First report of Cigar Tobacco Root Rot Caused by Setophoma terrestris in China.

Cigar tobacco (Nicotiana tabacum L.) is widely planted in Yunnan, which is becoming an important economic crop in China. In March 2023, root rot of cigar tobacco (cv. Yunxue 38) was observed in Baoshan (98°51'E, 24°58'N), and in July 2022 root rot of tobacco (cv. Yunyan 87) was observed in Dali (99°54'E, 26°30'N), Yunnan Province, China. The average disease incidences surveyed in the fields reached 10%. At the early stage, the bottom leaves showed wilting and turned yellow, and the roots became brown. Following the disease development, the color of roots turned to dark brown and ultimately necrosis. To isolate the causal agent, small pieces (5×5 mm) of diseased root from 6 symptomatic plant samples (three samples of cv. Yunxue 38 and three samples of cv. Yunyan 87) were cut. Pieces were surface-sterilized by dipping in 75% ethanol for 30 s, rinsed three times with sterile distilled water, then transferred to potato dextrose agar (PDA) medium and incubated at 28°C in the dark. Six fungal isolates cultured for 14 days were obtained. They were morphologically similar, so a representative isolate was selected for the following experiment. The colonies grew slowly on PDA, and their color were light pink initially, then changed to amaranth. Hyphae were hyaline and septate. Microconidia were hardly produced on PDA plates. After 14 days of culture on V8 juice agar, the colonies showed white aerial mycelia, and ellipsoidal and transparent conidia were observed, which measured 6.5 to 8.3 × 3.4 to 5.0 µm (n=20). Also, the pycnidia were measured 150 to 220 µm, that were subglobose in dark brown with brown setae. These morphological characteristics of 22DL91 were identical to S. terrestris (Boerema et al. 2004). For molecular identification, DNA was extracted and the PCR products of ITS region and polymerase II second largest subunit (RPB2), amplified with the primers ITS1/ITS4 and RPB2-5F/RPB2-7cR, were sequenced. By BLASTn analysis, the obtained ITS sequences showed 100% homology and the RPB2 sequences showed 95% homology with S. terrestris strains in GenBank (accession ON006851 and OM417590). The sequences were deposited in NCBI with accession numbers OR539491 (ITS) and OR554276 (RPB2), respectively. Based on the morphology and phylogenetic analysis, the isolate was 22DL91 identified as S. terrestris. Pathogenicity was evaluated on 50-day-old cigar tobacco seedlings (cv. Yunxue 38) and tobacco seedlings (cv. Yunyan 87). Ten plants were inoculated with 20 mL of conidial suspension of 105 conidia/mL poured onto the roots and ten control seedlings dipped in sterile water as controls (Luo et al. 2023). After 14 days, all inoculated seedlings showed the symptoms with leaves yellowing and root rot, whereas the control seedlings had no symptoms. Moreover, the fungus S. terrestris was reisolated from the infected roots, fulfilling Koch's postulates. This fungus was previously known to cause pink root on garlic in China (Zhang et al. 2019). To our knowledge, this is the first report of S. terrestris causing root rot of Nicotiana tabacum in China. Therefore, this finding will provide valuable information for prevention and management of root rot on tobacco.

A Convenient In Situ Preparation of Cu2ZnSnS4-Anatase Hybrid Nanocomposite for Photocatalysis/Photoelectrochemical Water-Splitting Hydrogen Production.

This study details the rational design and synthesis of Cu2ZnSnS4 (CZTS)-doped anatase (A) heterostructures, utilizing earth-abundant elements to enhance the efficiency of solar-driven water splitting. A one-step hydrothermal method was employed to fabricate a series of CZTS-A heterojunctions. As the concentration of titanium dioxide (TiO2) varied, the morphology of CZTS shifted from floral patterns to sheet-like structures. The resulting CZTS-A heterostructures underwent comprehensive characterization through photoelectrochemical response assessments, optical measurements, and electrochemical impedance spectroscopy analyses. Detailed photoelectrochemical (PEC) investigations demonstrated notable enhancements in photocurrent density and incident photon-to-electron conversion efficiency (IPCE). Compared to pure anatase electrodes, the optimized CZTS-A heterostructures exhibited a seven-fold increase in photocurrent density and reached a hydrogen production efficiency of 1.1%. Additionally, the maximum H2 production rate from these heterostructures was 11-times greater than that of pure anatase and 250-times higher than the original CZTS after 2 h of irradiation. These results underscore the enhanced PEC performance of CZTS-A heterostructures, highlighting their potential as highly efficient materials for solar water splitting. Integrating Cu2ZnSnS4 nanoparticles (NPs) within TiO2 (anatase) heterostructures implied new avenues for developing earth-abundant and cost-effective photocatalytic systems for renewable energy applications.

Thermally Activated Delayed Fluorescence with Nanosecond Emission Lifetimes and Minor Concentration Quenching: Achieving High-Performance Nondoped and Doped Blue OLEDs.

Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.

A multiplex direct PCR method for the rapid and accurate discrimination of three species of spider mites (Acari: Tetranychidae) in fruit orchards in Beijing.

Spider mites (Acari: Tetranychidae) are polyphagous pests of economic importance in agriculture, among which the two-spotted spider mite Tetranychus urticae Koch has spread widely worldwide as an invasive species, posing a serious threat to fruit tree production in China, including Beijing. The hawthorn spider mite, Amphitetranychus viennensis Zacher, is also a worldwide pest of fruit trees and woody ornamental plants. The cassava mite, Tetranychus truncatus Ehara, is mainly found in Asian countries, including China, Korea and Japan, and mainly affects fruit trees and agricultural crops. These three species of spider mites are widespread and serious fruit tree pests in Beijing. Rapid and accurate identification of spider mites is essential for effective pest and plant quarantine in Beijing orchard fields. The identification of spider mite species is difficult due to their limited morphological characteristics. Although the identification of insect and mite species based on PCR and real-time polymerase chain reaction TaqMan is becoming increasingly common, DNA extraction is difficult, expensive and time-consuming due to the minute size of spider mites. Therefore, the objective of this study was to establish a direct multiplex PCR method for the simultaneous identification of three common species of spider mites in orchards, A. viennensis, T. truncatus and T. urticae, to provide technical support for the differentiation of spider mite species and phytosanitary measures in orchards in Beijing. Based on the mitochondrial cytochrome c oxidase subunit I (COI) of the two-spotted spider mite and the cassava mite and the 18S gene sequence of the hawthorn spider mite as the amplification target, three pairs of specific primers were designed, and the primer concentrations were optimized to establish a direct multiplex PCR system for the rapid and accurate discrimination of the three spider mites without the need for DNA extraction and purification. The method showed a high sensitivity of 0.047 ng for T. truncatus and T. urticae DNA and 0.0002 ng for A. viennensis. This method eliminates the DNA extraction and sequencing procedures of spider mite samples, offers a possibility for rapid monitoring of multiple spider mites in an integrated microarray laboratory system, reducing the time and cost of leaf mite identification and quarantine monitoring in the field.

Excellent Charge Separation of NCQDs/ZnS Nanocomposites for the Promotion of Photocatalytic H2 Evolution.

Carbon Quantum dots (CQDs) are widely studied because of their good optical and electronic characteristics and because they can easily generate photocarriers. Nitrogen-doped CQDs (NCQDs) may exhibit improved hydrophilic, optical, and electron-transfer properties, which are conducive to photocatalytic hydrogen evolution. In this paper, NCQD-modified ZnS catalysts were successfully prepared. Under the irradiation of the full spectrum, the H2 evolution rate of the optimal catalyst 0.25 wt % NCQDs/ZnS achieves 5.70 mmol g-1 h-1, which is 11.88, 43.84, and 5.14 times the values of ZnS (0.48 mmol g-1 h-1), NCQDs (0.13 mmol g-1 h-1), and CQDs/ZnS (1.11 mmol g-1 h-1), respectively. Furthermore, it shows good stability, indicating that the modification of NCQDs prevents the photocorrosion and oxidation of ZnS. The enhanced performance is due to NCQD loading, which promotes the separation of photogenerated carriers, optimizes the structures, and increases the specific surface area. This work highlights the fact that NCQD-modified ZnS may afford a new strategy to synthesize ZnS-based photocatalysts with enhanced H2 production performance.

Enhancing Reverse Intersystem Crossing in Triptycene-TADF Emitters: Theoretical Insights into Reorganization Energy and Heavy Atom Effects.

Thermally activated delayed fluorescence (TADF) emitters based on the triptycene skeleton demonstrate exceptional performance, superior stability, and low efficiency roll-off. Understanding the interplay between the luminescent properties of triptycene-TADF molecules and their assembly environments, along with their excited-state characteristics, necessitates a comprehensive theoretical exploration. Herein, we predict the photophysical properties of triptycene-TADF molecules in a thin film environment using the quantum mechanics/molecular mechanics method and quantify their substantial dependency on the heavy atom effects and reorganization energies using the Marcus-Levich theory. Our calculated photophysical properties for two recently reported molecules closely align with experimental values. We design three novel triptycene-TADF molecules by incorporating chalcogen elements (O, S, and Se) to modify the acceptor units. These newly designed molecules exhibit reduced reorganization energies and enhanced reverse intersystem crossing (RISC) rates. The heavy atom effect amplifies spin-orbit coupling, thereby facilitating the RISC process, particularly at a remarkably high rate of ∼109 s-1.

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial.

BACKGROUND: As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP. OBJECTIVE: The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm. MAIN OUTCOME MEASURES: Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools. RESULTS: Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants' pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial. CONCLUSION: The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655). Please cite this article as: He JY, Tu XY, Yin ZF, Mu H, Luo MJ, Chen XY, Cai WB, Zhao X, Peng C, Fang FF, Lü C, Li B. Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial. J Integr Med. 2024; 22(1): 39-45.

Integrated transcriptomic and metabolomic analyses elucidate the mechanism of flavonoid biosynthesis in the regulation of mulberry seed germination under salt stress.

Seed propagation is the main method of mulberry expansion in China, an important economic forest species. However, seed germination is the most sensitive stage to various abiotic stresses, especially salinity stress. To reveal the molecular regulatory mechanism of mulberry seed germination under salt stress, flavonoid metabolomics and transcriptomics analyses were performed on mulberry seeds germinated under 50 and 100 mmol/L NaCl stress. Analysis of the flavonoid metabolome revealed that a total of 145 differential flavonoid metabolites (DFMs) were classified into 9 groups, 40 flavonols, 32 flavones, 16 chalcones and 14 flavanones. Among them, 61.4% (89) of the DFMs accumulated continuously with increasing salt concentration, reaching the highest level at a 100 mmol/L salt concentration; these DFMs included quercetin-3-O-glucoside (isoquercitrin), kaempferol (3,5,7,4'-tetrahydroxyflavone), quercetin-7-O-glucoside, taxifolin (dihydroquercetin) and apigenin (4',5,7-trihydroxyflavone), indicating that these flavonoids may be key metabolites involved in the response to salt stress. Transcriptional analysis identified a total of 3055 differentially expressed genes (DEGs), most of which were enriched in flavonoid biosynthesis (ko00941), phenylpropanoid biosynthesis (ko00940) and biosynthesis of secondary metabolites (ko01110). Combined analysis of flavonoid metabolomic and transcriptomic data indicated that phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), flavonol synthase (FLS), bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase (DFR) and anthocyanidin reductase (ANR) were the key genes involved in flavonoid accumulation during mulberry seed germination under 50 and 100 mmol/L NaCl stress. In addition, three transcription factors, MYB, bHLH and NAC, were involved in the regulation of flavonoid accumulation under salt stress. The results of quantitative real-time PCR (qRT‒PCR) validation showed that the expression levels of 11 DEGs, including 7 genes involved in flavonoid biosynthesis, under different salt concentrations were consistent with the transcriptomic data, and parallel reaction monitoring (PRM) results showed that the expression levels of 6 key enzymes (proteins) involved in flavonoid synthesis were consistent with the accumulation of flavonoids. This study provides a new perspective for investigating the regulatory role of flavonoid biosynthesis in the regulation of mulberry seed germination under salt stress at different concentrations.

Quantitative detection of the Ralstonia solanacearum species complex in soil by qPCR combined with a recombinant internal control strain.

IMPORTANCE: DNA-based detection and quantification of soil-borne pathogens, such as the Ralstonia solanacearum species complex (RSSC), plays a vital role in risk assessment, but meanwhile, precise quantification is difficult due to the poor purity and yield of the soil DNA retrieved. The internal sample process control (ISPC) strain RsPC we developed solved this problem and significantly improved the accuracy of quantification of RSSC in different soils. ISPC-based quantitative PCR detection is a method especially suitable for the quantitative detection of microbes in complex matrices (such as soil and sludge) containing various PCR inhibitors and for those not easy to lyse (like Gram-positive bacteria, fungi, and thick-wall cells like resting spores). In addition, the use of ISPC strains removes additional workload on the preparation of high-quality template DNA and facilitates the development of high-throughput quantitative detection techniques for soil microbes.

E3 ligase Trim35 inhibits LSD1 demethylase activity through K63-linked ubiquitination and enhances anti-tumor immunity in NSCLC.

Targeting lysine-specific histone demethylase 1A (LSD1) can improve tumor immunogenicity of poorly immunogenic tumors, such as non-small cell lung cancer (NSCLC), with elevated T cell infiltration and sensitize tumors to anti-PD-1 therapy. However, the lack of reliable biomarkers limits utilization of LSD1 inhibitors in cancer therapy. Here, we identify an E3 ligase, Trim35, as an effective biomarker for high activity of LSD1 to predict prognosis of LSD1-targeted therapy as well as immunotherapy. Mechanistically, Trim35 represses LSD1 demethylase activity by mediating K63 ubiquitination at lysine site 422 of LSD1. Suppressed LSD1 activity facilitates ERGIC1 transcription, followed by autophagy inhibition and IFNGR1 stabilization to activate IFN-γ signaling, leading to increased MHC class I expression and immune surveillance of NSCLC cells. Furthermore, combinational use of an LSD1 inhibitor and anti-PD-1 therapy can significantly eradicate poorly immunogenic lung cancer with low Trim35. These findings strongly suggest that Trim35 is a promising biomarker for prediction of immunotherapy outcome in NSCLC.

Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer.

BACKGROUND: Chronic inflammation is a significant factor in colorectal cancer (CRC) development, especially in colitis-associated CRC (CAC). T-cell exhaustion is known to influence inflammatory bowel disease (IBD) progression and antitumor immunity in IBD patients. This study aimed to identify unique immune infiltration characteristics in CAC patients. METHODS: We studied 20 CAC and 20 sporadic CRC (sCRC) patients, who were matched by tumor stage, grade, and location. Immunohistochemical staining targeted various T-cell markers (CD3, CD4, CD8, and FOXP3), T-cell exhaustion markers (TOX and TIGIT), a B-cell marker (CD20), and a neutrophil marker (CD66b) in tumor and tumor-free mucosa from both groups. The quantification of the tumor immune stroma algorithm assessed immune-infiltrating cells. RESULTS: CAC patients had significantly lower TOX+ cell infiltration than sCRC in tumors (p = 0.02) and paracancerous tissues (p < 0.01). Right-sided CAC showed increased infiltration of TOX+ cells (p = 0.01), FOXP3+ regulatory T-cells (p < 0.01), and CD20+ B-cells (p < 0.01) compared to left-sided CAC. In sCRC, higher tumor stages (III and IV) had significantly lower TIGIT+ infiltrate than stages I and II. In CAC, high CD3+ (p < 0.01) and CD20+ (p < 0.01) infiltrates correlated with improved overall survival. In sCRC, better survival was associated with decreased TIGIT+ cells (p < 0.038) and reduced CD8+ infiltrates (p = 0.02). CONCLUSION: In CAC, high CD3+ and CD20+ infiltrates relate to improved survival, while this association is absent in sCRC. The study revealed marked differences in TIGIT and TOX expression, emphasizing distinctions between CAC and sCRC. T-cell exhaustion appears to have a different role in CAC development.

Analysis of spatial distribution and drivers of gaseous energy combustion pollution in China based on SDM.

Air pollution is an important part of ecological environment problems. Gaseous energy combustion pollution is a key part of air pollution. Analysis of its spatial distribution and drivers is important to effectively manage air quality and promote regional green development. This paper uses panel data of 30 provinces in China from 2006 to 2019 to analyze the spatial distribution and drivers of gaseous energy combustion pollution in each province of China through a combination of quantitative and qualitative analysis based on the spatial Durbin model, and further decompose the spatial effects of each influencing factor. The empirical results show, firstly, that inter-provincial gaseous energy combustion pollution in China shows significant spatial differences and cluster characteristics. Secondly, most areas are located in high-high aggregation area and low-low aggregation area. Finally, population, energy consumption and other independent variables have different impacts on gaseous energy combustion pollution in different regions. The changes of these variables will affect the adjacent areas through spatial transmission while affecting a region. According to the empirical results, this study proposes policy recommendations to balance the pollution degree of gaseous energy combustion in various regions and effectively reduce the emissions of various pollution sources. The research results are helpful to understand the spatial distribution of gaseous energy combustion pollution in various regions of China, provide reference for the future development of various regions, and have important practical significance for the reduction and balance of pollution levels.

Rotational isomerization: spontaneous structural transformation of a thermally activated delayed fluorescence binuclear copper(I) complex.

A novel binuclear Cu(I) halide complex, Cu2I2(DPPCz)2, which emits efficient thermally activated delayed fluorescence (TADF), is reported. The crystal of this complex spontaneously undergoes ligand rotation and coordination-configuration transformation, converting to its isomer without any external stimulation.

Single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles in breast cancer.

BACKGROUND: In order to explore the surgical safety and the reliability of axillary staging of single-port endoscopic-sentinel lymph node biopsy, we combined it with indocyanine green that was excited by near-infrared fluorescence endoscopy and carbon nanoparticles as a tracer and compared this method to conventional open sentinel lymph node biopsy. METHODS: This is a retrospective and observational study, there were 20 patients in each group and the total sample size was 60: Group 1, single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles; Group 2, single-port endoscopic-sentinel lymph node biopsy with carbon nanoparticles only; Group 3, conventional sentinel lymph node biopsy with indocyanine green and carbon nanoparticles. Sentinel lymph node detection and upper extremity function were determined to measure the safety and efficacy of the novel single-port endoscopic-sentinel lymph node biopsy (SPE-SLNB) technique to the standard conventional sentinel lymph node biopsy technique. RESULTS: The detection rate of sentinel lymph nodes was 100% in Group 1, 100% in Group 2, and 95% in Group 3. There were no significant differences in upper arm function and pain scores between the three groups. CONCLUSION: The novel technique of combining indocyanine green and carbon nanoparticles with single-port endoscopic-sentinel lymph node biopsy achieved a similar detection rate and mean number of sentinel lymph nodes as conventional sentinel lymph node biopsy. Traditional open surgery requires two different incisions for breast surgery and SLNB. While the most important advantage of SPE-SLNB is that two procedures can be effectively performed through a single-port in the axilla Therefore, for patients who meet the indications, single-port endoscopic-sentinel lymph node biopsy is as safe and reliable as conventional sentinel lymph node biopsy but has the aesthetic advantage of only one incision.

Efficient photocatalytic hydrogen production by space separation of photo-generated charges from S-scheme ZnIn2S4/ZnO heterojunction.

ZnIn2S4/ZnO heterostructures have been achieved by a simple in-situ growth solvothermal method. Under full spectrum irradiation, the optimal photocatalyst 2ZnIn2S4/ZnO exhibits H2 evolution rate of 13,638 (water/ethanol = 1:1) and 3036 (water) µmol·g-1h-1, which is respectively 4 and 5 times higher than that of pure ZnIn2S4. In situ illumination X-ray photoelectron spectroscopy (ISI-XPS) analysis and density functional theory (DFT) calculations show that the electrons of ZnIn2S4 are removed to ZnO through hybridization and form an internal electric field between ZnIn2S4 and ZnO. The optical properties of the catalyst and the effect of internal electric field (IEF) can increase photo-generated electrons (e-)-holes (h+) transport rate and enhance light collection, resulting in profitable photocatalytic properties. The photoelectrochemical and EPR results show that a stepped (S-scheme) heterojunction is formed in the ZnIn2S4/ZnO redox center, which greatly promotes separation of e--h+ pairs and efficient H2 evolution. This research offers an effective method for constructing an efficient S-Scheme photocatalytic system for H2 evolution.

The expression profiles of signature genes from CD103+LAG3+ tumour-infiltrating lymphocyte subsets predict breast cancer survival.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs), including T and B cells, have been demonstrated to be associated with tumour progression. However, the different subpopulations of TILs and their roles in breast cancer remain poorly understood. Large-scale analysis using multiomics data could uncover potential mechanisms and provide promising biomarkers for predicting immunotherapy response. METHODS: Single-cell transcriptome data for breast cancer samples were analysed to identify unique TIL subsets. Based on the expression profiles of marker genes in these subsets, a TIL-related prognostic model was developed by univariate and multivariate Cox analyses and LASSO regression for the TCGA training cohort containing 1089 breast cancer patients. Multiplex immunohistochemistry was used to confirm the presence of TIL subsets in breast cancer samples. The model was validated with a large-scale transcriptomic dataset for 3619 breast cancer patients, including the METABRIC cohort, six chemotherapy transcriptomic cohorts, and two immunotherapy transcriptomic cohorts. RESULTS: We identified two TIL subsets with high expression of CD103 and LAG3 (CD103+LAG3+), including a CD8+ T-cell subset and a B-cell subset. Based on the expression profiles of marker genes in these two subpopulations, we further developed a CD103+LAG3+ TIL-related prognostic model (CLTRP) based on CXCL13 and BIRC3 genes for predicting the prognosis of breast cancer patients. CLTRP-low patients had a better prognosis than CLTRP-high patients. The comprehensive results showed that a low CLTRP score was associated with a high TP53 mutation rate, high infiltration of CD8 T cells, helper T cells, and CD4 T cells, high sensitivity to chemotherapeutic drugs, and a good response to immunotherapy. In contrast, a high CLTRP score was correlated with a low TP53 mutation rate, high infiltration of M0 and M2 macrophages, low sensitivity to chemotherapeutic drugs, and a poor response to immunotherapy. CONCLUSIONS: Our present study showed that the CLTRP score is a promising biomarker for distinguishing prognosis, drug sensitivity, molecular and immune characteristics, and immunotherapy outcomes in breast cancer patients. The CLTRP could serve as a valuable tool for clinical decision making regarding immunotherapy.

Molecular characteristics of microsatellite stable early-onset colorectal cancer as predictors of prognosis and immunotherapeutic response.

The incidence of early-onset colorectal cancer (EO-CRC, in patients younger than 50) is increasing worldwide. The specific gene signatures in EO-CRC patients are largely unknown. Since EO-CRC with microsatellite instability is frequently associated with Lynch syndrome, we aimed to comprehensively characterize the tumor microenvironment (TME) and gene expression profiles of EO-CRC with microsatellite stable (MSS-EO-CRC). Here, we demonstrated that MSS-EO-CRC has a similar pattern of tumor-infiltrating immune cells, immunotherapeutic responses, consensus molecular subtypes, and prognosis as late-onset CRC with MSS (MSS-LO-CRC). 133 differential expressed genes were identified as unique gene signatures of MSS-EO-CRC. Moreover, we established a risk score, which was positively associated with PD-L1 expression and could reflect both the level of tumor-infiltrating immune cells and the prognosis of MSS-EO-CRC patients. Application of this score on the anti-PD-L1 treatment cohort demonstrated that the low-risk score group has significant therapeutic advantages and clinical benefits. In addition, candidate driver genes were identified in the different-sidedness of MSS-EO-CRC patients. Altogether, MSS-EO-CRC exhibits distinct molecular profiles that differ from MSS-LO-CRC even though they have a similar TME characterization and survival pattern. Our risk score appears to be robust enough to predict prognosis and immunotherapeutic response and therefore could help to optimize the treatment of MSS-EO-CRC.

A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Rational Design of Highly Efficient Orange-Red/Red Thermally Activated Delayed Fluorescence Emitters with Submicrosecond Emission Lifetimes.

The development of orange-red/red thermally activated delayed fluorescence (TADF) materials with both high emission efficiencies and short lifetimes is highly desirable for electroluminescence (EL) applications, but remains a formidable challenge owing to the strict molecular design principles. Herein, two new orange-red/red TADF emitters, namely AC-PCNCF3 and TAC-PCNCF3, composed of pyridine-3,5-dicarbonitrile-derived electron-acceptor (PCNCF3) and acridine electron-donors (AC/TAC) are developed. These emitters in doped films exhibit excellent photophysical properties, including high photoluminescence quantum yields of up to 0.91, tiny singlet-triplet energy gaps of 0.01 eV, and ultrashort TADF lifetimes of less than 1 µs. The TADF-organic light-emitting diodes employing the AC-PCNCF3 as emitter achieve orange-red and red EL with high external quantum efficiencies of up to 25.0% and nearly 20% at doping concentrations of 5 and 40 wt%, respectively, both accompanied by well-suppressed efficiency roll-offs. This work provides an efficient molecular design strategy for developing high-performance red TADF materials.

Realizing High-Efficiency Orange-Red Thermally Activated Delayed Fluorescence Materials through the Construction of Intramolecular Noncovalent Interactions.

The development of highly efficient orange and red thermally activated delayed fluorescence (TADF) materials for constructing full-color and white organic light-emitting diodes (OLEDs) remains insufficient because of the formidable challenges in molecular design, such as the severe radiationless decay and the intrinsic trade-off between the efficiencies of radiative decay and reverse intersystem crossing (RISC). Herein, we design two high-efficiency orange and orange-red TADF molecules by constructing intermolecular noncovalent interactions. This strategy could not only ensure high emission efficiency via suppression of the nonradiative relaxation and enhancement of the radiative transition but also create intermediate triplet excited states to ensure the RISC process. Both emitters exhibit typical TADF characteristics, with a fast radiative rate and a low nonradiative rate. Photoluminescence quantum yields (PLQYs) of the orange (TPA-PT) and orange-red (DMAC-PT) materials reach up to 94 and 87%, respectively. Benefiting from the excellent photophysical properties and stability, OLEDs based on these TADF emitters realize orange to orange-red electroluminescence with high external quantum efficiencies reaching 26.2%. The current study demonstrates that the introduction of intermolecular noncovalent interactions is a feasible strategy for designing highly efficient orange to red TADF materials.