.91; p = 0.022; V2, HR, 0.44; 95 % CI, 0.24-0.81; p = 0.009). By integrating the DIST with clinicopathological factors, the integrated model (full model) had better discrimination for DFS in the discovery set (C-index, D1, 0.745 vs. 0.723) and the two validation sets (V1, 0.621 vs. 0.596; V2, 0.671 vs. 0.650). Furthermore, the computerized DIST was associated with immune phenotypes such as immune-desert and inflamed phenotypes. Conclusions: The integration of DIST with clinicopathological factors could improve the stratification performance of patients with resectable LUAD, was beneficial for the prognosis prediction of LUAD patients, and was also expected to assist physicians in individualized treatment.

A comparative study on epidemiological characteristics, transmissibility, and pathogenicity of three COVID-19 outbreaks caused by different variants.

OBJECTIVES: The Omicron BA.2 variant is probably the main epidemic strain worldwide at present. Comparing the epidemiological characteristics, transmissibility, and influencing factors of SARS-CoV-2, the results obtained in this paper will help to provide theoretical support for disease control. METHODS: This study was a historical information analysis, using the R programming language and SPSS 24.0 for statistical analysis. The Geoda and Arc GIS were used for spatial autocorrelation analysis. RESULTS: Local spatial autocorrelations of the incidence rate were observed in Delta and Omicron BA.1 outbreaks, whereas Omicron BA.2 outbreaks showed a random distribution in incidence rate. The time-dependent reproduction number of Delta, Omicron BA.1, and Omicron BA.2 were 3.21, 4.29, and 2.96, respectively, and correspondingly, the mean serial interval were 4.29 days (95% confidence interval [CI]: 0.37-8.21), 3.84 days (95% CI: 0-8.37), and 2.77 days (95% CI: 0-5.83). The asymptomatic infection rate of cases in Delta, Omicron BA.1, and Omicron BA.2 outbreaks were 21.71%, 6.25%, and 4.35%, respectively. CONCLUSION: The Omicron BA.2 variant had the greatest serial interval, transmissibility, and transmission speed, followed by BA.1, and then Delta. Compared with Delta and Omicron BA.1 variants, the Omicron BA.2 variant may be less pathogenic and more difficult to control than Omicron BA.1 and Delta.

Formation and degradation of strongly reducing cyanoarene-based radical anions towards efficient radical anion-mediated photoredox catalysis.

Cyanoarene-based photocatalysts (PCs) have attracted significant interest owing to their superior catalytic performance for radical anion mediated photoredox catalysis. However, the factors affecting the formation and degradation of cyanoarene-based PC radical anion (PC•‒) are still insufficiently understood. Herein, we therefore investigate the formation and degradation of cyanoarene-based PC•‒ under widely-used photoredox-mediated reaction conditions. By screening various cyanoarene-based PCs, we elucidate strategies to efficiently generate PC•‒ with adequate excited-state reduction potentials (Ered*) via supra-efficient generation of long-lived triplet excited states (T1). To thoroughly investigate the behavior of PC•‒ in actual photoredox-mediated reactions, a reductive dehalogenation is carried out as a model reaction and identified the dominant photodegradation pathways of the PC•‒. Dehalogenation and photodegradation of PC•‒ are coexistent depending on the rate of electron transfer (ET) to the substrate and the photodegradation strongly depends on the electronic and steric properties of the PCs. Based on the understanding of both the formation and photodegradation of PC•‒, we demonstrate that the efficient generation of highly reducing PC•‒ allows for the highly efficient photoredox catalyzed dehalogenation of aryl/alkyl halides at a PC loading as low as 0.001 mol% with a high oxygen tolerance. The present work provides new insights into the reactions of cyanoarene-based PC•‒ in photoredox-mediated reactions.

Curved Nanographenes: Multiple Emission, Thermally Activated Delayed Fluorescence, and Non-Radiative Decay.

The intriguing and rich photophysical properties of three curved nanographenes (CNG 6, 7, and 8) are investigated by time-resolved and temperature-dependent photoluminescence (PL) spectroscopy. CNG 7 and 8 exhibit dual fluorescence, as well as dual phosphorescence at low temperature in the main PL bands. In addition, hot bands are detected in fluorescence as well as phosphorescence, and, in the narrow temperature range of 100-140 K, thermally activated delayed fluorescence (TADF) with lifetimes on the millisecond time-scale is observed. These findings are rationalized by quantum-chemical simulations, which predict a single minimum of the S1 potential of CNG 6, but two S1 minima for CNG 7 and CNG 8, with considerable geometric reorganization between them, in agreement with the experimental findings. Additionally, a higher-lying S2 minimum close to S1 is optimized for the three CNG, from where emission is also possible due to thermal activation and, hence, non-Kasha behavior. The presence of higher-lying dark triplet states close to the S1 minima provides mechanistic evidence for the TADF phenomena observed. Non-radiative decay of the T1 state appears to be thermally activated with activation energies of roughly 100 meV and leads to disappearance of phosphorescence and TADF at T > 140 K.

Donor-Acceptor-Donor Triads with Flexible Spacers: Deciphering Complex Photophysics for Targeted Materials Design.

The complex photokinetics of donor-acceptor-donor triads with varying flexible spacer lengths (n = 4-10 carbon atoms) are investigated in liquid and solid solution, as well as in crystals, by steady-state and transient fluorescence spectroscopy combined with computational studies. For the short spacer (n = 4) in a liquid solution, dynamic charge-transfer (CT) state formation with subsequent, efficient exciplex emission is observed, effectively competing with quenching through electron transfer (eT) via a radical ion pair. In a solid solution, a fluorescent CT static complex is formed upon freezing for all spacer lengths. This allows the observations of a former seminal report on stimuli-responsive high-contrast fluorescence on/off switching in films of the triads to be reassigned (Adv. Mater. 2012, 24, 5487), now providing a holistic picture on varying spacer length. In fact, external stimuli of the film by modulating the geometry of the CT complex, which results in on/off fluorescence switching (for n > 4) or in a change of the emission color (n = 4). The work thus demonstrates how in-depth analysis of complex photophysics can be put to practical use in materials science.

Plasma cell-free DNA 5-hydroxymethylcytosine and whole-genome sequencing signatures for early detection of esophageal cancer.

Esophageal cancer is a highly incidence and deadly disease with a poor prognosis, especially in developing countries. Owing to the lack of specific symptoms and early diagnostic biomarkers, most patients are diagnosed with advanced disease, leading to a 5-year survival rate of less than 15%. Early (n = 50) and middle-advanced (n = 50) esophageal squamous cell carcinoma (ESCC) patients, as well as 71 healthy individuals, underwent 5-hydroxymethylcytosine (5hmC) sequencing on their plasma cell-free DNA (cfDNA). A Northern Chinese cohort of cfDNA 5hmC dataset of 150 ESCC patients and 183 healthy individuals were downloaded for validation. A diagnostic model was developed using cfDNA 5hmC signatures and then improved by low-pass whole genome sequencing (WGS) features of cfDNA. Conserved cfDNA 5hmC modification motifs were observed in the two independent ESCC cohorts. The diagnostic model with 5hmC features achieved an AUC of 0.810 and 0.862 in the Southern and Northern cohorts, respectively, with sensitivities of 69.3-74.3% and specificities of 82.4-90.7%. The performance was well maintained in Stage I to Stage IV, with accuracy of 70-100%, but low in Stage 0, 33.3%. Low-pass WGS of cfDNA improved the AUC to 0.934 with a sensitivity of 82.4%, a specificity of 88.2%, and an accuracy of 84.3%, particularly significantly in Stage 0, with an accuracy up to 80%. 5hmC and WGS could efficiently differentiate very early ESCC from healthy individuals. These findings imply a non-invasive and convenient method for ESCC detection when clinical treatments are available and may eventually prolong survival.

Inactivated SARS-CoV-2 Vaccine Booster Against Omicron Infection Among Quarantined Close Contacts.

Importance: Assessment of additional protection of a booster dose with an inactivated SARS-CoV-2 vaccine is key to developing vaccination strategies for billions of people worldwide who have received the primary 2-dose regimen. Objective: To estimate the relative effectiveness of a booster dose of an inactivated SARS-CoV-2 vaccine against Omicron infection. Design, Setting, and Participants: This cohort study was conducted among primary close contacts without previous SARS-CoV-2 infection identified in Shenzhen, China, between February and October 2022. Multiple strict nucleic acid testing and symptom surveillance for SARS-CoV-2 infection were regularly conducted during the 7-day centralized plus 7-day home-based quarantine. Exposure: A booster with an inactivated SARS-CoV-2 vaccine vs no booster after receipt of the primary 2-dose inactivated SARS-CoV-2 vaccine regimen. Main Outcomes and Measures: The primary outcomes were overall, symptomatic, and asymptomatic infections. Secondary outcomes were length of incubation and level of cycle threshold values. All the outcomes were assessed during the quarantine period. Results: Among 119 438 eligible participants (mean [SD] age, 37.6 [12.0] years; 66 201 men [55.4%]), 86 251 (72.2%) received a booster dose of an inactivated SARS-CoV-2 vaccine and 33 187 (27.8%) did not. A total of 671 cases infected with Omicron BA.2 were confirmed (464 symptomatic and 207 asymptomatic), and no severe infection or death events were observed. At a median (IQR) duration of 111 (75 to 134) days after booster vaccination, the relative effectiveness of a booster was 32.2% (95% CI, 11.3% to 48.2%) for overall infection, 23.8% (95% CI, -8.2% to 46.4%) for symptomatic infection, and 43.3% (95% CI, 12.3% to 63.3%) for asymptomatic infection. The effectiveness against overall infection changed nonlinearly over time following booster vaccination: 44.9% (95% CI, 4.9% to 68.1%) within 60 days, 50.4% (95% CI, 23.7% to 67.7%) at 61 to 120 days, 29.1% (95% CI, -4.8% to 52.1%) at 121 to 180 days, and 19.4% (95% CI, -14.4% to 43.2%) after 180 days (nonlinear P = .03). The effectiveness did not vary significantly according to the interval between booster vaccination and completion of primary vaccination. There was no association of booster vaccination with incubation or cycle threshold values. Conclusions and Relevance: In this cohort study, a booster dose of an inactivated SARS-CoV-2 vaccine provided additional moderate protection against mild infection for 120 days after receipt, but more research is needed to determine the optimal timing of a booster and its effectiveness in preventing severe infection for a longer duration.

A Prognostic Model for Colon Adenocarcinoma Patients Based on Ten Amino Acid Metabolism Related Genes.

Background: Amino acid metabolism plays a vital role in cancer biology. However, the application of amino acid metabolism in the prognosis of colon adenocarcinoma (COAD) has not yet been explored. Here, we construct an amino acid metabolism-related risk model to predict the survival outcome of COAD and improve clinical decision making. Methods: The RNA-sequencing-based transcriptome for 524 patients with COAD from The Cancer Genome Atlas (TCGA) was selected as a training set. The integrated Gene Expression Omnibus (GEO) dataset with 1,430 colon cancer samples was used for validation. Differential expression of amino acid metabolism-related genes (AAMRGs) was identified for prognostic gene selection. Univariate cox regression analysis, LASSO-penalized Cox regression analysis, and multivariate Cox regression analysis were applied to construct a prognostic risk model. Moreover, the correlation between risk score and microsatellite instability, immunotherapy response, and drug sensitivity were analyzed. Results: A prognostic signature was constructed based on 10 AAMRGs, including ASPG, DUOX1, GAMT, GSR, MAT1A, MTAP, PSMD12, RIMKLB, RPL3L, and RPS17. Patients with COAD were divided into high-risk and low-risk group based on the medianrisk score. Univariate and multivariate Cox regression analysis revealed that AAMRG-related signature was an independent risk factor for COAD. Moreover, COAD patients in the low-risk group were more sensitive to immunotherapy targeting PD-1 and CTLA-4. Conclusion: Our study constructed a prognostic signature based on 10 AAMRGs, which could be used to build a novel prognosis model and identify potential drug candidates for the treatment of COAD.

LncRNA miR205HG hinders HNRNPA0 translation: anti-oncogenic effects in esophageal carcinoma.

Esophageal carcinoma (ESCA) affects 4 450 000 people and causes approximately 400 000 deaths annually worldwide, making it the sixth most lethal and eighth most common cancer. Patients with ESCA are often diagnosed at the later stages in which cancer cell metastasis is the main factor contributing to the low 5-year survival rate (< 20%) of this disease. Long noncoding RNAs (lncRNAs) are a group of regulatory RNAs with a length of > 200 nucleotides but which fail to encode proteins. In this study, by using real-time quantitative PCR, we found that the expression of the miR205 host gene (miR205HG; a lncRNA) was downregulated in ESCA tumors when compared with normal esophageal tissues or adjacent normal tissues of tumors. Furthermore, we demonstrated that miR205HG modulates the expression of extracellular matrix-related genes in ESCA cells. In the transwell assay, downregulation of miR205HG contributes to migration and invasion of ESCA cells. In relation to the mechanism, our data show that miR205HG interacts with heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0) mRNA and then hamper its translation by interacting with lin-28 homolog A (LIN28A). Altogether, we highlight that the miR205HG-HNRNPA0 axis is implicated in the migration and invasion of ESCA cells and that these members of this pathway may serve as therapeutic targets to inhibit metastasis of ESCA.

A Water-Soluble Organic Photocatalyst Discovered for Highly Efficient Additive-Free Visible-Light-Driven Grafting of Polymers from Proteins at Ambient and Aqueous Environments.

Since the pioneering discovery of a protein bound to poly(ethylene glycol), the utility of protein-polymer conjugates (PPCs) is rapidly expanding to currently emerging applications. Photoinduced energy/electron-transfer reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization is a very promising method to prepare structurally well-defined PPCs, as it eliminates high-cost and time-consuming deoxygenation processes due to its oxygen tolerance. However, the oxygen-tolerance behavior of PET-RAFT polymerization is not well-investigated in aqueous environments, and thereby the preparation of PPCs using PET-RAFT polymerization needs a substantial amount of sacrificial reducing agents or inert-gas purging processes. Herein a novel water-soluble and biocompatible organic photocatalyst (PC) is reported, which enables visible-light-driven additive-free "grafting-from" polymerizations of a protein in ambient and aqueous environments. Interestingly, the developed PC shows unconventional "oxygen-acceleration" behavior for a variety of acrylic and acrylamide monomers in aqueous conditions without any additives, which are apparently distinct from previously reported systems. With such a PC, "grafting-from" polymerizations are successfully performed from protein in ambient buffer conditions under green light-emitting diode (LED) irradiation, which result in various PPCs that have neutral, anionic, cationic, and zwitterionic polyacrylates, and polyacrylamides. It is believed that this PC will be widely employed for a variety of photocatalysis processes in aqueous environments, including the living cell system.

SARS-CoV-2 Aerosol Transmission Through Vertical Sanitary Drains in High-Rise Buildings - Shenzhen, Guangdong Province, China, March 2022.

What is already known about this topic?: Aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via sanitary pipelines in high-rise buildings is possible, however, there is a lack of experimental evidence. What is added by this report?: The field simulation experiment confirmed the existence of a vertical aerosol transmission pathway from toilet flush-soil stack-floor drains without water seal. This report provided experimental evidence for vertical aerosol transmission of clustered outbreaks on 18 floors of a 33-story residential building. What are the implications for public health practice?: The water seal on floor drains is a necessary barrier to prevent the risk of vertical aerosol transmission of infectious disease pathogens in buildings. It is necessary not only to have a U-shaped trap in the drainage pipe, but also to be filled with water regularly.

Si-Bridged annulated BODIPYs: synthesis, unique structure and photophysical properties.

Two novel Si-bridged meso-annulated BODIPY dyes have been prepared through intermolecular C-I silylation and subsequent intramolecular C-H silylation in a one-pot reaction. A marked redshift of the main spectral bands was observed since the efficient σ*-π* conjugation results in a notable stabilization of the LUMOs. Si-annulation blocks the non-radiative decay and contributes to higher fluorescence quantum yields. This strategy is very attractive for the construction of highly emissive polycyclic aromatic hydrocarbons.

The first comprehensive database of germline pathogenic variants in East Asian cancer patients.

Pathogenic germline variants in cancer-associated genes are risk factors for cancer predisposition. However, systematic mining and summarizing of cancer pathogenic or likely pathogenic variants has not been performed for people of East Asian descent. This study aimed to investigate publicly available data to identify germline variants in East Asian cancer cohorts and compare them to variants in Caucasian cancer cohorts. Based on the data we retrieved, we built a comprehensive database, named COGVIC (Catalog of Germline Variants in Cancer). A total of 233 variants in the East Asian population were identified. The majority (87%) of genes with cancer-associated variants were not shared between the East Asian and Caucasian cohorts. This included pathogenic variants in BRCA2. Our study summarized the prevalence of germline variants in East Asian cancer cohorts and provides an easy-to-use online tool to explore germline mutations related to cancer susceptibility. DATABASE URL: http://www.cogvic.vip/.

Ideal Anatomical Landmark Points for Thoracic Esophagus Segmentation in the Chinese Population.

Introduction: The standards of esophagus segmentation remain different between the Japan Esophageal Society (JES) guideline and the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) guideline. This study aimed to present variations in the location of intrathoracic esophageal adjacent anatomical landmarks (EAALs) and determine an appropriate method for segmenting the thoracic esophagus based on the relatively fixed EAALs. Patients and Methods: The distances from the upper incisors to the upper border of the esophageal hiatus, lower border of the inferior pulmonary vein (LPV), tracheal bifurcation, lower border of the azygous vein (LAV), and thoracic inlet were measured in the patients undergoing thoracic surgery. The median distances between the EAALs and the specified starting points, as well as reference value ranges and ratios, were obtained. The variation coefficients of distances and ratios from certain starting points to different EAALs were calculated and compared to determine the relatively fixed landmarks. Results: This study included 305 patients. The average distance from the upper incisors to the upper border of the cardia, the midpoint between the tracheal bifurcation and esophageal hiatus (MTBEH), LPV, LAV, tracheal bifurcation, and thoracic inlet were 41.6, 35.3, 34.8, 29.4, 29.5, and 20.3 cm, respectively. The distances from the upper incisors or thoracic inlet to any intrathoracic EAALs in men were higher than in women. In addition, the height, weight, and body mass index (BMI) were correlated with the distances. The ratio of the distance between the upper incisors and tracheal bifurcation to the distance between the upper incisors and upper border of the cardia and the ratio of the distance between the thoracic inlet and tracheal bifurcation to the distance between the thoracic inlet and upper border of the cardia possessed relatively smaller coefficients of variation. Conclusion: The distances from the EAALs to the upper incisors vary with height, weight, BMI, and gender. Compared with distance, the ratios are more suitable for esophagus segmentation. Tracheal bifurcation and MTBEH are ideal EAALs for thoracic esophagus segmentation, and this is consistent with the JES guideline recommendation.

Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8+ T cell antitumor activity. Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion, we also found a non-canonical function of LDLR in CD8+ T cells: LDLR interacts with the T-cell receptor (TCR) complex and regulates TCR recycling and signaling, thus facilitating the effector function of cytotoxic T-lymphocytes (CTLs). Furthermore, we found that the tumor microenvironment (TME) downregulates CD8+ T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs. Moreover, genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+ T cells by alleviating the suppressive effect on CD8+ T cells and consequently inhibit tumor progression. While previously established as a hypercholesterolemia target, this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.

Oligosilanyl-Bridged Biscarbazoles: Structure, Synthesis, and Spectroscopic Properties.

Oligosilanyl-bridged systems are expected to give rise to unique optoelectronic properties because of σ-π conjugation between the Si-Si σ orbital and the aryl π orbital. Herein, we synthesized a small series of novel biscarbazoles bridged with permethylated oligosilanyl units (-[Si(CH3)2]n-, n = 1-4) and examined their spectroscopic properties in detail. In the target molecules BCzSin , n = 2-4, the efficient σ-π conjugation elevated the highest occupied molecular orbital energy level with no influence on the lowest unoccupied molecular orbital. In the solid state, the emission full width at half-maximum (fwhm) of all the compounds narrowed significantly, while the emission efficiency increased and the emission color of carbazole was retained. This research provided a very simple and general way of subtly manipulating the electronic properties of organic materials to construct an emissive color-retaining system for multifunctional applications.

Circular RNA circNELL2 Acts as the Sponge of miR-127-5p to Promote Esophageal Squamous Cell Carcinoma Progression.

INTRODUCTION: Owing to its involvement in both the initiation and progression of various cancers, aberrant circular RNA (circRNA) expression has been researched extensively in the recent times. In the present study, we aim to investigate the effect of a novel circRNA has_circ_0025933 (circNELL2) in the progression of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Sanger sequencing and the detection of circNELL2 level after RNase R or actinomycin D treatment were performed to identify the existence of cirNELL2 in ESCC cells. WST, EDU staining and colony-formation assay were used to assess the proliferation while transwell assay was used to evaluate the migration of ESCC cells. Luciferase assay, RNA pull down and the FISH assay were performed to verify the interaction between circNELL2 and miR-127-5p as well as miR-127-5p and CDC6. Xenograft model was carried out to evaluate the effect of circNELL2 in vivo. RESULTS: circNELL2 was proved to exist in ESCC cells. The up-regulated expression of circNELL2 in the clinical ESCC specimens was also verified. Next, function studies suggested that circNELL2 knockdown inhibited the proliferation of ESCC cells in vitro and in vivo, while circNELL2 overexpression promotes that of ESCC cells. Besides, this study mechanically predicted and verified the target miR of circNELL2, which is miR-127-5p. It was found that miR-127-5p was capable of reversing the effect of circNELL2 on ESCC cells. Moreover, miR-127-5p was also found to target CDC6 to participate in the regulation of cell phenotype. DISCUSSION: circNELL2 promoted the progression of ESCC cells via sponging miR-127-5p, and it has the potential to serve as a novel prognostic and therapeutic target for ESCC.