Metabolomic changes in Cryptocaryon irritans from Larimichthys crocea after exposure to copper plate

Cryptocaryon irritans is a highly detrimental parasite in mariculture, causing significant economic losses to the aquaculture industry of Larimichthys crocea. In recent years, copper and copper alloy materials have been used to kill parasites. In this study, the effect of copper plates on the tomont period of C. irritans was explored. The findings indicated that copper plates effectively eradicated tomonts, resulting in a hatching rate of 0. The metabolomic analysis revealed that a total of 2,663 differentially expressed metabolites (1,032 up-regulated and 1,631 down-regulated) were screened in the positive ion mode, and 2,199 differentially expressed metabolites (840 up-regulated and 1,359 down-regulated) were screened in the negative ion mode. L-arginine and L-aspartic acid could be used as potential biomarkers. Copper plate treatment affected 25 metabolic pathways in the tomont, most notably influencing histidine metabolism, retinol metabolism, the biosynthesis of phenylalanine, tyrosine, and tryptophan, as well as arginine and proline metabolism. It was shown that high concentrations of copper ions caused a certain degree of disruption to the metabolome of tomonts in C. irritans, thereby impacting their metabolic processes. Consequently, this disturbance ultimately leads to the rapid demise of tomonts upon exposure to copper plates. The metabolomic changes observed in this study elucidate the lethal impact of copper on C. irritans tomonts, providing valuable reference data for the prevention and control of C. irritans in aquaculture

An empirical comparison of fixed-strength and mixed-strength for interaction coverage based prioritization

Test case prioritization (TCP) plays an important role in identifying, characterizing, diagnosing and correcting faults quickly. TCP has been widely used to order test cases of different types, including model inputs (also called abstract test cases). Model inputs are constructed by modeling the program according to its input parameters, values, and constraints, and has been used in different testing methods, such as combinatorial interaction testing, and software product line testing. Interaction coveragebased test case prioritization (ICTCP) uses interaction coverage information derived from the model input to order inputs. Previous studies have focused generally on the fixed-strength ICTCP, which adopts a fixed strength(i.e.,thelevelofparameterinteractions)tosupporttheICTCPprocess.Itisgenerallyacceptedthat using more strengths for ICTCP, i.e., mixed-strength ICTCP, may give better ordering than fixed-strength. To confirm whether mixed-strength is better than fixed-strength, in this paper we report on an extensive empirical study using five real-world programs (written in C), each of which has six versions. The results oftheempiricalstudiesshowthatmixed-strengthhasbetterratesofinteractioncoverageoverallthanfixedstrength, but they have very similar rates of fault detection. Our results also show that fixed-strength should be used instead of the mixed-strength at the later stage of software testing. Finally, we offer some practical guidelinesfortesterswhenusinginteractioncoverageinformationtoprioritizemodelinputs,underdifferent testing scenarios and resources

Chinese Herbal Medicines as an Adjunctive Therapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

Pancreatic cancer is a common malignancy with a high mortality. Most patients present clinically with advanced pancreatic cancer. Moreover, the effect of radiotherapy or chemotherapy is limited. Complementary and alternative medicines represent exciting adjunctive therapies. In this study, we ascertained the beneficial and adverse effects of Chinese herbal medicine (CHM) in combination with conventional therapy for inoperable pancreatic cancer by using meta-analysis methods for controlled clinical trials. We extracted data for studies searched from six electronic databases that were searched and also assessed the methodological quality of the included studies. We evaluated the following outcome measures: 6-month and 1-year survival rate, objective response rate, disease control rate, quality of life, and adverse effects. The final analysis showed CHM is a promising strategy as an adjunctive therapy to treat advanced or inoperable pancreatic cancer and that CHM in combination with conventional therapy is a promising strategy for resistant disease. However, convincing evidence must be obtained and confirmed by high-quality trials in future studies

Regression test case prioritization by code combinations coverage

Regression test case prioritization (RTCP) aims to improve the rate of fault detection by executing more important test cases as early as possible. Various RTCP techniques have been proposed based on different coverage criteria. Among them, a majority of techniques leverage code coverage information to guide the prioritization process, with code units being considered individually, and in isolation. In this paper, we propose a new coverage criterion, code combinations coverage, that combines the concepts of code coverage and combination coverage. We apply this coverage criterion to RTCP, as a new prioritization technique, code combinations coverage based prioritization (CCCP). We report on empirical studies conducted to compare the testing effectiveness and efficiency of CCCP with four popular RTCP techniques: total, additional, adaptive random, and search-based test prioritization. The experimental results show that even when the lowest combination strength is assigned, overall, the CCCP fault detection rates are greater than those of the other four prioritization techniques. The CCCP prioritization costs are also found to be comparable to the additional test prioritization technique. Moreover, our results also show that when the combination strength is increased, CCCP provides higher fault detection rates than the state-of-the-art, regardless of the levels of code coverage

Characterization of the SWI/SNF complex and nucleosome organization in sorghum

The switch defective/sucrose non-fermentable (SWI/SNF) multisubunit complex plays an important role in the regulation of gene expression by remodeling chromatin structure. Three SWI/SNF complexes have been identified in Arabidopsis including BAS, SAS, and MAS. Many subunits of these complexes are involved in controlling plant development and stress response. However, the function of these complexes has hardly been studied in other plant species. In this study, we identified the subunits of the SWI/SNF complex in sorghum and analyzed their evolutionary relationships in six grass species. The grass species conserved all the subunits as in Arabidopsis, but gene duplication occurred diversely in different species. Expression pattern analysis in sorghum (Sorghum bicolor) showed that most of the subunit-encoding genes were expressed constitutively, although the expression level was different. Transactivation assays revealed that SbAN3, SbGIF3, and SbSWI3B possessed transactivation activity, which suggests that they may interact with the pre-initiation complex (PIC) to activate transcription. We chose 12 subunits in sorghum to investigate their interaction relationship by yeast two-hybrid assay. We found that these subunits displayed distinct interaction patterns compared to their homologs in Arabidopsis and rice. This suggests that different SWI/SNF complexes may be formed in sorghum to perform chromatin remodeling functions. Through the integrated analysis of MNase-seq and RNA-seq data, we uncovered a positive relationship between gene expression levels and nucleosome phasing. Furthermore, we found differential global nucleosome enrichments between leaves and roots, as well as in response to PEG treatment, suggesting that dynamics of nucleosome occupancy, which is probably mediated by the SWI/SNF complex, may play important roles in sorghum development and stress response

Case Report: Sequential Chemotherapy and Immunotherapy Produce Sustained Response in Osteosarcoma With High Tumor Mutational Burden

BackgroundImmunotherapy has provided an effective method for the treatment of many cancers. However, its efficacy in osteosarcoma is not satisfactory so far.Case PresentationHere, we presented a case of osteosarcoma treated with sequential chemotherapy and immunotherapy and showed promising therapeutic potential. The 29-year-old female patient presented 9th rib osteosarcoma with suspected right lung lower lobe metastasis. Surgery was performed to remove the primary lesion, and a series of chemotherapies were given afterward in consideration of the response and tolerance. The right lung lower lobe metastasis was under control first but progressed (PD) 9 months after the initiation of therapy. The lesion was surgically removed and subsequent chemotherapy was implemented. The patient had good tolerance with chemotherapy and maintained well for approximately 11 months before the discovery of 11th rib and right lung upper lobe metastases. Surgery was then performed on both lesions and achieved complete response. Post-surgical brief chemotherapy and subsequent long-term immunotherapy (pembrolizumab) maintained continuous remission for 33 months. The patient survived for 60 months with well-controlled disease from the time of confirmed diagnosis. Genetic alterations of all primary and metastatic lesions were investigated by whole-exome sequencing (WES). Substantial similarity in mutational landscape between the primary lesion and 11th rib metastasis and between the two lung metastases were revealed, while substantial heterogeneity was found between the rib lesions and lung metastases. The tumor mutational burden (TMB) for the 9th rib primary lesion, the metastatic 11th rib lesion, and the metastatic right upper and lower lobe nodule tissues was 8.02, 2.38, 4.61, and 0.14 mutations/Mb, respectively. The primary lesion exhibited the most diverse copy number variation (CNV) changes among all lesions. Furthermore, pathway enrichment analysis also suggested significant heterogeneity among the lesions.ConclusionsSurgery with sequential chemotherapy and maintenance immunotherapy was shown to have good response for the first time on osteosarcoma patient who had high TMB tumor lesions and good tolerance for chemotherapy and immunotherapy

Pervasive hybridization during evolutionary radiation of Rhododendron subgenus Hymenanthes in mountains of southwest China

Radiations are especially important for generating species biodiversity in mountainous ecosystems. The contribution of hybridization to such radiations has rarely been examined. Here, we use extensive genomic data to test whether hybridization was involved in evolutionary radiation within Rhododendron subgenus Hymenanthes, whose members show strong geographic isolation in the mountains of southwest China. We sequenced genomes for 143 species of this subgenus and 93 species of four other subgenera, and found that Hymenanthes was monophyletic and radiated during the late Oligocene to middle Miocene. Widespread hybridization events were inferred within and between the identified clades and subclades. This suggests that hybridization occurred both early and late during diversification of subgenus Hymenanthes, although the extent to which hybridization, speciation through mixing-isolation-mixing or hybrid speciation, accelerated the diversification needs further exploration. Cycles of isolation and contact in such and other montane ecosystems may have together promoted species radiation through hybridization between diverging populations and species. Similar radiation processes may apply to other montane floras in this region and elsewhere

Overexpression of TaNAC2D displays opposite responses to abiotic stresses between seedling and mature stage of transgenic Arabidopsis

Environmental stresses frequently affect plant growth and development, and many genes have been found to be induced by unfavorable environmental conditions. Here, we reported the biological functions of TaNAC2D, a stress-related NAC (NAM, ATAF, and CUC) gene from wheat. TaNAC2D showed transcriptional activator activity in yeast. TaNAC2D-GFP fusion protein was localized in the nucleus of wheat mesophyll protoplasts. TaNAC2D transcript abundance was significantly induced by NaCl, PEG6000, and abscisic acid (ABA) at seedling stage, and repressed by NaCl and PEG6000 at mature plant stage. When TaNAC2D was introduced into Arabidopsis, the 35-day-old soil-grown TaNAC2D-overexpression (TaNAC2D-OX) plants displayed slower stomatal closure, higher water loss rate, and more sensitivity to salt and drought stresses compared with WT plants. In contrast, TaNAC2D-OX seedlings, grown on 1/2 MS medium supplemented with different concentrations of NaCl, Mannitol, and MV, had enhanced tolerances to salt, osmotic and oxidative stresses during seed germination and post-germination periods. The opposite stress-responsive phenotypes of transgenic Arabidopsis were consistent with the expression patterns of TaNAC2D in wheat. Moreover, under high salinity and dehydration conditions, three marker genes, including NCED3, RD29A, and RD29B, were down-regulated in 35-d-old TaNAC2D-OX plants grown in soil and up-regulated in 14-d-old TaNAC2D-OX seedlings grown on 1/2 MS medium. Our results suggest that the change in growth stages and environmental conditions may regulate TaNAC2D’s function

The complete chloroplast genome of Gentaina urnula (Gentianaceae)

Gentiana urnula, is an alpine medicinal endemic to the Qinghai-Tibetan Plateau. In this study, the complete chloroplast DNA sequence of G. urnula was assembled，and its genome is 149,064 bp in length, including a large single-copy region (LSC) of 81,158 bp and a small single-copy region (SSC) of 17,034 bp, which was separated by a pair of 25,436 bp inverted repeat regions (IRs). A total of 130 genes are detected, including 86 protein-coding genes, 37 tRNA genes, and 7 rRNA genes. The complete chloroplast genomes of G. urnula will help to study the genetic diversity and phylogenetic analysis of Gentianales