Hypoxia-related signature to risk stratify patients for the benefit of immune checkpoint inhibitors therapy in head and neck squamous cell carcinoma: An experimental study.

BACKGROUND: Increasing evidence has shown that hypoxia is a biomarker of tumor proliferation and metastasis. This research aimed to identify a hypoxia-associated gene prognostic index (HAGPI) in head and neck squamous cell carcinoma (HNSCC) and based on HAGPI-defined subgroups to predict prognosis and response to immune checkpoint inhibitors therapy. METHODS: RNA-sequencing transcriptomic data for patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA). Protein-protein interaction network analysis was performed to select hypoxia-related hub genes. Univariate and multivariate cox regression analyses were used to identify hub genes to develop the HAGPI. Afterward expression data were imported into CIBERSORT to evaluate the relative proportion of 22 immune cells and compared the relative proportions of immune cells between the 2 HAGPI subgroups. The relationship between immunopheno score (IPS) and HAGPI was validated for immune checkpoint inhibitors (ICIs) response in TCGA cohorts. RESULTS: The HAGPI was constructed based on HS3ST1, HK1, PGK1, STC2, SERPINE1, PKLR genes. In high-HAGPI patients, the primary and secondary endpoint events in TCGA and GEO cohorts were significantly lower than low-HAGPI groups (P < .05). HAGPI-high patients exhibited a poorer prognosis than HAGPI-low patients did. The abundance of M2 macrophages and NK cell were significantly enhanced in the high-HAGPI while T cells regulatory and T cells CD8, were markedly elevated in the low-HAGPI. Meanwhile, patients in the low-HAGPI patients had higher levels of immunosuppressant expression and less aggressive phenotypes. Furthermore, IPS analysis showed that the low-HAGPI group with higher IPS represented a more immunogenic phenotype. CONCLUSION: The current study developed and verified a HAPGI model that can be considered as an independent prognostic biomarker and elucidated the tumor immune microenvironment of HNSCC.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

Recent developments in immunotherapy for gastrointestinal tract cancers.

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.

Predicting protein conformational motions using energetic frustration analysis and AlphaFold2.

Proteins perform their biological functions through motion. Although high throughput prediction of the three-dimensional static structures of proteins has proved feasible using deep-learning-based methods, predicting the conformational motions remains a challenge. Purely data-driven machine learning methods encounter difficulty for addressing such motions because available laboratory data on conformational motions are still limited. In this work, we develop a method for generating protein allosteric motions by integrating physical energy landscape information into deep-learning-based methods. We show that local energetic frustration, which represents a quantification of the local features of the energy landscape governing protein allosteric dynamics, can be utilized to empower AlphaFold2 (AF2) to predict protein conformational motions. Starting from ground state static structures, this integrative method generates alternative structures as well as pathways of protein conformational motions, using a progressive enhancement of the energetic frustration features in the input multiple sequence alignment sequences. For a model protein adenylate kinase, we show that the generated conformational motions are consistent with available experimental and molecular dynamics simulation data. Applying the method to another two proteins KaiB and ribose-binding protein, which involve large-amplitude conformational changes, can also successfully generate the alternative conformations. We also show how to extract overall features of the AF2 energy landscape topography, which has been considered by many to be black box. Incorporating physical knowledge into deep-learning-based structure prediction algorithms provides a useful strategy to address the challenges of dynamic structure prediction of allosteric proteins.

Feasibility of simultaneous optimization of Anammox start-up and nitrogen removal performance by intermittent dosing of nanoscale zero-valent iron.

The long acclimation period and sensitivity to environmental conditions of Anammox are the bottlenecks for its promotion and application. An innovative strategy was adopted to accelerate functional microbial enhancement and improve nitrogen removal performance by inoculating cryopreserved Anammox sludge and activated sludge with intermittent dosing of nanoscale zero-valent iron (nZVI). The acclimation time was shortened by 76 days with nitrogen removal efficiency (NRE) reaching up to 91.07 %. Anammox, NDFO (nitrate/nitrite-dependent Fe(II) oxidation), Feammox (Fe(III) reduction coupled with anaerobic ammonium oxidation) and abiotic reactions were coupled in the system with nZVI, contributing to 69.79 %, 15.14 %, 9.84 % and 0.25 % of nitrogen removal, respectively. Further microbial analysis demonstrated significant enrichment of functional microorganisms, such as Candidatus Jettenia, Acidovorax and Comamonas. High-efficient nitrogen removal was attribute to the increase of functional genes involved in Anammox, electronic transfer, heme C synthesis and iron metabolism. This work provides an inspiring idea for the mainstream Anammox application.

Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study.

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.

Rapidly damping hydrogels engineered through molecular friction.

Hydrogels capable of swift mechanical energy dissipation hold promise for a range of applications including impact protection, shock absorption, and enhanced damage resistance. Traditional energy absorption in such materials typically relies on viscoelastic mechanisms, involving sacrificial bond breakage, yet often suffers from prolonged recovery times. Here, we introduce a hydrogel designed for friction-based damping. This hydrogel features an internal structure that facilitates the motion of a chain walker within its network, effectively dissipating mechanical stress. The hydrogel network architecture allows for rapid restoration of its damping capacity, often within seconds, ensuring swift material recovery post-deformation. We further demonstrate that this hydrogel can significantly shield encapsulated cells from mechanical trauma under repetitive compression, owing to its proficient energy damping and rapid rebound characteristics. Therefore, this hydrogel has potential for dynamic load applications like artificial muscles and synthetic cartilage, expanding the use of hydrogel dampers in biomechanics and related areas.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Dietary lipid sources affect growth performance, lipid deposition, antioxidant capacity and inflammatory response of largemouth bass (Micropterus salmoides).

The present study explored the effects of different lipid sources on growth performance, lipid deposition, antioxidant capacity, inflammatory response and disease resistance of largemouth bass (Micropterus salmoides). Four isonitrogenous (crude protein 50.46 %) and isolipidic (crude lipid 11.12 %) diets were formulated to contain 7 % of different oil sources including fish oil (FO) (control), soybean oil (SO), linseed oil (LO) and coconut oil (CO). Largemouth bass with initial body weight of 36.0 ± 0.2 g were randomly distributed into 12 tanks, with 30 fish per tank and 3 tanks per treatment. The fish were fed with the experiment diets twice daily for 8 weeks. The results indicated that the weight gain of largemouth bass fed the FO diet was significantly higher than that of fish fed the LO and CO diets. The liver crude lipid content in FO group was significantly higher than other groups, while the highest liver triglyceride content was showed in SO group and the lowest was detected in LO group. At transcriptional level, expression of lipogenesis related genes (pparγ, srebp1, fas, acc, dgat1 and dgat2) in the SO and CO group were significantly higher than the FO group. However, the expression of lipolysis and fatty acids oxidation related genes (pparα, cpt1, and aco) in vegetable oils groups were significantly higher than the FO group. As to the antioxidant capacity, vegetable oils significantly reduced the malondialdehyde content of largemouth bass. Total antioxidant capacity in the SO and LO groups were significantly increased compared with the FO group. Catalase in the LO group was significantly increased compared with the FO group. Furthermore, the ER stress related genes, such as grp78, atf6α, atf6ß, chop and xbp1 were significantly enhanced in the vegetable oil groups compared with the FO group. The activity of serum lysozyme in vegetable oil groups were significantly higher than in FO group. Additionally, the relative expression of non-specific immune related genes, including tlr2, mapk11, mapk13, mapk14, rela, tgf-ß1, tnfα, 5lox, il-1ß and il10, were all significantly increased in SO and CO groups compared to the other groups. In conclusion, based on the indexes including growth performance, lipid deposition, antioxidant capacity and inflammatory response, SO and LO could be alternative oil sources for largemouth bass.

MiR-2284b regulation of α-s1 casein synthesis in mammary epithelial cells of dairy goats.

The lactation character of dairy goats is the most important characteristic, and milk protein is an important index to evaluate milk quality. Casein accounts for more than 80% of the total milk protein in goat milk and is the main component of milk protein. Using GMECs (goat mammary epithelial cells) as the research object, the CHECK2 vector of the CSN1S1 gene and the overexpression vector of pcDNA 3.1 were constructed, and the mimics of miR-2284b and the interfering RNA of CSN1S1 were synthesized. Using PCR, RT-qPCR, a dual luciferase activity detection system, EdU, CCK8, cell apoptosis detection and ELISA detection, we explored the regulatory mechanism and molecular mechanism of miR-2284b regulation of αs1-casein synthesis in GMECs. miR-2284b negatively regulates proliferation and apoptosis of GMECs and αs1-casein synthesis. Two new gene sequences of CSN1S1 were discovered. CSN1S1-1/-2 promoted the proliferation of GMECs and inhibited cell apoptosis. However, it had no effect on αs1-casein synthesis. MiR-2284b negatively regulates αs1-casein synthesis in GMECs by inhibiting the CSN1S1 gene. These results all indicated that miR-2284b could regulate αs1-casein synthesis, thus playing a theoretical guiding role in the future breeding process of dairy goats and accelerating the development of dairy goat breeding.

The relationship between anxiety symptoms and disturbances in biological rhythms in patients with depression.

BACKGROUND: Biological rhythms denote the cyclical patterns of life activities anchored to a 24-hour cycle. Research shows that depression exhibits disturbances in biological rhythms. Yet, the relationship between these biological rhythms and concomitant anxiety symptoms is insufficiently investigated in structured clinical assessments. METHODS: This multicenter study, carried out in four Chinese hospitals, comprehensively examined the relationship between anxiety and disruptions in biological rhythms among patients with depression. The study encompassed 218 patients diagnosed with depression and 205 matched healthy controls. The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry was utilized to evaluate the participants' biological rhythms, focusing on four dimensions: sleep, activity, social, and diet. RESULTS: In patients with depression, there is a significant positive correlation between the severity of anxiety symptoms and the disturbances in biological rhythms. The severity of anxiety and depression, along with the quality of life, are independently associated with disruptions in biological rhythms. The mediation model reveals that anxiety symptoms mediate the relationship between depressive symptoms and biological rhythms. CONCLUSION: This research highlights the role of anxiety within the spectrum of depressive disorders and the associated disturbances in biological rhythms. Our findings shed light on potential pathways towards more targeted preventive strategies and therapeutic interventions for individuals battling depression and anxiety.

Strong Linearly Polarized Light Emission by Coupling Out-of-Plane Exciton to Anisotropic Gap Plasmon Nanocavity.

With exceptional quantum confinement, 2D monolayer semiconductors support a strong excitonic effect, making them an ideal platform for exploring light-matter interactions and as building blocks for novel optoelectronic devices. Different from the well-known in-plane excitons in transition metal dichalcogenides (TMD), the out-of-plane excitons in indium selenide (InSe) usually show weak emission, which limits their applications as light sources. Here, by embedding InSe in an anisotropic gap plasmon nanocavity, we have realized plasmon-enhanced linearly polarized photoluminescence with an anisotropic ratio up to ∼140, corresponding to degree of polarization (DoP) of ∼98.6%. Such polarization selectivity, originating from the polarization-dependent plasmonic enhancement supported by the "nanowire-on-mirror" nanocavity, can be well tuned by the InSe thickness. Moreover, we have also realized an InSe-based light-emitting diode with polarized electroluminescence. Our research highlights the role of excitonic dipole orientation in designing nanophotonic devices and paves the way for developing InSe-based optoelectronic devices with polarization control.

Adipocyte-Specific Hnrnpa1 Knockout Aggravates Obesity-Induced Metabolic Dysfunction via Upregulation of CCL2.

Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is involved in lipid and glucose metabolism via mRNA processing. However, whether and how HNRNPA1 alters adipocyte function in obesity remain obscure. Here, we found that the obese state downregulated HNRNPA1 expression in white adipose tissue (WAT). The depletion of adipocyte HNRNPA1 promoted markedly increased macrophage infiltration and expression of proinflammatory and fibrosis genes in WAT of obese mice, eventually leading to exacerbated insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, HNRNPA1 interacted with Ccl2 and regulated its mRNA stability. Intraperitoneal injection of CCL2-CCR2 signaling antagonist improved adipose tissue inflammation and systemic glucose homeostasis. Furthermore, HNRNPA1 expression in human WAT was negatively correlated with BMI, fat percentage, and subcutaneous fat area. Among individuals with 1-year metabolic surgery follow-up, HNRNPA1 expression was positively related to percentage of total weight loss. These findings identify adipocyte HNRNPA1 as a link between adipose tissue inflammation and systemic metabolic homeostasis, which might be a promising therapeutic target for obesity-related disorders.

Patterns and Prognosis of Local Recurrence of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy.

Objective: To investigate the patterns of local failure and prognosis in patients with locally recurrent nasopharyngeal carcinoma (rNPC) after primary intensity-modulated radiotherapy (IMRT). Methods: The data of 298 patients with locally rNPC after IMRT were retrospectively analyzed. Magnetic resonance images of the initial and recurrent tumors were reviewed and, for patients with extra-nasopharyngeal local recurrence, the gross tumor volume of local recurrence was transferred to the original IMRT plan for dosimetry analysis. Significant prognostic factors for overall survival (OS) were selected by multivariate Cox regression analysis. Results: The commonest recurrence sites were the nasopharynx (93%, 277/298) and skull base (53.7%, 160/298). Of the 21 patients with extra-nasopharyngeal recurrence (19 cases valid), 12 had in-field failures, 4 had marginal failures, and 3 had out-field failures. The ethmoid sinus (57.1%, 4/7) and nasal cavity (28.6%, 2/7) were the most frequent sites of marginal and out-field failures. After median follow-up of 37 months, the 3-year and estimated 5-year OS rates were 57.3% and 41.7%, respectively. Multivariate analysis showed that age, recurrence interval, plasma Epstein-Barr virus (EBV) DNA level, and recurrent T stage were independent prognostic factors for OS. Conclusions: Local failure after IMRT occurs most commonly in the nasopharynx and skull base. In patients with extra-nasopharyngeal recurrence, in-field failure remains the main failure pattern, and marginal and out-field failures mainly occur in the ethmoid sinus and nasal cavity. Elder age, shorter recurrence interval, detectable plasma EBV DNA, and advanced recurrent T stage are negative predictors of OS in patients with rNPC.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Unambiguous discrimination of all 20 proteinogenic amino acids and their modifications by nanopore.

Natural proteins are composed of 20 proteinogenic amino acids and their post-translational modifications (PTMs). However, due to the lack of a suitable nanopore sensor that can simultaneously discriminate between all 20 amino acids and their PTMs, direct sequencing of protein with nanopores has not yet been realized. Here, we present an engineered hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore containing a sole Ni2+ modification. It enables full discrimination of all 20 proteinogenic amino acids and 4 representative modified amino acids, Nω,N'ω-dimethyl-arginine (Me-R), O-acetyl-threonine (Ac-T), N4-(ß-N-acetyl-D-glucosaminyl)-asparagine (GlcNAc-N) and O-phosphoserine (P-S). Assisted by machine learning, an accuracy of 98.6% was achieved. Amino acid supplement tablets and peptidase-digested amino acids from peptides were also analyzed using this strategy. This capacity for simultaneous discrimination of all 20 proteinogenic amino acids and their PTMs suggests the potential to achieve protein sequencing using this nanopore-based strategy.

Dietary inclusion of Clostridium butyricum cultures alleviated impacts of high-carbohydrate diets in largemouth bass (Micropterus salmoides).

A 60-d feeding trial was conducted to explore the potential regulatory effects of dietary Clostridium butyricum cultures (CBC) supplementation in high-carbohydrate diet (HCD) on carbohydrate utilisation, antioxidant capacity and intestinal microbiota of largemouth bass. Triplicate groups of largemouth bass (average weight 35·03 ± 0·04 g), with a destiny of twenty-eight individuals per tank, were fed low-carbohydrate diet and HCD supplemented with different concentration of CBC (0 %, 0·25 %, 0·50 % and 1·00 %). The results showed that dietary CBC inclusion alleviated the hepatic glycogen accumulation induced by HCD intake. Additionally, the expression of hepatic ampkα1 and insulin signaling pathway-related genes (ira, irb, irs, p13kr1 and akt1) increased linearly with dietary CBC inclusion, which might be associated with the activation of glycolysis-related genes (gk, pfkl and pk). Meanwhile, the expression of intestinal SCFA transport-related genes (ffar3 and mct1) was significantly increased with dietary CBC inclusion. In addition, the hepatic antioxidant capacity was improved with dietary CBC supplementation, as evidenced by linear decrease in malondialdehyde concentration and expression of keap1, and linear increase in antioxidant enzyme activities (total antioxidative capacity, total superoxide dismutase and catalase) and expression of antioxidant enzyme-related genes (nrf2, sod1, sod2 and cat). The analysis of bacterial 16S rRNA V3-4 region indicated that dietary CBC inclusion significantly reduced the enrichment of Firmicutes and potential pathogenic bacteria genus Mycoplasma but significantly elevated the relative abundance of Fusobacteria and Cetobacterium. In summary, dietary CBC inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota of largemouth bass fed HCD.

A tumor microenvironment-associated circRNA predictor for tumor relapse and chemotherapy vulnerability in nasopharyngeal carcinoma.

Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

Room-temperature high-speed electrical modulation of excitonic distribution in a monolayer semiconductor.

Excitons in monolayer semiconductors, benefitting from their large binding energies, hold great potential towards excitonic circuits bridging nano-electronics and photonics. However, achieving room-temperature ultrafast on-chip electrical modulation of excitonic distribution and flow in monolayer semiconductors is nontrivial. Here, utilizing lateral bias, we report high-speed electrical modulation of the excitonic distribution in a monolayer semiconductor junction at room temperature. The alternating charge trapping/detrapping at the two monolayer/electrode interfaces induces a non-uniform carrier distribution, leading to controlled in-plane spatial variations of excitonic populations, and mimicking a bias-driven excitonic flow. This modulation increases with the bias amplitude and eventually saturates, relating to the energetic distribution of trap density of states. The switching time of the modulation is down to 5 ns, enabling high-speed excitonic devices. Our findings reveal the trap-assisted exciton engineering in monolayer semiconductors and offer great opportunities for future two-dimensional excitonic devices and circuits.