Eimeria media is a principal pathogen responsible for rabbit coccidiosis, targeting the rabbit\'s intestinal epithelial cells. This parasitism damages the intestinal mucosal barrier, initiating a systemic immune and inflammatory response that jeopardizes the sustainable growth of rabbit farming. To understand the implications of infection on the host\'s immune and metabolic responses, we employed RNA-Seq to analyze RNA from the liver and duodenum tissues of post-infected rabbits infected with both the precocious line and wild-type strain of E.media. Comprehensive transcriptomic analysis revealed that the two parasites exhibit divergent transcriptomic imprints on host tissues. While the precocious line predominantly modulates immune-centric pathways with significant differential gene enrichment, wild-type strain favors pathways that affect metabolism. In addition, our study pinpointed a set of genes that undergo significant modifications in response to these effects. These revelations grant a fresh avenue to probe deeper into the symbiotic intricacies of the E.media and its rabbit host.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disease with skin mucosal pigment spots and gastrointestinal (GI) multiple hamartoma polyps as clinical characteristics. At present, it is considered that the germline mutation of STK11 gene is the genetic cause of PJS. However, not all PJS patients can be detected STK11 germline mutations. The specific clinical characteristics of these PJS patients without STK11 mutation is an interesting clinical question. Or, like wild type GI stromal tumor, whether these PJS without STK11 mutation are also called PJS is worth discussing. Therefore, we designed the study to understand the clinical characteristics of these PJS patients without STK11 mutation.
OBJECTIVE: To investigates whether PJS patients with known STK11 mutations have a more severe spectrum of clinical phenotypes compared to those without.
METHODS: A total of 92 patients with PJS admitted to the Air Force Medical Center from 2010 to 2022 were randomly selected for study. Genomic DNA samples were extracted from peripheral blood samples, and pathogenic germline mutations of STK11 were detected by high-throughput next-generation gene sequencing. Clinical-pathologic manifestations of patients with and without STK11/LKB1 mutations were compared.
RESULTS: STK11 germline mutations were observed in 73 patients with PJS. Among 19 patients with no detectable STK11 mutations, six had no pathogenic germline mutations of other genes, while 13 had other genetic mutations. Compared with PJS patients with STK11 mutations, those without tended to be older at the age of initial treatment, age of first intussusception and age of initial surgery. They also had a lower number of total hospitalizations relating to intussusception or intestinal obstruction, and a lower load of small intestine polyps.
CONCLUSIONS: PJS patients without STK11 mutations might have less severe clinical-pathologic manifestations than those with.

OBJECTIVE: Waning vaccine-induced immunity and emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants which may lead to immune escape, pose a major threat to the COVID-19 pandemic. Currently, enhanced efficacy of the neutralization antibodies (NAb) produced after the booster dose of vaccinations against the Omicron variant is the main focus of vaccine strategy research. In this study we have analyzed the potency of the NAbs and IgGs produced after the third vaccine dose in patients infected with Omicron variant and wild-type (WT) SARS-CoV-2.
METHODS: We enrolled 75 patients with Omicron variant breakthrough infections, and 87 patients with WT infections. We recorded the clinical characteristics and vaccination information of all patients and measured the NAb and anti-S1 (spike protein) + N (nucleocapsid protein) IgG-binding antibodies against SARS-CoV-2 in serum samples of Omicron variant-infected patients at admission, and patients with WT COVID-19 infection from the time of admission and discharge, and one-year to two-years follow-ups.
RESULTS: Our results demonstrated higher NAb levels, fewer clinical symptoms, and faster viral shedding in Omicron variant infected patients vaccinated with the booster dose. Hybrid immunity (natural infection plus vaccination) induces higher NAb levels than vaccine-only immunity. NAb and IgG levels decreased significantly at one-year follow-up in WT convalescents with natural infection. The NAb and IgG levels in booster-vaccinated COVID-19 patients were higher than those in two-dose-vaccinated patients.
CONCLUSIONS: Our results suggest that booster vaccinations are required to improve the level of protective NAbs. Moreover, our data provide important evidence for vaccination strategies based on existing vaccines.

Introduction. The Candida parapsilosis complex can be divided into C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis subtypes. It is uncommon for drug sensitivity tests to type them.Gap Statement. In routine susceptibility reports, drug susceptibility of C. parapsilosis complex subtypes is lacking.Aim. The aim of this study is to investigate the antifungal susceptibility and clinical distribution characteristics of the C. parapsilosis complex subtypes causing deep infection in patients.Methodology. Non-repetitive strains of C. parapsilosis complex isolated from deep infection from 2017 to 2019 were collected. Species-level identification was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer and confirmed using ITS gene sequencing, when necessary. Antifungal susceptibility testing was performed using the Sensititre YeastOne system method.Results. A total of 244 cases were included in the study, including 176 males (72.13 %, 60.69±13.43 years) and 68 females (27.87 %, 60.21±10.59 years). The primary diseases were cancer (43.44 %), cardiovascular disease (25.00 %), digestive system diseases, (18.44 %), infection (6.97 %), and nephropathy (6.15 %). Strains were isolated from the bloodstream (63.11 %), central venous catheters (15.16 %), pus (6.56 %), ascites (5.74 %), sterile body fluid (5.33 %), and bronchoalveolar lavage fluid (BALF, 4.09 %). Of the 244 C. parapsilosis complex strains, 179 (73.26 %) were identified as C. parapsilosis sensu stricto, 62 (25.41 %) were C. orthopsilosis, and three (1.23 %) were C. metapsilosis. Only one C. parapsilosis sensu stricto strain was resistant to anidulafungin, micafungin, caspofungin, and voriconazole, and it was non-wild-type (NWT) to amphotericin B. Furthermore, six C. parapsilosis sensu stricto strains were resistant to fluconazole, and one was dose-dependent susceptible. Five C. parapsilosis sensu stricto strains were NWT to posaconazole. Only one C. orthopsilosis strain was NWT for anidulafungin, micafungin, caspofungin, fluconazole, voriconazole, amphotericin B, and posaconazole, while the rest of the strains were wild-type.Conclusion. C. parapsilosis sensu stricto was the main clinical isolate from the C. parapsilosis complex in our hospital. Most strains were isolated from the bloodstream. The susceptibility rate to commonly used antifungal drugs was more than 96 %. Furthermore, most of the infected patients were elderly male cancer patients.

Dysferlin (DYSF) has drawn much attention due to its involvement in dysferlinopathy and was reported to affect monocyte functions in recent studies. However, the role of DYSF in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVD) and the regulation mechanism of DYSF expression have not been fully studied. In this study, Gene Expression Omnibus (GEO) database and epigenome-wide association study (EWAS) literatures were searched to find the DNA methylation-driven genes (including DYSF) of ASCVD. The hub genes related to DYSF were also identified through weighted correlation network analysis (WGCNA). Regulation of DYSF expression through its promoter methylation status was verified using peripheral blood leucocytes (PBLs) from ASCVD patients and normal controls, and experiments on THP1 cells and Apoe-/- mice. Similarly, the expressions of DYSF related hub genes, mainly contained SELL, STAT3 and TMX1, were also validated. DYSF functions were then evaluated by phagocytosis, transwell and adhesion assays in DYSF knock-down and overexpressed THP1 cells. The results showed that DYSF promoter hypermethylation up-regulated its expression in clinical samples, THP1 cells and Apoe-/- mice, confirming DYSF as a DNA methylation-driven gene. The combination of DYSF expression and methylation status in PBLs had a considerable prediction value for ASCVD. Besides, DYSF could enhance the phagocytosis, migration and adhesion ability of THP1 cells. Among DYSF related hub genes, SELL was proven to be the downstream target of DYSF by wet experiments. In conclusion, DYSF promoter hypermethylation upregulated its expression and promoted monocytes activation, which further participated in the pathogenesis of ASCVD.

Background: As delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevailed in the current coronavirus disease 2019 (COVID-19) pandemic, its clinical characteristics with the difference from those of wild-type strains have been little studied. Methods: We reported one cohort of 341 wild-type patients with COVID-19 admitted at Wuhan, China in 2020 and the other cohort of 336 delta variant patients with COVID-19 admitted at Yangzhou, China in 2021, with comparisons of their demographic information, medical history, clinical manifestation, and hematological data. Furthermore, within the delta variant cohort, patients with none, partial, and full vaccination were also compared to assess vaccine effectiveness. Findings: For a total of 677 patients with COVID-19 included in this study, their median age was 53.0 years [interquartile range (IQR): 38.0-66.0] and 46.8% were men. No difference was found in age, gender, and percentage of patients with the leading comorbidity between wild-type and delta variant cohorts, but delta variant cohort showed a lessened time interval between disease onset to hospitalization, a reduced portion of patients with smoking history, and a lowered frequency of clinical symptoms. For hematological parameters, most values demonstrated significant differences between wild-type and delta variant cohorts, while full vaccination rather than partial vaccination alleviated the disease condition. This reflected the viremic effect of delta variant when vaccination succeeds or fails to protect. Interpretation: Delta variant of SARS-CoV-2 may cause severe disease profiles, but timely diagnosis and full vaccination could protect patients with COVID-19 from worsened disease progression.

BACKGROUND: Current therapeutic drugs show positive effects on non-small-cell lung cancer (NSCLC) patients with mutant epidermal growth factor receptor (EGFR) expression, whereas a lesser beneficial effect is generally noted on NSCLC patients with wild-type EGFR. Therefore, identification of new detection methods for the accurate clinical diagnosis of NSCLC is essential.
METHODS: In this study, tumor-derived exosomes from the plasma of EGFR mutation and wild-type NSCLC patients were isolated. Extensive exosomal miRNA profiling of EGFR mutation and wild-type NSCLC patients, in comparison with healthy individuals, was performed using miRNA-sequencing analysis.
RESULTS: The variation of exosomal miRNA expression between control group (NR) and NCSLC samples (AM and AW) was identified. 96 significantly different expressed miRNAs were identified. Of these, 39 miRNAs were upregulated and 57 were downregulated. 11 miRNAs were downregulated, and 31 miRNAs were upregulated in the miRNA expression between NR and AM. Compared with healthy donors, 54 upregulated miRNAs and 36 downregulated miRNAs were observed in samples from AW patients. 40 different expressed miRNAs were identified in AM samples, compared with AW. Ten of upregulated miRNAs are miR-260, miR-1169, miR-117, miR-15b-5p, miRNA-731, miR-342-5p, miR- 898, miR-1384, miR-56, and miR-1214. Ten of downregulated miRNAs are miR-99b-5p, miR-1116, miR-689, miR-818, miR-604, miR-72, miR-955, miR-403, miR-1228, and miR-836.
CONCLUSIONS: The exosomal miR-1169 and miR-260 as potential candidates, which contain specific characteristics that can distinguish between wild-type EGFR and mutant EGFR NSCLC patients in early-stage cancers.

A central approach for better understanding the forces involved in maintaining protein structures is to investigate the protein folding and thermodynamic properties. The effect of the folding process is often disturbed in mutated states. To explore the dynamic properties behind mutations, molecular dynamic (MD) simulations have been widely performed, especially in unveiling the mechanism of drug failure behind mutation. When comparing wild type (WT) and mutants (MTs), the structural changes along with solvation free energy (SFE), and Gibbs free energy (GFE) are calculated after the MD simulation, to measure the effect of mutations on protein structure. Pyrazinamide (PZA) is one of the first-line drugs, effective against latent Mycobacterium tuberculosis isolates, affecting the global TB control program 2030. Resistance to this drug emerges due to mutations in pncA and rpsA genes, encoding pyrazinamidase (PZase) and ribosomal protein S1 (RpsA) respectively. The question of how the GFE may be a measure of PZase and RpsA stabilities, has been addressed in the current review. The GFE and SFE of MTs have been compared with WT, which were already found to be PZA-resistant. WT structures attained a more stable state in comparison with MTs. The physiological effect of a mutation in PZase and RpsA may be due to the difference in energies. This difference between WT and MTs, depicted through GFE plots, might be useful in predicting the stability and PZA-resistance behind mutation. This study provides useful information for better management of drug resistance, to control the global TB problem.

BACKGROUND: A first-line biologic treatment for metastatic colorectal cancer (mCRC) is still controversial. We, therefore, performed a meta-analysis to determine the efficacy of first-line cetuximab versus bevacizumab for RAS and BRAF wild-type mCRC.
METHODS: In March 2018, an electronic search of the following biomedical databases was performed: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov and Web of Knowledge. Randomized controlled trials (RCTs) and prospective or observational cohort studies (OCSs) were included. Subgroup analyses of all RCTs were performed in all outcomes. All statistical analyses were performed using RevMan software 5.3.
RESULTS: Two RCTs and three OCSs, involving a total 2576 patients, were included. The meta-analysis reported that cetuximab was associated with a longer overall survival (OS) [HR 0.89, 95% CI (0.81-0.98); p = 0.02], a higher ORR [RR 1.11, 95% CI (1.03-1.19); p = 0.006], higher complete response [RR 3.21, 95% CI (1.27-8.12); p = 0.01] and a greater median depth of response than bevacizumab. However, no significant difference was observed between cetuximab and bevacizumab groups for PFS, DCR, partial response, progressive disease, curative intent metastasectomy, EORR and incidence of grade 3 or higher adverse events. In the subgroup meta-analyses of the RCTs, inconsistent results compared to the main analysis, however, were found, in the ORR, DCR and curative intent metastasectomy.
CONCLUSIONS: The current evidence indicates that compared to bevacizumab treatment, cetuximab provides a clinically relevant effect in first-line treatment against mCRC, at the cost of having lower stable disease.

Plants have developed a number of survival strategies which are significant for enhancing their adaptation to various biotic and abiotic stress factors. At the transcriptome level, G-protein-coupled receptors (GPCRs) are of great significance, enabling the plants to detect a wide range of endogenous and exogenous signals which are employed by the plants in regulating various responses in development and adaptation. In this research work, we carried out genome-wide analysis of target of Myb1 (TOM1), a member of the GPCR gene family. The functional role of TOM1 in salt stress tolerance was studied using a transgenic Arabidopsis plants over-expressing the gene. By the use of the functional domain PF06454, we obtained 16 TOM genes members in Gossypium hirsutum, 9 in Gossypium arboreum, and 11 in Gossypium raimondii. The genes had varying physiochemical properties, and it is significant to note that all the grand average of hydropathy (GRAVY) values were less than one, indicating that all are hydrophobic in nature. In all the genes analysed here, both the exonic and intronic regions were found. The expression level of Gh_A07G0747 (GhTOM) was significantly high in the transgenic lines as compared to the wild type; a similar trend in expression was observed in all the salt-related genes tested in this study. The study in epidermal cells confirmed the localization of the protein coded by the gene TOM1 in the plasma membrane. Analysis of anti-oxidant enzymes showed higher concentrations of antioxidants in transgenic lines and relatively lower levels of oxidant substances such as H₂O₂. The low malondialdehyde (MDA) level in transgenic lines indicated that the transgenic lines had relatively low level of oxidative damage compared to the wild types. The results obtained indicate that Gh_A07G0747 (GhTOM) can be a putative target gene for enhancing salt stress tolerance in plants and could be exploited in the future for the development of salt stress-tolerant cotton cultivars.