Predicting rectal cancer prognosis from histopathological images and clinical information using multi-modal deep learning.

Objective: The objective of this study was to provide a multi-modal deep learning framework for forecasting the survival of rectal cancer patients by utilizing both digital pathological images data and non-imaging clinical data. Materials and methods: The research included patients diagnosed with rectal cancer by pathological confirmation from January 2015 to December 2016. Patients were allocated to training and testing sets in a randomized manner, with a ratio of 4:1. The tissue microarrays (TMAs) and clinical indicators were obtained. Subsequently, we selected distinct deep learning models to individually forecast patient survival. We conducted a scanning procedure on the TMAs in order to transform them into digital pathology pictures. Additionally, we performed pre-processing on the clinical data of the patients. Subsequently, we selected distinct deep learning algorithms to conduct survival prediction analysis using patients' pathological images and clinical data, respectively. Results: A total of 292 patients with rectal cancer were randomly allocated into two groups: a training set consisting of 234 cases, and a testing set consisting of 58 instances. Initially, we make direct predictions about the survival status by using pre-processed Hematoxylin and Eosin (H&E) pathological images of rectal cancer. We utilized the ResNest model to extract data from histopathological images of patients, resulting in a survival status prediction with an AUC (Area Under the Curve) of 0.797. Furthermore, we employ a multi-head attention fusion (MHAF) model to combine image features and clinical features in order to accurately forecast the survival rate of rectal cancer patients. The findings of our experiment show that the multi-modal structure works better than directly predicting from histopathological images. It achieves an AUC of 0.837 in predicting overall survival (OS). Conclusions: Our study highlights the potential of multi-modal deep learning models in predicting survival status from histopathological images and clinical information, thus offering valuable insights for clinical applications.

Microvascular Decompression Plus Partial Resection of Trigeminal Nerve Motor Root for Hemimasticatory Spasm Combined With Hemifacial Atrophy: A Good Choice or Not?

Hemimasticatory spasm (HMS) combined with hemifacial atrophy is a rare clinical entity with an unclear etiology. The authors report a 58-year-old female suffering from HMS and hemifacial atrophy, which performed microvascular decompression plus partial resection of the trigeminal nerve motor root, which is the first report in worldwide. The vascular compression of the trigeminal nerve motor root was found in surgery, the authors completed the aforementioned surgical method. The symptoms of HMS disappeared after surgery but recurred after 8 months.

Alternations of Blood Pressure Following Surgical or Drug Therapy for Prolactinomas.

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.

3D genome structural variations play important roles in regulating seed oil content of Brassica napus.

Dissecting the complex regulatory mechanism of seed oil content (SOC) is one of the main research goals in Brassica napus. Increasing evidence suggests that genome architecture is linked to multiple biological functions. However, the effect of genome architecture on SOC regulation remains unclear. Here, we used high-throughput chromatin conformation capture to characterize differences in the three-dimensional (3D) landscape of genome architecture of seeds from two B. napus lines, N53-2 (with high SOC) and Ken-C8 (with low SOC). Bioinformatics analysis demonstrated that differentially accessible regions and differentially expressed genes between N53-2 and Ken-C8 were preferentially enriched in regions with quantitative trait loci (QTLs)/associated genomic regions (AGRs) for SOC. A multi-omics analysis demonstrated that expression of SOC-related genes was tightly correlated with genome structural variations in QTLs/AGRs of B. napus. The candidate gene BnaA09g48250D, which showed structural variation in a QTL/AGR on chrA09, was identified by fine-mapping of a KN double-haploid population derived from hybridization of N53-2 and Ken-C8. Overexpression and knockout of BnaA09g48250D led to significant increases and decreases in SOC, respectively, in the transgenic lines. Taken together, our results reveal the 3D genome architecture of B. napus seeds and the roles of genome structural variations in SOC regulation, enriching our understanding of the molecular mechanisms of SOC regulation from the perspective of spatial chromatin structure.

LEARN algorithm: a novel option for predicting non-alcoholic steatohepatitis.

Background: There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis (NASH). Since impedance-based measurements of body composition are simple, repeatable and have a strong association with non-alcoholic fatty liver disease (NAFLD) severity, we aimed to develop a novel and fully automatic machine learning algorithm, consisting of a deep neural network based on impedance-based measurements of body composition to identify NASH [the bioeLectrical impEdance Analysis foR Nash (LEARN) algorithm]. Methods: A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China, of which 766 patients with biopsy-proven NAFLD were included in final analysis. These patients were randomly subdivided into the training and validation groups, in a ratio of 4:1. The LEARN algorithm was developed in the training group to identify NASH, and subsequently, tested in the validation group. Results: The LEARN algorithm utilizing impedance-based measurements of body composition along with age, sex, pre-existing hypertension and diabetes, was able to predict the likelihood of having NASH. This algorithm showed good discriminatory ability for identifying NASH in both the training and validation groups [area under the receiver operating characteristics (AUROC): 0.81, 95% CI: 0.77-0.84 and AUROC: 0.80, 95% CI: 0.73-0.87, respectively]. This algorithm also performed better than serum cytokeratin-18 neoepitope M30 (CK-18 M30) level or other non-invasive NASH scores (including HAIR, ION, NICE) for identifying NASH (P value <0.001). Additionally, the LEARN algorithm performed well in identifying NASH in different patient subgroups, as well as in subjects with partial missing body composition data. Conclusions: The LEARN algorithm, utilizing simple easily obtained measures, provides a fully automated, simple, non-invasive method for identifying NASH.

New insight into the genetic basis of oil content based on noninvasive three-dimensional phenotyping and tissue-specific transcriptome in Brassica napus.

BACKGROUND: Increasing seed oil content is the most important breeding goal in Brassica napus, and phenotyping is crucial to dissect its genetic basis in crops. To date, QTL mapping for oil content has been based on whole seeds, and the lipid distribution is far from uniform in different tissues of seeds in B. napus. In this case, the phenotype based on whole seeds was unable to sufficiently reveal the complex genetic characteristics of seed oil content. RESULTS: Here, the three-dimensional (3D) distribution of lipid was determined for B. napus seeds by magnetic resonance imaging (MRI) and 3D quantitative analysis, and ten novel oil content-related traits were obtained by subdividing the seeds. Based on a high-density genetic linkage map, 35 QTLs were identified for 4 tissues, the outer cotyledon (OC), inner cotyledon (IC), radicle (R) and seed coat (SC), which explained up to 13.76% of the phenotypic variation. Notably, 14 tissue-specific QTLs were reported for the first time, 7 of which were novel. Moreover, haplotype analysis showed that the favorable alleles for different seed tissues exhibited cumulative effects on oil content. Furthermore, tissue-specific transcriptomes revealed that more active energy and pyruvate metabolism influenced carbon flow in the IC, OC and R than in the SC at the early and middle seed development stages, thus affecting the distribution difference in oil content. Combining tissue-specific QTL mapping and transcriptomics, 86 important candidate genes associated with lipid metabolism were identified that underlie 19 unique QTLs, including the fatty acid synthesis rate-limiting enzyme-related gene CAC2, in the QTLs for OC and IC. CONCLUSIONS: The present study provides further insight into the genetic basis of seed oil content at the tissue-specific level.

Cartilage structure-inspired elastic silk nanofiber network hydrogel for stretchable and high-performance supercapacitors.

Flexible supercapacitors are an important portable energy storage but suffer from low capacitance, inability to stretch, etc. Therefore, flexible supercapacitors must achieve higher capacitance, energy density, and mechanical robustness to expand the applications. Herein, a hydrogel electrode with excellent mechanical strength was created by simulating the collagen fiber network and proteoglycan in cartilage using silk nanofiber (SNF) network and polyvinyl alcohol (PVA). The Young's modulus and breaking strength of the hydrogel electrode increased by 205 % and 91 % compared with PVA hydrogel owing to the enhanced effect of the bionic structure, respectively, which are 1.22 MPa and 1.3 MPa. The fracture energy and fatigue threshold reached 1813.5 J/m2 and 1585.2 J/m2, respectively. The SNF network effectively connected carbon nanotubes (CNTs) and polypyrrole (PPy) in series, affording a capacitance of 13.62 F/cm2 and energy density of 1.2098 mWh/cm2. This capacitance is the highest among currently reported PVA hydrogel capacitors, which can maintain >95.2 % after 3000 charge-discharge cycles. This capacitance Notably, the cartilage-like structure endowed the supercapacitor with high resilience; thus, the capacitance remained >92.1 % under 150 % deformation and >93.35 % after repeated stretching (3000 times), which was far superior to that of other PVA-based supercapacitors. Overall, this effective bionic strategy can endow supercapacitors with ultrahigh capacitance and effectively ensure the mechanical reliability of flexible supercapacitors, which will help expand the applications of supercapacitors.

Effects of quercetin on granulosa cells from prehierarchical follicles by modulating MAPK signaling pathway in chicken.

Quercetin (Que), widely found in a huge variety of plants, plays important roles in ovarian function. However, to data, there have been no reports about Que regulating granulosa cells (GCs) in prehierarchical follicles in chicken. Herein, GCs from follicles diameter from 4 to 8 mm in chicken were treated by Que in vitro culture to investigate how Que exerts its effect on follicular development. GCs treated by Que in concentrations of 10, 100, and 1,000 ng/mL were tested for cell proliferation and progesterone secretion. Eight cDNA libraries were constructed from GCs (4 samples per group) to explore transcriptome expression changes. The role of the MAPK/ERK signaling pathway was validated in this process. Treatment with 100 and 1,000 ng/mL levels of Que significantly promoted cell proliferation and progesterone secretion (P < 0.05). RNA-seq analysis data showed that 402 and 263 differentially expressed genes (DEGs) were up- and down-regulated, respectively. Functional enrichment analysis that the pathways related to follicular development included biosynthesis of amino acids, MAPK signaling pathway, and calcium signaling pathway. Notably, the function exerted in GCs of the different levels of Que was associated with the suppression of the MAPK pathway. In conclusion, our results proved that low levels of Que could promote MAPK signaling pathway, but high levels of Que inhibit MAPK signaling pathway in GCs from the prehierarchical follicles, promote cell proliferation and progesterone secretion, and benefit follicle selection.

Segmentation of thyroid glands and nodules in ultrasound images using the improved U-Net architecture.

BACKGROUND: Identifying thyroid nodules' boundaries is crucial for making an accurate clinical assessment. However, manual segmentation is time-consuming. This paper utilized U-Net and its improved methods to automatically segment thyroid nodules and glands. METHODS: The 5822 ultrasound images used in the experiment came from two centers, 4658 images were used as the training dataset, and 1164 images were used as the independent mixed test dataset finally. Based on U-Net, deformable-pyramid split-attention residual U-Net (DSRU-Net) by introducing ResNeSt block, atrous spatial pyramid pooling, and deformable convolution v3 was proposed. This method combined context information and extracts features of interest better, and had advantages in segmenting nodules and glands of different shapes and sizes. RESULTS: DSRU-Net obtained 85.8% mean Intersection over Union, 92.5% mean dice coefficient and 94.1% nodule dice coefficient, which were increased by 1.8%, 1.3% and 1.9% compared with U-Net. CONCLUSIONS: Our method is more capable of identifying and segmenting glands and nodules than the original method, as shown by the results of correlational studies.

Whole genome sequence of mulberry crinivirus, a new member of the genus Crinivirus.

The whole genome sequence of mulberry crinivirus (MuCV), a novel member of the genus Crinivirus (family Closteroviridae) identified in mulberry (Morus alba L), was determined. The virus possesses a bipartite genome. RNA1 contains 8571 nucleotides (nt) with four open reading frames (ORFs). ORF1a encodes a putative polyprotein with papain-like protease, methyltransferase, and RNA helicase domains. ORF1b putatively encodes an RNA-dependent RNA polymerase (RdRp), which is probably expressed via a + 1 ribosomal frameshift. RNA2 consists of 8082 nt, containing eight ORFs that are similar in size and position to orthologous genes of other criniviruses. Phylogenetic analysis based on RdRp amino acid sequences of criniviruses placed MuCV in group 1.

Verapamil Regulates the Macrophage Immunity to Mycobacterium tuberculosis through NF-κB Signaling.

BACKGROUND: Verapamil enhances the sensitivity of Mycobacterium tuberculosis to anti-tuberculosis (TB) drugs, promotes the macrophage anti-TB ability, and reduces drug resistance, but its mechanism is unclear. Herein, we have investigated the effect of verapamil on cytokine expression in mouse peritoneal macrophages. METHODS: Macrophages from mice infected with M. tuberculosis or S. aureus were cultured with verapamil, the cytokines were detected by enzyme-linked immunosorbent assay, and the RNA was measured with quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The intracellular calcium signaling was measured by confocal microscopy. RESULTS: Significantly higher levels of NF-κB, IL-12, TNF-α, and IL-1ß were observed after TB infection. The levels of NF-κB and IL-12 increased when verapamil concentration was less than 50 µg/ml, but decreased when verapamil concentration was greater than 50µg/ml. With the increase in verapamil concentration, TNF-α and IL-1ß expressed by macrophages decreased. The L-type calcium channel transcription significantly increased in M. tuberculosis rather than S. aureus-infected macrophages. Furthermore, during bacillus Calmette-Guerin (BCG) infection, verapamil stimulated a sharp peak in calcium concentration in macrophages, while calcium concentration increased mildly and decreased smoothly over time in the absence of verapamil. CONCLUSION: Verapamil enhanced macrophage immunity via the NF-κB pathway, and its effects on cytokine expression may be achieved by its regulation of intracellular calcium signaling.

Lysophosphatidic acid acyltransferase 2 and 5 commonly, but differently, promote seed oil accumulation in Brassica napus.

BACKGROUND: Increasing seed oil content (SOC) of Brassica napus has become one of the main plant breeding goals over the past decades. Lysophosphatidic acid acyltransferase (LPAT) performs an important molecular function by regulating the production of phosphatidic acid (PA), a key intermediate in the synthesis of membrane and storage lipids. However, the mechanism underlying the effect of LPAT on the SOC of B. napus remains unclear. RESULTS: In the present study, significant elevation of SOC was achieved by overexpressing BnLPAT2 and BnLPAT5 in B. napus. RNAi and CRISPR-Cas9 were also successfully used to knock down and knock out these two genes in B. napus where SOC significantly decreased. Meanwhile, we found an accumulation of lipid droplets and oil bodies in seeds of BnLPAT2 and BnLPAT5 overexpression lines, whereas an increase of sugar and protein in Bnlpat2 and Bnlpat5 mutant seeds. Sequential transcriptome analysis was further performed on the developing seeds of the BnLPAT2 and BnLPAT5 overexpression, knockdown, and knockout rapeseed lines. Most differentially expressed genes (DEGs) that were expressed in the middle and late stages of seed development were enriched in photosynthesis and lipid metabolism, respectively. The DEGs involved in fatty acid and lipid biosynthesis were active in the overexpression lines but were relatively inactive in the knockdown and knockout lines. Further analysis revealed that the biological pathways related to fatty acid/lipid anabolism and carbohydrate metabolism were specifically enriched in the BnLPAT2 overexpression lines. CONCLUSIONS: BnLPAT2 and BnLPAT5 are essential for seed oil accumulation. BnLPAT2 preferentially promoted diacylglycerol synthesis to increase SOC, whereas BnLPAT5 tended to boost PA synthesis for membrane lipid generation. Taken together, BnLPAT2 and BnLPAT5 can jointly but differently promote seed oil accumulation in B. napus. This study provides new insights into the potential mechanisms governing the promotion of SOC by BnLPAT2 and BnLPAT5 in the seeds of B. napus.

A positive feedback loop between LINC01605 and NF-κB pathway promotes tumor growth in nasopharyngeal carcinoma.

zong non-coding RNAs (lncRNAs) have been identified as crucial effector in modulating the progression of assorted malignancies. In our study, the main aim was to unveil the role and the underlying regulatory mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in nasopharyngeal carcinoma (NPC). RT-qPCR analysis results suggested that LINC01605 was upregulated in NPC cells. According to the results of function experiments, LINC01605 promoted NPC cell proliferation and impeded cell apoptosis. The oncogenic role of LINC01605 in NPC was further validated by animal experiments. Additionally, we verified that LINC01605 regulated Ikbkb expression to promote the nuclear translocation of p65 and thereby activated the NF-κB pathway in NPC cells. Mechanism experiments further suggested that LINC01605 could regulate Ikbkb expression via sponging miR-942-5p. Moreover, LINC01605 recruited IGF2BP2 to stabilize ubiquitin-specific protease 3 (USP3) mRNA and thereby enhanced the stability of IkB subunit beta (IKKß) protein. In addition, p65 acted as a transcription activator to upregulate LINC01605 in NPC cells. In conclusion, this study demonstrated a positive feedback loop between LINC01605 and the NF-κB signalling pathway that promoted NPC cell growth, thus providing new insights to better understand NPC. [Figure: see text].

A major yellow-seed QTL on chromosome A09 significantly increases the oil content and reduces the fiber content of seed in Brassica napus.

KEY MESSAGE: A major yellow-seed QTL on chromosome A09 significantly increases the oil content and reduces the fiber content of seed in Brassica napus. The yellow-seed trait (YST) has always been a main breeding objective for rapeseed because yellow-seeded B. napus generally contains higher oil contents, fewer pigments and polyphenols and lower fiber content than black-seeded B. napus, although the mechanism controlling this correlation remains unclear. In this study, QTL mapping was implemented for YST based on a KN double haploid population derived from the hybridization of yellow-seeded B. napus N53-2 with a high oil content and black-seeded Ken-C8 with a relatively low oil content. Ten QTLs were identified, including four stable QTLs that could be detected in multiple environments. A major QTL, cqSC-A09, on chromosome A09 was identified by both QTL mapping and BSR-Seq technology, and explained more than 41% of the phenotypic variance. The major QTL cqSC-A09 for YST not only controls the seed color but also affects the oil and fiber contents in seeds. More importantly, the advantageous allele could increase the oil content and reduce the pigment and fiber content at the same time. This is the first QTL reported to control seed color, oil content and fiber content simultaneously with a large effect and has great application value for breeding high oil varieties with high seed quality. Important candidate genes, including BnaA09. JAZ1, BnaA09. GH3.3 and BnaA09. LOX3, were identified for cqSC-A09 by combining sequence variation annotation, expression differences and an interaction network, which lays a foundation for further cloning and breeding applications in the future.

Lowering energy consumption for fermentable sugar production from Ramulus mori: Engineered xylanase synergy and improved pretreatment strategy.

Biorefinery of Ramulus mori with lower energy consumption through improved enzyme and pretreatment strategies was reported. Directed evolution and saturation mutagenesis were used for the modification of xylanase, the yield of fermentable sugars and the degree of synergy (DS) were determined for different pretreatment (seawater/non-seawater) and enzyme treatment groups (xylanase/cellulase/co-treatment). The dominant mutant I133A/Q143Y of Bispora sp. xylanase XYL10C_ΔN was obtained with improved specific activity (1860 U/mg), catalytic efficiency (1150 mL/s∙mg) at 40 °C, and thermostability (T50 increased by 7 °C). With the pretreatment of seawater immersion, the highest yield of fermentable sugars for Ramulus mori at 40 °C reached 199 µmol/g when hydrolyzed with cellulase and I133A/Q143Y, with the highest DS of 2.6; this was 4.5-fold that of the group hydrolyzed by cellulase alone with non-seawater pretreatment. Thus, bioconversion of reducing sugar from Ramulus mori was improved significantly at lower temperatures, which provides an efficient and energy-saving wayfor biofuel production.

Metabolomics Response to Drought Stress in Morus alba L. Variety Yu-711.

Mulberry is an economically significant crop for the sericulture industry worldwide. Stresses such as drought exposure have a significant influence on plant survival. Because metabolome directly reflects plant physiological condition, performing a global metabolomic analysis is one technique to examine this influence. Using a liquid chromatography-mass spectrometry (LC-MS) technique based on an untargeted metabolomic approach, the effect of drought stress on mulberry Yu-711 metabolic balance was examined. For this objective, Yu-711 leaves were subjected to two weeks of drought stress treatment and control without drought stress. Numerous differentially accumulated metabolic components in response to drought stress treatment were revealed by multivariate and univariate statistical analysis. Drought stress treatment (EG) revealed a more differentiated metabolite response than the control (CK). We found that the levels of total lipids, galactolipids, and phospholipids (PC, PA, PE) were significantly altered, producing 48% of the total differentially expressed metabolites. Fatty acyls components were the most abundant lipids expressed and decreased considerably by 73.6%. On the other hand, the prenol lipids class of lipids increased in drought leaves. Other classes of metabolites, including polyphenols (flavonoids and cinnamic acid), organic acid (amino acids), carbohydrates, benzenoids, and organoheterocyclic, had a dynamic trend in response to the drought stress. However, their levels under drought stress decreased significantly compared to the control. These findings give an overview for the understanding of global plant metabolic changes in defense mechanisms by revealing the mulberry plant metabolic profile through differentially accumulated compounds.

Drug-Eluting Beads Bronchial Arterial Chemoembolization in Treating Relapsed/Refractory Small Cell Lung Cancer Patients: Results from a Pilot Study.

BACKGROUND: We aimed to explore the efficacy and tolerance of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) treatment in relapsed/refractory small cell lung cancer (SCLC) patients. METHODS: Eleven relapsed/refractory SCLC patients were enrolled and treated with DEB-BACE. Then, treatment response and tumor marker levels were assessed at the first, second and sixth month post treatment. Quality of life was assessed by the EORTC QLQ-C30 scale. Progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: At the first, second and sixth month post treatment, the objective response rates were 63.6%, 54.5%, and 36.4%, respectively; and the disease control rates were 90.9%, 90.9% and 54.5%, respectively. In addition, the neuron-specific enolase (NSE) and progastrin-releasing peptide levels were reduced at the second and sixth month. Quality of life assessed by EORTC QLQ-C30 scale, which included subscales of general health status, functional domains, symptom domains, and single domains except for financial difficulty, was markedly improved at second month post treatment. Median values of PFS and OS were 5.1 (95% CI: 4.1-5.9) months and 9.0 (95% CI: 6.0-12.0) months, respectively. The ECOG score and preoperative NSE level were independent predictive factors for PFS, and age as well as lesion location were independent predictive factors for OS. Adverse events were all mild and manageable with chest pain and chest stuffiness the most common ones. CONCLUSION: DEB-BACE could be a therapeutic option for relapsed/refractory SCLC patients regarding its favorable treatment response, quality of life, survival benefit and safety profile.

FUNDC1 Regulates Autophagy by Inhibiting ROS-NLRP3 Signaling to Avoid Apoptosis in the Lung in a Lipopolysaccharide-Induced Mouse Model.

ABSTRACT: The incidence and mortality of acute respiratory distress syndrome (ARDS) are high, but the relevant mechanism for this disorder remains unclear. Autophagy plays an important role in the development of ARDS. The mitochondrial outer membrane protein FUNDC1 is involved in hypoxia-mediated mitochondrial autophagy, which may contribute to ARDS development. This study explored whether FUNDC1 regulates autophagy by inhibiting ROS-NLRP3 signaling to avoid apoptosis in the lung in a lipopolysaccharide-induced mouse model. In this study, FUNDC1 knockout mice were constructed, and a lipopolysaccharide-induced mouse model was generated. HE staining of pathological sections from the lung, wet/dry lung measurements, myeloperoxidase concentration/neutrophil counts in BALF and survival time of mice were examined to determine the effect of modeling. The release of cytokines (TNF-α, IL-1ß, IL-6, and IL-10) in response to LPS in the BALF and plasma was assessed using ELISA. The effects of oxidative stress (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase) in lung tissue in response to LPS were detected by biochemical analysis. Oxidative stress damage was validated by iNOS staining, and apoptosis was assessed by TUNEL staining after LPS. Finally, the expression of autophagy-associated proteins and inflammasome-associated proteins in lung tissue after LPS intervention was analyzed by western blot. We found that wild-type control, FUNDC1 knockout control, lipopolysaccharide-induced wild-type, and FUNDC1 knockout mouse models were used to investigate whether FUNDC1-mediated autophagy is involved in lung injury and its possible molecular mechanisms. Compared with the normal control group, lung tissue FUNDC1 and LC3 II increased and p62/SQSTM1 decreased after LPS intervention, and increased ROS levels led to a decrease in corresponding antioxidant enzymes along with an increased inflammatory response and apoptosis. Levels of autophagy in lipopolysaccharide-induced mice deficient in FUNDC1 were significantly decreased, but the expression of ROS and inflammatory factors in lung tissue was more severe than in lipopolysaccharide-induced wild-type mice, and the survival rate was significantly decreased. Western blot analysis showed that autophagy was significantly inhibited in the FUNDC1 KO+LPS group, and there was a significant increase in NLRP3, caspase-1, IL-1ß, and ASC compared with the lipopolysaccharide-induced wild-type group. In summary, lipopolysaccharide-induced wild-type mice exhibit ROS-dependent activation of autophagy, and knocking out FUNDC1 promotes inflammasome activation and exacerbates lung injury.

The complete chloroplast genome of Pluchea pteropoda Hemsl, a mangrove associate plant.

Pluchea pteropoda Hemsl is a mangrove associate plant of Asteraceae with medicinal properties such as anti-inflammation and fever-relieving. Here, our study presented the complete chloroplast (cp) genome of Pluchea pteropoda Hemsl. The cp genome of P. pteropoda was 152,300 bp in length, including a large single copy (LSC) region of 84,127 bp, a small single copy (SSC) region of 18,093 bp and a pair of inverted repeats (IR) regions of 25,040 bp. A total of 111 unique genes were found, comprising 79 protein-coding genes, 28 tRNA genes, and 4 rRNA genes. The GC content of the cp genome was 37.5%. Phylogenetic analysis suggested that P. pteropoda nested in Pluchea clade, which was closely related to Ageratina adenophora and Senecio scandens. The work provides beneficial data for following researches on the genetic variation, species delimitation, phylogeny and classification of Pluchea genus.

Drug-eluting beads bronchial arterial chemoembolization plus intercostals arterial infusion chemotherapy is effective and well-tolerated in treating non-small cell lung cancer patients with refractory malignant pleural effusion.

BACKGROUND: The study aimed to explore the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) plus intercostals arterial infusion chemotherapy in non-small cell lung cancer (NSCLC) patients with refractory malignant pleural effusion (MPE). METHODS: 17 NSCLC patients with refractory MPE treated by DEB-BACE plus the intercostals arterial infusion chemotherapy (DEB-BACE group) were recruited. Their treatment response [complete remission (CR), partial remission (PR), overall efficacy, failure] for MPE was assessed at 1 month after therapy; adverse effects were recorded; MPE progression-free survival and overall survival (OS) were calculated. Moreover, 19 NSCLC patients with refractory MPE treated by conventional chemotherapy were reviewed as control (chemotherapy group), then their medical records were collected. RESULTS: With respect to MPE response, DEB-BACE group exhibited increased CR (82.4% vs. 10.5%, P<0.001) and overall efficacy (100.0% vs. 52.6%, P=0.001), similar PR (17.6% vs. 42.1%, P=0.112) while less failure (0.0% vs. 47.4%, P=0.001) compared to chemotherapy group. Furthermore, OS was prolonged in DEB-BACE group (median: 13.4; 95% CI: 11.0-15.8 months) than chemotherapy group (median: 7.0; 95% CI: 4.4-9.6 months) (P=0.002). Further analyses displayed that in DEB-BACE group, CR was associated with improved ECOG score and longer MPE progression-free survival, and adverse events mainly included fever, chest distress/pain, gastrointestinal side effects, myelosuppression, rash and hemoptysis, which were all mild and tolerable. CONCLUSIONS: DEB-BACE plus intercostals arterial infusion chemotherapy could serve as a salvage treatment option for NSCLC patients with refractory MPE.