Prognostic value of genomic mutation signature associated with immune microenvironment in southern Chinese patients with esophageal squamous cell carcinoma.

The genomic landscape of esophageal squamous cell cancer (ESCC), as well as its impact on the regulation of immune microenvironment, is not well understood. Thus, tumor samples from 92 patients were collected from two centers and subjected to targeted-gene sequencing. We identified frequently mutated genes, including TP53, KMT2C, KMT2D, LRP1B, and FAT1. The most frequent mutation sites were ALOX12B (c.1565C > T), SLX4 (c.2786C > T), LRIG1 (c.746A > G), and SPEN (c.6915_6917del) (6.5%). Pathway analysis revealed dysregulation of cell cycle regulation, epigenetic regulation, PI3K/AKT signaling, and NOTCH signaling. A 17-mutated gene-related risk model was constructed using random survival forest analysis and showed significant prognostic value in both our cohort and the validation cohort. Based on the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE) algorithm, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, and the MCPcounter algorithm, we found that the risk score calculated by the risk model was significantly correlated with stimulatory immune checkpoints (TNFSF4, ITGB2, CXCL10, CXCL9, and BTN3A1; p < 0.05). Additionally, it was significantly associated with markers that are important in predicting response to immunotherapy (CD274, IFNG, and TAMM2; p < 0.05). Furthermore, the results of immunofluorescence double staining showed that patients with high risk scores had a significantly higher level of M2 macrophage than those with low risk scores (p < 0.05). In conclusion, our study provides insights into the genomic landscape of ESCC and highlights the prognostic value of a genomic mutation signature associated with the immune microenvironment in southern Chinese patients with ESCC.

Oligo-residual disease in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer: incidence, pattern of failure, and clinical value of local consolidative therapy.

OBJECTIVES: To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients with measurable disease in three academic centers were screened and those with adequate follow-up were included. Oligo-residual disease (ORD) was defined as residual tumors limited to three organs and five lesions evaluated at the best response among patients with partial response or stable disease after PD-1/PD-L1 inhibitors. Oligometastatic and multiple-metastatic disease (OMD/MMD) were similarly classified at baseline. Locoregional interventions, administered after effective treatment of PD-1/PD-L1 inhibitors and before initial disease progression, were defined as LCT. Patterns of initial progressive disease (PD) were classified as involving only residual sites (RP), only new sites (NP), or a combination of both (BP). RESULTS: Among the 698 patients included, ORD was documented in 73 (47.1%) of 155 patients with baseline OMD and 60 (11.0%) of 543 patients with baseline MMD. With a median follow-up of 31.0 (range, 6.0-53.0) months, 108 patients with ORD developed initial PD, with RP, NP, and BP occurring in 51 (47%), 23 (21.3%), and 34 (31.5%), respectively. Among the 133 patients with ORD, those receiving LCT (n = 43) had longer progression-free survival (HR = 0.58, 95% CI 0.40-0.85, p = 0.01) and overall survival (HR = 0.49, 95% CI 0.30-0.79, p < 0.0001). CONCLUSION: ORD occurs with a clinically relevant frequency among PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients and LCT may provide extra survival benefits in those with ORD.

Reduction of flavonoid content in honeysuckle via Erysiphe lonicerae-mediated inhibition of three essential genes in flavonoid biosynthesis pathways.

Honeysuckle, valued for its wide-ranging uses in medicine, cuisine, and aesthetics, faces a significant challenge in cultivation due to powdery mildew, primarily caused by the Erysiphe lonicerae pathogen. The interaction between honeysuckle and E. lonicerae, especially concerning disease progression, remains insufficiently understood. Our study, conducted in three different locations, found that honeysuckle naturally infected with E. lonicerae showed notable decreases in total flavonoid content, with reductions of 34.7%, 53.5%, and 53.8% observed in each respective site. Controlled experiments supported these findings, indicating that artificial inoculation with E. lonicerae led to a 20.9% reduction in flavonoid levels over 21 days, worsening to a 54.8% decrease by day 42. Additionally, there was a significant drop in the plant's total antioxidant capacity, reaching an 81.7% reduction 56 days after inoculation. Metabolomic analysis also revealed substantial reductions in essential medicinal components such as chlorogenic acid, luteolin, quercetin, isoquercetin, and rutin. Investigating gene expression revealed a marked decrease in the relative expression of the LjPAL1 gene, starting as early as day 7 post-inoculation and falling to a minimal level (fold change = 0.29) by day 35. This trend was mirrored by a consistent reduction in phenylalanine ammonia-lyase activity in honeysuckle through the entire process, which decreased by 72.3% by day 56. Further analysis showed significant and sustained repression of downstream genes LjFNHO1 and LjFNGT1, closely linked to LjPAL1. We identified the mechanism by which E. lonicerae inhibits this pathway and suggest that E. lonicerae may strategically weaken the honeysuckle's disease resistance by targeting key biosynthetic pathways, thereby facilitating further pathogen invasion. Based on our findings, we recommend two primary strategies: first, monitoring medicinal constituent levels in honeysuckle from E. lonicerae-affected areas to ensure its therapeutic effectiveness; and second, emphasizing early prevention and control measures against honeysuckle powdery mildew due to the persistent decline in crucial active compounds.

Integrated Hfq-interacting RNAome and transcriptomic analysis reveals complex regulatory networks of nitrogen fixation in root-associated Pseudomonas stutzeri A1501.

The RNA chaperone Hfq acts as a global regulator of numerous biological processes, such as carbon/nitrogen metabolism and environmental adaptation in plant-associated diazotrophs; however, its target RNAs and the mechanisms underlying nitrogen fixation remain largely unknown. Here, we used enhanced UV cross-linking immunoprecipitation coupled with high-throughput sequencing to identify hundreds of Hfq-binding RNAs probably involved in nitrogen fixation, carbon substrate utilization, biofilm formation, and other functions. Collectively, these processes endow strain A1501 with the requisite capabilities to thrive in the highly competitive rhizosphere. Our findings revealed a previously uncharted landscape of Hfq target genes. Notable among these is nifM, encoding an isomerase necessary for nitrogenase reductase solubility; amtB, encoding an ammonium transporter; oprB, encoding a carbohydrate porin; and cheZ, encoding a chemotaxis protein. Furthermore, we identified more than 100 genes of unknown function, which expands the potential direct regulatory targets of Hfq in diazotrophs. Our data showed that Hfq directly interacts with the mRNA of regulatory proteins (RsmA, AlgU, and NifA), regulatory ncRNA RsmY, and other potential targets, thus revealing the mechanistic links in nitrogen fixation and other metabolic pathways. IMPORTANCE: Numerous experimental approaches often face challenges in distinguishing between direct and indirect effects of Hfq-mediated regulation. New technologies based on high-throughput sequencing are increasingly providing insight into the global regulation of Hfq in gene expression. Here, enhanced UV cross-linking immunoprecipitation coupled with high-throughput sequencing was employed to identify the Hfq-binding sites and potential targets in the root-associated Pseudomonas stutzeri A1501 and identify hundreds of novel Hfq-binding RNAs that are predicted to be involved in metabolism, environmental adaptation, and nitrogen fixation. In particular, we have shown Hfq interactions with various regulatory proteins' mRNA and their potential targets at the posttranscriptional level. This study not only enhances our understanding of Hfq regulation but, importantly, also provides a framework for addressing integrated regulatory network underlying root-associated nitrogen fixation.

A high-performance organic lithium salt-doped OFET with the optical radical effect for photoelectric pulse synaptic simulation and neuromorphic memory learning.

Simulation of synaptic characteristics is essential for the application of organic field effect transistors (OFETs) in neural morphology. Although excellent performance, including bias stability and mobility, as well as photoelectric pulse synaptic simulation, has been achieved in SiO2-gated OFETs with PDVT-10 as an organic channel, there are relatively few studies on photoelectric pulse synaptic simulation of electrolyte-gated OFETs based on environmentally friendly and low-voltage operation. Herein, synaptic transistors based on organic semiconductors are reported to simulate the photoelectric pulse response by developing solution-based organic semiconductor PDVT-10, and polyvinyl alcohol (PVA) with an electric double layer (EDL) effect to act as a channel and gate dielectric layer, respectively, and organic lithium salt-doped PVA is used to enhance the EDL effect. The presence of electrical pulses in doped devices not only achieves basic electrical synaptic characteristics, but also significantly realizes the long-term characteristics, pain perception, memory and sensitization applications. Furthermore, the introduction of photoinitiator molecules into the channel layer leads to improved photosynaptic performances by using light-induced free radicals, and the photoelectric synergistic effect has been actualized by introducing heterojunction architecture. This work provides promising prospects for achieving photoelectric pulse modulation based on organic synaptic devices, which shows great potential for the development of artificial intelligence.

Characterisation of a Novel Insect-Specific Virus Discovered in Rice Thrips, Haplothrips aculeatus.

Insects constitute the largest proportion of animals on Earth and act as significant reservoirs and vectors in disease transmission. Rice thrips (Haplothrips aculeatus, family Phlaeothripidae) are one of the most common pests in agriculture. In this study, the full genome sequence of a novel Ollusvirus, provisionally named "Rice thrips ollusvirus 1" (RTOV1), was elucidated using transcriptome sequencing and the rapid amplification of cDNA ends (RACE). A homology search and phylogenetic tree analysis revealed that the newly identified virus is a member of the family Aliusviridae (order Jingchuvirales). The genome of RTOV1 contains four predicted open reading frames (ORFs), including a polymerase protein (L, 7590 nt), a glycoprotein (G, 4206 nt), a nucleocapsid protein (N, 2415 nt) and a small protein of unknown function (291 nt). All of the ORFs are encoded by the complementary genome, suggesting that the virus is a negative-stranded RNA virus. Phylogenetic analysis using polymerase sequences suggested that RTOV1 was closely related to ollusvirus 1. Deep small RNA sequencing analysis reveals a significant accumulation of small RNAs derived from RTOV1, indicating that the virus replicated in the insect. According to our understanding, this is the first report of an Ollusvirus identified in a member of the insect family Phlaeothripidae. The characterisation and discovery of RTOV1 is a significant contribution to the understanding of Ollusvirus diversity in insects.

Interactions between the gut bacterial community of Exopalaemon carinicauda and infection by Enterocytozoon hepatopenaei.

To explore the relationship between the intestinal flora of Exopalaemon Carinicauda and infection by Enterocytozoo Hepatopenaei (EHP), we analyzed the species and richness of gut microbiota in infected individuals in different EHP load groups [i.e., control (C), high load (H), and low load (L)] using gene sequencing after infection. The results showed that the abundance of intestinal flora in the high-load EHP group was significantly lower than that in the healthy group. Based on the UPGMA cluster tree and PCoA analysis, with comparisons to healthy shrimp, the gut microbiota of the EHP high load and low load groups were clustered into one branch, which indicated that EHP infection changed the composition of the gut microbiota of infected shrimps. The heat map analysis of species abundance clustering revealed that the dominant bacteria in the low EHP load group and the control group were beneficial genera such as Lactococcus, Ligilactobacillius, and Bifidobacterium, but the dominant bacteria in the high EHP load group were harmful genera such as Pseudomonas, Photobacterium, and Candidatus hepatincola. The functions of the intestinal flora predicted that most genes related to metabolism were more abundant in healthy shrimp, most genes related to metabolism and the organisms' system were more abundant in the low EHP load group, and most genes related to diseases and environmental information processing were more abundant in the high EHP load group. After separation and purification, the dominant bacteria (Bifidobacterium animalis in healthy shrimp and Lactococcus garvieae in the low EHP load group) and the non-dominant bacteria (Macrococus caseolyticus in the low EHP load group) were obtained. Each of these isolated strains were used together with EHP to infect E. carinicauda, and the results showed that Bifidobacterium animali and Lactococcus garvieae significantly reduced the EHP load in EHP-infected individuals. At the same time, the morphology and structure of the hepatopancreas and intestinal tissue of EHP-infected E. carinicauda were improved. No improvement was seen in tissue that was infected with Macrococus caseolyticus.

Cochlear implantation for rare Streptococcus suis meningitis with hearing loss.

OBJECTIVES: This study aimed to explore the diagnostic sensitivity of 3D heavily weighted T2-weighted MRI (T2MRI) and high-resolution computed tomography (HRCT) in patients with cochlear fibrosis associated with Streptococcus suis (S. suis) meningitis and the practicality of Cochlear implantation (CI) treatments. METHODS: Between January 2020 and December 2022, we enrolled four patients with rare cochlear S. suis meningitis with associated hearing loss despite aggressive or non-aggressive follow-up antibiotic treatment. Clinical imaging data, surgical performances and post-surgical-electrode impedance were evaluated. RESULTS: Combined with HRCT and T2MRI, the cochlea had varying degrees of fibrosis and ossification in different cases. However, the electrodes were successfully and wholly inserted after intraoperative removal of the ossified and fibrotic foci. Post-surgical electrode impedance values of MP1 + 2 mode were normal in all 4 cases at initial activation. CONCLUSION: In patients with S. suis meningitis and associated cochlear fibrosis, T2MRI examination of the inner ear was more sensitive than HRCT. This research highlights the feasibility of CI treatment in S. suis meningitis patients with severe cochlear fibrosis.

Long Non-Coding RNA Analysis: Severe Pathogenicity in Chicken Embryonic Visceral Tissues Infected with Highly Virulent Newcastle Disease Virus-A Comparison to the Avirulent Vaccine Virus.

There are significant variations in pathogenicity among different virulent strains of the Newcastle disease virus (NDV). Virulent NDV typically induces severe pathological changes and high mortality rates in infected birds, while avirulent NDV usually results in asymptomatic infection. Currently, the understanding of the specific mechanisms underlying the differences in host pathological responses and symptoms caused by various virulent NDV strains remains limited. Long non-coding RNA (lncRNA) can participate in a range of biological processes and plays a crucial role in viral infection and replication. Therefore, this study employed RNA-Seq to investigate the transcriptional profiles of chicken embryos' visceral tissues (CEVTs) infected with either the virulent NA-1 strain or avirulent LaSota strain at 24 hpi and 36 hpi. Using bioinformatic methods, we obtained a total of 2532 lncRNAs, of which there were 52 and 85 differentially expressed lncRNAs at 24 hpi and 36 hpi, respectively. LncRNA analysis revealed that the severe pathological changes and symptoms induced by virulent NDV infection may be partially attributed to related target genes, regulated by differentially expressed lncRNAs such as MSTRG.1545.5, MSTRG.14601.6, MSTRG.7150.1, and MSTRG.4481.1. Taken together, these findings suggest that virulent NDV infection exploits the host's metabolic resources and exerts an influence on the host's metabolic processes, accompanied by excessive activation of the immune response. This impacts the growth and development of each system of CEVTs, breaches the blood-brain barrier, inflicts severe damage on the nervous system, and induces significant lesions. These observations may be attributed to variations in pathology. Consequently, novel insights were obtained into the intricate regulatory mechanisms governing NDV and host interactions. This will aid in unraveling the molecular mechanisms underlying both virulent and avirulent forms of NDV infection.

Effects of Telemedicine on Informal Caregivers of Patients in Palliative Care: Systematic Review and Meta-Analysis.

Background: Telemedicine technology is a rapidly developing field that shows immense potential for improving medical services. In palliative care, informal caregivers assume the primary responsibility in patient care and often face challenges such as increased physical and mental stress and declining health. In such cases, telemedicine interventions can provide support and improve their health outcomes. However, research findings regarding the use of telemedicine among informal caregivers are controversial, and the efficacy of telemedicine remains unclear. Objective: This study aimed to evaluate the impacts of telemedicine on the burden, anxiety, depression, and quality of life of informal caregivers of patients in palliative care. Methods: A systematic literature search was conducted using the PubMed, Embase, Web of Science, CENTRAL, PsycINFO, CINAHL Plus with Full Text, CBM, CNKI, WanFang, and VIP databases to identify relevant randomized controlled trials published from inception to March 2023. Two authors independently screened the studies and extracted the relevant information. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Intervention effects were estimated and sensitivity analysis was conducted using Review Manager 5.4, whereas 95% prediction intervals (PIs) were calculated using R (version 4.3.2) and RStudio. Results: A total of 9 randomized controlled trials were included in this study. The meta-analysis indicated that telemedicine has reduced the caregiving burden (standardized mean differences [SMD] -0.49, 95% CI -0.72 to -0.27; P<.001; 95% PI -0.86 to -0.13) and anxiety (SMD -0.23, 95% CI -0.40 to -0.06; P=.009; 95% PI -0.98 to 0.39) of informal caregivers; however, it did not affect depression (SMD -0.21, 95% CI -0.47 to 0.05; P=.11; 95% PI -0.94 to 0.51) or quality of life (SMD 0.35, 95% CI -0.20 to 0.89; P=.21; 95% PI -2.15 to 2.85). Conclusions: Although telemedicine can alleviate the caregiving burden and anxiety of informal caregivers, it does not significantly reduce depression or improve their quality of life. Further high-quality, large-sample studies are needed to validate the effects of telemedicine. Furthermore, personalized intervention programs based on theoretical foundations are required to support caregivers.

MoViT: Memorizing Vision Transformers for Medical Image Analysis.

The synergy of long-range dependencies from transformers and local representations of image content from convolutional neural networks (CNNs) has led to advanced architectures and increased performance for various medical image analysis tasks due to their complementary benefits. However, compared with CNNs, transformers require considerably more training data, due to a larger number of parameters and an absence of inductive bias. The need for increasingly large datasets continues to be problematic, particularly in the context of medical imaging, where both annotation efforts and data protection result in limited data availability. In this work, inspired by the human decision-making process of correlating new "evidence" with previously memorized "experience", we propose a Memorizing Vision Transformer (MoViT) to alleviate the need for large-scale datasets to successfully train and deploy transformer-based architectures. MoViT leverages an external memory structure to cache history attention snapshots during the training stage. To prevent overfitting, we incorporate an innovative memory update scheme, attention temporal moving average, to update the stored external memories with the historical moving average. For inference speedup, we design a prototypical attention learning method to distill the external memory into smaller representative subsets. We evaluate our method on a public histology image dataset and an in-house MRI dataset, demonstrating that MoViT applied to varied medical image analysis tasks, can outperform vanilla transformer models across varied data regimes, especially in cases where only a small amount of annotated data is available. More importantly, MoViT can reach a competitive performance of ViT with only 3.0% of the training data. In conclusion, MoViT provides a simple plug-in for transformer architectures which may contribute to reducing the training data needed to achieve acceptable models for a broad range of medical image analysis tasks.

A High-Performance and Durable Direct-Ammonia Symmetrical Solid Oxide Fuel Cell with Nano La0.6Sr0.4Fe0.7Ni0.2Mo0.1O3-δ-Decorated Doped Ceria Electrode.

Solid oxide fuel cells (SOFCs) offer a significant advantage over other fuel cells in terms of flexibility in the choice of fuel. Ammonia stands out as an excellent fuel choice for SOFCs due to its easy transportation and storage, carbon-free nature and mature synthesis technology. For direct-ammonia SOFCs (DA-SOFCs), the development of anode catalysts that have efficient catalytic activity for both NH3 decomposition and H2 oxidation reactions is of great significance. Herein, we develop a Mo-doped La0.6Sr0.4Fe0.8Ni0.2O3-δ (La0.6Sr0.4Fe0.7Ni0.2Mo0.1O3-δ, LSFNM) material, and explore its potential as a symmetrical electrode for DA-SOFCs. After reduction, the main cubic perovskite phase of LSFNM remained unchanged, but some FeNi3 alloy nanoparticles and a small amount of SrLaFeO4 oxide phase were generated. Such reduced LSFNM exhibits excellent catalytic activity for ammonia decomposition due to the presence of FeNi3 alloy nanoparticles, ensuring that it can be used as an anode for DA-SOFCs. In addition, LSFNM shows high oxygen reduction reactivity, indicating that it can also be a cathode for DA-SOFCs. Consequently, a direct-ammonia symmetrical SOFC (DA-SSOFC) with the LSFNM-infiltrated doped ceria (LSFNM-SDCi) electrode delivers a superior peak power density (PPD) of 487 mW cm-2 at 800 °C when NH3 fuel is utilised. More importantly, because Mo doping greatly enhances the reduction stability of the material, the DA-SSOFC with the LSFN-MSDCi electrode exhibits strong operational stability without significant degradation for over 400 h at 700 °C.

Non-small cell lung cancer and immune checkpoint inhibitor therapy: does non-alcoholic fatty liver disease have an effect?

BACKGROUND: Immunotherapy based on the application of immune checkpoint inhibitors (ICIs) is one of the standard treatments for advanced non-small cell lung cancer (NSCLC). Non-alcoholic fatty liver Disease (NAFLD) has demonstrated predictive value for response to immunotherapy in non-lung cancer types. Our study investigated the effect of NAFLD on the efficacy of real-life use of ICIs for patients with stage III / IV NSCLC. METHODS: The clinical and imaging data of patients with stage III / IV NSCLC who were first admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to July 2022 were retrospectively collected to ensure that they underwent at least one CT scan before treatment. A total of 479 patients were divided into the NAFLD group (Liver/Spleen density ratio ≤ 1) and the non-NAFLD group (Liver/Spleen density ratio > 1) by measuring the baseline liver and spleen CT value. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the patients were obtained. RESULTS: A total of 118 patients with NAFLD and 361 patients without NAFLD were included in the study. Patients with NAFLD tended to have higher BMI and higher total bilirubin compared to patients without NAFLD. The median duration of follow-up in the study was 22 m (IQR, 17-29 m). Both of 2 groups had a higher DCR (94% vs. 92%, p = 0.199) and ORR (38.1% vs. 44.9%, p = 0.452) respectively. There was no difference in efficacy between the two groups. In univariate analysis, NAFLD had no significant effect on PFS (p = 0.785) and OS (p = 0.851). Surprisingly, the presence of hypertension was observed to be associated with a higher OS (HR 1.471 95%CI 1.018-2.127, p = 0.040). Besides, based on multivariate analysis, lactic dehydrogenase was associated with PFS (HR 1.001 95%CI 1.000,1.002, p = 0.037) and OS (HR 1.002, 95%CI 1.001-1.003, p < 0.001). CONCLUSIONS: Among patients with NSCLC, NAFLD did not result in changes in survival or disease progression after immune checkpoint inhibitor therapy.

Extrasynaptic GABAA receptors in central medial thalamus mediate anesthesia in rats.

Neuronal depression in the thalamus underlies anesthetic-induced loss of consciousness, while the precise sub-thalamus nuclei and molecular targets involved remain to be elucidated. The present study investigated the role of extrasynaptic GABAA receptors in the central medial thalamic nucleus (CM) in anesthesia induced by gaboxadol (THIP) and diazepam (DZP) in rats. Local lesion of the CM led to a decrease in the duration of loss of righting reflex induced by THIP and DZP. CM microinjection of THIP but not DZP induced anesthesia. The absence of righting reflex in THIP-treated rats was consistent with the increase of low frequency oscillations in the delta band in the medial prefrontal cortex. CM microinjection of GABAA receptor antagonist SR95531 significantly attenuated the anesthesia induced by systemically-administered THIP, but not DZP. Moreover, the rats with declined expression of GABAA receptor δ-subunit in the CM were less responsive to THIP or DZP. These findings explained a novel mechanism of THIP-induced loss of consciousness and highlighted the role of CM extrasynaptic GABAA receptors in mediating anesthesia.

A novel phage putative depolymerase, Depo16, has specific activity against K1 capsular-type Klebsiella pneumoniae.

Klebsiella pneumoniae, especially hypervirulent K. pneumoniae (hvKP), is a common opportunistic pathogen that often causes hospital- and community-acquired infections. Capsular polysaccharide (CPS) is an important virulence factor of K. pneumoniae. Some phages encode depolymerases that can recognize and degrade bacterial polysaccharides. In this study, the lytic bacteriophage vB_KpnP_ZK1 (abbreviated as ZK1) was isolated using serotype K1 hvKP as the host. Although amino acid sequence BLAST analysis indicated that the tail fiber protein Depo16 of phage ZK1 showed no significant similarity to any reported phage depolymerases, it displayed enzymatic activities that are characteristic of phage depolymerases. After expression and purification, Depo16 could efficiently remove the capsular polysaccharide layer that surrounds the surface of serotype K1 K. pneumoniae. Although no bactericidal activity was detected, Depo16 makes serotype K1 K. pneumoniae sensitive to peritoneal macrophages (PMs). In addition, in a mouse bacteremia model of serotype K1 K. pneumoniae, 25 µg of Depo16 was effective in significantly prolonging survival. Depo16 treatment can reduce the bacterial load in blood and major tissues and alleviate tissue damage in mice. This indicates that the putative depolymerase Depo16 is a potential antibacterial agent against serotype K1 K. pneumoniae infections.IMPORTANCEKlebsiella pneumoniae often causes hospital-acquired infections and community-acquired infections. Capsular polysaccharide (CPS) is one of the crucial virulence factors of K. pneumoniae. K1 and K2 capsular-type K. pneumoniae strains are the most prevalent serotypes of hypervirulent K. pneumoniae (hvKP). In this study, a novel K. pneumoniae phage named vB_KpnP_ZK1 was isolated, and its putative depolymerase Depo16 showed low homology with other reported phage depolymerases. Depo16 can specifically degrade the K. pneumoniae K1 capsule making this serotype sensitive to peritoneal macrophages. More importantly, Depo16 showed a significant therapeutic effect in a mouse bacteremia model caused by serotype K1 K. pneumoniae. Thus, Depo16 is a potential antibacterial agent to combat serotype K1 K. pneumoniae infections.

Prognosis and chemotherapy drug sensitivity in liver hepatocellular carcinoma through a disulfidptosis-related lncRNA signature.

Disulfidptosis, a new type of regulated cell death associated with the actin cytoskeleton, provides a new therapeutic tool for cancers. The direct relationship between disulfidptosis-related lncRNAs(DRLs) in liver hepatocellular carcinoma(HCC) remains unclear. We acquired transcriptomic data, corresponding clinical data, and tumor mutation data of HCC from the TCGA database. First of all, DRLs were determined through correlation analysis. Then, a prognostic model containing six DRLs was created by adopting univariate Cox regression, LASSO algorithm and multivariate Cox regression analysis. Based on the model, 424 HCC patients were divided into high- and low-risk groups. Next, we structured ROC curves and PCA through combining the model and clinical data. Enrichment analysis and immune infiltration analysis were adopted to further explore the relationship between the model and prognosis. In addition, we explored the relationship between the model and tumor mutation burden (TMB). There were significant differences between high- and low- risk groups, and patients in the high-risk group showed poor prognosis. Enrichment analysis suggested that metabolic progress was obviously different between the two groups. According to the analysis of immune infiltration, there were several differences in immune cells, function, and checkpoints. Patients with high-risk and high TMB demonstrated the least favorable prognosis. The two risk groups both manifested visiblly in chemotherapy drug sensitivity. To sum up, we set up a DRL-based signature and that may provide a predictable value for the prognosis and use of chemotherapy drugs for HCC patients.

Intra- and peritumoral radiomics features based on multicenter automatic breast volume scanner for noninvasive and preoperative prediction of HER2 status in breast cancer: a model ensemble research.

The aim to investigate the predictive efficacy of automatic breast volume scanner (ABVS), clinical and serological features alone or in combination at model level for predicting HER2 status. The model weighted combination method was developed to identify HER2 status compared with single data source model method and feature combination method. 271 patients with invasive breast cancer were included in the retrospective study, of which 174 patients in our center were randomized into the training and validation sets, and 97 patients in the external center were as the test set. Radiomics features extracted from the ABVS-based tumor, peritumoral 3 mm region, and peritumoral 5 mm region and clinical features were used to construct the four types of the optimal single data source models, Tumor, R3mm, R5mm, and Clinical model, respectively. Then, the model weighted combination and feature combination methods were performed to optimize the combination models. The proposed weighted combination models in predicting HER2 status achieved better performance both in validation set and test set. For the validation set, the single data source model, the feature combination model, and the weighted combination model achieved the highest area under the curve (AUC) of 0.803 (95% confidence interval [CI] 0.660-947), 0.739 (CI 0.556,0.921), and 0.826 (95% CI 0.689,0.962), respectively; with the sensitivity and specificity were 100%, 62.5%; 81.8%, 66.7%; 90.9%,75.0%; respectively. For the test set, the single data source model, the feature combination model, and the weighted combination model attained the best AUC of 0.695 (95% CI 0.583, 0.807), 0.668 (95% CI 0.555,0.782), and 0.700 (95% CI 0.590,0.811), respectively; with the sensitivity and specificity were 86.1%, 41.9%; 61.1%, 71.0%; 86.1%, 41.9%; respectively. The model weighted combination was a better method to construct a combination model. The optimized weighted combination models composed of ABVS-based intratumoral and peritumoral radiomics features and clinical features may be potential biomarkers for the noninvasive and preoperative prediction of HER2 status in breast cancer.

An integrative pan-cancer bioinformatics analysis of MSRB1 and its association with tumor immune microenvironment, prognosis, and immunotherapy.

Methionine sulfoxide reductase B1 (MSRB1) is involved in the development and immune regulation of multiple tumors. However, the role of MSRB1 in the tumor microenvironment and its potential as a therapeutic target remain largely unknown. In this study, MSRB1 expression patterns were evaluated using pan-cancer RNA sequencing data from multiple cell lines, tissues, and single cells. The pan-cancer prognostic role of MSRB1 was assessed and the association between MSRB1 expression and certain cancer characteristics was analyzed. We showed that MSRB1 expression levels were increased in several types of cancer (P < 0.05) and in certain cell types (macrophages, dendritic cells, and malignant tumor cells). The upregulation of MSRB1 expression was due to DNA copy number amplification. Furthermore, MSRB1 was significantly associated with the activation of immune pathways (P < 0.05, NES > 0), immune cell infiltration, and expression of immune checkpoint molecules. In addition, high expression of MSRB1 was found in a series of in vivo and in vitro immunotherapy response models (P < 0.05), and showed resistance to most targeted drugs. Our results indicated that MSRB1 may regulate the tumor immune microenvironment through an immunoresponse and potentially influence cancer development. This could make it a promising predictive biomarker and therapeutic target for precise tumor immunotherapy.

Relevant Research of Inflammatory Cytokines Spectrum in Peripheral Blood of Sudden Hearing Loss.

OBJECTIVE: To investigate whether there is a correlation between the inflammatory state and the pathogenesis and clinical features of sudden hearing loss (SHL) by studying the expression of inflammation-related cytokines in the peripheral blood of patients with SHL. METHODS: In this work, we analyzed the cytokine profiles of 48 analytes in 38 patients with SHL compared to 38 healthy donors using a multiplex immunoassay. This study used appropriate statistical methods to screen for inflammatory cytokines associated with the pathogenesis of SHL, to analyze their network correlation, and to analyze the relationship between clinical features of SHL and inflammatory cytokines. RESULTS: Several cytokines, including CTACK, Eotaxin, HGF, INF-α2, IFN-ß, IL-1ß, IL-1ra, IL-2Rα, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12(p40), IL-13, MIG, ß-NGF, SCF, and TNF-α, exhibited significantly higher levels in the peripheral blood of the SHL group compared to the control group. An inflammatory network composed of multiple cytokines, including IL-1ß, is a risk factor for the development of SHL. CONCLUSION: This study identified several inflammatory cytokines with elevated expression, which may be linked with the onset of SHL. The results of this study also provide a basis for the theoretical hypothesis of inflammation in SHL. LEVEL OF EVIDENCE: III Laryngoscope, 2024.