Gender-specific effects of polystyrene nanoplastic exposure on triclosan-induced reproductive toxicity in zebrafish (Danio rerio).

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.

Preparation and measurement of a sandwiched Sn atomic beam source for laser resonance ionization mass spectrometry.

Isotope analysis of Sn plays a crucial role in geochemical studies and in monitoring nuclear contamination. Nevertheless, prevalent analytical techniques for examining Sn isotopes encounter the issue of isobaric interference, markedly impacting the accuracy of the test results. Laser resonance ionization mass spectrometry (LRIMS) can effectively overcome the difficulties associated with the isobaric interference inherent in commercial mass spectrometry. In this paper, different amounts of Sn were prepared on Re filaments by electrodeposition and tested via LRIMS. The results showed that the average detection efficiency of LRIMS decreased with increasing total Sn content from 1 µg to 4 µg, and the fluctuations in the test results among the samples increased significantly. Therefore, the electrodeposition process, as well as the composition and morphology of the deposits were characterized by SEM, EDS and XPS; results showed that the degradation of the samples with increasing Sn content was attributed to the complexity of the composition, micro-structure, valence of the deposits, and the interference of various elements. To cope with the anomalies encountered above, the deposits were heat-treated at 600 °C in a hydrogen atmosphere to eliminate detrimental impurities, like Cl, and Sn was effectively reduced to an almost singular atomic state. Furthermore, a titanium layer was covered on the surface of the heat-treated deposit by magnetron sputtering. Ultimately, a highly efficient and stable Sn atomic beam source with a sandwiched structure has been successfully developed and exhibits broad application prospect.

MiR-99a-3p downregulates TRIM21 to promote gastric cancer development.

Gastric cancer (GC) stands as one of the most formidable malignancies worldwide. It is well-established that miRNAs play a crucial role in the initiation and progression of various human cancers. Among these, miR-99a-3p has been implicated in the pathogenesis of GC. In the context of our study, we embarked on the comprehensive examination of miR-99a-3p expression in GC cells. Additionally, we sought to establish a correlation between miR-99a-3p expression levels and the overall survival (OS) of GC patients, and our findings hinted at its potential role in predicting an unfavorable prognosis. To further investigate the functional implications of miR-99a-3p in GC, we conducted a series of cell-based experiments after successfully knocking down miR-99a-3p. These investigations uncovered a substantial inhibition of cellular events associated with tumor progression. Moreover, employing TargetScan, we identified Tripartite motif-containing protein 21 (TRIM21) as a putative target with a binding site for miR-99a-3p. Subsequent dual-luciferase reporter gene assay confirmed the direct interaction between miR-99a-3p and TRIM21. Western blot analysis validated the alteration in TRIM21 expression levels, revealing an upregulation upon miR-99a-3p knockdown. Building on these molecular findings, we extended our investigations to human GC tissues, where we observed a downregulation of TRIM21, which, notably, correlated with shorter overall survival. Lastly, to further solidify our conclusions, we conducted a series of in vitro and in vivo rescue experiments, collectively suggesting that miR-99a-3p promoted the progression of GC cells through the downregulation of TRIM21. In summary, our study comprehensively explored the role of miR-99a-3p in GC, revealing its association with unfavorable patient outcomes, functional implications in tumor progression, and a direct regulatory relationship with TRIM21. These findings collectively underscore the significance of miR-99a-3p in the pathogenesis of GC and present a potential therapeutic avenue for further investigation.

Half-life determination of the ground state decay of 167Tm and 168Tm.

Precise determination of half-lives of 167Tm and 168Tm are important for their application in nuclear medicine diagnostics, nuclear forensics, and other nuclear data measurements. We produced 167Tm and 168Tm sources using an α-particle beam bombarded 165Ho target and a series purification steps. A series of 173 measurements was performed over a period of 44 days using a high-purity germanium (HPGe) detector to track the count rate change as a function of time by following the 207.8 keV and 531.5 keV γ-lines to determine the radioactive decay half-life of 167Tm. The measurement of half-life of 168Tm ground state has been performed using the same HPGe γ-ray spectrometer to observe γ-lines at 198.3 keV, 816.0 keV, 184.3 keV, 741.4 keV and 914.9 keV. Weighted least-squares fits of exponential decay curves were performed for the dataset of each γ-ray emission, with final determined half-lives of 9.250(15) d and 93.41(12) d for 167Tm and 168Tm, respectively. The uncertainty budgets are presented and discussed in detail. Our result of 167Tm half-life is consistent with the Evaluated Nuclear Structure Data File (ENSDF) recommended half-life of 9.25(2) d. The outcome of 168Tm half-life determination is longer than the ENSDF recommended half-life of 93.1(2) d. Further independent measurements would be ideal to resolve the discrepancy.

Improved deep learning for automatic localisation and segmentation of rectal cancer on T2-weighted MRI.

INTRODUCTION: The automatic segmentation approaches of rectal cancer from magnetic resonance imaging (MRI) are very valuable to relieve physicians from heavy workloads and enhance working efficiency. This study aimed to compare the segmentation accuracy of a proposed model with the other three models and the inter-observer consistency. METHODS: A total of 65 patients with rectal cancer who underwent MRI examination were enrolled in our cohort and were randomly divided into a training cohort (n = 45) and a validation cohort (n = 20). Two experienced radiologists independently segmented rectal cancer lesions. A novel segmentation model (AttSEResUNet) was trained on T2WI based on ResUNet and attention mechanisms. The segmentation performance of the AttSEResUNet, U-Net, ResUNet and U-Net with Attention Gate (AttUNet) was compared, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance to agreement (MDA) and Jaccard index. The segmentation variability of automatic segmentation models and inter-observer was also evaluated. RESULTS: The AttSEResUNet with post-processing showed perfect lesion recognition rate (100%) and false recognition rate (0), and its evaluation metrics outperformed other three models for two independent readers (observer 1: DSC = 0.839 ± 0.112, HD = 9.55 ± 6.68, MDA = 0.556 ± 0.722, Jaccard index = 0.736 ± 0.150; observer 2: DSC = 0.856 ± 0.099, HD = 11.0 ± 10.1, MDA = 0.789 ± 1.07, Jaccard index = 0.673 ± 0.130). The segmentation performance of AttSEResUNet was comparable and similar to manual variability (DSC = 0.857 ± 0.115, HD = 10.0 ± 10.0, MDA = 0.704 ± 1.17, Jaccard index = 0.666 ± 0.139). CONCLUSION: Comparing with other three models, the proposed AttSEResUNet model was demonstrated as a more accurate model for contouring the rectal tumours in axial T2WI images, whose variability was similar to that of inter-observer.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Phase II study of novel orally PI3Kα/δ inhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma.

This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

Direct Oxidative Cyclization of 3-Arylpropionic Acids to 3,4-Dihydrocoumarins: Reinvestigation of the Reaction Mechanism.

Instigated by olfactory analysis of odorant molecules, the constitutions of 3,4-dihydrocoumarins prepared by PIFA-based oxidative cyclizations of 3-arylpropionic acids were revised by means of 2D NMR and X-ray analysis. Supported by computational analysis, the migratory mechanism of intermediate spirolactonic cations has been amended: 1,2-alkyl shifts instead of 1,2-carboxylic shifts were selectively obtained.

Design and analysis of a complementary structure-based high selectivity tri-band frequency selective surface.

This work presents a novel tri-band bandpass frequency selective surface (FSS) that achieves high-order filtering responses in different frequency bands by means of a complementary structure. The proposed FSS is composed of three metal periodic arrays, which are separated by multilayer dielectric substrates. The gridded-double convoluted loop (G-DCL) structure, which is the middle layer structure, is a hybrid resonator that generates different resonant frequencies. The top and bottom layer structures are designed as complementary structures to the middle layer. To accurately describe the frequency responses, an equivalent circuit model (ECM) has been constructed over the entire band from 0 to 16 GHz. The results of the simulation indicate that the developed FSS can generate three pass-bands operating at 3.79 GHz, 8.34 GHz, and 12.52 GHz, respectively, and - 3 dB fractional bandwidths are 52.8%, 13.7%, and 19.7%. The transmission responses at the edges of each passband show a quick roll-off from the passband to the stopband, and there is significant out-of-band suppression between adjacent passbands. Moreover, the FSS maintains excellent angular and polarization stability within a 50° range. For verification, the tri-band FSS has been fabricated and tested. The experimental results match the simulation results, validating the accuracy of the FSS design.

GAS41 modulates ferroptosis by anchoring NRF2 on chromatin.

YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).

FBXO24 modulates mRNA alternative splicing and MIWI degradation and is required for normal sperm formation and male fertility.

Spermiogenesis is a critical, post-meiotic phase of male gametogenesis, in which the proper gene expression is essential for sperm maturation. However, the underFlying molecular mechanism that controls mRNA expression in the round spermatids remains elusive. Here, we identify that FBXO24, an orphan F-box protein, is highly expressed in the testis of humans and mice and interacts with the splicing factors (SRSF2, SRSF3, and SRSF9) to modulate the gene alternative splicing in the round spermatids. Genetic mutation of FBXO24 in mice causes many abnormal splicing events in round spermatids, thus affecting a large number of critical genes related to sperm formation that were dysregulated. Further molecular and phenotypical analyses revealed that FBXO24 deficiency results in aberrant histone retention, incomplete axonemes, oversized chromatoid body, and abnormal mitochondrial coiling along sperm flagella, ultimately leading to male sterility. In addition, we discovered that FBXO24 interacts with MIWI and SCF subunits and mediates the degradation of MIWI via K48-linked polyubiquitination. Furthermore, we show that FBXO24 depletion could lead to aberrant piRNA production in testes, which suggests FBXO24 is required for normal piRNA counts. Collectively, these data demonstrate that FBXO24 is essential for sperm formation by regulating mRNA alternative splicing and MIWI degradation during spermiogenesis.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

In Situ Implanting ZrW2 O7 (OH)2 (H2 O)2 Nanorods into Hierarchical Functionalized Metal-Organic Framework via Solvent-Free Approach for Upgrading Catalytic Performance.

Host-guest catalyst provides new opportunities for targeted applications and the development of new strategies for preparing host-guest catalysts is highly desired. Herein, an in situ solvent-free approach is developed for implanting ZrW2 O7 (OH)2 (H2 O)2 nanorods (ZrW-NR) in nitro-functionalized UiO-66(Zr) (UiO-66(Zr)-NO2 ) with hierarchical porosity, and the encapsulation of ZrW-NR enables the as-prepared host-guest catalyst remarkably enhanced catalytic performance for both for oxidative desulfurization (ODS) and acetalization reactions. ZrW-NR@UiO-66(Zr)-NO2 can eliminate 500 ppm sulfur within 9 min at 40 °C in ODS, and can transform 5.6 mmol benzaldehyde after 3 min at room temperature in acetalization reaction. Its turnover frequencies reach 72.3 h-1 at 40 °C for ODS which is 33.4 times higher than UiO-66(Zr)-NO2 , and 28140 h-1 for acetalization which is the highest among previous reports. Density functional theory calculation result indicates that the W sites in ZrW-NR can decompose H2 O2 to WVI -peroxo intermediates that contribute to catalytic activity for the ODS reaction. This work opens a new solvent-free approach for preparing MOFs-based host-guest catalysts to upgrade their redox and acid performance.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

PHLDA2-mediated phosphatidic acid peroxidation triggers a distinct ferroptotic response during tumor suppression.

Although the role of ferroptosis in killing tumor cells is well established, recent studies indicate that ferroptosis inducers also sabotage anti-tumor immunity by killing neutrophils and thus unexpectedly stimulate tumor growth, raising a serious issue about whether ferroptosis effectively suppresses tumor development in vivo. Through genome-wide CRISPR-Cas9 screenings, we discover a pleckstrin homology-like domain family A member 2 (PHLDA2)-mediated ferroptosis pathway that is neither ACSL4-dependent nor requires common ferroptosis inducers. PHLDA2-mediated ferroptosis acts through the peroxidation of phosphatidic acid (PA) upon high levels of reactive oxygen species (ROS). ROS-induced ferroptosis is critical for tumor growth in the absence of common ferroptosis inducers; strikingly, loss of PHLDA2 abrogates ROS-induced ferroptosis and promotes tumor growth but has no obvious effect in normal tissues in both immunodeficient and immunocompetent mouse tumor models. These data demonstrate that PHLDA2-mediated PA peroxidation triggers a distinct ferroptosis response critical for tumor suppression and reveal that PHLDA2-mediated ferroptosis occurs naturally in vivo without any treatment from ferroptosis inducers.

Erratum: Author correction to "Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy" [Acta Pharm Sin B (2022) 4204-4223].

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

Revealing new insights: Two-center evidence of microplastics in human vitreous humor and their implications for ocular health.

Microplastics (MPs), an emerging environmental contaminant, have raised growing health apprehension due to their detection in various human biospecimens. Despite extensive research into their prevalence in the environment and the human body, the ramifications of their existence within the enclosed confines of the human eye remain largely unexplored. Herein, we assembled a cohort of 49 patients with four ocular diseases (macular hole, macular epiretinal membrane, retinopathy and rhegmatogenous retinal detachment) from two medical centers. After processing the samples with an optimized method, we utilized Laser Direct Infrared (LD-IR) spectroscopy and Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) to analyze 49 vitreous samples, evaluating the characteristics of MPs within the internal environment of the human eye. Our results showed that LD-IR scanned a total of 8543 particles in the composite sample from 49 individual vitreous humor samples, identifying 1745 as plastic particles, predominantly below 50 µm. Concurrently, Py-GC/MS analysis of the 49 individual samples corroborated these findings, with nylon 66 exhibiting the highest content, followed by polyvinyl chloride, and detection of polystyrene. Notably, correlations were observed between MP levels and key ocular health parameters, particularly intraocular pressure and the presence of aqueous humor opacities. Intriguingly, individuals afflicted with retinopathy demonstrated heightened ocular health risks associated with MPs. In summary, this research provides significant insights into infiltration of MP pollutants within the human eye, shedding light on their potential implications for ocular health and advocating for further exploration of this emerging health risk.

Non-invasive detection of lymphoma with circulating tumor DNA features and protein tumor markers.

Background: According to GLOBOCAN 2020, lymphoma ranked as the 9th most common cancer and the 12th leading cause of cancer-related deaths worldwide. Traditional diagnostic methods rely on the invasive excisional lymph node biopsy, which is an invasive approach with some limitations. Most lymphoma patients are diagnosed at an advanced stage since they are asymptomatic at the beginning, which has significantly impacted treatment efficacy and prognosis of the disease. Method: This study assessed the performance and utility of a newly developed blood-based assay (SeekInCare) for lymphoma early detection. SeekInCare utilized protein tumor markers and a comprehensive set of cancer-associated genomic features, including copy number aberration (CNA), fragment size (FS), end motif, and lymphoma-related virus, which were profiled by shallow WGS of cfDNA. Results: Protein marker CA125 could be used for lymphoma detection independent of gender, and the sensitivity was 27.8% at specificity of 98.0%. After integrating these multi-dimensional features, 77.8% sensitivity was achieved at specificity of 98.0%, while its NPV and PPV were both more than 92% for lymphoma detection. The sensitivity of early-stage (I-II) lymphoma was up to 51.3% (47.4% and 55.0% for stage I and II respectively). After 2 cycles of treatment, the molecular response of SeekInCare was correlated with the clinical outcome. Conclusion: In summary, a blood-based assay can be an alternative to detect lymphoma with adequate performance. This approach becomes particularly valuable in cases where obtaining tissue biopsy is difficult to obtain or inconclusive.