Immunoinformatics Design and In Vivo Immunogenicity Evaluation of a Conserved CTL Multi-Epitope Vaccine Targeting HPV16 E5, E6, and E7 Proteins.

Human papillomavirus type 16 (HPV16) infection is responsible for more than 50% of global cervical cancer cases. The development of a vaccine based on cytotoxic T-lymphocyte (CTL) epitopes is a promising strategy for eliminating pre-existing HPV infections and treating patients with cervical cancer. In this study, an immunoinformatics approach was used to predict HLA-I-restricted CTL epitopes in HPV16 E5, E6, and E7 proteins, and a set of conserved CTL epitopes co-restricted by human/murine MHCs was screened and characterized, with the set containing three E5, four E6, and four E7 epitopes. Subsequently, the immunogenicity of the epitope combination was assessed in mice, and the anti-tumor effects of the multi-epitope peptide vaccine E5E6E7pep11 and the recombinant protein vaccine CTB-Epi11E567 were evaluated in the TC-1 mouse tumor model. The results demonstrated that mixed epitope peptides could induce antigen-specific IFN-γ secretion in mice. Prophylactic immunization with E5E6E7pep11 and CTB-Epi11E567 was found to provide 100% protection against tumor growth in mice. Moreover, both types of the multi-epitope vaccine significantly inhibited tumor growth and prolonged mouse survival. In conclusion, in this study, a multi-epitope vaccine targeting HPV16 E5, E6, and E7 proteins was successfully designed and evaluated, demonstrating potential immunogenicity and anti-tumor effects and providing a promising strategy for immunotherapy against HPV-associated tumors.

DeepCBS: shedding light on the impact of mutations occurring at CTCF binding sites.

CTCF-mediated chromatin loops create insulated neighborhoods that constrain promoter-enhancer interactions, serving as a unit of gene regulation. Disruption of the CTCF binding sites (CBS) will lead to the destruction of insulated neighborhoods, which in turn can cause dysregulation of the contained genes. In a recent study, it is found that CTCF/cohesin binding sites are a major mutational hotspot in the cancer genome. Mutations can affect CTCF binding, causing the disruption of insulated neighborhoods. And our analysis reveals a significant enrichment of well-known proto-oncogenes in insulated neighborhoods with mutations specifically occurring in anchor regions. It can be assumed that some mutations disrupt CTCF binding, leading to the disruption of insulated neighborhoods and subsequent activation of proto-oncogenes within these insulated neighborhoods. To explore the consequences of such mutations, we develop DeepCBS, a computational tool capable of analyzing mutations at CTCF binding sites, predicting their influence on insulated neighborhoods, and investigating the potential activation of proto-oncogenes. Futhermore, DeepCBS is applied to somatic mutation data of liver cancer. As a result, 87 mutations that disrupt CTCF binding sites are identified, which leads to the identification of 237 disrupted insulated neighborhoods containing a total of 135 genes. Integrative analysis of gene expression differences in liver cancer further highlights three genes: ARHGEF39, UBE2C and DQX1. Among them, ARHGEF39 and UBE2C have been reported in the literature as potential oncogenes involved in the development of liver cancer. The results indicate that DQX1 may be a potential oncogene in liver cancer and may contribute to tumor immune escape. In conclusion, DeepCBS is a promising method to analyze impacts of mutations occurring at CTCF binding sites on the insulator function of CTCF, with potential extensions to shed light on the effects of mutations on other functions of CTCF.

Comparison of Glenohumeral Bone Morphology Between Patients With Versus Without Anterior Shoulder Instability.

Background: The stability of the glenohumeral joint is associated with anatomic characteristics including bony structures and soft tissues. Purpose: To compare the differences in specific bony glenohumeral geometries between shoulders with anterior shoulder instability (ASI), unaffected contralateral shoulders, and healthy control shoulders. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Shoulder computed tomography (CT) scans of 36 patients with ASI and 36 matched healthy controls were retrieved and 3-dimensionally reconstructed. We measured the glenoid radius of curvature (GROC) in the anterior-posterior (AP) and superior-inferior directions, humeral head radius of curvature (HROC) in the AP direction, conformity index, glenoid height, glenoid width, glenoid index, stability angle, glenoid version, and glenoid depth. The differences between the groups were statistically calculated. CT scans of the unaffected contralateral shoulders from 21 of the ASI patients were also collected to identify the consistency of the bony structures in bilateral shoulders. Results: Patients with ASI had greater GROC in the AP direction (P < .001), HROC in the AP direction (P = .002), glenoid height (P = .005), and glenoid index (P < .001) and smaller conformity index (P < .001), glenoid width (P = .002), stability angle (P < .001), and glenoid depth (P < .001). In addition, the glenoid of the ASI patients was more anteverted compared with that of controls (P = .001). There was no statistical difference in half the measurements between the bilateral shoulder joints in patients with ASI. Conclusion: In this study, glenohumeral geometric differences were found between ASI patients and healthy control participants. Glenoid curvature and conformity index, based on bilateral comparisons of affected and contralateral shoulders, appear inherent and may predict ASI risk.

Florid reactive periostitis of the clavicle: A case report and literature review.

RATIONALE: Florid reactive periostitis (FRP), a rare reactive bone lesion, typically presents in the short tubular bones of the extremities, with infrequent occurrences in the long tubular bones. This report discusses a unique case of FRP in the clavicle, managed through comprehensive lesion debridement and bone grafting, yielding positive results over a 3-year duration. PATIENT CONCERN: A 25-year-old male presented with a discernible mass at the left sternal end of the clavicle, discovered incidentally 2 weeks prior. The patient exhibited no clinical signs of inflammation, pain, sinus tract, or suppuration. DIAGNOSIS: Initial pathological examination of the local excision suggested benign lesions, although malignancy could not be ruled out. A definitive diagnosis of clavicular FRP was reached post complete lesion resection, with supporting evidence from postoperative pathology, imaging, and clinical symptoms. INTERVENTION: The left clavicle was reconstructed through an open surgical procedure involving total mass removal and ipsilateral extraction of an iliac bone of suitable dimensions. This was implanted into the clavicular bone defect and internally fixed with a plate. OUTCOMES: Three years of consecutive follow-up revealed no recurrence of hyperplasia, absence of mass or tenderness at the left sternal end of the clavicle, and unimpaired function of adjacent joints. LESSONS: The primary clinical challenge with FRP is its diagnosis. While pathological diagnosis remains crucial, it is also important to incorporate imaging and clinical symptoms for a comprehensive assessment. Complete mass excision may offer specific benefits in distinguishing FRP from its malignant counterparts.

Accumulation Potential Cadmium and Lead by Sunflower (Helianthus annuus L.) under Citric and Glutaric Acid-Assisted Phytoextraction.

Organic acid assistance is one of the effective methods for phytoremediation of heavy metal contaminated soil. In this experiment, the addition of citric and glutaric acids was selected to improve the accumulation of cadmium and lead by Helianthus annuus L. Results showed that citric and glutaric acids elevated the growth of the plants and stimulated Cd/Pb uptake by plant in single Cd/Pb treatments, but glutaric acid showed inhibitory action on the uptake of metals in complex treatments. Organic acids impacted the translocation of Cd/Pb differently, and citric acids (30 mg·L-1) enhanced the translocation of Cd to aerial parts of the plants in Cd (5 mg·kg-1) and Cd (10 mg·kg-1) plus Pb treatments. Glutaric acid (30 mg·L-1) could promote the translocation factors in the complex treatments of Cd (5 mg·kg-1) with Pb (50, 100 mg·kg-1) added. The application of citric and glutaric acid could be conducive to increase floral growth when proper doses are used, and incorporation of these organic acids can be a useful approach to assist cadmium and lead uptake by sunflower. However, growth, bioaccumulation, and translocation of metals may differ due to the metals' property, kinds, and concentrations of organic acids.

STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming.

The cohesin complex participates in the organization of 3D genome through generating and maintaining DNA loops. Stromal antigen 2 (STAG2), a core subunit of the cohesin complex, is frequently mutated in various cancers. However, the impact of STAG2 inactivation on 3D genome organization, especially the long-range enhancer-promoter contacts and subsequent gene expression control in cancer, remains poorly understood. Here we show that depletion of STAG2 in melanoma cells leads to expansion of topologically associating domains (TADs) and enhances the formation of acetylated histone H3 lysine 27 (H3K27ac)-associated DNA loops at sites where binding of STAG2 is switched to its paralog STAG1. We further identify Interferon Regulatory Factor 9 (IRF9) as a major direct target of STAG2 in melanoma cells via integrated RNA-seq, STAG2 ChIP-seq and H3K27ac HiChIP analyses. We demonstrate that loss of STAG2 activates IRF9 through modulating the 3D genome organization, which in turn enhances type I interferon signaling and increases the expression of PD-L1. Our findings not only establish a previously unknown role of the STAG2 to STAG1 switch in 3D genome organization, but also reveal a functional link between STAG2 and interferon signaling in cancer cells, which may enhance the immune evasion potential in STAG2-mutant cancer.

Osteoradionecrosis of the Hip, a Troublesome Complication of Radiation Therapy: Case Series and Systematic Review.

Background: Osteoradionecrosis of the hip is a serious complication of radiotherapy that is easily overlooked by physicians and patients in the early stages. There are relatively few reports on this subject, so there is no clear scientific consensus for the pathogenesis, early diagnosis, and clinical treatment of hip osteoradionecrosis. In this paper, we report two cases of hip osteoradionecrosis and systematically review the related literature. Case Presentation: We report two cases of hip osteoradionecrosis. One patient successfully underwent total hip arthroplasty in our hospital and recovered well postoperatively. Another patient although we offered a variety of surgical options for this patient, the patient was worried that the bone loss would lead to poor prosthesis fixation, resulting in prosthesis loosening and infection, and therefore ultimately refused surgical treatment. Conclusion: With the development of radiological techniques, the incidence of hip osteoradionecrosis is decreasing year by year, but early diagnosis and rational treatment remain challenging. The effects of non-surgical treatment are limited. Early prevention, early detection, and early intervention are crucial to delay or prevent the emergence of more serious complications.

Slipped capital femoral epiphysis with hypopituitarism in adults: A case report and literature review.

RATIONALE: Slipped capital femoral epiphysis (SCFE) is a common disease in pediatric orthopedics. Most research on SCFE has focused on high-risk groups or the whole population, and studies focusing on adult SCFE patients are rare. In the present study, we report the case of an adult patient with SCFE. PATIENT CONCERN: A 37-year-old man presented to our clinic with persistent pain that was poorly localized to both hips, groin regions, and thighs for more than 1 year. DIAGNOSES: A bilateral hip X-ray examination was performed, and the femoral epiphyses were found to be unfused on both sides. Low levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), triiodothyronine (T3), thyroxine (T4), follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone, and high levels of thyroid-stimulating hormone, prolactin, and cortisol. INTERVENTIONS: Hormone-substitution therapies (levothyroxine sodium to treat hypothyroidism and testosterone enanthate to treat hypogonadism) were prescribed. Total hip arthroplasty was performed to treat femoral epiphysis slippage. OUTCOMES: After 6 months of postoperative follow-up, the patient's gait improved significantly, and bilateral hip pain was relieved. LESSONS: When treating adults with SCFE, clinicians must be alert to endocrine disorders. Comprehensive imaging evaluation is crucial for the accurate diagnosis and selection of an appropriate treatment.

Total and Methylmercury of Suaeda heteroptera Wetland Soil Response to a Salinity Gradient Under Wetting and Drying Conditions.

Mercury (Hg) methylation could occur in freshwater ecosystems with low or high salinity. However, few studies are available about the effects of salinity change on mercury(Hg) release and methylation. In-situ experiments using Suaeda heteroptera wetland soil column from the Liaohe estuary were performed to decipher how total mercury (THg) and methylmercury (MeHg) contents change under fluctuant salinity and wet and dry soil conditions. Salinity gradients were set to 0.50% (S1), 1.00% (S2), 1.50% (S3) and 1.80% (S4), and pure deionized water was used as a blank control (CK). Wet and dry soil conditions were set to full inundation condition (WD1) and naturally dried treatment (WD2). Results indicated that the highest THg and MeHg contents were found in surface and bottom soil when water salinity treatment was CK under WD1. THg and MeHg decreased with salinity under WD1. THg contents in overlying water varied from 0.854 to 1.243 µg L-1 under WD1 treatments and increased with salinity change. When under WD2 treatment, THg contents in both soil layers gradually decreased with rising salinity. Meanwhile, MeHg contents in both soil layers reached the lowest level at CK (1.666 µg kg-1and 2.520 µg kg-1) and increased gradually with the rising salinity. By comparison, THg content of the soil was much lower in WD1 than that in WD2. Under the WD1 condition, the MeHg contents and %MeHg decreased with rising salinity and showed significantly different in different salinity treatment, however, its showed an opposite trend with rising salinity under the WD2 condition.

Dynamics of three organic acids (malic, acetic and succinic acid) in sunflower exposed to cadmium and lead.

Sunflower (Helianthus annuus L.) has been considered as a good candidate for bioaccumulation of heavy metals. In the present study, sunflower was used to enrich the cadmium and lead in sand culture during 90 days. Biomass, Cd and Pb uptake, three organic acids and pH in cultures were investigated. Results showed that the existence of Cd and Pb showed different interactions on the organic acids exudation. In single Cd treatments, malic and acetic acids in Cd10 showed an incremental tendency with time. In the mixed treatments of Cd and Pb, malic acids increased when 10 and 40 mg x L(-1) Cd were added into Pb50, but acetic acids in Pb50 were inhibited by Cd addition. The Cd10 supplied in Pb10 stimulated the secretion of malic and succinic acids. Moreover, the Cd or Pb uptake in sunflower showed various correlations with pH and some organic acids, which might be due to the fact that the Cd and Pb interfere with the organic acids secretion in rhizosphere of sunflower, and the changes of organic acids altered the form and bioavailability of Cd and Pb in cultures conversely.

Effect of electric intensity on the microbial degradation of petroleum pollutants in soil.

Electro-bioremediation is an innovative method to remedy organic-polluted soil. However, the principle of electrokinetic technology enhancing the function of microbes, especially the relationship of electric intensity and biodegradation efficiency, is poorly investigated. Petroleum was employed as a target organic pollutant at a level of 50 g/kg (mass of petroleum/mass of dry soil). A direct current power supply was used for tests with a constant direct current electric voltage (1.0 V/cm). The petroleum concentrations were measured at 3275-3285 nm after extraction using hexane, the group composition of crude oil was analyzed by column chromatography. The water content of soil was kept 25% (m/m). The results indicated the degradation process was divided into two periods: from day 1 to day 40, from day 41 to day 100. The treatment of soil with an appropriate electric field led the bacteria to have a persistent effect in the whole period of 100 days. The highest biodegradation efficiency of 45.5% was obtained after treatment with electric current and bacteria. The electric-bioremediation had a positive effect on alkane degradation. The degradation rate of alkane was 1.6 times higher in the soil exposed to electric current than that treated with bacteria for 100 days. A proper direct current could stimulate the microbial activities and accelerate the biodegradation of petroleum. There was a positive correlation between the electric intensities and the petroleum bioremediation efficiencies with a coefficient of 0.9599.

Iron-deficiency induces cadmium uptake and accumulation in Solanum nigrum L.

Phytoremediation is a promising tool in removing pollutants from the environment or in rendering them harmless. The objective of this research was to determine the effect of iron-deficiency on the uptake of cadmium by Solanum nigrum L. Results showed that iron-deficiency induced cadmium uptake, biomass decrease and changes in pH and Eh in hydroponic culture. Under iron-deficiency status, the decrease in pH and the increase in Eh might result in higher cadmium availability. Bioconcentration and translocation factors indicated that iron-deficiency status affected cadmium accumulation and translocation in Solanum nigrum L.

Effects of amendments of N, P, Fe on phytoextraction of Cd, Pb, Cu, and Zn in soil of Zhangshi by mustard, cabbage, and sugar beet.

Soil contaminated with Cd, Pb, Cu, and Zn in the Zhangshi irrigation area is very hard to be remediated. Phytoextraction is considered as an efficient method to remove these toxic metals from soil. In the present study, three vegetables including sugar beet (Beta vulgaris), mustard (Brassica juncea L.), and cabbage (Brassica oleracea L. var. capitata Linn.) were used to bioaccumulate heavy metals in soil through pots experiment for 90 days; and nutrient elements were applied to stimulate the phytoextraction of metals. Results of bioconcentration factors (BCF) and translocation factors (TF) from this study showed that these plants could phytoextract heavy metals, but the accumulation and translocation of metals differed with species of plants, categories of heavy metals, and some environmental conditions (e.g. nutrients). Meanwhile, the addition of nutrient elements, such as N, P, and Fe, could affect the phytoremediation of heavy metals via promoting the normal metabolism of vegetables or changing forms of metals. Results of this study could provide some available information for in-site bioremediation of soil from Zhangshi irrigation area.