Flowering Ocimum gratissimum intercropped in tea plantations attracts and reduces Apolygus lucorum populations.

BACKGROUND: Apolygus lucorum is one of the most important piercing-sucking insect pests of the tea plant In this study, we assessed the attractiveness of basil plants to A. lucorum and the effectiveness of Ocimum gratissimum L. in the control of A. lucorum. The control efficiency of main volatile chemicals emitted from O. gratissimum flowers was also evaluated. RESULTS: Among seven basil varieties, O. gratissimum was more attractive to A. lucorum adults and was selected as a trap plant to assess its attractiveness to A. lucorum and effects on natural enemies in tea plantations. The population density of A. lucorum on trap strips of O. gratissimum in tea plantations was significantly higher than that on tea at 10-20 m away from the trap strips. Intercropping O. gratissimum with tea plants, at high-density significantly reduced A. lucorum population levels. Eucalyptol, limonene, ß-ocimene, and linalool were the four dominant components in the O. gratissimum flower volatiles, and their emissions showed a gradual upward trend over the sampling period. Olfactometer assays indicated that eucalyptol and dodecane showed attraction to A. lucorum. High numbers of A. lucorum were recorded on limonene, eucalyptol, and myrcene-baited yellow sticky traps in field trials in which 11 dominant volatiles emitted by O. gratissimum flowers were evaluated. CONCLUSION: Our research indicated that the aromatic plant O. gratissimum and its volatiles could attract A. lucorum and planting O. gratissimum has the potential as a pest biocontrol method to manipulate A. lucorum populations in tea plantations. © 2024 Society of Chemical Industry.

Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development.

Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.

An Antennae-Enriched Odorant-Binding Protein EonuOBP43 Mediate the Behavioral Response of the Tea Green Leafhopper, Empoasca onukii Matsuda to the Host and Nonhost Volatiles.

Olfaction is crucial for Empoasca onukii Matsuda to recognize odors from the host and nonhost plants, and it has been proposed that odorant binding proteins are directly required for odorant discrimination and represent potential targets of interest for pest control. Here, we cloned EonuOBP43 and expressed the recombinant EonuOBP43 protein. Furthermore, competitive fluorescence binding assays with 19 ligands indicated that terpenoids and alkanes showed a relatively higher than for other classes of chemicals. Additionally, ligand docking and site-directed mutagenesis results revealed that seven hydrophobic residues, including Val-86, Met-89, Phe-90, Ile-104, Ile-105, Leu-130, and Val-134, played a key role in the binding of EonuOBP43 to plant volatiles. In olfactometer tests, E. onukii were significantly attracted to α-farnesene and repelled to ß-caryophyllene, and dsOBP43 treated adult lost response to α-farnesene and ß-caryophyllene. In summary, our results demonstrated that EonuOBP43 may function as a carrier in the process of sensing plant compounds of E. onukii.

ΔRDW Could Predict Major Adverse Cardiovascular Events in Patients with Heart Failure with Reduced Ejection Fraction After Sacubitril/Valsartan Treatment.

Objective: This study aimed to evaluate the association between red blood cell distribution width (RDW) changes and major adverse cardiovascular event (MACE) occurrences during sacubitril/valsartan treatment in patients with heart failure with reduced ejection fraction (HFrEF). Methods: This study retrospectively analyzed the medical records of patients with HFrEF hospitalized from April 2018 to February 2021. The patients were divided into two groups according to the inclusion of sacubitril/valsartan in the personal drug treatment regimen, the traditional and the sacubitril/valsartan group. RDW values before and after sacubitril/valsartan treatment were recorded respectively as RDW1 and RDW2. ΔRDW was defined as the difference between RDW2 and RDW1. The patients in the sacubitril/valsartan group were divided into two subgroups according to ΔRDW >0 or ≤0. MACEs, such as readmission for HF, acute myocardial infarction, ischemic stroke, and malignant arrhythmia and death, were recorded during the 1-year follow-up period in each group. Results: MACE development was lower in patients treated with sacubitril/valsartan than those treated with conventional therapy (log-rank, P<0.001). The incidence of cardiac events during the follow-up period was greater in the group with ΔRDW >0 than in the group with ΔRDW ≤0 (Breslow, P<0.001). Increased RDW was associated with a higher likelihood of developing MACE than decreased RDW (odds ratio [OR] =2.055, 95% confidence interval [CI]:1.301-3.246), and the risk of developing MACE increased by 22.1% for each unit increase in RDW (OR=1.221, 95% CI:1.074-1.389). Conclusion: Sacubitril/valsartan treatment is effective in reducing the risk of MACEs in HFrEF. Additionally, RDW changes are predictors of MACEs after sacubitril/valsartan treatment.

Photonic generation of frequency-doubling Nyquist pulses using external modulation.

In this paper, an approach to generate frequency-doubling sinc-shaped optical Nyquist pulses based on external modulation is proposed and demonstrated. First, four flat optical frequency comb (OFC) lines are obtained after optical carrier suppression modulation in a dual-electrode Mach-Zehnder modulator. Then an optical interleaver is introduced to split the phase-locked OFC into two paths, of which one is transmitted to a dual-parallel Mach-Zehnder modulator for quadrupling RF modulation and another is applied to the remodulated signal to acquire comb lines with equal intervals. Thus, a phase-locked 12-line flat OFC with equal frequency intervals and corresponding Nyquist pulses is finally obtained, and Nyquist pulses at 2.5 GHz, 5 GHz, 10 GHz, and 15 GHz are achieved.

Characterization of Ionotropic Receptor Gene EonuIR25a in the Tea Green Leafhopper, Empoasca onukii Matsuda.

Ionotropic receptors (IRs) play a central role in detecting chemosensory information from the environment and guiding insect behaviors and are potential target genes for pest control. Empoasca onukii Matsuda is a major pest of the tea plant Camellia sinensis (L.) O. Ktze, and seriously influences tea yields and quality. In this study, the ionotropic receptor gene EonuIR25a in E. onukii was cloned, and the expression pattern of EonuIR25a was detected in various tissues. Behavioral responses of E. onukii to volatile compounds emitted by tea plants were determined using olfactometer bioassay and field trials. To further explore the function of EonuIR25a in olfactory recognition of compounds, RNA interference (RNAi) of EonuIR25a was carried out by ingestion of in vitro synthesized dsRNAs. The coding sequence (CDS) length of EonuIR25a was 1266 bp and it encoded a 48.87 kD protein. EonuIR25a was enriched in the antennae of E. onukii. E. onukii was more significantly attracted by 1-phenylethanol at a concentration of 100 µL/mL. Feeding with dsEonuIR25a significantly downregulated the expression level of EonuIR25a, after 3 h of treatment, which disturbed the behavioral responses of E. onukii to 1-phenylethanol at a concentration of 100 µL/mL. The response rate of E. onukii to 1-phenylethanol was significantly decreased after dsEonuIR25a treatment for 12 h. In summary, the ionotropic receptor gene EonuIR25a was highly expressed in the antennae of E. onukii and was involved in olfactory recognition of the tea plant volatile 1-phenylethanol. The present study may help us to use the ionotropic receptor gene as a target for the behavioral manipulation of E. onukii in the future.

Lactobacillus acidophilus supernatant alleviates osteoporosis by upregulating colonic SERT expression.

Aims: To investigate the involvement of serotonin transporter (SERT) in colonic epithelial cells in the anti-osteoporosis role of Lactobacillus acidophilus (LA) supernatant (LAS). Methods: The abundance of fecal LA and bone mineral density (BMD) in patients with osteoporosis (OP) or severe osteoporosis were assessed. The protective role of LA in osteoporosis and the expression of SERT and relative signaling were evaluated. Results: Abundance of fecal LA was decreased in patients with severe OP and was positively correlated with BMD. Supplementing LAS to mice alleviated senile osteoporosis. In vitro, NOD2/RIP2/NF-κB signaling was inhibited by LAS due to increased SERT expression. Conclusion: LAS alleviates OP in mice by producing protective metabolites and upregulating SERT expression and represents a promising therapeutic agent.

POSTN Secretion by Extracellular Matrix Cancer-Associated Fibroblasts (eCAFs) Correlates with Poor ICB Response via Macrophage Chemotaxis Activation of Akt Signaling Pathway in Gastric Cancer.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment, but its clinical benefit is limited in advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) have been reported to be associated with ICB resistance, but the underlying mechanism has not been fully elucidated. Our previous single-cell RNA-seq analysis of GC revealed that POSTN+FAP+ extracellular matrix CAFs (eCAFs) communicate with macrophages. Here, we evaluated the correlation between eCAFs and ICB response in TCGA-STAD and real-world cohorts. Immune infiltration analysis and correlation analysis were performed to assess the relationship between eCAFs and macrophages. We first confirmed a negative correlation between the abundance of eCAFs and the overall response rate (ORR) to anti-PD-1 treatment in TCGA-STAD and real-world GC cohorts. Overexpression of POSTN in CAFs enhanced macrophage chemotaxis, while POSTN interference showed the opposite effect in vitro and in vivo. Furthermore, the cell density of POSTN+ CAFs was positively correlated with the infiltration level of CD163+ macrophages in GC patient tissues. The results demonstrated that POSTN secreted by CAFs enhances macrophage chemotaxis by activating the Akt signaling pathway in macrophages. Additionally, we found that POSTN+FAP+ eCAFs may exist in multiple solid tumors and are associated with ICB resistance. eCAFs promote macrophage chemotaxis through the secretion of POSTN, thereby leading to ICB resistance. High expression of POSTN is likely to predict a poor response to ICB. POSTN downregulation may be considered as a candidate therapeutic strategy to improve ICB efficacy.

Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota.

INTRODUCTION: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. METHODS: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. RESULTS: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1ß and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. CONCLUSION: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

Peripheral CD8+CD28+ T lymphocytes predict the efficacy and safety of PD-1/PD-L1 inhibitors in cancer patients.

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes. Methods: We retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry. Results: Patients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/µL, p < 0.001). Using 190/µL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/µL. Conclusions: High circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/µL) may also indicate the emergence of severe irAEs.

Multidimensional Cell-Free DNA Fragmentomic Assay for Detection of Early-Stage Lung Cancer.

Rationale: Cell-free DNA (cfDNA) analysis holds promise for early detection of lung cancer and benefits patients with higher survival. However, the detection sensitivity of previous cfDNA-based studies was still low to suffice for clinical use, especially for early-stage tumors. Objectives: Establish an accurate and affordable approach for early-stage lung cancer detection by integrating cfDNA fragmentomics and machine learning models. Methods: This study included 350 participants without cancer and 432 participants with cancer. The participants' plasma cfDNA samples were profiled by whole-genome sequencing. Multiple cfDNA features and machine learning models were compared in the training cohort to achieve an optimal model. Model performance was evaluated in three validation cohorts. Measurements and Main Results: A stacked ensemble model integrating five cfDNA features and five machine learning algorithms constructed in the training cohort (cancer: 113; healthy: 113) outperformed all the models built on individual feature-algorithm combinations. This integrated model yielded superior sensitivities of 91.4% at 95.7% specificity for cohort validation I (area under the curve [AUC], 0.984), 84.7% at 98.6% specificity for validation II (AUC, 0.987), and 92.5% at 94.2% specificity for additional validation (AUC, 0.974), respectively. The model's high performance remained consistent when sequencing depth was down to 0.5× (AUC, 0.966-0.971). Furthermore, our model is sensitive to identifying early pathological features (83.2% sensitivity for stage I, 85.0% sensitivity for <1 cm tumor at the 0.66 cutoff). Conclusions: We have established a stacked ensemble model using cfDNA fragmentomics features and achieved superior sensitivity for detecting early-stage lung cancer, which could promote early diagnosis and benefit more patients.

Natural killer cells promote intra-cellular-infected trophoblasts survival via APOD-LRP1 axis.

Natural killer (NK) cells are known for their potent ability to kill stressed cells, whereas host cells infected with intra-cellular bacteria may also be benefit from the selective killing function of NK cells and survive. The mechanism of how NK cells protect host cells infected with intra-cellular bacteria is still unclear. Here, we discovered that decidual NK (dNK) cells cannot only eliminate intra-cellular bacteria which infected trophoblasts, but can also synthesize more lipids and transport lipids to trophoblasts to avoid their apoptosis. Mechanically, NK cells synthesize more lipids accompanied by increasing expression of apolipoprotein APOD. Lipids in NK cells can be delivered to trophoblast cells through APOD, maintaining adequate lipid droplet content and lipid metabolism homeostasis in trophoblasts. Blocking the APOD receptor LRP1 abolished lipid transport from NK cells to trophoblasts, and the reduction of lipid droplets caused by bacterial infection in trophoblast cells could not be restored, culminating in cell apoptosis. Our study provides new evidence for the immune surveillance and protective effect of NK cells on embryos during early pregnancy.

Patients with non-functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20-year single-center retrospective analysis.

Pancreatic neuroendocrine tumor (pNET) is the most common subset (31.5%) of gastroenteropancreatic neuroendocrine tumor in China. Based on real-world data from a single center, the present study aimed to evaluate the influence of clinical characteristics, medical treatment and surgery on the survival of non-functional metastatic G2 pNET. In total, 114 metastatic non-functional G2 pNET patients, who were treated and followed up in the Department of Medical Oncology, Peking Union Medical College Hospital (PUMCH) from 2001 until 2019, were analyzed retrospectively. The primary endpoint, overall survival (OS), was calculated from the date of diagnosis to the date of death. The second endpoint, progression-free survival (PFS), was calculated from the date of diagnosis to the date of disease progression. Statistical data were analyzed to evaluate the effects of a clinical characteristic, medical treatment and surgery on OS and PFS. Sixty-nine (60.5%) patients were male and 87 (76.3%) were aged < 60 years. The liver was the most common metastatic organ, with a total of 84 cases (73.7%). With respect to surgery, 32 (28.1%) patients underwent radical surgery and 37 (32.5%) underwent palliative surgery. Survival analysis showed that the 5-year and 10-year survival rates were 79.36% and 70.0%, respectively. Univariate and multivariate Cox regression analyses suggested that both radical (p < .001/.003) and palliative surgery (p < .001/.002) significantly prolonged OS, as revealed by the Kaplan-Meier test (p < .001). Subgroup analysis showed that palliative resection also significantly improves the prognosis in patients with multiple liver metastases. However, the first-line systemic anti-tumor therapy option showed no statistical differences in the present study. Overall, patients with non-functional metastatic G2 pNET receiving palliative or radical surgery demonstrated significantly better survival. Prospective clinical trials are suggested to validate our findings.

Observation and characterization of the high order modes in a six-mode fiber using an OFDR method.

High order modes in a six-mode fiber are separately observed and characterized using an Optical Frequency Domain Reflectometry (OFDR) method. Due to the difference in group refractive index between fundamental mode and the high order modes, Fresnel reflection peaks for each mode can be separated in beat frequency domain with their corresponding time delay. In the experiment, the fundamental mode and high order modes are excited in turn and observed at a 6.6 m six-mode fiber end, which agree with their beat frequency difference in theoretical simulation. The demonstration provides a flexible and feasible method for mode identification and characterization of all kinds of fibers.

Intelligent Optimization Method of Resource Recommendation Service of Mobile Library Based on Digital Twin Technology.

In order to improve the Resource Recommendation and sharing ability of mobile library, an intelligent optimization model of Mobile Library Resource Recommendation Service Based on digital twin technology is proposed. Build the association rule feature distribution set of mobile library resource recommendation service, carry out text information retrieval in the process of Mobile Library Resource Recommendation and sharing, carry out semantic correlation feature registration according to the retrieval preference of mobile library reading user object, establish the association rule data set of mobile library reading user object preference for mobile library Resource Recommendation and sharing, carry out feature block processing, and analyze the library reader preference. Complete the collaborative filtering recommendation of Mobile Library Resource Recommendation sharing. The simulation results show that the collaborative recommendation under the intelligent optimization mode of mobile library resource recommendation service using this method has high accuracy and good confidence level, which improves the intelligent level of Mobile Library Resource Recommendation and user satisfaction.

Symptom recognition of disease and insect damage based on Mask R-CNN, wavelet transform, and F-RNet.

Brown blight, target spot, and tea coal diseases are three major leaf diseases of tea plants, and Apolygus lucorum is a major pest in tea plantations. The traditional symptom recognition of tea leaf diseases and insect pests is mainly through manual identification, which has some problems, such as low accuracy, low efficiency, strong subjectivity, and so on. Therefore, it is very necessary to find a method that could effectively identify tea plants diseases and pests. In this study, we proposed a recognition framework of tea leaf disease and insect pest symptoms based on Mask R-CNN, wavelet transform and F-RNet. First, Mask R-CNN model was used to segment disease spots and insect spots from tea leaves. Second, the two-dimensional discrete wavelet transform was used to enhance the features of the disease spots and insect spots images, so as to obtain the images with four frequencies. Finally, the images of four frequencies were simultaneously input into the four-channeled residual network (F-RNet) to identify symptoms of tea leaf diseases and insect pests. The results showed that Mask R-CNN model could detect 98.7% of DSIS, which ensure that almost disease spots and insect spots can be extracted from leaves. The accuracy of F-RNet model is 88%, which is higher than that of the other models (like SVM, AlexNet, VGG16 and ResNet18). Therefore, this experimental framework can accurately segment and identify diseases and insect spots of tea leaves, which not only of great significance for the accurate identification of tea plant diseases and insect pests, but also of great value for further using artificial intelligence to carry out the comprehensive control of tea plant diseases and insect pests.

Sensitive detection of stage I lung adenocarcinoma using plasma cell-free DNA breakpoint motif profiling.

BACKGROUND: Early diagnosis benefits lung cancer patients with higher survival, but most patients are diagnosed after metastasis. Although cell-free DNA (cfDNA) analysis holds promise, its sensitivity for detecting early-stage lung cancer is unsatisfying. We leveraged cfDNA fragmentomics to develop a predictive model for invasive stage I lung adenocarcinoma (LUAD). METHODS: 292 stage I LUAD patients from three medical centers were included together with 230 healthy controls whose plasma cfDNA samples were profiled by whole-genome sequencing (WGS). Multiple cfDNA fragmentomic motif features and machine learning models were compared in the training cohort to select the best model. Model performance was assessed in the internal and external validation cohorts and an additional dataset. FINDINGS: A logistic regression model using the 6bp-breakpoint-motif feature was selected. It yielded 98·0% sensitivity and 94·7% specificity in the internal validation cohort [Area Under the Curve (AUC): 0·985], while 92·5% sensitivity and 90·0% specificity were achieved in the external validation cohort (AUC: 0·954). It is sensitive for early-stage (100% sensitivity for minimally invasive adenocarcinoma, MIA) and <1 cm (92·9%-97·7% sensitivity) tumors. The predictive power remained high when reducing sequencing depth to 0·5× (AUC: 0·977 and 0·931 for internal and external cohorts). INTERPRETATION: Here we have established a cfDNA breakpoint motif-based model for detecting early-stage LUAD, including MIA and very small-size tumors, shedding light on early cancer diagnosis in clinical practice. FUNDING: National Key R&D Program of China; National Natural Science Foundation of China; CAMS Initiative for Innovative Medicine; Special Research Fund for Central Universities, Peking Union Medical College; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences; Beijing Hope Run Special Fund of Cancer Foundation of China.

Safety and Efficacy of PD-1/PD-L1 Inhibitors in Cancer Patients With Preexisting Autoantibodies.

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood. Methods: The present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed. Results: 67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS. Conclusions: The presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.

Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection.

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

Uterine NK cell functions at maternal-fetal interface†.

During pregnancy, maternal decidual tissue interacts with fetal trophoblasts. They constitute the maternal-fetal interface responsible for supplying nutrition to the fetus. Uterine natural killer (uNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy and play critical roles throughout pregnancy. This review provides current knowledge about the functions of uNK cells. uNK cells have been shown to facilitate remodeling of the spiral artery, control the invasion of extravillous trophoblast (EVT) cells, contribute to the induction and maintenance of immune tolerance, protect against pathogen infection, and promote fetal development. Pregnancy-trained memory of uNK cells improves subsequent pregnancy outcomes. In addition, this review describes the distinct functions of three uNK cell subsets: CD27-CD11b-, CD27+, and CD27-CD11b+ uNK cells.