Immunotherapy has made great strides in the treatment of lung cancer, but a significant proportion of patients still do not respond to treatment. Therefore, the identification of novel targets is ...crucial to improving the response to immunotherapy. The tumor microenvironment (TME) is a complex niche composed of diverse pro-tumor molecules and cell populations, making the function and mechanism of a unique cell subset difficult to understand. However, the advent of single-cell RNA sequencing (scRNA-seq) technology has made it possible to identify cellular markers and understand their potential functions and mechanisms in the TME. In this review, we highlight recent advances emerging from scRNA-seq studies in lung cancer, with a particular focus on stromal cells. We elucidate the cellular developmental trajectory, phenotypic remodeling, and cell interactions during tumor progression. Our review proposes predictive biomarkers and novel targets for lung cancer immunotherapy based on cellular markers identified through scRNA-seq. The identification of novel targets could help improve the response to immunotherapy. The use of scRNA-seq technology could provide new strategies to understand the TME and develop personalized immunotherapy for lung cancer patients.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, ...death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/-ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-α2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-α levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.
There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried ...out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making.
PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC.
Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34–52 %) with two cycles and 33 % (95%CI, 22–45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28–50 %) and 56 % (95%CI, 44–68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21–50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15–35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates.
There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.
Background
Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to ...the existence of abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as the dominant immunosuppressive population, impede the antitumor immune response; however, the underlying mechanisms have not been fully elucidated yet.
Methods
Single-cell RNA sequencing analysis was performed to portray macrophage landscape and revealed the underlying mechanism of component 1q (C1q)
+
TAMs. Malignant pleural effusion (MPE) of human and mouse was used to explore the phenotypes and functions of C1q
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TAMs.
Results
C1q
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TAMs highly expressed multiple inhibitory molecules and their high infiltration was significantly correlated with poor prognosis. C1q
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TAMs promote MPE immunosuppression through impairing the antitumor effects of CD8
+
T cells. Mechanistically, C1q
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TAMs enhance fatty acid binding protein 5 (FABP5)-mediated fatty acid metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing the gene expression of inhibitory molecules. A high-fat diet increases the expression of inhibitory molecules in C1q
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TAMs and the immunosuppression of MPE microenvironment, whereas a low-fat diet ameliorates these effects. Moreover, FABP5 inhibition represses the expression of inhibitory molecules in TAMs and tumor progression, while enhancing the efficacy of ICB therapy in MPE and lung cancer.
Conclusions
C1q
+
TAMs impede antitumor effects of CD8
+
T cells promoting MPE immunosuppression. Targeting C1q
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TAMs effectively alleviates the immunosuppression and enhances the efficacy of ICB therapy. C1q
+
TAMs subset has great potential to be a therapeutic target for cancer immunotherapy.
Circular RNAs (circRNAs) have been found to have significant impacts on non-small cell lung cancer (NSCLC) progression through various mechanisms. However, the mechanism of circRNAs modulating tumor ...immune evasion in NSCLC has yet to be well-revealed.
Through analyzing the expression profiles of circRNAs in NSCLC tissues, RNA FISH, pull-down assay, mass spectrometry analysis, and RIP, circCRIM1 was identified, and its interaction with IGF2BP1 was confirmed. The effects of circCRIM1 on modulating tumor immune evasion were explored via co-culture in vitro and in tumor xenograft models. Subsequently, we evaluated the regulatory effects of circCRIM1 on IGF2BP1 and screened its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circCRIM1 could regulate the stability of target mRNA.
circCRIM1 was downregulated in NSCLC, and its expression was positively correlated with favorable prognoses. Furthermore, circCRIM1 was more stable than its linear transcript and was mainly localized in the cytoplasm. Mechanistically, circCRIM1 destabilized HLA-F mRNA via competitive binding to IGF2BP1. Importantly, the overexpression of circCRIM1 suppressed the immune evasion of NSCLC and promoted the expressions of Granzyme B, IFN-γ, and TNF-α of CD8+ T and NK cell in vitro co-culture assays and tumor xenograft models.
This study identifies circCRIM1 as a new tumor suppressor that inhibits tumor immune evasion through a competitive combination with IGF2BP1 to destabilize HLA-F mRNA.
Abstract
Background
The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and ...abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed.
Methods
The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3–40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate.
Results
The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity.
Conclusions
The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.
Antibodies against severe acute respiratory syndrome coronavirus 2 can be detected in the middle and later stages of coronavirus disease 2019 (COVID-19). Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.
Size effect exerts a significant influence on the photocatalytic properties of materials. Nanometer CdS/TiO2 hollow nanoboxes (TiO2-HNBs) (tetragonal phase) Z-scheme heterojunctions were ...lattice-matched controllably fabricated by using cubic TiOF2 as a template and loading with micrometer CdS micron rods (hexagonal phase) or sub-nanometer CdS quantum dots (cubic phase) through one-pot template ultrasonic hydrothermal method. The morphology, constitution, physical property, as well as photocatalytic properties of as-prepared samples were investigated comprehensively. Under visible light irradiation (λ ≥ 420 nm), the hydrogen production rates of CdS micron rods, CdS nanorods/TiO2-HNBs (CT-7), CdS quantum dots/TiO2-HNBs (CTQ-7) and CdS quantum dots was 1642.61, 455.35, 148.92 and 1025.53 μmol/g/h, which was 26.39, 7.32, 2.39 and 16.48 times that of TiO2-HNBs, respectively. Meanwhile, the photodegradation rate of Rhodamine B by CdS micron rods, CT-7, CTQ-7 and CdS quantum dots within 60 min was 69.59%, 99.90%, 89.96% and 40.70%, which were 4.77, 6.85, 6.17 and 2.79 times that of P25, respectively. CdS micron rods had the largest size but the strongest photo-hydrogen production properties. Due to its Z-scheme heterojunction structure and Ti-S bond, CT-7 exhibited enhanced electron-hole separation rate and electron transfer rate, resulting in superior RhB degradation performance. Although CdS quantum dots had the smallest size, it did not boast the best performance, indicating that smaller size does not necessarily correlate with better photocatalytic performance. This study provides a reference for comparing the performance of photocatalytic materials with different sizes.
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•CdS-based catalysts of different sizes were prepared by one pot template ultrasonic hydrothermal method.•It was found that the lattice of hexagonal phase CdS was more matched with tetragonal phase TiO2 compared to cubic phase.•A new method has been designed to construct Ti-S bonds in CdS/TiO2 Z-scheme heterojunction.•The prepared CdS-based catalysts demonstrated excellent photocatalytic hydrogen production and degradation performance.•This study found that the performance of catalysts is greatly affected by size and lattice-matched.
Factors affecting rice aroma biosynthesis have been well documented previously, however the molecular mechanism lies behind the regulations in grain 2-acetyl-1-pyrroline (2AP) biosynthesis under ...alternate wetting and drying (AWD) remained largely unexplored. Present study investigated the effects of three irrigation regimes i.e., conventional irrigation (CI), alternate wetting and moderate drying (WMD), and alternate wetting and severe drying (WSD) on the yield, quality traits, intermediates, enzyme activities and genes involved in 2-acetyl-1-pyrroline biosynthesis in two fragrant rice cultivars viz, Meixiangzhan2 and Xiangyaxiangzhan. Results revealed that the levels of intermediates such as Δ1-pyrroline-5-carboxylate (P5C) and Δ1-pyrroline, and the activity of enzymes such as proline dehydrogenase (PRODH), Δ1-pyrroline-5-carboxylate synthetase (P5CS), diamine oxidase (DAO), and gene expressions of PRODH, P5CS2 and DAO were comparatively higher under AWD than CI in both aromatic rice cultivars. The levels of gamma-aminobutyric acid (GABA), betaine aldehyde dehydrogenase 2 (BADH2) and BADH2 gene were lower that together led to enhanced 2-AP contents in rice grains. Moreover, WMD irrigation improved yield and yield characters, while WSD irrigation reduced yield and quality traits of rice. Overall, up-regulation of P5C and Δ1-pyrroline and down-regulation of GABA under AWD treatments resulted in enhanced 2AP biosynthesis in both rice cultivars. Evaluation and adoption of AWD (within safe limits) at field level could be an alternative option to conventional flooded rice to get better yield and quality.
•Alternate wetting and drying (AWD) modulated 2-acetyl-1-pyrroline (2AP) in rice.•Precursors and enzymes involved in 2AP synthesis were higher in AWD than control.•Lower levels of gama amino butyric acid due to badh2 led to enhanced 2AP under AWD.•Yield and quality traits were higher in moderate than severe soil drying.•AWD under safe limits could be an alternative approach to flooded rice.
•Graphene contact-induced phase transition 3D/2D to 2D/2D In2S3/G hybrid is synthesized by simple hydrothermal method.•Carbon and oxygen replace the indium vacancies and sulfur of β-In2S3 to convert ...it to α-In2S3 at a lower temperature.•The In2S3/G composite exhibits excellent phenol, Cr6+ and various dyes degradation ability.•It has broad prospects for photocatalysis applications and preparation of nanostructured composites with controllable structures.
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We report the synthesis of a series of graphene-induced self-assembly phase transformations of tetragonal β-In2S3 into cubic α-In2S3 at lower temperatures based on the principles of molecular and crystal engineering and a simple one-pot soft integration strategy based on wet chemistry. Controlled contact In2S3/G heterojunction hybrids with sizes ranging from 3D/2D to 2D/2D. In the process, the 3D petal-like In2S3 is transformed into 2D nanosheets grown on the 2D graphene "mat". Due to effective charge separation and close interfacial contact, the excellent visible catalytic purification performance for the degradation of organic pollutants, benzyl alcohol selective oxidation and reduction of Cr2O72- has been achieved. The significantly improved photocatalytic purification efficiency is mainly due to the graphene-induced phase transition which increases the number of active sites and strengthens the two-dimensional/two-dimensional contact of the interface, which promotes the effective transmission and separation of photo-excited carriers, thereby Effectively improve the photocatalytic purification ability. This research provides new insights for the preparation of high-efficiency graphene-based nano-hybrid photocatalysts with controllable structure through rational use of the structure-oriented and induced phase transition effects of graphene, and expands its visible light catalytic purification applications.
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