Insights into treatment-specific prognostic somatic mutations in NSCLC from the AACR NSCLC GENIE BPC cohort analysis.

BACKGROUND: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing-based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. METHODS: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. RESULTS: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type-specific mutation signature for chemotherapy selection. CONCLUSION: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Thickened photoreceptor outer segment layer in children with hyperopic anisometropic amblyopia.

PURPOSE: To quantitatively investigate the reflectivity and structure of the outer retinal layers in children with hyperopic anisometropic amblyopia by using swept-source optical coherence tomography (SS-OCT). METHODS: Seventy-eight patients with amblyopia and 64 age-matched children with normal vision were included in this study. All participants underwent SS-OCT and detailed ophthalmic examinations. Longitudinal reflectance profile measurements were measured using Image J. The reflectivity of outer retinal layers was measured at the three selected positions: subfovea, 1 mm nasal to the fovea, and 1 mm temporal to the fovea. The reflectivity ratios were calculated by outer retinal layers divided by the nuclear layer (ONL) for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the amblyopia and normal controls. The possible effects of age, sex, and axial length on results were adjusted by generalized estimating equations. RESULTS: Photoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41 ± 1.83 vs. 16.84 ± 1.39, P < 0.001 at the fovea; 14.78 ± 1.34 vs. 14.19 ± 1.40, P = 0.030 at 1 mm nasal to the foveal; 14.92 ± 1.48 vs. 14.41 ± 1.32, P = 0.049 at 1 mm temporal to the fovea). The reflectivity ratio of outer segment/ONL was higher only at 1 mm nasal to the fovea (2.94 ± 0.61 vs. 2.70 ± 0.42, P = 0.02). Subfoveal OS thickness was positively correlated with choroidal thickness (r = 0.248, P = 0.018) but was not correlated with spherical equivalent, age, axial length, or logMAR visual acuity. CONCLUSION: Quantitative measurement of SS-OCT images revealed greater photoreceptor outer segments in both eyes of children with amblyopia than in normal control eyes. A thicker OS thickness is somehow related to amblyopia, and this may be a new useful diagnostic parameter for amblyopia.

Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure.

Background and aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005). Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.

Improved efficacy of cisplatin delivery by peanut agglutinin­modified liposomes in non­small cell lung cancer.

Globally, non­small cell lung cancer (NSCLC) is a significant threat to human health, and constitutes >80% of lung cancer cases. Cisplatin (CDDP), a commonly used drug in clinical treatment, has been the focus of research aiming to mitigate its potent toxicity through encapsulation within liposomes. However, challenges, such as a reduced drug loading efficiency and nonspecific release, have emerged as obstacles. The present study aimed to improve the encapsulation efficiency of CDDP within liposomes by pre­preparation of CDDP and modifying the liposome surface through the incorporation of peanut agglutinin (PNA) as a ligand [CDDP­loaded PNA­modified liposomes (CDDP­PNA­Lip)]. This strategy was designed to enhance the delivery of CDDP to tumour tissues, thereby reducing associated side effects. The effect of CDDP­PNA­Lip on the proliferation and migration of NSCLC cell lines with high MUC1 expression was elucidated through in vitro studies. Additionally, the capacity of PNA modification to augment the targeted anti­tumour efficacy of liposomes was assessed through xenograft tumour experiments. The results indicated that in an in vitro uptake assay Rhodamine B (RhB)­loaded PNA­modified liposomes were taken up by cells with ~50% higher efficiency compared with free RhB. In addition, CDDP­PNA­Lip resulted in a 2.65­fold enhancement of tumour suppression in vivo compared with free CDDP. These findings suggested that the encapsulation of CDDP within ligand­modified liposomes may significantly improve its tumour­targeting capabilities, providing valuable insights for clinical drug development.

Dynamic memristor for physical reservoir computing.

Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.

RuCo/ZrO2 Tandem Catalysts with Photothermal Confinement Effect for Enhanced CO2 Methanation.

Photothermal CO2 methanation reaction represents a promising strategy for addressing CO2-related environmental issues. The presence of efficient tandem catalytic sites with a localized high-temperature is an effective pathway to enhance the performance of CO2 methanation. Here the bimetallic RuCo nanoparticles anchored on ZrO2 fiber cotton (RuCo/ZrO2) as a photothermal catalyst for CO2 methanation are prepared. A significant photothermal CO2 methanation performance with optimal CH4 selectivity (99%) and rate (169.93 mmol gcat -1 h-1) is achieved. The photothermal energy of the RuCo bimetallic nanoparticles, confined by the infrared insulation and low thermal conductivity of the ZrO2 fiber cotton (ZrO2 FC), provides a localized high-temperature. In situ spectroscopic experiments on RuCo/ZrO2, Ru/ZrO2, and Co/ZrO2 indicate that the construction of tandem catalytic sites, where the Co site favors CO2 conversion to CO while incorporating Ru enhances CO* adsorption for subsequent hydrogenation, results in a higher selectivity toward CH4. This work opens a new insight into designing tandem catalysts with a photothermal confinement effect in CO2 methanation reaction.

Constructing Adsorption Site-Enhanced Vo-BiOCl/rGO Heterostructures for Efficient Response to NO2/NH3 Gases at Room Temperature.

Real-time detection of harmful gases at room temperature has become a serious problem in public health and environmental monitoring. Two-dimensional materials with semiconductor properties BiOCl is a promising gas-sensitive material due to its large specific surface area and adjustable band gap as well as outstanding safety characteristics. However, limited by the weak gas adsorption sites and sluggish charge-transfer ability, the performance of BiOCl could not be fully exploited. Oxygen vacancy (Vo) engineering can introduce lattice defects, thereby significantly increasing the local charge density and enhancing the adsorption of gases, which is an effective strategy to enhance the gas-sensing performance. In this work, we composite BiOCl with a vacancy (Vo-BiOCl) and reduced graphene oxide (rGO) to construct a Vo-BiOCl/rGO heterostructure with enhanced gas adsorption sites. Experimental and theoretical calculations show that Vo can enhance the adsorption of gases and the introduction of rGO forms a high-quality heterostructure with BiOCl, which can effectively reduce the band gap of BiOCl and promote electron transfer, thereby improving the sensitivity of the sensor. Benefiting from above, Vo-BiOCl/rGO achieves the ability to detect low concentrations of NO2/NH3 at room temperature, with high sensitivity (55% at 1 ppm of NO2 and -28% at 1 ppm of NH3), fast response time (40 s at 1 ppm of NO2 and 2 s at 1 ppm of NH3), good stability (over 150 days), and fully recoverable gas sensitivity.

VX-509 (Decernotinib)-modified tolerogenic dendritic cells alleviate experimental autoimmune neuritis by promoting Th17/Treg rebalance.

BACKGROUND: Guillain-Barré syndrome (GBS) is an auto-inflammatory peripheral nerve disease. Dendritic cell-mediated T cell polarization is of pivotal importance in demyelinating lesions of peripheral nerves and nerve roots. However, the regulatory function of VX-509 (Decernotinib)-modified tolerogenic dendritic cells (VX-509-tolDCs) during immune remodeling following GBS remains unclear. Here, we used experimental autoimmune neuritis (EAN) as a model to investigate these aspects of GBS. METHODS: DCs were treated with varying concentrations of VX-509 (0.25, 1, and 4 µM) or served as a control using 10-8 M 1,25-(OH)2D3. Flow cytometry was employed to assess the apoptosis, phenotype, and capacity to induce T cell responses of the treated DCs. In the in vivo experiments, EAN mice received administration of VX-509-tolDCs or 1,25-(OH)2D3-tolDCs via the tail vein at a dose of 1x106 cells/mouse on days 5, 9, 13, and 17. RESULTS: VX-509 inhibited the maturation of DCs and promoted the development of tolDCs. The function of antigen-specific CD4 + T cells ex vivo was influenced by VX-509-tolDCs. Furthermore, the adoptive transfer of VX-509-tolDCs effectively alleviated inflammatory demyelinating lesions in EAN by promoting Th17/Treg (T helper 17 and regulatory T cells) rebalance. CONCLUSION: The adoptive transfer of VX-509-tolDCs alleviated inflammatory demyelinating lesions in a mouse model of GBS, known as the EAN mouse, by partially restoring the balance between Treg and Th17 cells.

Hypoxia-induced Semaphorin 3A promotes the development of endometriosis through regulating macrophage polarization.

BACKGROUND: Semaphorin 3A (Sema3A) is a member of neural guidance factor family well-known for inducing the collapse of nerve cell growth cone and regulating nerve redistribution. It also has been characterized as an immunoregulatory and tumor promoting factor. Our previous study showed that Sema3A was involved in the regulation of sympathetic innervation and neuropathic pain of endometriosis. Nevertheless, the role of Sema3A in the development of endometriosis and its potential upstreaming factor are still not clear. METHODS: Histology experiments were carried to detect the expression of Sema3A, hypoxia -inducible factor 1α (HIF-1α) and the distribution of macrophages. Cell experiments were used to explore the effect of Sema3A on the proliferation and migration of endometrial stromal cells (ESCs) and to confirm the regulatory action of HIF-1α on Sema3A. In vivo experiments were carried out to explore the role of Sema3A on the development of endometriosis. RESULTS: Sema3A was highly expressed in endometriotic lesions and could enhanced the proliferation and migration abilities of ESCs. Aberrant macrophage distribution was found in endometriotic lesions. Sema3A also promoted the differentiation of monocytes into anti-inflammatory macrophages, so indirectly mediating the proliferation and migration of ESCs. Hypoxic microenvironment induced Sema3A mRNA and protein expression in ESCs via HIF-1α. Administration of Sema3A promoted the development of endometriosis in a mouse model. CONCLUSIONS: Sema3A, which is regulated by HIF-1α, is a promoting factor for the development of endometriosis. Targeting Sema3A may be a potential treatment strategy to control endometriotic lesions.

From macroautophagy to mitophagy: Unveiling the hidden role of mitophagy in gastrointestinal disorders.

In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

Demineralized Frozen-dried Allogeneic Bone Blocks with Suture Fixation Technique for reconstruction of maxillary alveolar bone deficiency: A Case Series.

PURPOSE: This study aims to evaluate the clinical outcomes of using demineralized freeze-dried allogeneic bone blocks (DFDABB) combined with the periosteal vertical mattress suture (PVMS) technique for the reconstruction of severe horizontal alveolar bone deficiencies in the maxilla. METHOD: In continuous horizontal maxillary defects cases, bone augmentation was performed using DFDABB and deproteinized bovine bone matrix (DBBM) filling the interstice. Subsequently, a resorbable collagen membrane was carefully placed over the graft surface, and both the membrane and bone graft were firmly secured using the periosteal vertical mattress suture technique (PVMS). Linear changes were assessed through superimposed cone-beam computed tomography (CBCT) scans obtained before the operation and after a healing period of 6-10 months. RESULTS: A total of 7 female patients with ten bone blocks and 13 implants were included in this study. One of the wounds was slightly ruptured postoperatively without infection, and all implants showed successful osseointegration. The average alveolar ridge width at a point 5 mm below the crest was 4.52 ± 2.03 mm before bone graft and 9.79 ± 1.57 mm after implantation, with an average increase of 5.26 ± 1.97 mm. Similarly, at a point 10 mm below the crest, the pre-graft alveolar ridge width measured 7.23 ± 3.60 mm, and post-implantation, it expanded to 11.81 ± 2.90 mm, showing an average gain of 4.58 ± 2.01 mm. CONCLUSION: This case series demonstrates the successful application of DFDABB combined with the PVMS technique to achieve adequate bone width for implantation at severe continuous horizontal bone deficiency of the maxilla. DFDABB with the PVMS technique resulted in superior horizontal bone gain during maxillary bone augmentation with horizontal continuity deficiency. However, further studies are necessary to validate these findings.

Establishment of a prognostic model for pancreatic cancer based on vesicle-mediated transport protein-related genes.

This study attempted to build a prognostic riskscore model for pancreatic cancer (PC) patients based on vesicle-mediated transport protein-related genes (VMTGs). We initially conducted differential expression analysis and Cox regression analysis, followed by the construction of a riskscore model to classify PC patients into high-risk (HR) and low-risk (LR) groups. The GEO GSE62452 dataset further validated the model. Kaplan-Meier survival analysis was employed to analyze the survival rate of the HR group and LR group. Cox analysis confirmed the independent prognostic ability of the riskscore model. Additionally, we evaluated immune status in both HR and LR groups, utilizing data from the GDSC database to predict drug response among PC patients. We identified six PC-specific genes from 724 VMTGs. Survival analysis revealed that the survival rate of the HR group was lower than that of the LR group (P<0.05). Cox analysis confirmed that the prognostic riskscore model could independently predict the survival status of PC patients (P<0.001). Immunological analysis revealed that the ESTIMATE score, immune score, and stroma score of the HR group were considerably lower than those of the LR group, and the tumor purity score of the HR group was higher. The IC50 values of Gemcitabine, Irinotecan, Oxaliplatin, and Paclitaxel in the LR group were considerably lower than those in the HR group (P<0.001). In summary, the VMTG-based prognostic riskscore model could stratify PC risk and effectively predict the survival of PC patients.

Preoperative prediction of high-grade osteosarcoma response to neoadjuvant therapy based on a plain CT radiomics model: A dual-center study.

Objective: To develop a model combining clinical and radiomics features from CT scans for a preoperative noninvasive evaluation of Huvos grading of neoadjuvant chemotherapy in patients with HOS. Methods: 183 patients from center A and 42 from center B were categorized into training and validation sets. Features derived from radiomics were obtained from unenhanced CT scans.Following dimensionality reduction, the most optimal features were selected and utilized in creating a radiomics model through logistic regression analysis. Integrating clinical features, a composite clinical radiomics model was developed, and a nomogram was constructed. Predictive performance of the model was evaluated using ROC curves and calibration curves. Additionally, decision curve analysis was conducted to assess practical utility of nomogram in clinical settings. Results: LASSO LR analysis was performed, and finally, three selected image omics features were obtained.Radiomics model yielded AUC values with a good diagnostic effect for both patient sets (AUCs: 0.69 and 0.68, respectively). Clinical models (including sex, age, pre-chemotherapy ALP and LDH levels, new lung metastases within 1 year after surgery, and incidence) performed well in terms of Huvos grade prediction, with an AUC of 0.74 for training set. The AUC for independent validation set stood at 0.70. Notably, the amalgamation of radiomics and clinical features exhibited commendable predictive prowess in training set, registering an AUC of 0.78. This robust performance was subsequently validated in the independent validation set, where the AUC remained high at 0.75. Calibration curves of nomogram showed that the predictions were in good agreement with actual observations. Conclusion: Combined model can be used for Huvos grading in patients with HOS after preoperative chemotherapy, which is helpful for adjuvant treatment decisions.

Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based prospective study.

BACKGROUND: The current recommended starting age for gastric cancer (GC) lacks unified guideline and individualized criteria. We aimed to determine risk-stratified starting age for GC screening in China based on individuals' risk profiles, and develop an online calculator for clinical application. METHODS: In this multi-center population-based prospective study, we divided participants enrolled during 2015-2017 (n = 59,771, aged 40-69) into screened and unscreened groups and observed them for primary endpoints-GC occurrence, all-cause and GC-specific deaths. The median follow-up was 6.07 years. To determine the reference starting age, the effectiveness of GC screening was assessed by age-groups after propensity-score-matching. Further, we categorized the calculated individual risk scores (using well-established risk factors) by quantiles. Subsequently, we used age-specific 10-year cumulative risk curves to estimate the risk-stratified starting age-when the individual's risk level matches reference starting age risk threshold. RESULTS: During follow-up, 475 GC cases, 182 GC deaths and 1,860 all-cause deaths occurred. All-cause and GC-specific mortality decreased among screened individuals aged ≥45 and 50-59 years, respectively. Thus, the average population (reference) starting age was set as 50 years. The 10-year cumulative risk of GC in average population aged 50 was 1.147%. We stratified the starting age using eight risk factors, and categorized participants as low-, medium-, and high-risk individuals, whose risk-stratified starting age was 58, 50, and 46, respectively. CONCLUSION: While high-risk individuals warrant 3-5 years earlier GC screening than average population (age 50), low-risk individuals can tolerate delayed screening. Our online, personalized starting-age calculator will help risk-adapted GC screening (https://web.consultech.com.cn/gastric/#/).

Effects of Retrograde Colonic Enema Based Fecal Microbiota Transplantation in the Treatment of Childhood Constipation: A Randomized, Double-blind Controlled Trial.

OBJECTIVE: Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established although both have demonstrated potential in gastrointestinal diseases. The aim of the current study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children. METHODS: A randomized, double-blind, controlled trial with 110 children was conducted. The subjects were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements (SBMs) ≥ 3 per week were the main outcomes and the risk ratio (RR) with 95% CI was calculated. Changes in the intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms. RESULTS: At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 SBMs per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; RR: 1.364, 95% CI: 1.063-1.749; P<0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms. CONCLUSIONS: FMT enhances the efficacy of RCE and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.

TurboID-mediated proximity labeling technologies to identify virus co-receptors.

Virus receptors determine the tissue tropism of viruses and have a certain relationship with the clinical outcomes caused by viral infection, which is of great importance for the identification of virus receptors to understand the infection mechanism of viruses and to develop entry inhibitor. Proximity labeling (PL) is a new technique for studying protein-protein interactions, but it has not yet been applied to the identification of virus receptors or co-receptors. Here, we attempt to identify co-receptor of SARS-CoV-2 by employing TurboID-catalyzed PL. The membrane protein angiotensin-converting enzyme 2 (ACE2) was employed as a bait and conjugated to TurboID, and a A549 cell line with stable expression of ACE2-TurboID was constructed. SARS-CoV-2 pseudovirus were incubated with ACE2-TurboID stably expressed cell lines in the presence of biotin and ATP, which could initiate the catalytic activity of TurboID and tag adjacent endogenous proteins with biotin. Subsequently, the biotinylated proteins were harvested and identified by mass spectrometry. We identified a membrane protein, AXL, that has been functionally shown to mediate SARS-CoV-2 entry into host cells. Our data suggest that PL could be used to identify co-receptors for virus entry.

Systematic evaluation of the meat qualities of free-range chicken (Xuan-Zhou) under different ages explored the optimal slaughter age.

Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age.

Copper toxicity in the liver of broiler chicken: insights from metabolomics and AMPK-mTOR mediated autophagy perspective.

Exposure to copper (Cu) has been associated with metabolic disorders in animals and humans, but the underlying mechanism remains unclear. One-day-old broiler chickens, numbering a total of 192, were nourished with dietary intakes that contained varying concentrations of Cu, specifically 11, 110, 220, and 330 mg/kg of Cu, for a period extending over a duration of 7 wk. As a result of the study, Cu exposure resulted in vacuolization, fragmentation of mitochondria cristae, and the increase of autophagosomes in hepatocytes. Metabolomics analysis illustrated that Cu caused a total of 59 different metabolites in liver, predominantly associated with the glycerophospholipid metabolic pathway, leading to metabolic disruption. Moreover, high-Cu diet markedly reduced the levels of AMPKα1, p-AMPKα1, mTOR, and p-mTOR and enhanced the expression levels of the autophagy-related factors (Atg5, Dynein, Beclin1, and LC3-II). Overall, Cu exposure caused chicken liver injury and resulted in disturbed metabolic processes and mediated autophagy primarily through the AMPK-mTOR axis.

Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment. METHODS: The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer. RESULTS: A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group. CONCLUSIONS: High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.