Background: Vaccination is one of the effective measures to prevent latent tuberculosis infection (LTBI) from developing into active tuberculosis (TB). Applying bioinformatics methods to pre-evaluate the biological characteristics and immunogenicity of vaccines can improve the efficiency of vaccine development. Objectives: To evaluate the immunogenicity of tuberculosis vaccine W541 and explore the application of bioinformatics technology in tuberculosis vaccine research. Methods: This study concatenated the immunodominant sequences of Ag85A, Ag85B, Rv3407, and Rv1733c to construct the W541 DNA vaccine. Then, bioinformatics methods were used to analyze the physicochemical properties, antigenicity, allergenicity, toxicity, and population coverage of the vaccine, identify its epitopes, and perform molecular docking with MHC alleles and Toll-like receptor 4 (TLR4) of the host. Finally, the immunogenicity of the vaccine was evaluated through animal experiments. Results: the W541 vaccine protein is a soluble cytoplasmic protein with a half-life of 1.1 hours in vivo and an instability index of 45.37. It has good antigenicity and wide population coverage without allergenicity and toxicity. It contains 138 HTL epitopes, 73 CTL epitopes, 8 linear and 14 discontinuous epitopes of B cells, and a strong affinity for TLR4. Immune simulations showed it could effectively stimulate innate and adaptive immune responses. Animal experiments have confirmed that the W541 DNA vaccine could effectively activate the Th1- and Th17-type immune responses, producing high levels of IFN-γ and IL-17A, but could not significantly increase antibody levels. Conclusion: the W541 DNA vaccine can induce strong cellular immune responses. However, further optimization of the vaccine design is needed to make the expressed protein more stable in vivo. Bioinformatics analysis could reveal vaccines’ physicochemical and immunological information, which is critical for guiding vaccine design and development.

A document by Sevil Gaffarzadeh rad . Click on the document to view its contents.

Peach Leaf Curl Disease, caused by the fungus Taphrina deformans, is characterized by reddish hypertrophic and hyperplasic leaf areas. To comprehend the biochemical imbalances caused by the disease an integrated approach including metabolomics, lipidomics, proteomics and complementary biochemical techniques was undertaken. Symptomatic and asymptomatic areas were dissected from leaves with increasing extension of the disease. A differential metabolic behaviour was identified in symptomatic areas with respect to either asymptomatic areas or healthy leaves. Symptomatic areas showed an altered chloroplastic functioning and composition which includes decrease in the photosynthetic machinery, alteration in plastidic lipids, and decreased starch, carotenoid and chlorophyll biosynthesis. In symptomatic areas, decreases in chloroplast redox-homeostasis proteins and in triacylglycerols double bond index were observed. Proteomic data revealed an up-regulation of phenylpropanoid and mevalonate pathways and down-regulation of the plastidic methylerythritol phosphate route. Amino acid pools were affected, with up-regulation of proteins involved in asparagine synthesis. Curled areas exhibited a metabolic shift towards functioning as a sink tissue importing sugars and producing energy through fermentation and respiration and reductive power via the pentose phosphate route. As the disease progresses, reduced asymptomatic areas and healthy leaves diminishes photosynthates production thereby limiting fruit production and ultimately tree survival.

Although the etio-pathogenesis of inflammatory bowel diseases (IBD) is not entirely clear, the interaction between genetic and adverse environmental factors may reduce the variety of the intestinal microbiota (dysbiosis), resulting in a chronic inflammation having effects on the large-scale brain network through the gut-brain axis. In this paper, we hypothesized the presence of inflammation-related changes in brain topology of IBD patients, regardless of the specific clinical form (ulcerative colitis (UC) or Crohn’s disease (CD)). To test this hypothesis, we analyzed source-reconstructed magnetoencephalography (MEG) signals in 25 IBD patients and 28 healthy controls (HC) in resting-state condition, and evaluated the brain network topology. Finally, to assess whether these changes were linked to IBD clinical evolution, we correlated brain topology to disease duration. We found that the betweenness centrality (BC) of the left hippocampus was higher in patients as compared to controls, in the gamma frequency band. BC is a nodal topological parameter indicating how much a brain region is involved in the flow of information through the brain network. Furthermore, the comparison among UC, CD and HC showed statistically significant differences between UC and HC and between CD and HC, but not between the two clinical forms. Our results demonstrated that the topological changes observed in IBD patients were not dependent on the specific clinical form, but due to the gastro-intestinal inflammatory process itself. However, although these findings are promising, we need to enlarge the sample size to monitor the brain involvement in IBD and to clarify the clinical impact.

Objective: In this article, we review the clinical data of a case involving chemotherapy-induced bone marrow suppression complicated by pyogenic liver abscess, leading to endogenous endophthalmitis (EE). By consulting the relevant literature, we comprehensively analyse and summarise the information, ultimately offering diagnostic and therapeutic insights for similar cases. Methods: This article presents the case of a 65-year-old female patient with breast cancer who developed bone marrow suppression during postoperative chemotherapy. Imaging examinations revealed the presence of a pyogenic liver abscess, and the patient subsequently experienced visual impairment. Following a thorough examination, the diagnosis indicated secondary EE resulting from a pyogenic liver abscess caused by Klebsiella pneumoniae. Upon hospitalisation, the patient underwent treatment with granulocyte colony-stimulating factor (G-CSF) to stimulate bone marrow haematopoiesis and she also received comprehensive systemic anti-infective therapy. Additionally, a pyogenic liver abscess drainage procedure was performed, coupled with intravitreal injection of antibiotics into the vitreous cavity of the affected eye. Results: After comprehensive systemic and local treatments, the patient’s laboratory parameters normalised. The volume of the pyogenic liver abscess reduced noticeably, allowing for the removal of the drainage tube. At the time of discharge, there was a reduction in intraocular inflammation. Nevertheless, complete loss of vision persisted in the affected eye. Conclusion: In patients with bone marrow suppression following chemotherapy, it is crucial to conduct liver imaging examinations to promptly exclude the possibility of bacterial pyogenic liver abscess. To prevent serious complications such as EE leading to blindness, timely pyogenic liver abscess drainage procedures must be performed. Administering antibiotics empirically for comprehensive systemic anti-infective therapy, along with localised ocular treatment, is also essential. This approach preserves vision as much as possible and enhances the overall prognosis for patients

A main bearing (MB) preforms the critical role of supporting the rotor and whole drive train in a wind turbine. It endures very heavy and complex load coming from the rotor, meanwhile, high reliability in whole operation life is required for the high cost of MB replacement. Taking a spherical roller bearing (SRB) MB as an example, the paper analyzed complex load characters of a SRB MB configuration and discussed how to simplify the complex load in MB design works, then the key aspects influencing the MB performance were discussed, including raceway performance and shrink fit. Further more, thresholds of raceway contact pressure occurrence, fitting contact pressure and hoop stress were presented based on the state of art experiences. The paper gives an overview of SRB MB design for field operation performance.

Objective: To delineate the natural history of splenic complications other than the loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children’s Hospital. Methods: We determined the dates of diagnoses of splenic complications, the number of ASSC events, and hydroxyurea treatment in patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC. Results: The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of all splenic complications was highest in patients with hemoglobin Sβ 0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sβ +. The overall event-rate of ASSC was 8.3 per hundred patient-years. The event-rate was 28.4 in the hemoglobin Sβ 0, 10.9 in hemoglobin SS, and 3.5 in hemoglobin SC Patients with hemoglobin SS and hemoglobin Sβ 0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event-rates of 14.2 and 3.1, respectively. The event-rate was also higher for children who started hydroxyurea before age 2 years than for those who started after this age (19.8 and 9.2 respectively). Conclusions: The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sβ 0 having the most severe complications. Hydroxyurea therapy is strongly associated with incidence of ASSC, particularly when initiated before two years of age.

A heteronuclear dual transition metal atom catalyst is a promising strategy to solve and relieve the increasing energy and environment crisis. However, the role of each atom still does not efficiently differentiate due to the high activity but low detectivity of each transition metal in the synergistic catalytic process when considering the influence of heteronuclear induced atomic difference for each transition metal atom, thus seriously hindering intrinsic mechanism finding. Herein, we proposed coordinate environment vary induced heterogenization of homonuclear dual transition metal, which inherits the advantage of heteronuclear transition metal atom catalyst but also controls the variable of the two atoms to explore the underlying mechanism. Based on this proposal, employing density functional theory study and machine learning, 23 kinds of homonuclear transition metals are doping in four asymmetric C3N for heterogenization to evaluate the underlying catalytic mechanism. Our results demonstrate that five catalysts exhibit excellent catalytic performance with a low limiting potential of -0.28 to -0.48 V. In the meantime, a new mechanism, ‘capture-charge distribution-recapture-charge redistribution’, is developed for both side-on and end-on configuration. More importantly, the pronate site of the first hydrogenation is identified based on this mechanism. Our work not only initially makes a deep understanding of the transition dual metal-based heteronuclear catalyst indirectly but also broadens the development of complicated homonuclear dual atom catalysts in the future.

Case reportHalim et al

Optimization of hybrid dynamic systems typically involves characterizing switching times and mode sequences. Operating autonomous hybrid systems with varying event timings presents multiple challenges. Complexity often arises from optimal mode sequence determination, making optimization of the corresponding hybrid automaton more difficult. An experimental autonomous hybrid dynamic system experiencing switching due to choked flow conditions is presented. Implementing gradient-based optimization algorithms may be difficult due to complex switching patterns of the hybrid dynamic systems. To mitigate this, an approximation of the Heaviside step function is applied to transform the hybrid switching functions to a continuous and smooth forms. Using the Control Vector Parameterization (CVP) approach and evaluating gradients using the variational method, an open-loop time-optimal control problem is presented. Modeling and control methods are demonstrated using an experimental two-tank air system. The optimal control formulation can include constraints to avoid specific undesirable modes of operation.

The precise syntheses of transition–rare-earth metal clusters with desired structures remain a great challenge. Herein, by utilizing SO4 2– anion released by in-situ decomposition of sodium dodecyl sulfate (SDS) as a template, a series of novel high-nuclear ity 3d-4f clusters, formulated as [Ni24Pr22(μ3-OH)31(pida)24(SO4)4 (NO3)9(CH3 COO)3]·Br4·(NO3)11· 16H 2O·25CH3OH (1, H2pida = N-phenyliminodiacetic acid), [Ni24Nd22(μ3-OH)31(pida)24(SO4)4(NO3)9(CH3COO)3 ]·Br4·(NO3)11·14H2O· 24CH3OH·(2)·and [Ni24Gd22 (μ3-OH)36(bida)24(SO4)7(NO3)3(CH3 COO) 3]·(SO4)·Br4 ·(NO3)4·31H2O 32CH3OH (3, H 2 bida = N-benzyliminodiacetic acid), have been successfully isolated. X-ray crystal structure analyses reveal that all the cationic {Ni24 RE22}cores in 1–3 possess a ball-like structure with C3v symmetry, and can be viewed as consisting of an inner {RE22} core and an outer {Ni24} shell. From 1 and 2 to 3, due to the lanthanide contraction effect, the coordina -tion numbers for rare-earth metal centers in {RE22} are different, resulting in differ-ent number of SO42– and NO3– anions to support and stabilize the skeleton structures. Meanwhile, the magnetic properties of com-plexes 1–3 were also studied. The result revealed that complexes 1–3 show antiferromagnetic /ferrimagnetic interactions, and 3 ex-hibits magneto-caloric effect at ultralow temperatures with a maximum –ΔSm (magnetic entropy change) value of 33.03 J·kg−1 ·K−1 at 3.0 K and 7 T.

Hydatid cyst of the sacrum :A case report

Organisms inhabiting highly seasonal environments must cope with a wide range of environmentally induced challenges. Many seasonal challenges require extensive physiological modification to survive. In winter, to survive extreme cold and limited resources, insects commonly enter diapause, which is an endogenously derived dormant state associated with minimized cellular processes and low energetic expenditure. Due to the high degree of complexity involved in diapause, substantial cellular regulation is required, of which our understanding primarily derives from the transcriptome via messenger RNA expression dynamics. Here we aim to advance our understanding of diapause by investigating microRNA (miRNA) expression in diapausing and direct developing pupae of the butterfly Pieris napi. We identified coordinated patterns of miRNA expression throughout diapause in both head and abdomen tissues of pupae, and via miRNA target identification, found several expression patterns to be enriched for relevant diapause-related physiological processes. We also identified two candidate miRNAs, miR-14-5p and miR-2a-3p, that are likely involved in diapause progression through the ecdysone synthesis pathway, a critical regulator of diapause termination. miR-14-5p targets phantom, a gene in the ecdysone synthesis pathway, and miR-2a-3p, which has been found to be expressed in response to ecdysone. Together, the expression patterns of these two miRNAs match our current understanding of the timing of hormonal regulation of diapause in P. napi and provide interesting candidates to further explore the mechanistic role of microRNAs in diapause regulation.

The identification of the critical quality attributes (CQAs) of monoclonal antibodies (mAbs) is a key component of quality by design. Traditional detection methods for the identification of mAbs, such as peptide mapping and weak cation-exchange chromatography (WCX-HPLC), require sophisticated equipment, experienced staff, and a considerable amount of time. In this study, the novel identification of mAbs was performed using Raman spectroscopy, combined with the evaluation of other CQAs, such as the appearance and purity of size-exclusion high-performance liquid chromatography(SEC-HPLC), charge heterogeneity of WCX-HPLC, and bioassay. Raman spectroscopy achieved comparable results to the conventional, but complex, approach to identifying anti-vascular endothelial growth factor antibodies. Raman spectroscopy was used to identify and distinguish between different antibody types. Additionally, the Raman technique with principal component analysis of multivariate algorithms is rapid, efficient, and accurate for mAb identification; this technique has great potential to support biopharmaceutical development and counterfeiters.

Background: Bacterial coinfection in patients with SARS-CoV-2 infection is an important risk factor for death. This study investigated and analyzed whether there were differences in levels of serum inflammatory markers in patients with SARS-CoV-2 and bacterial coinfection compared with those without bacterial infection. Methods: A total of 121 inpatients with SARS-CoV-2 infection admitted to Qingdao Central Hospital from December 7, 2022, to February 7, 2023, were included. Patients were divided into a bacteria-positive group (61 cases) and a bacteria-negative group (60 cases) according to whether they had bacterial infections. PCT, CRP, and 12 cytokines were compared between groups, and the composition of bacterial species in the positive group was statistically analyzed. Results: The serum levels of CRP (Z = 3.95, P < 0.001), PCT (Z = 3.20, P = 0.001), IL-1β (t = 2.90, P = 0.008), IL-2 (t = 3.83, P = 0.001), IL-12p70 (t = 3.28, P = 0.004), IL-17 (t = 2.22, P = 0.039) and TNF-α (t = 3.02, P = 0.007) between the two groups were significantly different. IL-17 increased more significantly than other markers, while IL-6, IL-8, IL-10, interferon-α, interferon-γ, IL-4 and IL-5 were not statistically significant (P > 0.05). Among the 61 bacteria-positive patients, 27 patients were positive for one species, mainly Staphylococcus aureus, Haemophilus influenzae, and Acinetobacter baumannii. Eleven patients were two species positive, and Acinetobacter baumannii combined with Pseudomonas aeruginosa was common. Conclusions: Serum PCT and CRP levels in SARS-CoV-2-infected patients with bacterial coinfection are higher than those in patients without bacterial infection. Cytokines such as IL-1β, IL-2, IL-12 p70, IL-17, and TNF-α may be involved in the progression of COVID-19 combined with bacterial infection. They can be used as potential markers to evaluate the disease condition and prognosis.

Background and Purpose: Lycorine is an alkaloid that was in the bulb of the genus Lycoris. It has properties of anti-inflammatory. This study aimed to investigate the molecular mechanism by which lycorine can reduce acute lung injury (ALI). Experimental Approach: ALI model was established by intranasal injection of lipopolysaccharide (LPS). In vitro, A549 cells were treated with LPS and pretreated with lycorine for 1 hour. Key Results: The results showed that lycorine reduced histopathological changes in lung, myeloperoxidase (MPO) activity, and the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in mice. Lycorine dose-dependently inhibited the production of TNF-α, IL-1β, and IL-6. It also inhibited the transmission of TLR4/NF-κB passway in LPS-stimulated A549 cells. Lycorine increased cholesterol efflux through the activated LXRα-ABCA1/ABCG pathway. Lycorine has a good binding ability with LXRα. After adding the LXRα inhibitor, the anti-inflammatory effect of lycorine was eliminated. Conclusion and Implications: Lycorine can reduce ALI that was induced by lipopolysaccharide. The anti-inflammatory mechanism of lycorine is related to the up-regulation of the LXRα-ABCA1/ABCG pathway, which inhibits TLR4-mediated inflammation by increasing cholesterol efflux and reducing TLR4 transport to lipid rafts.

This paper demonstrates that the multivariate monitoring methods are capable to underpin the systematic investigation of the hysteretic behavior occurring during gradually-varied flows. For this purpose, we present simultaneous measurements of stage, index velocity, and free-surface slope acquired continuously with high-frequency sampling instruments deployed at several river gauging sites exposed to a range of storm magnitudes. The experimental evidence reveals intrinsic features of unsteady open-channel flow mechanics that are hinted by pertinent governing equations but rarely substantiated with in-situ measurements. The illustrations are intentionally made for fluvial waves propagating at sites located in lowland areas where the relationships among flow variables are most likely displaying hysteretic loops and phasing in the hydraulic variable progression. The set of presented measurements highlights that: a) the hysteretic behavior is apparent in both time-independent and time-dependent graphical representations of any two of the hydraulic variables; b) the severity of the hysteresis is commensurate with the geomorphic, hydraulic, and hydrological characteristics of the measurement site; and c) there is a pressing need for changing the flow paradigms currently used in tracking flow variables during gradually-varied flows. Also discussed are research needs associated with flow hysteresis for advancing the understanding of the mechanisms underlying the movement and storage of water in the lowland river environments as well as for increasing the accuracy of streamflow monitoring, modeling, and forecasting.

Kinship estimation is widely used in ecological and evolutionary research, particularly in studies of human genealogy and genome-wide associations. In conservation, restoration, agriculture, and forestry, identifying relationships between individuals can be crucial for successful population management and can provide insight into inheritance patterns. Kinship estimation methods are typically designed for large datasets with hundreds of thousands of single-nucleotide polymorphisms. However, studies of non-model species often use much smaller datasets obtained using reduced-representation sequencing. To evaluate the performance of kinship estimation methods under these circumstances, we applied six algorithms to datasets from six non-model Australian flowering plant species (_Acacia terminalis_, _Acacia suaveolens_, _Banksia serrata_, _Banksia aemula_, _Hakea sericea_, and _Hakea teretifolia_), encompassing 3,390 individuals and 369 families. Our results show different performances of kinship methods on reduced-representation sequence data compared with prior evaluations. PC-Relate, RelateAdmix, and Goudet’s beta dosage exhibited limited precision, KING Homo and KING Robust demonstrated high precision with limited sensitivity, while PLINK displayed variable sensitivity and precision. The sensitivity and precision of the methods were affected in various ways by filtering parameters; each method showed its best performance under different thresholds for minor allele frequency and locus missingness. We also present a case study that illustrates a practical application of the methods, demonstrating how estimates of kinship can inform management of seed production areas of the broadleaf hopbush (_Dodonaea viscosa_). Based on our findings, we offer specific recommendations for utilizing kinship estimation methods in studies of reduced-representation sequence data from non-model species.