Two nomograms constructed for predicting the efficacy and prognosis of advanced non­small cell lung cancer patients treated with anti­PD­1 inhibitors based on the absolute counts of lymphocyte subsets.

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.

A bibliometric analysis of acupuncture for cerebral infarction from 1993 to 2023.

Objective: This research aims to explore the trends and knowledge domain of acupuncture for cerebral infarction through bibliometrics. Methods: Publications related to acupuncture for cerebral infarction were retrieved from the Web of Science core collection database from 1993 to December 31, 2023. A domain knowledge graph was then constructed using VOSviewer, CiteSpace, GraphPad Prism, and Scimago Graphica. Results: The cumulative publication trend shows a steady increase over the years, with China being the most productive country. Notably, Europe exhibits significant close collaboration. Institutional cooperation is primarily observed among Chinese universities specializing in traditional Chinese medicine. Tao Jing is the most prolific author, with his highest number of publications is in "Stroke" journal, and Acupuncture Electro Therapeutics Research is the significant journal. Zhang SH is the most cited author, and Si QM is a prominent author in this field. Rehabilitation treatment after cerebral infarction emerges as a prevalent research focus, with nerve regeneration being a keyword. Long EZ's 1989 paper, published in the journal Stroke, holds significant importance. The prominent papers are Donnan et al. and Wu et al., which covers the following topics: "population-based study," "Baihui Acupoint," "memory deficits," "neurotrophic factor," and "randomized trial." Conclusion: This bibliometric analysis of acupuncture for cerebral infarction offers insights into the Web of Science database, delineates a knowledge map of countries, authors, institutions, cited authors, keywords, cited references in the field of acupuncture for cerebral infarction, which has a momentous guiding significance for quickly and accurately positioning the key information in the field.

Effects and mechanisms of proanthocyanidins-derived carbon dots on alleviating salt stress in rice by muti-omics analysis.

Carbon dots (CDs) with different structures were prepared by electrolysis (PE-CDs) and hydrothermal (PH-CDs) methods using proanthocyanidins as precursors. The smaller size and lower zeta potential enabled the PE-CDs treated rice seedlings to exhibit greater resistance to salt stress. The fresh weight of rice seedlings under salt stress was significantly increased by spraying CDs every other day for two weeks. PE-CDs treated group exhibited a faster electron transport rate, and the SOD activity and flavonoid content were 2.5-fold and 0.23-fold higher than those of the salt stress-treated group. Furthermore, the metabolomics and transcriptomics analysis revealed that the PsaC gene of photosystem I was significantly up-regulated under PE-CDs treatment, which accelerated electron transfer in photosystem I. The up-regulation of BX1 and IGL genes encoding indole synthesis allowed rice to enhance stress tolerance through tryptophan and benzoxazine biosynthesis pathways. These findings offer help in purposefully synthesizing CDs and boosting food production.

A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus.

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Treatment of mixed and refractory post-tuberculosis tracheobronchial stenosis with L-shaped silicone stents: case series and a literature review.

The two patients included in the study had mixed and refractory post-tuberculosis tracheobronchial stenosis (PTTS), having experienced unsuccessful interventional therapies such as balloon dilation and V-shaped stent placement before the operation. Following the secure placement of L-shaped silicone stents, examinations with a fiberbronchoscope during the first and third months post-operation revealed a significant reduction in bronchial mucosa inflammation for both patients. Additionally, the opening diameter of the upper and lower branch segments increased, and chest CT scans indicated a noticeable absorption of left pulmonary lesions. Three months post-operation, fiberbronchoscopy confirmed the stable fixation of the stent without any movement. The patients exhibited substantial improvements in pulmonary function, dyspnea index, and blood gas analysis, with no reported adverse complications. After 7 months, a follow-up fiberbronchoscope for one case revealed excellent stent fixation. Simultaneously, the chest CT scan indicated favorable re-expansion. The placement of L-shaped silicone stents proves effective in preventing displacement, alleviating airway stenosis or obstruction, and ensuring the safety and efficacy of PTTS treatment - particularly in cases where V-shaped silicone stent placement has failed. To our knowledge, this is the first study describing the L-shaped silicone stent in two patients with PTTS.

Successful treatment of severe airway narrowing due to tuberculosis using special L-shaped silicone stentsThis article tells the story of two patients who suffered from a complex lung condition called post-tuberculosis tracheobronchial stenosis (PTTS). Imagine your airways - the tubes that carry air to your lungs - getting severely scarred and narrowed due to a past bout with tuberculosis. These two patients had tried previous treatments like balloon dilation (where a small balloon is inflated inside the narrowed airway to widen it) and using V-shaped stents (flexible supports placed in the airway to keep it open), but these methods didn't provide lasting relief. In this innovative approach, doctors used L-shaped silicone stents specifically designed to fit in the affected parts of the patients' airways. After placing these stents, regular checks showed remarkable improvements. The swelling in the airway lining reduced significantly, and the openings leading to the upper and lower parts of the lungs got wider. Chest X-rays (CT scans) even showed that the patient's left lung was healing well. Three months later, the stents stayed firmly in place, and neither patient experienced any problems. Breathing became easier, lung function tests improved, and blood tests showed better oxygen levels. Seven months down the line, one patient continued to do extremely well, with the stent securely fixed and the chest scan showing good lung expansion. This groundbreaking study shows that using L-shaped silicone stents can effectively treat PTTS when other methods fail. Not only do they stay in place, preventing blockages, but they also safely and effectively alleviate narrowing of the airways. It's the first time such L-shaped stents have been used successfully in PTTS patients, offering new hope for those facing similar challenges.

Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis.

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

New Potential Energy Surface for the H + Cl2 Reaction and Quantum Dynamics Studies.

The reaction of H + Cl2 → HCl + Cl plays a crucial role in various fields. However, no previous study has investigated this reaction using accurate quantum mechanical methods. In this paper, we construct a global potential energy surface (PES) using the neural network method with more than 20,000 ab initio energies obtained by the MRCI-F12+Q method with the aug-cc-pV5Z basis and extrapolated to the complete basis set limit. The spin-orbit coupling of the Cl atom has been considered in the PES. With this new PES, product state-resolved quantum dynamics calculations for the H + Cl2 (v0 = 0, j0 = 0-2) → HCl + Cl reaction was carried out. Numerical results show that the initial rotational excitation of the Cl2 has negligible effects on the reactivity. Product state-resolved integral cross sections (ICS) and rate constants reveal that the HCl is most favorably produced in its v' = 2 vibrational state. The calculated product vibrational state-resolved and total reaction rate constants suggest that the new global PES is accurate enough, as compared with the available experimental measurements.

UV damage induces production of mitochondrial DNA fragments with specific length profiles.

UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with anti-damage antibodies and sequenced (XR-seq) to produce high resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria.

Occurrence, distribution and potential environmental risks of pollutants in aquaculture ponds during pond cleaning in Taihu Lake Basin, China.

During the process of cleaning aquaculture ponds, the drainage contributes significantly to antibiotic pollution in the surrounding water environment. Therefore, we conducted a study on the distribution of 26 antibiotics in 57 ponds within the Taihu Lake basin. The results revealed that the detection frequency of antibiotics ranged from 1.75 % to 80.7 %, with the overall detection concentrations ranging from 3.27 to 708.72 ng/L. Among them, the detection rate of 8 antibiotics exceeded 50 %. Regarding the spatial distribution, the concentration of antibiotics was relatively high in aquaculture ponds located in the Changzhou area, with the highest concentration reaching 708.72 ng/L. This observation is likely due to the large size and intensive breeding practices in Changzhou. Fish ponds exhibited a significantly higher total antibiotic concentration of 3.27 to 445.57 ng/L compared to crab ponds (13.01 to 206.30 ng/L) and shrimp ponds (23.17 to 107.40 ng/L). Quinolones and sulfonamides were the predominant antibiotic classes found in fish ponds, accounting for 51.49 % of the total antibiotic concentration. Notably, sulfamethoxazole (SMX) and enrofloxacin (ENR) exhibited the highest antibiotic concentrations. Risk assessments demonstrated that SMX, ENR, and ofloxacin (OFX) contributed significantly to ecological risks. Furthermore, the study found that the tertiary constructed wetland treatment process achieved a remarkable removal rate of 92.44 % for antibiotics in aquaculture wastewater, while other treatment processes displayed limited effectiveness in removing antibiotics. This study addresses the knowledge gap concerning antibiotic pollution during the cleaning process of aquaculture ponds within the Taihu Lake basin.

Engineering Properties and Microstructure of Soils Stabilized by Red-Mud-Based Cementitious Material.

Red mud (RM) is an industrial waste generated in the process of aluminum refinement. The recycling and reusing of RM have become urgent problems to be solved. To explore the feasibility of using RM in geotechnical engineering, this study combined magnesium oxide (MgO) (or calcium oxide (CaO)) with RM as an RM-based binder, which was then used to stabilize the soil. The physical, mechanical, and micro-structural properties of the stabilized soil were investigated. As the content of MgO or CaO in the mixture increased, the unconfined compressive strength (UCS) of the RM-based cementitious materials first increased and then decreased. For the soils stabilized with RM-MgO or RM-CaO, the UCS increased and then decreased, reaching a maximum at RM:MgO = 5:5 or RM:CaO = 8:2. The addition of sodium hydroxide (NaOH) promoted the hydration reaction. The UCS enhancement ranged from 8.09% to 66.67% for the RM-MgO stabilized soils and 204.6% to 346.6% for the RM-CaO stabilized soils. The optimum ratio of the RM-MgO stabilized soil (with NaOH) was 2:8, while that of the RM-CaO stabilized soil (with NaOH) was 4:6. Freeze-thaw cycles reduced the UCS of the stabilized soil, but the resistance of the stabilized soil to freeze-thaw erosion was significantly improved by the addition of RM-MgO or RM-CaO, and the soil stabilized with RM-MgO had better freeze-thaw resistance than that with RM-CaO. The hydrated magnesium silicate generated by the RM-MgO stabilized soil and the hydrated calcium silicate generated by the RM-CaO stabilized soil helped to improve the UCS of the stabilized soil. The freeze-thaw cycles did not weaken the formation of hydration products in the stabilized soil but could result in physical damage to the stabilized soils. The decrease in the UCS of the stabilized soil was mainly due to physical damage.

miRNA-27b-3p, let-7f-5p and miRNA-142-5p can be Used in a Novel Serum Diagnostic Panel for Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a prevalent malignant tumor affecting the urinary system. Due to its unfavorable prognosis, there is a pressing need to discover effective approaches for early diagnosis and treatment of ccRCC. Extensive research has consistently demonstrated the presence of stable microRNAs (miRNAs) in human serum. Accordingly, the objective of this study was to identify a specific panel of miRNAs in serum that can serve as a reliable and non-invasive biomarker for the early detection of ccRCC. METHODS: The study comprised of training and validation phases to identify potential biomarkers. In the training phase, a total of 10 miRNAs exhibiting the most significant differential expression among 28 ccRCC patients and 28 healthy controls (HCs) were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). In the subsequent validation phase, these 10 miRNAs were assessed in serum samples obtained from an additional 80 ccRCC patients and 84 HCs using RT-qPCR. To construct a panel with optimal diagnostic capability, backward stepwise logistic regression analysis was conducted. Furthermore, bioinformatics analysis was performed on this selected miRNA panel. RESULTS: In ccRCC patients, the serum expression level of miRNA-142-5p was found to be significantly elevated compared to healthy controls (HCs), whereas the expression levels of let-7f-5p, miRNA-27b-3p, miRNA-212-3p, and miRNA-216-5p were significantly reduced. To assess their diagnostic potential for ccRCC, receiver operating characteristic (ROC) curve analysis was performed. The analysis revealed that miRNA-27b-3p, let-7f-5p, and miRNA-142-5p exhibited moderate diagnostic capabilities for ccRCC, with area under the curve (AUC) values of 0.826, 0.828, and 0.643, respectively. To further enhance diagnostic accuracy, a final diagnostic panel consisting of these three miRNAs was constructed, demonstrating good diagnostic value with an AUC of 0.952. CONCLUSIONS: The miRNA serum biomarker panel (miRNA-27b-3p, let-7f-5p, and miRNA-142-5p) identified in this study holds promise for early, non-invasive, and accurate diagnosis of ccRCC. This panel could potentially provide a valuable tool in clinical settings to aid in the timely detection and management of ccRCC.

New Diabatic Potential Energy Surfaces for the Li + H2 Reaction and Time-Dependent Quantum Wave Packet Studies.

New global diabatic potential energy surfaces (DPESs) for the ground (12A') and first excited (22A') states for the Li + H2 system were developed, with more than 30,000 energy points at the IC-MRCI+Q level of theory, utilizing the aug-cc-pV5Z basis set for the H atoms and the cc-pCV5Z basis set for the Li atom, fitted by a single neural network (NN) with symmetry. Product state-resolved quantum dynamics calculations of the nonadiabatic reaction Li (2P) + H2 (X 1 ∑g+, v0 = 0, j0 = 0) → LiH (X 1∑+) + H(2S) were carried out using these new DPESs and also the previous HYLC-DPESs. The numerical results suggested that our newly constructed DPESs provided an accurate description of the LiH2 system.

African swine fever virus MGF505-6R attenuates type I interferon production by targeting STING for degradation.

African swine fever (ASF) is an acute hemorrhagic and devastating infectious disease affecting domestic pigs and wild boars. It is caused by the African swine fever virus (ASFV), which is characterized by genetic diversity and sophisticated immune evasion strategies. To facilitate infection, ASFV encodes multiple proteins to antagonize host innate immune responses, thereby contributing to viral virulence and pathogenicity. The molecular mechanisms employed by ASFV-encoded proteins to modulate host antiviral responses have not been comprehensively elucidated. In this study, it was observed that the ASFV MGF505-6R protein, a member of the multigene family 505 (MGF505), effectively suppressed the activation of the interferon-beta (IFN-ß) promoter, leading to reduced mRNA levels of antiviral genes. Additional evidence has revealed that MGF505-6R antagonizes the cGAS-STING signaling pathway by interacting with the stimulator of interferon genes (STING) for degradation in the autophagy-lysosomal pathway. The domain mapping revealed that the N-terminal region (1-260aa) of MGF505-6R is the primary domain responsible for interacting with STING, while the CTT domain of STING is crucial for its interaction with MGF505-6R. Furthermore, MGF505-6R also inhibits the activation of STING by reducing the K63-linked polyubiquitination of STING, leading to the disruption of STING oligomerization and TANK binding kinase 1 (TBK1) recruitment, thereby impairing the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3). Collectively, our study elucidates a novel strategy developed by ASFV MGF505-6R to counteract host innate immune responses. This discovery may offer valuable insights for further exploration of ASFV immune evasion mechanisms and antiviral strategies.

Product State-Resolved Reactive Scattering Studies of the H + Cl2 (v0 = 1-3, j0 = 0) → HCl + Cl Reaction by the Time-Dependent Wave Packet Method.

The typical hydrogen atom plus halogen molecule reaction H + Cl2 → HCl + Cl has implications across many fields. In this paper, product state-resolved quantum dynamics calculations for the vibrationally excited reaction H + Cl2 (v0 = 1-3, j0 = 0) → HCl + Cl were conducted using the time-dependent wave packet method on a newly developed accurate potential energy surface. Numerical results indicate that the initial vibrational excitation of Cl2 does enhance the reactivity for this early barrier reaction, although less than the enhancement of the translational energy. The calculated product vibrational state-resolved integral cross sections and rate constants reveal that the product vibrational state distribution and the initial vibrational state of Cl2 are highly correlated. The thermal rate constant in the temperature range from 100 to 1000 K was given and is found to be in reasonable agreement with the experimental measurements.

A porcine kidney-derived clonal cell line with clear genetic annotation is highly susceptible to African swine fever virus.

African Swine Fever virus (ASFV), the causative agent of African swine fever, is a highly lethal hemorrhagic virus affecting domestic pigs and wild boars. The primary target cells for ASFV infection are porcine alveolar macrophages (PAMs), which are difficult to obtain and maintain in vitro, and less subjective to genetic editing. To overcome these issues and facilitate ASFV research, we obtained a subclonal cell line PK1-C5 by subcloning LLC-PK1 cells that support stable ASFV proliferation. This consequential cell line exhibited high ASFV infection levels and similar viral growth characteristics to PAMs, while also allowing high-efficiency genomic editing through transfection or lentivirus transduction of Cas9. Taken together, our study provided a valuable tool for research aspects including ASFV-host interactions, pathogenicity, and vaccine development.

Local Tumor Progression Predictive Model Based on MRI for Colorectal Cancer Liver Metastases after Radiofrequency Ablation.

PURPOSE: To investigate the post-radiofrequency ablation (RFA) magnetic resonance imaging (MRI) characteristics in patients with liver metastases from colorectal cancer and to build a predictive model for local tumor progression based on these imaging markers. MATERIALS AND METHODS: A cohort of 73 patients with 110 colorectal cancer liver metastases (CRCLM) who underwent RFA and MRI one month post-ablation was included in image signs analysis and predictive model training. Using a newly developed MRI appearance scoring criteria, MR Image Appearance Scoring at One Month after RFA (MRIAS 1MO), the semi-quantitative analysis of MRI findings within the ablation zone were conducted independently by two radiologists. The intraclass correlation coefficient (ICC) was calculated to evaluate measurement reliability. Differences in MRIAS 1MO scores were compared using Mann-Whitney U test, focusing on local tumor response outcomes. Using local tumor progression (LTP) as the primary end point, MRIAS 1MO scores and other lesion morphological and clinical characteristics were included to establish predictive model. Predication accuracy was subsequently evaluated using calibration curve, time-dependent concordance index (C index) curve, and LTP-free survival (LTPFS) curve. Another cohort comprising 60 patients with 76 CRCLMs provided additional MRIAS 1MO scores and clinical data associated with LTP. We evaluated the performance of the established predictive model using calibration curve, time-dependent C index curve, and LTPFS curve. RESULTS: The MRIAS 1MO criteria exhibited strong measurement reliability. The ICC values of T1S (scores from T1WI), T2S (scores form T2WI) and NCES (scores by adding T1S to T2S) MRIS (the overall scores) were 0.825, 0.779, 0.826 and 0.873, respectively. Lesions with LTP showed significantly higher median values for the overall MRIAS 1MO score (MRIS) compared to lesions without LTP (16 vs. 12, p < 0.001). MRIS and lesion diameter were independent prognostic factors of LTP and were included in predictive model (hazard ratio: MRIS over 13.5:4.275, lesion diameter larger than 30 mm: 2.056). The predictive model demonstrated an overall C index of 0.721 and risk stratification using the predictive model resulted in significantly different LPTFS times. In the validation cohort, the C index were 0.825, 0.794 and 0.764 at six, twelve and twenty-four months, respectively. Patients classified as high-risk in the validation cohort had a median LTPFS time of 10.0 months, while the median LTPFS time was not reached in the low-risk group. CONCLUSIONS: The semi-quantitative MRIAS 1MO criteria, used for post-RFA MRI appearance analysis, exhibited strong measurement reliability. Prediction models established based on overall MRIAS 1MO score (MRIS) and lesion diameter had good predictive performance for LTP in patients undergoing RFA for CRCLM treatment.

Anti-Coronavirus Potential of Polyether Ionophores: The New Application of Veterinary Antibiotics in Livestock.

Coronaviruses have consistently posed a major global concern in the field of livestock industry and public health. However, there is currently a lack of efficient drugs with broad-spectrum antiviral activity to address the challenges presented by emerging mutated strains or drug resistance. Additionally, the method for identifying multitarget drugs is also insufficient. Aminopeptidase N (APN) and 3C-like proteinase (3CLpro) represent promising targets for host-directed and virus-directed strategies, respectively, in the development of effective drugs against various coronaviruses. In this study, maduramycin ammonium demonstrated a broad-spectrum antiviral effect by targeting both of the proteins. The binding domains 4 Å from the ligand of both target proteins shared a structural similarity, suggesting that screening and designing drugs based on these domains might exhibit broad-spectrum and highly effective antiviral activity. Furthermore, it was identified that the polyether ionophores' ability to carry zinc ion might be one of the reasons why they were able to target APN and exhibit antiviral effect. The findings of this experiment provide novel perspectives for future drug screening and design, while also offering valuable references for the utilization of polyether ionophores in the management of livestock health.

ARF6 promotes Streptococcus suis suilysin induced apoptosis in HBMECs.

Streptococcus suis (S. suis) is a significant zoonotic microorganism that causes a severe illness in both pigs and humans and is characterized by severe meningitis and septicemia. Suilysin (SLY), which is secreted by S. suis, plays a crucial role as a virulence factor in the disease. To date, the interaction between SLY and host cells is not fully understood. In this study, we identified the interacting proteins between SLY and human brain microvascular endothelial cells (HBMECs) using the TurboID-mediated proximity labeling method. 251 unique proteins were identified in TurboID-SLY treated group, of which six plasma membrane proteins including ARF6, GRK6, EPB41L5, DSC1, TJP2, and PNN were identified. We found that the proteins capable of interacting with SLY are ARF6 and PNN. Subsequent investigations revealed that ARF6 substantially increased the invasive ability of S. suis in HBMECs. Furthermore, ARF6 promoted SLY-induced the activation of p38 MAPK signaling pathway in HBMECs. Moreover, ARF6 promoted the apoptosis in HBMECs through the activation of p38 MAPK signaling pathway induced by SLY. Finally, we confirmed that ARF6 could increase the virulence of SLY in C57BL/6 mice. These findings offer valuable insights that contribute to a deeper understanding of the pathogenic mechanism of SLY.

Habitat-based radiomics analysis for evaluating immediate response in colorectal cancer lung metastases treated by radiofrequency ablation.

PURPOSE: To create radiomics signatures based on habitat to assess the instant response in lung metastases of colorectal cancer (CRC) after radiofrequency ablation (RFA). METHODS: Between August 2016 and June 2019, we retrospectively included 515 lung metastases in 233 CRC patients who received RFA (412 in the training group and 103 in the test group). Multivariable analysis was performed to identify independent risk factors for developing the clinical model. Tumor and ablation regions of interest (ROI) were split into three spatial habitats through K-means clustering and dilated with 5 mm and 10 mm thicknesses. Radiomics signatures of intratumor, peritumor, and habitat were developed using the features extracted from intraoperative CT data. The performance of these signatures was primarily evaluated using the area under the receiver operating characteristics curve (AUC) via the DeLong test, calibration curves through the Hosmer-Lemeshow test, and decision curve analysis. RESULTS: A total of 412 out of 515 metastases (80%) achieved complete response. Four clinical variables (cancer antigen 19-9, simultaneous systemic treatment, site of lung metastases, and electrode type) were utilized to construct the clinical model. The Habitat signature was combined with the Peri-5 signature, which achieved a higher AUC than the Peri-10 signature in the test set (0.825 vs. 0.816). The Habitat+Peri-5 signature notably surpassed the clinical and intratumor radiomics signatures (AUC: 0.870 in the test set; both, p < 0.05), displaying improved calibration and clinical practicality. CONCLUSIONS: The habitat-based radiomics signature can offer precise predictions and valuable assistance to physicians in developing personalized treatment strategies.

Heterologous expression of taxane genes confers resistance to fall armyworm in Nicotiana benthamiana.

KEY MESSAGE: Taxadiene synthase, taxadiene-5α-hydroxylase, and taxane 13α-hydroxylase genes were introduced into Nicotiana benthamiana, and the improved resistance to lepidoptera pest fall armyworm was reported. Fall armyworm (FAW) is a serious agricultural pest. Genetic engineering techniques have been used to create pest-resistant plant varieties for reducing pest damage. Paclitaxel is a diterpenoid natural metabolite with antineoplastic effects in medicine. However, the effects of taxanes on the growth and development of lepidoptera pests, such as the FAW, are unknown. Here, selected paclitaxel precursor biosynthesis pathway genes, taxadiene synthase, taxane 5α-hydroxylase, and taxane 13α-hydroxylase, were engineered in the heterologous host Nicotiana benthamiana plants. Bioassay experiments showed that the transgenic N. benthamiana plants displayed improved resistance to FAW infestation, with degeneration of gut tissues and induced expression of apoptosis-related genes. Cytotoxicity experiment showed that the paclitaxel precursor, 10-deacetylbaccatin III, is cytotoxic to Sf9 cells, causing cell cycle arrest at the G2/M phase and disorder of the cytoskeleton. Metabolome analysis showed that heterologous expression of taxane genes in N. benthamiana affected the digestive system, steroid hormone and purine metabolism pathways of FAW larvae. In summary, this study provides a candidate approach for FAW control.