Coniogramme intermedia Hieron. is a morphologically distinctive species in the genus. It is identified by lanceolate pinnules with serrated margins, free veins, hydathodes extending into teeth, and laminae abaxially hairy. It is mainly distributed in the tropical and subtropical regions of Asia. Herein, we report the first complete chloroplast genome sequence of C. intermedia. Also, it is the opening one of the genus Coniogramme Fée. The chloroplast genome sequence is 153,561 bp in length. The genome has a typical quadripartite structure, including a large single-copy (LSC) region of 82,817 bp, a small single-copy (SSC) region of 21,236 bp, and two inverted repeat (IR) regions of 24,754bp each. The total GC content is 45.0%. The complete plastome sequence contains 114 genes, including, 81 protein-coding, 29 tRNA, and four rRNA genes. The phylogenetic analysis of Pteridaceae based on the complete chloroplast genomes was also presented in this study.

Severe trauma and burns accompanied by sepsis are associated with high morbidity and mortality. Little is known about the transcriptional similarity between trauma, burns, sepsis, and systemic inflammatory response syndrome (SIRS). Uncovering key genes and molecular networks is critical to understanding the biology of disease. Conventional analysis of gene changes (fold change) analysis is difficult for time-serial data such as post-injury blood transcriptome.

BACKGROUND The aim of this work was to systematically compare the differences between sorafenib and lenvatinib for patients with hepatocellular carcinoma (HCC) from genetic and clinical perspectives. MATERIAL AND METHODS The mRNA and miRNA sequencing information of patients with HCC treated with either sorafenib or lenvatinib was analyzed using differential expression and a protein-protein interaction assay. The clinical manifestations and adverse events of the 2 drugs were also investigated. RESULTS Compared with patients with HCC treated with sorafenib, patients treated with lenvatinib developed 8 differentially expressed genes (DEGs, FGF4, FGF23, UNC13C, RIMBP2, STXBP5L, PHOX2B, NEUROD4, and POU4F2) and 3 miRNAs (DEMs, has-miR-548ah, has-miR-888, and has-miR-196a-1), of which hsa-miR-548 regulated 4 target genes, the largest number among the 3 miRNAs. The functions of these DEMs and DEGs were verified by external experiments in the HCC cell line Hep3B2.1-7. We further investigated the adverse events of the drugs for patients with advanced HCC in clinical treatment. The patients in the sorafenib group developed less frequent symptoms of hypertension and diarrhea. Also, the frequency of hand-foot skin reactions in patients treated with lenvatinib was lower than that of patients treated with sorafenib (P<0.05). There were no significant differences in nausea, fatigue, frequent urination, and dizziness (P>0.05). CONCLUSIONS In a time of increasing interest in chemotherapy drug treatments for patients with HCC, this study provided a better understanding of the clinical evaluations of sorafenib and lenvatinib.

This study evaluated the effects of Lactiplantibacillus plantarum subsp. plantarum ZA3, Artemisia argyi and their combination, on the fermentation characteristics, microbial community, mycotoxins and crude flavonoids content of fermented soybean meal during fermentation (under anaerobic conditions) and aerobic exposure (under aerobic conditions). The results showed that ZA3, Artemisia argyi and ZA3+ Artemisia argyi groups had lower pH values and higher lactic acid concentrations compared with controls, and additives increased the abundance of Lactiplantibacillus and decreased those of Acetobacter and Enterobacter; in particular, Artemisia argyi and ZA3+ Artemisia argyi reduced the abundance of fungi, such as Aspergillus, Pichia, Fusarium, Cladosporium and Xeromyces. Meanwhile, the contents of mycotoxins were lower in treated groups, and even mycotoxins in the control were significantly reduced after 30 d (p < 0.05). Crude flavonoids that were correlated positively with Lactococcus and negatively with Bacillus, Aspergillus, Enterobacter and Kazachstania were significantly higher in the Artemisia argyi and ZA3+ Artemisia argyi groups (p < 0.05).

Melon (Cucumis melo L.) is an agronomically important vegetable. Most cultivars of melon are andromonoecious and bisexual flowers only emerged from the leaf axil of lateral branches. However, the regulatory mechanism contributing to the occurrence of bisexual flowers were still obscure. In this study, ethephon was applied in two common cultivars of melon. In control without ethephon treatment, no bisexual flower was made in the main stem. However, 6.56 ± 1.42 and 6.63 ± 0.55 bisexual flowers were respectively induced in main stem of 'Yangjiaocui-QX' and 'Lvbao' after ethephon treatment, and induced bisexual flowers distributed in 12-20 nodes of main stem. During the formation of bisexual flowers, 41 metabolites were significantly up-regulated and 98 metabolites were significantly down-regulated. According to the KEGG enrichment analysis of 139 different metabolites, a total of 30 pathways were mapped and KEGG terms of "Phenylalanine, tyrosine and tryptophan biosynthesis", "Phenylalanine metabolism" and "Flavone and flavonol biosynthesis" were significantly enriched. In three significantly enriched KEGG terms, shikimic acid, L-tryptophan, L-phenylalanine, and kaempferol were significantly up-regulated while L-tyrosine, 4-hydroxycinnami acid and luteolin were significantly down-regulated in ET compared to CK. Different metabolites were also classified depend on major class features and 14 classes were acquired. The results of metabonomics and endogenous hormone identification indicated that ethylene could enhance the concentration of salicylic acid, methyl jasmonate, ABA and IAA. This study provided an important theoretical foundation for inducing bisexual flowers in main stem and breeding new varieties of melon in future.

Huang Bai Jian Pi (HBJP) decoction, a Chinese herbal formula based on the Pulsatilla decoction (PD) and Si Junzi decoction, is efficacy to treat clinical diarrhea in calves.

Lactic acid bacteria (LAB), which are characterized by producing various functional metabolites, including antioxidants, organic acids, and antimicrobial compounds, are widely used in the food industry to improve gut health and prevent the growth of spoilage microorganisms. With the continual incidence of foodborne disease and advocacy of consumers for gut health, LAB have been designated as vital biopreservative agents in recent years. Therefore, LAB with excellent antimicrobial properties and environmental tolerance should be explored further. In this study, we focus on screening the LAB strains from a specialty pig (Bamei pig) feces of the Tibetan plateau region and determine their antimicrobial properties and environmental tolerance to evaluate their potential probiotic values. A total of 116 LAB strains were isolated, from which the LAB strain Qinghai (QP)28-1 was identified as Lactiplantibacillus (L.) plantarum subsp. plantarum using 16S rDNA sequencing and recA amplification, showing the best growth capacity, acid production capacities, environmental tolerance, hydrophobicity, antibiotic susceptibility, and bacteriocin production capacity. Furthermore, this strain inhibited the growth of multiple pathogens by producing organic acids and bacteriocin. These bacteriocin-encoding genes were identified using PCR amplification, including plnS, plnN, and plnW. In conclusion, bacteriocin-producing L. plantarum subsp. plantarum QP28-1 stands out among these 116 LAB strains, and was considered to be a promising strain used for LAB-related food fermentation. Moreover, this study provides a convenient, comprehensive, and shareable profile for screening of superior functional and bacteriocin-producing LAB strains, which can be used in the food industry.

Ferroptosis is a type of cell death driven by iron accumulation and lipid peroxidation, which is involved in the pathogenesis of various tumors. Small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) is a critical SUMO-specific protease, which controls multiple cellular signaling processes. However, the roles and mechanisms of SENP1-mediated protein SUMOylation in the regulation of cell death and ferroptosis remain unexplored.

Background: Colorectal cancer is a commonly diagnosed cancer with high mortality worldwide. Postoperative recidivation and metastasis still are the main challenges in clinical treatments. Thus, it is urgent to develop new therapies against colorectal cancer. Epithelial Cell Adhesion Molecule (EpCAM) is overexpressed in colorectal cancer cells and strongly associated with cancer development. Bispecific antibody (BsAb) is a kind of promising immunotherapy, which could recognize T cells and cancer cells simultaneously to achieve the anti-tumor effects. Methods: A bispecific antibody targeting EpCAM and CD3 with IgG format was genereated by split intein based on the Bispecific Antibody by Protein Splicing" platform. In vitro, the affinity of CD3×EpCAM BsAb was determined by Biolayer interferometry, its cytotoxicity was detected by LDH release assay, T cell recruitment and activation was detected by Flow Cytometry. In vivo, its pharmacokinetic parameters were detected, and anti-tumor effects were evaluated on the tumor cell xenograft mouse model. Results: The results showed that the CD3×EpCAM BsAb could activate and recruit T cells via binding colorectal cells and T cells, which could lead to more potent cytotoxicity to various colorectal cell lines than its parent EpCAM monoclonal antibody (mAb) in vitro. The CD3×EpCAM BsAb had similar pharmacokinetic parameters with EpCAM mAb and inhibits tumor growth on the SW480 tumor cell xenograft mouse model. Conclusion: The CD3×EpCAM BsAb could be a promising candidate for colorectal cancer treatment.

Maximizing grain yields with effective fertilization technologies and minimizing nitrogen losses is essential in agroecosystems. In this research, we conducted a two-year field experiment to explore whether dripline spacing and fertilization rate would affect maize grain yield. Two dripline spacings (i.e., one drip line per row of maize with a row space of 60 cm and one drip line per two rows of maize) and two fertilization rates (i.e., high fertilization level: N, 180 kg ha-1; P2O5, 90 kg ha-1; and K2O, 90 kg ha-1 and low level: N, 139.5 kg ha-1; P2O5, 76.5 kg ha-1; and K2O, 76.5 kg ha-1) were employed in this research. The results showed that maize yield was significantly affected by both dripline spacing and fertilization rate. The maize yield was 10.2% higher in the treatment with one drip line per two rows than that in the treatment with one drip line per row. Maize yield increased by 10.9% at the high fertilization level compared to that at the low fertilization level. The quantity of cumulative ammonia volatilization was reduced by 15.1% with one drip line per two rows compared to that with one drip line per row, whereas it increased by 26.9% at the high fertilization level compared with that at the low fertilization level. These results indicated that one drip line per two rows with a high fertilization rate increased the yield and could reduce the environmental burden, which may be economically beneficial and environmentally sound for maize fertigation for green agricultural development.

Changes in maternal diet and metabolic defects in mothers can profoundly affect health and disease in their progeny. However, the biochemical mechanisms that induce the initial reprogramming events at the cellular level have remained largely unknown owing to limitations in obtaining pure populations of quiescent oocytes. Here, we show that the precocious onset of mitochondrial respiratory quiescence causes a reprogramming of progeny metabolic state. The premature onset of mitochondrial respiratory quiescence drives the lowering of Drosophila oocyte NAD+ levels. NAD+ depletion in the oocyte leads to reduced methionine cycle production of the methyl donor S-adenosylmethionine in embryos and lower levels of histone H3 lysine 27 trimethylation, resulting in enhanced intestinal lipid metabolism in progeny. In addition, we show that triggering cellular quiescence in mammalian cells and chemotherapy-resistant human cancer cell models induces cellular reprogramming events identical to those seen in Drosophila, suggesting a conserved metabolic mechanism in systems reliant on quiescent cells.

Due to higher morbidity and mortality, ST-segment elevation myocardial infarction (STEMI) causes many public health problems.

Oncolytic viruses are emerging as therapeutic agents in oncology. However, resistance of tumor cells to HSV oncolysis pose significant barriers to antitumor response. Thus, study on the mechanisms of therapeutic resistance to oHSV and finding strategies for overcoming these mechanisms are needed. In this study, Rab27a, a small GTPase involved in exosome biogenesis, was noticed to highly correlate with the susceptibility of tumor cells to oHSV. We found that i) lower abundance of Rab27a in oHSV resistant mouse tumor cells was shown when compared to that of sensitive tumor cells through deep-sequencing; ii) the resistance of human tumor cells to oHSV infection is associated with a downregulation of Rab27a expression and overexpression of Rab27a can promote the replication capacity of oHSV; iii) Interestingly, a stabilizer protein of Rab27a, KIBRA, highly accumulated in oHSV resistant tumor cells, which is in contrast with the expression pattern of Rab27a. Furthermore, knockdown of KIBRA expression reduced oHSV replication in oHSV resistant tumor cells. Consequently, Rab27a was found to be relevant with oHSV replication without cell type specificity, and low abundance of Rab27a contributes to oHSV resistance in both mouse and human tumor cells, which will give new insights in the identification of potential targets or biomarkers for oHSV cancer therapy.

Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). In this study, the ex vivo effect of combining NY-ESO-1-specific T cells with the clinically approved pan HDACis panobinostat or vorionstat was investigated. Our data demonstrated that STS cells were sensitive to HDACis. Administration of HDACi prior to NY-ESO-1-specific T cells exerted enhanced lysis against the NY-ESO-1+ STS cell line SW982. This correlated with an increase in the NY-ESO-1 and HLA-ABC expression of SW982 cells, as well as increased CD25 expression on NY-ESO-1-specific T cells. Furthermore, the immune reactivity of NY-ESO-1-specific CD8+ T cells in terms of cytokine release was enhanced by HDACis. In summary, pretreatment with HDACis represents a potential means of enhancing the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive STS.

Due to the abuse of traditional antibiotics and the continuous mutation of microbial resistance genes, microbial infections have become serious problems for human health. Therefore, novel antibacterial agents are urgently required, and amphibian antimicrobial peptides (AMP) are among the most interesting potential antibacterial leads. In this research, a novel peptide, named kassporin-KS1 (generically QUB-1641), with moderate antibacterial activity against Gram-positive bacteria, was discovered in the skin secretion of the Senegal running frog, Kassina senegalensis. Using site-specific sequence enrichment with a motif "glycine-lysine" that frequently occurs in ranid frog temporin peptides, a series of QUB-1641 analogues were synthesized, and effects on selected bioactivities were studied. The greatest activity enhancement was obtained when the "glycine-lysine" motif was located at the eighth and ninth position as in QUB-1570.QUB-1570 had a broader antibacterial spectrum than QUB-1641, and was eight-fold more potent. Moreover, QUB-1570 inhibited S. aureus biofilm most effectively, and significantly enhanced the viability of insect larvae infected with S. aureus. When the "glycine-lysine" motif of QUB-1570 was substituted to reduce the helix ratio and positive charge, the antibacterial activities of these synthetic analogues decreased. These data revealed that the "glycine-lysine" motif at positions 8 and 9 had the greatest enhancing effect on the antibacterial properties of QUB-1570 through increasing positive charge and helix content. This research may provide strategies for the site's selective amino acid modification of some natural peptides to achieve the desired enhancement of activity.

Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and γ-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.

The majority of solitary brain metastases appear similar to glioblastomas (GBMs) on magnetic resonance imaging (MRI). This study aimed to develop and validate an MRI-based model to differentiate intracranial metastases from GBMs using automated machine learning.

Regardless of great progress in early detection of hepatocellular carcinoma (HCC), unresectable HCC (uHCC) still accounts for the majority of newly diagnosed HCC with poor prognosis. With the promising results of a double combination of transarterial chemo(embolization) and tyrosine kinase inhibitors (TKIs), and TKIs and immune checkpoint inhibitors (ICIs), a more aggressive strategy, a triple combination of transarterial chemo(embolization), TKIs, and ICIs has been tried in the recent years. Hence, we aimed to conduct a systematic review to verify the safety and efficacy of the triple therapy for uHCC.

MicroRNA-139-5p (miR-139-5p) is one of the most differentially expressed miRNAs in the brain between healthy people and depressed patients. However, its function in depression is unclear. Therefore, we investigated the function of miR-139-5p in depression. Here, miR-139-5p expression was found to be upregulated in the model group. MiR-139-5p inhibition could increase sucrose preference and decrease mice immobility time after chronic corticosterone (CORT) injection. Furthermore, compared with the antago-NC group, 3 weeks of antagomiR-139-5p treatment significantly decreased miR-139-5p level in model group hippocampus, increased sucrose preference index, reduced neuron damages, and enhanced the levels of nuclear receptor subfamily 3 group C member 1 (NR3C1), brain-derived neurotrophic factor (BDNF), phosphorylated/total tyrosine kinase receptor B (p-TrkB/TrkB), phosphorylated/total cAMP-response element-binding protein (p-CREB/CREB) and phosphorylated/total extracellular regulated protein kinases (p-ERK/ERK). Moreover, as a potential target for miR-139-5p, NR3C1 level was reduced by miR-139-5p mimic. Altogether, by activating the BDNF-TrkB signaling pathway, miR-139-5p inhibition plays an antidepressant-like role and might serve as an effective depression target (Fig. graphical abstract).

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.