Single-cell and spatial proteo-transcriptomic profiling reveals immune infiltration heterogeneity associated with neuroendocrine features in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive pulmonary neuroendocrine malignancy featured by cold tumor immune microenvironment (TIME), limited benefit from immunotherapy, and poor survival. The spatial heterogeneity of TIME significantly associated with anti-tumor immunity has not been systemically studied in SCLC. We performed ultra-high-plex Digital Spatial Profiling on 132 tissue microarray cores from 44 treatment-naive limited-stage SCLC tumors. Incorporating single-cell RNA-sequencing data from a local cohort and published SCLC data, we established a spatial proteo-transcriptomic landscape covering over 18,000 genes and 60 key immuno-oncology proteins that participate in signaling pathways affecting tumorigenesis, immune regulation, and cancer metabolism across 3 pathologically defined spatial compartments (pan-CK-positive tumor nest; CD45/CD3-positive tumor stroma; para-tumor). Our study depicted the spatial transcriptomic and proteomic TIME architecture of SCLC, indicating clear intra-tumor heterogeneity dictated via canonical neuroendocrine subtyping markers; revealed the enrichment of innate immune cells and functionally impaired B cells in tumor nest and suggested potentially important immunoregulatory roles of monocytes/macrophages. We identified RE1 silencing factor (REST) as a potential biomarker for SCLC associated with low neuroendocrine features, more active anti-tumor immunity, and prolonged survival.

Fiber-integrated quantum microscopy system for cells.

Quantum entanglement serves as an essential resource across various fields, including quantum communication, quantum computing, and quantum precision measurement. Quantum microscope, as one of the significant applications in quantum precision measurement, could bring revolutionary advancements in both signal-to-noise ratio (SNR) and spatial resolution of imaging. Here, we present a quantum microscopy system that relies on a fully fiber-integrated high-performance energy-time entangled light source operating within the near-infrared II (NIR-II) window. Complemented by tailored real-time data acquisition and processing software, we successfully demonstrate the quantum imaging of a standard target, achieving a SNR of 131.51 ± 6.74 and a spatial resolution of 4.75 ± 0.27 µm. Furthermore, we showcase quantum imaging of cancer cells, unveiling the potential of quantum entanglement in biomedical applications. Our fiber-integrated quantum microscope, characterized by high imaging SNR, instantaneous image capture, and analysis capabilities, marks an important step toward the practical application in life sciences.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and c-ros oncogene 1 (ROS1) rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer (NSCLC) and are typically considered to be mutually exclusive. EGFR/ROS1 co-mutation is a rare event, and the standard treatment approach for such cases is still equivocal. CASE SUMMARY: Herein, we report the case of a 64-year-old woman diagnosed with lung adenocarcinoma, with concomitant EGFR L858R mutation and ROS1 rearrangement. The patient received two cycles of chemotherapy after surgery, but the disease progressed. Following 1-month treatment with gefitinib, the disease progressed again. However, after switching to crizotinib, the lesion became stable. Currently, crizotinib has been administered for over 53 months with a remarkable treatment effect. CONCLUSION: The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation. This report will aid future treatment of such patients.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization.

BACKGROUND: Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma (PDAC) metastasis. AIM: To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis. Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis. METHODS: Cell culture and various experiments, including protein analysis, immunohistochemistry, and animal model experiments, were conducted. We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features. Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers. Finally, we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms. RESULTS: Our research showed that there was a significant increase in FAM53B levels in PDAC tissues, which was linked to adverse tumor features. Experimental findings indicated that FAM53B can enhance macrophage M2 polarization, leading to increased anti-inflammatory factor release. The results from the mouse model further supported the role of FAM53B in PDAC metastasis, as blocking FAM53B prevented tumor cell invasion and metastasis. CONCLUSION: FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization. This discovery could lead to the development of new strategies for treating PDAC. For example, interfering with the FAM53B signaling pathway may prevent cancer spread. Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is an aggressive and lethal malignancy. Achaete-scute homolog 1 (ASCL1) is essential for the initiation of SCLC in mice and the development of pulmonary neuroendocrine cells (PNEC), which are the major cells of origin for SCLC. However, the regulatory mechanism of ASCL1 in SCLC remains elusive. Here, we found that ASCL1 expression gradually increases as the tumors grow in a mouse SCLC model, and is regulated by the cell cycle. Mechanistically, CDK2-CyclinA2 complex phosphorylates ASCL1, which results in increased proteasome-mediated ASCL1 protein degradation by E3 ubiquitin ligase HUWE1 during mitosis. TCF3 promotes the multisite phosphorylation of ASCL1 through the CDK2-CyclinA2 complex and the interaction between ASCL1 and TCF3 protects ASCL1 from degradation. The dissociation of TCF3 from ASCL1 during mitosis accelerates the degradation of ASCL1. In addition, chemotherapy drugs greatly reduce the transcription of ASCL1 in SCLC cells. Depletion of ASCL1 sensitizes SCLC cells to chemotherapy drugs. Together, our study demonstrates that ASCL1 is a cell-cycle-regulated protein and provides a theoretical basis for applying cell-cycle-related antitumor drugs in SCLC treatment. Implications:Our study revealed a novel regulatory mechanism of ASCL1 by cell cycle and chemotherapy drugs in SCLC. Treating patients with SCLC with a combination of ASCL1-targeting therapy and chemotherapy drugs could potentially be beneficial.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

Bioinspired Self-Assembly of Metalloporphyrins and Polyelectrolytes into Hierarchical Supramolecular Nanostructures for Enhanced Photocatalytic H2 Production in Water.

Polypeptides, as natural polyelectrolytes, are assembled into tailored proteins to integrate chromophores and catalytic sites for photosynthesis. Mimicking nature to create the water-soluble nanoassemblies from synthetic polyelectrolytes and photocatalytic molecular species for artificial photosynthesis is still rare. Here, we report the enhancement of the full-spectrum solar-light-driven H2 production within a supramolecular system built by the co-assembly of anionic metalloporphyrins with cationic polyelectrolytes in water. This supramolecular photocatalytic system achieves a H2 production rate of 793 and 685 µmol h-1 g-1 over 24 h with a combination of Mg or Zn porphyrin as photosensitizers and Cu porphyrin as a catalyst, which is more than 23 times higher than that of free molecular controls. With a photosensitizer to catalyst ratio of 10000 : 1, the highest H2 production rate of >51,700 µmol h-1 g-1 with a turnover number (TON) of >1,290 per molecular catalyst was achieved over 24 h irradiation. The hierarchical self-assembly not only enhances photostability through forming ordered stackings of the metalloporphyrins but also facilitates both energy and electron transfer from antenna molecules to catalysts, and therefore promotes the photocatalysis. This study provides structural and mechanistic insights into the self-assembly enhanced photostability and catalytic performance of supramolecular photocatalytic systems.

Morphological and phylogenetic analyses reveal a new species of Anthracophyllum (Omphalotaceae, Agaricales) in Zhejiang Province, China.

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.

Elevating nucleic acid delivery via a stable anionic peptide-dextran ternary system.

Nucleic acid-based therapies hold promise for treating previously intractable diseases but require effective delivery vectors to protect the therapeutic agents and ensure efficient transfection. Cationic polymeric vectors are particularly notable for their adaptability, high transfection efficiency, and low cost, but their positive charge often attracts blood proteins, causing aggregation and reduced transfection efficiency. Addressing this, we designed an anionic peptide-grafted dextran (Dex-LipE5H) to serve as a cross-linkable coating to bolster the stability of cationic polymer/nucleic acid complexes. The Dex-LipE5H was synthesized through a Michael addition reaction, combining an anionic peptide (LipE5H) with dextran modified by divinyl sulfone. We demonstrated Dex-lipE5H utility in a novel ternary nucleic acid delivery system, CDex-LipE5H/PEI/nucleic acid. CDex-LipE5H/PEI/nucleic acid demonstrated lower cytotoxicity and superior anti-protein absorption ability compared to PEI/pDNA and Dex-LipE5H/PEI/pDNA. Most notably, the crosslinked CDex-LipE5H/PEI/pDNA demonstrated remarkable transfection performance in HepG2 cells, which poses significant transfection challenges, even in a medium with 20% serum. This system's effective siRNA interference performance was further validated through a PCSK9 gene knockdown assay. This investigation provides novel insights and contributes to the design of cost-effective, next-generation nucleic acid delivery systems with enhanced blood stability and transfection efficiency.

PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer.

Our previous study revealed that PI3K/AKT/mTOR signaling was associated with SCLC radioresistance. SBC2 cells were used as primary radioresistance models, while H446 cells were continuously exposed to ionizing radiation (IR) to develop acquired radioresistance. Cell viability and apoptosis assays were used to investigate synergistic effects of BEZ235/GSK2126458 and IR in vitro, while immunoblotting, metabolite quantitative analysis and bioinformatic analyses were utilized to explore the underlying mechanism. Both genetically engineered mouse models (GEMM) and subcutaneous tumor models were used to confirm the synergistic effect in vivo. Key molecules of PI3K/AKT/mTOR signaling were upregulated after IR, which was correlated with primary radioresistance, and they were more expressed in acquired radioresistant cells. BEZ235/GSK2126458 effectively enhanced the cytotoxic effects of IR. BEZ235/GSK2126458 plus IR elevated γ-H2AX and p-Nrf2 expression, suggesting DNA and oxidative stress damage were intensified. Mechanistically, BEZ235/GSK2126458 plus IR significantly reduced the expression of G6PD protein, the rate-limiting enzyme of the pentose phosphate pathway (PPP). In detail, PI3K/mTOR inhibitors reinforced interaction between G6PD and HSPA8/HSC70, and G6PD was degraded by chaperone-mediated autophagy processes. Their metabolites (NADPH and R-5P) were decreased, and ROS levels were indirectly elevated, both of which exacerbated cell death. PI3K/AKT/mTOR signaling activator, insulin, enhanced SCLC radioresistance, while the synergistic effect of BEZ235/GSK2126458 and IR can be attenuated by N-acetylcysteine, and enhanced by 6-amino niacinamide. GEMM and allograft transplantation assays further confirmed their synergistic effect in vivo. This study provided insights into the connection between PI3K/AKT/mTOR signaling and the PPP underlying radioresistance and provided evidence of mechanisms supporting PI3K/mTOR inhibitors as possible therapeutic strategies to abrogate SCLC radioresistance.

Transcriptomic, 16S ribosomal ribonucleic acid and network pharmacology analyses shed light on the anticoccidial mechanism of green tea polyphenols against Eimeria tenella infection in Wuliangshan black-boned chickens.

BACKGROUND: Eimeria tenella is an obligate intracellular parasitic protozoan that invades the chicken cecum and causes coccidiosis, which induces acute lesions and weight loss. Elucidating the anticoccidial mechanism of action of green tea polyphenols could aid the development of anticoccidial drugs and resolve the problem of drug resistance in E. tenella. METHODS: We constructed a model of E. tenella infection in Wuliangshan black-boned chickens, an indigenous breed of Yunnan Province, China, to study the efficacy of green tea polyphenols against the infection. Alterations in gene expression and in the microbial flora in the cecum were analyzed by ribonucleic acid (RNA) sequencing and 16S ribosomal RNA (rRNA) sequencing. Quantitative real-time polymerase chain reaction was used to verify the host gene expression data obtained by RNA sequencing. Network pharmacology and molecular docking were used to clarify the interactions between the component green tea polyphenols and the targeted proteins; potential anticoccidial herbs were also analyzed. RESULTS: Treatment with the green tea polyphenols led to a reduction in the lesion score and weight loss of the chickens induced by E. tenella infection. The expression of matrix metalloproteinase 7 (MMP7), MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2 was significantly altered in the E. tenella infection plus green tea polyphenol-treated group and in the E. tenella infection group compared with the control group; these genes were also predicted targets of tea polyphenols. Furthermore, the tea polyphenol (-)-epigallocatechin gallate acted on most of the targets, and the molecular docking analysis showed that it has good affinity with interferon induced with helicase C domain 1 protein. 16S ribosomal RNA sequencing showed that the green tea polyphenols had a regulatory effect on changes in the fecal microbiota induced by E. tenella infection. In total, 171 herbs were predicted to act on two or three targets in MMP7, MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2. CONCLUSIONS: Green tea polyphenols can directly or indirectly regulate host gene expression and alter the growth of microbiota. The results presented here shed light on the mechanism of action of green tea polyphenols against E. tenella infection in chickens, and have implications for the development of novel anticoccidial products.

Long non-coding RNA X-Inactive Specific Transcript (XIST) interacting with USF2 promotes osteogenic differentiation of periodontal ligament stem cells through regulation of WDR72 transcription.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.

Immunological effects of recombinant Lactobacillus casei expressing pilin MshB fused with cholera toxin B subunit adjuvant as an oral vaccine against Aeromonas veronii infection in crucian carp.

Aeromonas veronii is a zoonotic agent capable of infecting fish and mammals, including humans, posing a serious threat to the development of aquaculture and public health safety. Currently, few effective vaccines are available through convenient routes against A. veronii infection. Herein, we developed vaccine candidates by inserting MSH type VI pili B (MshB) from A. veronii as an antigen and cholera toxin B subunit (CTB) as a molecular adjuvant into Lactobacillus casei and evaluated their immunological effect as vaccines in a crucian carp (Carassius auratus) model. The results suggested that recombinant L. casei Lc-pPG-MshB and Lc-pPG-MshB-CTB can be stably inherited for more than 50 generations. Oral administration of recombinant L. casei vaccine candidates stimulated the production of high levels of serum-specific immunoglobulin M (IgM) and increased the activity of acid phosphatase (ACP), alkaline phosphatase (AKP) superoxide dismutase (SOD), lysozyme (LZM), complement 3 (C3) and C4 in crucian carp compared to the control group (Lc-pPG612 group and PBS group) without significant changes. Moreover, the expression levels of interleukin-10 (IL-10), interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) genes in the gills, liver, spleen, kidney and gut of crucian carp orally immunized with recombinant L. casei were significantly upregulated compared to the control groups, indicating that recombinant L. casei induced a significant cellular immune response. In addition, viable recombinant L. casei can be detected and stably colonized in the intestine tract of crucian carp. Particularly, crucian carp immunized orally with Lc-pPG-MshB and Lc-pPG-MshB-CTB exhibited higher survival rates (48% for Lc-pPG-MshB and 60% for Lc-pPG-MshB-CTB) and significantly reduced loads of A. veronii in the major immune organs after A. veronii challenge. Our findings indicated that both recombinant L. casei strains provide favorable immune protection, with Lc-pPG-MshB-CTB in particular being more effective and promising as an ideal candidate for oral vaccination.

[Retracted] TRIM16 suppresses the progression of prostate tumors by inhibiting the Snail signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by concerned readers that the western blotting data shown in Figs. 4C and 7B and D, the scratch­wound assay images shown in Figs. 5A and 6A, and certain of the cell migration and invasion assay data shown in Figs. 5B and 6B were strikingly similar to data that had previously appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 38: 1734­1742, 2016; DOI: 10.3892/ijmm.2016.2774].

Recombinant measles virus vaccine rMV-Hu191 exerts an oncolytic effect on esophageal squamous cell carcinoma via caspase-3/GSDME-mediated pyroptosis.

Oncolytic viruses have recently been proven to be an effective and promising cancer therapeutic strategy, but there is rare data about oncolytic therapy in esophageal squamous cell carcinoma (ESCC), especially oncolytic measles virotherapy. Therefore, this study aimed to explore whether the recombinant measles virus vaccine strain rMV-Hu191 has an oncolytic effect against ESCC cells in vitro and in vivo and elucidate the underlying mechanisms. Our results showed that rMV-Hu191 could efficiently replicate in and kill ESCC cells through caspase-3/GSDME-mediated pyroptosis. Mechanistically, rMV-Hu191 triggers mitochondrial dysfunction to induce pyroptosis, which is mediated by BAK (BCL2 antagonist/killer 1) or BAX (BCL2 associated X). Further analysis revealed that rMV-Hu191 activates inflammatory signaling in ESCC cells, which may enhance the oncolytic efficiency. Moreover, intratumoral injection of rMV-Hu191 induced dramatic tumor regression in an ESCC xenograft model. Collectively, these findings imply that rMV-Hu191 exhibits an antitumor effect through BAK/BAX-dependent caspase-3/GSDME-mediated pyroptosis and provides a potentially promising new therapy for ESCC treatment.

Low iron ameliorates the salinity-induced growth cessation of seminal roots in wheat seedlings.

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline-alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split-root experiments showed that low Fe-alleviating the salinity-induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X-ray few differences in the root Na+ uptake and vacuolar Na+ sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity-induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe-mediated amelioration of the salinity-induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress.

Eight TRIM32 isoforms from oriental river prawn Macrobrachium nipponense are involved in innate immunity during white spot syndrome virus infection.

Tripartite motif (TRIM) proteins comprise a large family of RING-type ubiquitin E3 ligases that regulate important biological processes. In this study, full-length MnTRIM32 cDNA was obtained from oriental river prawn Macrobrachium nipponense, and eight MnTRIM32 isoforms generated by alternative splicing were identified. The open reading frames of the eight MnTRIM32 isoforms were predicted to be separately composed of 402, 346, 347, 346, 414, 358, 359, and 358 amino acid residues. Protein structural analysis revealed that all MnTRIM32 isoforms contained a RING domain and a coiled coil region. MnTRIM32 was ubiquitously expressed in all tissues tested, with the highest expression in the hepatopancreas. The mRNA levels of MnTRIM32 in the gills, stomach, and intestine of prawns were found to undergo time-dependent enhancement following white spot syndrome virus (WSSV) stimulation. Double-stranded RNA interference studies revealed that MnTRIM32 silencing significantly downregulated the expression levels of interferon (IFN) regulatory factor MnIRF, IFN-like factor MnVago4, and tumor necrosis factor MnTNF. Furthermore, knockdown of MnTRIM32 in WSSV-challenged prawns increased the expression of VP28 and the number of WSSV copies, suggesting that MnTRIM32 plays a positive role in limiting WSSV infection. These findings provided strong evidence for the important role of MnTRIM32 in the antiviral innate immunity of M. nipponense.

Considerations of single-lung ventilation in neonatal thoracoscopic surgery with cardiac arrest caused by bilateral pneumothorax: A case report.

BACKGROUND: Tension pneumothorax of the contralateral lung during single-lung ventilation (SLV) combined with artificial pneumothorax can cause cardiac arrest due to bilateral pneumothorax. If not rapidly diagnosed and managed, this condition can lead to sudden death. We describe the emergency handling procedures and rapid diagnostic methods for this critical emergency situation. CASE SUMMARY: We report a case of bilateral pneumothorax in a neonatal patient who underwent thoracoscopic esophageal atresia and tracheoesophageal fistula repair under the combined application of SLV and artificial pneumothorax. The patient suffered sudden cardiac arrest and received emergency treatment to revive her. The recognition of dangerous vital sign parameters, rapid evacuation of the artificial pneumothorax, and initiation of lateral position cardiopulmonary resuscitation while simultaneously removing the endotracheal tube to the main airway are critically important. Moreover, even though the sinus rhythm was restored, the patient's continued tachycardia, reduced pulse pressure, and depressed pulse oximeter waveform were worrisome. We should highly suspect the possibility of pneumothorax and use rapid diagnostic methods to make judgment calls. Sometimes thoracoscopy can be used for rapid examination; if the mediastinum is observed to be shifted to the right, it may indicate tension pneumothorax. This condition can be immediately relieved by needle thoracentesis, ultimately allowing the safe completion of the surgical procedure. CONCLUSION: Bilateral pneumothorax during SLV combined with artificial pneumothorax is rare but can occur at any time in neonatal thoracoscopic surgery. Therefore, anesthesiologists should consider this possibility, be alert, and address this rare but critical complication in a timely manner.

Deep Learning Promotes the Screening of Natural Products with Potential Microtubule Inhibition Activity.

Natural microtubule inhibitors, such as paclitaxel and ixabepilone, are key sources of novel medications, which have a considerable influence on anti-tumor chemotherapy. Natural product chemists have been encouraged to create novel methodologies for screening the new generation of microtubule inhibitors from the enormous natural product library. There have been major advancements in the use of artificial intelligence in medication discovery recently. Deep learning algorithms, in particular, have shown promise in terms of swiftly screening effective leads from huge compound libraries and producing novel compounds with desirable features. We used a deep neural network to search for potent ß-microtubule inhibitors in natural goods. Eleutherobin, bruceine D (BD), and phorbol 12-myristate 13-acetate (PMA) are three highly effective natural compounds that have been found as ß-microtubule inhibitors. In conclusion, this paper describes the use of deep learning to screen for effective ß-microtubule inhibitors. This research also demonstrates the promising possibility of employing deep learning to develop drugs from natural products for a wider range of disorders.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.