Phylogenetic relationships and adaptation in deep-sea carideans revealed by mitogenomes.

The deep-sea environment is characterized by extreme and inhospitable conditions, including oxygen depletion, low temperatures, high pressure, absence of light, and limited food availability. Mitochondria and mitogenomes play a crudial role in aerobic respiration to generate energy for eukaryotes. Here, using the Illumina Hiseq 4000 platform, we performed mitogenome sequencing for five deep-sea caridean species: Lebbeus shinkaiae, Lebbeus Formosus, Glyphocrangon regalis, Heterocarpus dorsalis, and Heterocarpus laevigatus, and five deep-sea caridean mitogenomes were assembled and identified. Each of the five mitogenomes contained 13 protein-coding genes, 2 rRNAs and 22 tRNAs. Specific elements, such as tandem repeats and AT-rich sequences, were observed in the control regions of Lebbeus formosus and Lebbeus shinkaiae, potentially take a role in regulating mitochondrial genome replication and transcription. The gene order of all obtained mitogenomes follows caridean ancestral type organization. Phylogenetic analysis shows a robustly supported phylogenetic tree for the infraorder Caridea. The monophyly of the families included in this study was strongly supported. This study supports the monophyly of Oplophoroidea, but rejects the monophyletic status of Nematocarcinoidea, Crangonoidea, and Alpheoidea. At the genus level, Plesionika is polyphyletic and Rimicaris is paraphyletic in our analysis. Furthermore, Paralebbeus may be considered invalid and synonymous with Lebbeus. Positive selection analysis reveals evidence for adaptive changes in the mitogenome of different deep-sea caridean lineages. Nine residues located in cox1, cox3, atp6, nad1, nad2, nad4, nad5, nad6 and cytb were determined to have undergone positive selection. Mitogenome of different deep-sea lineages experienced different positive selection, and the lineage represented by Alvinocarididae living in deep-sea hydrothermal vents experienced the strongest positive selection. This study provides valuable insights into the adaptive evolution of deep-sea shrimps at the mitochondrial, highlighting the mitogenomic strategy that contribute to their unique adaptations in the deep-sea environment.

Safety of COVID-19 Vaccination in Patients With Breast Cancer: Cross-Sectional Study in China.

BACKGROUND: The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. OBJECTIVE: This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. METHODS: Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. RESULTS: A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. CONCLUSIONS: Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882.

Co-infection with human papillomavirus and sexually transmitted infections among Chinese individuals.

OBJECTIVES: This study aimed to investigate the prevalence of Human Papillomavirus (HPV), Sexually Transmitted Infections (STIs) and their co-infections on different genders and ages. METHODS: Different samples of secretions from the reproductive system were collected from 459 males and 494 females for HPV and STI detection. RESULTS: Total HPV infection rate was 49.46 % for males and 48.99 % for females, and the distribution of HPV subtypes varied significantly between different genders. The infection rate of HR-HPV 52 and 31 in females was higher than that in males (p = 0.002 and 0.039, respectively). In contrast, the infection rate of LR-HPV 6 and 11 in males was higher than that in females (p = 0.01 and 0.001, respectively). Females had a significantly higher infection rate of Ureaplasma urealyticum (UU). Besides, these STIs were stratified based on age and the results indicated that the highest incidence of STIs was observed in younger patients (<20 years old). Patients with HPV infections had a higher incidence of Chlamydia trachomatis (CT) in both males and females. CONCLUSIONS: There is a need to perform HPV, CT and UU screening among patients, and more thorough health education for younger patients is of great clinical significance to improve treatment and prognosis.

A pathogenesis-related protein 1 of Cucurbita moschata responds to powdery mildew infection.

Pumpkin (Cucurbita moschata Duch.) productivity is severely hindered by powdery mildew (PM) worldwide. The causative agent of pumpkin PM is Podosphaera xanthii, a biotrophic fungus. Pathogenesis-related protein 1 (PR1) homolog was previously identified from transcriptomic analysis of a PM-resistant pumpkin. Here, we investigated the effects of CmPR1 gene from pumpkin for resistance to PM. Subcellular localization assay revealed that CmPR1 is a cytoplasmic protein in plants. The expression of CmPR1 gene was strongly induced by P. xanthii inoculation at 48 h and exogenous ethylene (ET), jasmonic acid (JA) and NaCl treatments, but repressed by H2O2 and salicylic acid (SA) treatments. Visual disease symptoms, histological observations of fungal growth and host cell death, and accumulation of H2O2 in transgenic tobacco plants indicated that CmPR1 overexpression significantly enhanced the resistance to Golovinomyces cichoracearum compared to wild type plants during PM pathogens infection, possibly due to inducing cell death and H2O2 accumulation near infected sites. The expression of PR1a was significantly induced in transgenic tobacco plants in response to G. cichoracearum, suggesting that CmPR1 overexpression positively modulates the resistance to PM via the SA signaling pathway. These findings indicate that CmPR1 is a defense response gene in C. moschata and can be exploited to develop disease-resistant crop varieties.

Biomimetic redox-responsive smart coatings with resistance-release functions for reverse osmosis membranes.

Membrane fouling induces catastrophic loss of separation performance and seriously restricts the applications of reverse osmosis (RO) membranes. Inspired by the mussel structure, polydopamine (PDA) and cystamine molecules (CA) with excellent anti-fouling properties were used to prepare accessible, biocompatible, and redox-responsive coatings for RO membranes. The PDA/CA-coated RO membranes exhibit a superior water flux of 65 L m-2 h-1 with a favourable NaCl rejection exceeding 99%. The water permeability through the PDA/CA-coated membrane is much higher than that of most membranes with similar rejection rates. Due to the formed protective hydration layers by PDA/CA coatings, anti-fouling properties against proteins, polysaccharides and surfactants were evaluated separately, and ultralow fouling properties were demonstrated. Moreover, the disulfide linkages in CA molecules can cleave in a reducing environment, yielding the degradation of PDA/CA coatings, thereby removing the foulants deposited on the coatings. The degradation endows the coated membranes with satisfying longtime anti-fouling properties, where the flux recovery reaches up to 90%. The construction of redox-responsive smart coatings not only provided a promising route to alleviate membrane fouling but can also be upscaled for use in numerous practical applications like sensors, medical devices, and drug delivery.

Biochar-Stimulated Pumpkin Performance Under Cadmium Stress Is Strongly Linked to Metabolite Pattern.

In this study, pumpkin seedlings were subjected to cadmium stress (100 mg/L cadmium ion solution, 10 days) without or with wheat straw biochar at different concentrations (0%, 0.5%, 1%, and 2% w/v). As the biochar concentration increased, the amount of cadmium accumulated in the root and stem of pumpkin seedlings decreased and the fresh weight of root, stem and leaf increased. The highest cadmium concentration was in the root, followed by the stem and then the leaf. 1% and 2% biochar treatments reduced the oxidative stress of cadmium to seedlings, and added the contents of fatty acid, carbohydrate, amino acid and indoleacetic acid in the root. With the increase of biochar concentration, the metabolites promoting root growth increased. These results provide new information about how biochar alleviates cadmium stress by affecting the metabolic response.

Genome-Wide Identification of APETALA2/ETHYLENE RESPONSIVE FACTOR Transcription Factors in Cucurbita moschata and Their Involvement in Ethylene Response.

APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF), a plant-specific transcription factor (TF) family, plays an essential role in the growth and development of plants, and in their response to biotic and abiotic stresses. However, information on AP2/ERF in Cucurbita moschata (pumpkin), an edible and medicinal vegetable used worldwide, is scarce. A total of 212 AP2/ERF genes were identified in the C. moschata genome (CmoAP2/ERFs). Based on phylogenetic analysis, they were divided into four groups-28 AP2s, 92 ERFs, 86 dehydration-responsive element-binding (DREB) factors, and 6 ABI3/VPs (RAV). The 212 AP2/ERF genes were unevenly distributed on the 20 chromosomes of C. moschata. The results of structural analysis showed the absence of introns on 132 CmoAP2/ERFs. Four pairs of tandem duplication and 155 pairs of segmental duplication events were identified, which indicated that segmental duplications might be the main reason for the expansion of the CmoAP2/ERF family. The analysis of cis-regulatory elements (CREs) showed that most of the CmoAP2/ERFs contained hormone response elements (ABREs, EREs) in their promoters, suggesting that AP2/ERFs could contribute to the processes regulated by ethylene and abscisic acid. By comparing the transcriptome of ethephon-treated and control plants, we found that 16 CmoAP2/ERFs were significantly upregulated after ethephon treatment. Furthermore, we determined the expression patterns of these genes at different developmental stages of female and male flowers. This study provides insights into the identification, classification, physicochemical property, phylogenetic analysis, chromosomal location, gene structure, motif identification, and CRE prediction of the AP2/ERF superfamily in C. moschata. Sixteen CmoAP2/ERF genes were identified as ethylene-inducible genes. The results of this study will be valuable for understanding the roles of CmoAP2/ERFs in ethylene response and should provide a foundation for elucidating the function of AP2/ERF TFs in C. moschata.

Transcriptome Analysis Revealed the Molecular Response Mechanism of Non-heading Chinese Cabbage to Iron Deficiency Stress.

Iron is a trace metal that is found in animals, plants, and the human body. Human iron absorption is hampered by plant iron shortage, which leads to anemia. Leafy vegetables are one of the most direct and efficient sources of iron for humans. Despite the fact that ferrotrophic disorder is common in calcareous soil, however, non-heading Chinese cabbage performs a series of reactions in response to iron deficiency stress that help to preserve iron homeostasis in vivo. In this study, we discovered that iron deficiency stress caused leaf yellowing and impeded plant development in both iron-deficient and control treatments by viewing or measuring phenotypic, chlorophyll content, and Fe2+ content in both iron-deficient and control treatments. We found a total of 9213 differentially expressed genes (DEGs) in non-heading Chinese cabbage by comparing root and leaf transcriptome data with iron deficiency and control treatments. For instance, 1927 DEGs co-expressed in root and leaf, including 897 up-regulated and 1030 down-regulated genes, respectively. We selected some key antioxidant genes, hormone signal transduction, iron absorption and transport, chlorophyll metabolism, and transcription factors involved in the regulation of iron deficiency stress utilizing GO enrichment, KEGG enrichment, multiple types of functional annotation, and Weighted Gene Co-expression Network Analysis (WGCNA). This study identifies prospective genes for maintaining iron homeostasis under iron-deficient stress, offering a theoretical foundation for further research into the molecular mechanisms of greater adaptation to iron-deficient stress, and perhaps guiding the development of iron-tolerant varieties.

Corrigendum: Expression of Pumpkin CmbHLH87 Gene Improves Powdery Mildew Resistance in Tobacco.

[This corrects the article DOI: 10.3389/fpls.2020.00163.].

Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C.

In view of the role of miR-138 in cancer cells, we predicted the target of miR-138 and its targeting to SEMA4C by bioinformatics software and luciferase experiment. The expression levels of miR-138 in human normal breast epithelial cells and two kinds of BC cells were compared, and the transfection cells were selected. MiR-138 mimetic negative control (miR-NC), miR-138 mimic and miR-138 inhibitor were designed for cell transfection. The results showed that the expression level of miR-138 in MCF-7 cells was the lowest. The up regulation of miR-138 would lead to the high expression of E-cad and the low expression of N-cad, vim and SEMA4C, and the vitality and invasion of BC cells would decrease. The down regulation of miR-138 would lead to the low expression of E-cad and the high expression of N-cad, vim and SEMA4C, and the vitality and invasion of BC cells would increase. miR-138 targeted regulation of SEMA4C can promote the expression of N-cad, inhibit the expression of E-cad, vim and SEMA4C, reverse the EMT of BC cells, and inhibit the activity and invasion of BC cells. MiR-138 has clinical potential as a tumor marker of BC.

The roles of cadmium on growth of seedlings by analysing the composition of metabolites in pumpkin tissues.

Changes in the types and contents of metabolites in plants can occur in response to environmental stress. In this study, pumpkin seeds were cultivated in a cadmium ion solution (cadmium sulfate) for 7 days, and growth parameters, antioxidant enzyme activities, and metabolites in the root, stem, and leaf were analyzed. The results showed that cadmium accumulation characteristics were in the order of root > stem > leaf. Cadmium restrained root growth and promoted superoxide dismutase, peroxidase, catalase activities in the root, but inhibited their activities in the leaf. Cadmium did not change the total biomass of pumpkin seedlings. Orthogonal partial least squares (OPLS) analyses were conducted to detect the relationships between fresh weight and metabolites. These analyses revealed that maltose had significantly positive relationships with the fresh weight of the root, stem, and leaf. Cadmium influenced glyoxylate and dicarboxylate metabolism, aminoacyl-tRNA biosynthesis, sulfur metabolism, butanoate metabolism, alanine, aspartate and glutamate metabolism, glutathione metabolism, glycine, serine and threonine metabolism in the root; glycolysis/gluconeogenesis in the stem; and biosynthesis of unsaturated fatty acids, galactose metabolism, cutin, suberine and wax biosynthesis in the leaf. It is important that cadmium inhibited root growth by inhibiting carbohydrate transport from the leaf to the root and promoted leaf growth by the accumulation of carbohydrates in the leaf. Furthermore, cadmium also restrained amino acid metabolism in the root of pumpkin seedlings. These results provide new information about how pumpkin seedlings respond to cadmium stress.

Transcriptomic analysis reveals ethylene signal transduction genes involved in pistil development of pumpkin.

Development of female flowers is an important process that directly affects the yield of Cucubits. Little information is available on the sex determination and development of female flowers in pumpkin, a typical monoecious plant. In the present study, we used aborted and normal pistils of pumpkin for RNA-Seq analysis and determined the differentially expressed genes (DEGs) to gain insights into the molecular mechanism underlying pistil development in pumpkin. A total of 3,817 DEGs were identified, among which 1,341 were upregulated and 2,476 were downregulated. The results of transcriptome analysis were confirmed by real-time quantitative RT-PCR. KEGG enrichment analysis showed that the DEGs were significantly enriched in plant hormone signal transduction and phenylpropanoid biosynthesis pathway. Eighty-four DEGs were enriched in the plant hormone signal transduction pathway, which accounted for 12.54% of the significant DEGs, and most of them were annotated as predicted ethylene responsive or insensitive transcription factor genes. Furthermore, the expression levels of four ethylene signal transduction genes in different flower structures (female calyx, pistil, male calyx, stamen, leaf, and ovary) were investigated. The ethyleneresponsive DNA binding factor, ERDBF3, and ethylene responsive transcription factor, ERTF10, showed the highest expression in pistils and the lowest expression in stamens, and their expression levels were 78- and 162-times more than that in stamens, respectively. These results suggest that plant hormone signal transduction genes, especially ethylene signal transduction genes, play an important role in the development of pistils in pumpkin. Our study provides a theoretical basis for further understanding of the mechanism of regulation of ethylene signal transduction genes in pistil development and sex determination in pumpkin.

Expression of Pumpkin CmbHLH87 Gene Improves Powdery Mildew Resistance in Tobacco.

Powdery mildew (PM), caused by Podosphaera xanthii, is a major threat to the global cucurbit yield. The molecular mechanisms underlying the PM resistance of pumpkin (Cucurbita moschata Duch.) are largely unknown. A homolog of the basic helix-loop-helix (bHLH) transcription factor was previously identified through a transcriptomic analysis of a PM-resistant pumpkin. In this study, this bHLH homolog in pumpkin has been functionally characterized. CmbHLH87 is present in the nucleus. CmbHLH87 expression in the PM-resistant material was considerably downregulated by PM; and abscisic acid, methyl jasmonate, ethephon, and NaCl treatments induced CmbHLH87 expression. Ectopic expression of CmbHLH87 in tobacco plants alleviated the PM symptoms on the leaves, accelerated cell necrosis, and enhanced H2O2 accumulation. The expression levels of PR1a, PR5, and NPR1 were higher in the PM-infected transgenic plants than in PM-infected wild-type plants. Additionally, the chlorosis and yellowing of plant materials were less extensive and the concentration of bacteria at infection sites was lower in the transgenic tobacco plants than in the wild-type plants in response to bacterial wilt and scab pathogens. CmbHLH87 may be useful for genetic engineering of novel pumpkin cultivars in the future.

Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial.

PURPOSE: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS: This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS: Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION: Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

Comprehensive analysis of prognosis-related methylated sites in breast carcinoma.

BACKGROUND: Breast carcinoma has become a nonnegligible public health problem in China with its increasing incidence and mortality in woman. As a early event regulating tumorigenesis and development, DNA methylation became one of the focuses of current carcinoma researches on potential diagnostic and therapeutic targets. METHODS: In this study, we comprehensively analyzed the gene expression data and DNA methylation data of breast carcinoma and adjacent normal tissues samples in the Gene Expression Omnibus database. Influences of tumor stage, adjuvant therapy, hormone therapy, and chemotherapy on CpG methylation level were explored by linear regression analysis. Correlations between methylation and gene expression levels were determined by spearman rank correlation analysis. Log-rank test was applied for determining significance of associations between CpG sites methylation level and breast cancer patients' Kaplan-Meier survival. RESULTS: A total of 229 CpG sites were found to be significantly associated with tumor stage or treatment, and eight of which were potential markers that affect the survival of breast carcinoma and negatively correlated with their genes' expression levels. CONCLUSIONS: We reported eight CpG sites as potential breast cancer prognosis signatures through comprehensively analyzed gene expression and DNA methylation datasets, and excluding influences of tumor stage and treatment. This should be helpful for breast cancer early diagnosis and treatment.

Improved Powdery Mildew Resistance of Transgenic Nicotiana benthamiana Overexpressing the Cucurbita moschata CmSGT1 Gene.

Powdery mildew (PM), which is mainly caused by Podosphaera xanthii, is a serious biotrophic pathogen disease affecting field-grown and greenhouse-grown cucurbit crops worldwide. Because fungicides poorly control PM, the development and cultivation of PM-resistant varieties is critical. A homolog of SGT1 (suppressor of the G2 allele of skp1), which encodes a key component of the plant disease-associated signal transduction pathway, was previously identified through a transcriptomic analysis of a PM-resistant pumpkin (Cucurbita moschata) inbred line infected with PM. In this study, we have characterized this SGT1 homolog in C. moschata, and investigated its effects on biotic stress resistance. Subcellular localization results revealed that CmSGT1 is present in the nucleus. Additionally, CmSGT1 expression levels in the PM-resistant material was strongly induced by PM, salicylic acid (SA) and hydrogen peroxide (H2O2). In contrast, SA and H2O2 downregulated CmSGT1 expression in the PM-susceptible material. The ethephon (Eth) and methyl jasmonate (MeJA) treatments upregulated CmSGT1 expression in both plant materials. The constitutive overexpression of CmSGT1 in Nicotiana benthamiana (N. benthamiana) minimized the PM symptoms on the leaves of PM-infected seedlings, accelerated the onset of cell necrosis, and enhanced the accumulation of H2O2. Furthermore, the expression levels of PR1a and PR5, which are SA signaling transduction markers, were higher in the transgenic plants than in wild-type plants. Thus, the transgenic N. benthamiana plants were significantly more resistant to Erysiphe cichoracearum than the wild-type plants. This increased resistance was correlated with cell death, H2O2 accumulation, and upregulated expression of SA-dependent defense genes. However, the chlorosis and yellowing of plant materials and the concentration of bacteria at infection sites were greater in the transgenic N. benthamiana plants than in the wild-type plants in response to infections by the pathogens responsible for bacterial wilt and scab. Therefore, CmSGT1-overexpressing N. benthamiana plants were hypersensitive to these two diseases. The results of this study may represent valuable genetic information for the breeding of disease-resistant pumpkin varieties, and may also help to reveal the molecular mechanism underlying CmSGT1 functions.

A randomized multicenter phase II trial of mecapegfilgrastim single administration versus granulocyte colony-stimulating growth factor on treating chemotherapy-induced neutropenia in breast cancer patients.

BACKGROUND: This study aimed to evaluate the efficacy and safety of mecapegfilgrastim (HHPG-19K) with different doses compared to granulocyte colony-stimulating growth factor (G-CSF) in treating chemotherapy-induced neutropenia in breast cancer patients. METHODS: A total of 182 breast cancer patients were enrolled in this multi-center, randomized, phase II trial and developed neutropenia after first cycle chemotherapy. Patients were then assigned as 1:1:1 ratio to receive 100 µg/kg HHPG-19K single injection (HHPG-19K-N group), 150 µg/kg HHPG-19Ksingle injection (HHPG-19K-H group) and 5 µg/kg G-CSF daily injection (G-CSF group) at day 3 of the second cycle (cycle 2) chemotherapy. The primary endpoint was incidence of grade ≥3 neutropenia during cycle 2. Study drug-related adverse events during cycle 2 were recorded for safety assessment. RESULTS: During cycle 2 chemotherapy, both HHPG-19K-N and HHPG-19K-H groups exhibited lower incidence of grade ≥3 neutropenia compared with G-CSF group, while no difference was observed between HHPG-19K-N and HHPG-19K-H groups. Also, better outcomes were observed in HHPG-19K-N and HHPG-19K-H groups compared with G-CSF group regarding to grade 4 neutropenia, duration of grade ≥3 neutropenia, duration of grade 4 neutropenia, incidence of febrile neutropenia (FN) and rescue application of G-CSF, time to ANC recovery, while no difference of these outcomes between HHPG-19K-N and HHPG-19K-H groups was observed. For safety analysis, the incidences of hematologic and non-hematologic adverse events were similar among the 3 groups. CONCLUSIONS: HHPG-19K presents with better clinical efficacy as well as equal tolerance compared with G-CSF in treating chemotherapy-induced neutropenia in breast cancer patients.

Characterization of the IRF2 proteins isolated from the deep-sea mussel Bathymodiolus platifrons and the shallow-water mussel Modiolus modiolus.

Interferon regulatory factors (IRFs) are transcription factors that play important roles in immune defense, stress response, hematopoietic differentiation, and cell apoptosis. IRFs of invertebrate organisms and their functions remain largely unexplored. In the present study, for the first time new IRFs (BpIRF2 and MmIRF2) were identified in the deep-sea mussel Bathymodiolus platifrons and the shallow-water mussel Modiolus modiolus. The open reading frame of BpIRF2 and MmIRF2 encoded putative proteins of 354 and 348 amino acids, respectively. Comparison and phylogenetic analysis revealed that both IRF2 proteins were new identified invertebrate IRF molecular. As transcriptional factors, both BpIRF2 and MmIRF2 could activate the interferon-stimulated response element-containing promoter and BpIRF2 could interact with itself. Moreover, both BpIRF2 and MmIRF2 were localized to the cytoplasm and nucleus. Collectively, these results demonstrated that IRF2 proteins might be crucial in the innate immunity of deep-sea and shallow-water mussels.

Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients: updated follow-up data from NATT study.

OBJECTIVE: A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide (TC) regimen was inferior to docetaxel, anthracycline and cyclophosphamide (TAC) in neoadjuvant treatment of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2-(HER2)-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated. METHODS: TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission (pCR). Secondary endpoints included clinical response rate, event-free survival (EFS), and overall survival (OS). RESULTS: A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of 53 (range, 8-76) months, the patients achieving pCR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without pCR (P<0.05). TAC treatment resulted in consistently better EFS than TC treatment: the estimated 5-year EFS was 66.1% vs. 29.8% (P=0.002). Moreover, the estimated 5-year OS was also in favor of TAC: 88.4% vs. 51.6% (P<0.001). Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.26-0.90; P=0.021] and OS (HR, 0.20; 95% CI, 0.08-0.60; P=0.003). CONCLUSIONS: The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.

Systematic investigation on topological properties of layered GaS and GaSe under strain.

The topological properties of layered ß-GaS and ε-GaSe under strain are systematically investigated by ab initio calculations with the electronic exchange-correlation interactions treated beyond the generalized gradient approximation (GGA). Based on the GW method and the Tran-Blaha modified Becke-Johnson potential approach, we find that while ε-GaSe can be strain-engineered to become a topological insulator, ß-GaS remains a trivial one even under strong strain, which is different from the prediction based on GGA. The reliability of the fixed volume assumption rooted in nearly all the previous calculations is discussed. By comparing to strain calculations with optimized inter-layer distance, we find that the fixed volume assumption is qualitatively valid for ß-GaS and ε-GaSe, but there are quantitative differences between the results from the fixed volume treatment and those from more realistic treatments. This work indicates that it is risky to use theoretical approaches like GGA that suffer from the band gap problem to address physical properties, including, in particular, the topological nature of band structures, for which the band gap plays a crucial role. In the latter case, careful calibration against more reliable methods like the GW approach is strongly recommended.