Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. Mechanistic study by Biacore and docking analysis revealed that YZH-106 bound directly to PreS2 domain of L- and M-HBsAg, thereby blocking their entry to the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provide basis for design of novel compound therapy to target HBsAg against HBV infection.

: (1) Background: Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However atypical HBV serologies occur and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. (2) Methods: Plasma samples from an HIV-1 cohort in Botswana (2013-2018) were used. Samples were screened for HBsAg and anti-HBc. Next generation sequencing was done using the GridION platform. Wilcoxon rank-sum test and Chi-squared tests were used for comparison of continuous and categorical variables respectively. (3) Results: HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1 – 18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p<0.001), female (p=0.02), ART naïve (p=0.04) and had detectable HIV viral load (p=0.02). There were no mutational differences in sequences isolated from participants with HBsAg+/anti-HBc- versus those with HBsAg+/anti-HBc+ serology. (4) Conclusions: We report a high HBsAg+/anti-HBc– atypical serology profile prevalence among PWH in Botswana. We caution against HBV testing algorithms that consider only anti-HBc+ samples for HBsAg testing as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems, complicating the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In this review, the clinical usefulness and remaining problems of anti-HBc antibody and HBcrAg were summarized.

(1) Background: Hepatitis B virus (HBV) viral load (VL) is useful in determining treatment eligibility, however, due to high costs associated with the test, hepatitis B e antigen (HBeAg) is recommended as a proxy for HBV VL in resource-limited settings. (2) Methods: We used 299 archived plasma samples with hepatitis B surface antigen (HBsAg), HBeAg, and HBV VL (cut-off of 20,000 IU/mL and 200,000 IU/mL) results from people living with human immunodeficiency virus (PLWH). HBeAg and HBV VL results were analyzed to evaluate the use of HBeAg to determine CHB treatment eligibility and qualification of HBV prevention of mother-to-child transmission (PMTCT) prophylaxis for the first time in Botswana. (3) Results: Approximately 70.8% and 87.5% of participants with HBeAg-positive serology had HBV viral loads ≥20,000 IU/mL and 200,000 IU/mL respectively. Using logistic regression, the odds of having a qualifying HBV VL for CHB treatment and PMTCT prophylaxis were respectively 55.5 and 110.4 times higher in participants with positive HBeAg serology indicating a statistically significant association between HBeAg status and HBV VL. (4) Conclusions: HBeAg detection may not always correlate with high HBV VL, warranting further research focusing on this association, and other biomarkers that correlate better with HBV VL.

Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Density functional theory (DFT) calculations of hydrogen adsorption on titanium nitride had previously shown that hydrogen may adsorb on both titanium and nitrogen sites with a moderate adsorption energy. Further, the diffusion barrier was also found to be low. These findings may qualify TiN, a versatile multifunctional material with electronic conductivity, as electrode material for the hydrogen evolution reaction (HER). This was the main impetus of this work which aims to experimentally and theoretically investigate the electrocatalytic properties of TiN-layers that were processed on Ti substrate using reactive ion sputtering. The properties are discussed focusing on the role of oxygen defects introduced during the sputtering process on the HER. Based on DFT calculations, it is shown that these oxygen defects alter the electronic environment of the Ti atoms which entails a low hydrogen adsorption energy in the range of -0.1 eV; this leads to HER performances that match those of Pt-NPs in acidic media. When a few nanometr thick layer of Pd-NPs is sputtered on-top of the TiN-layer, the performance is drastically reduced. This is interpreted in terms of oxygen defects being scavenged by the Pd-NPs near the surface which is thought to reduce the hydrogen adsorption sites.

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV in the host. Theoretically, suppression of Treg functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating Mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To determine the efficacy of anti-CHB, 2ug/ml MAF was combined with the GMI-HBVac in an HBV-infected animal model as an anti-Treg treatment. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and upregulation of IFN-gamma producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulates T cell infiltration in HBV-infected liver. These conditions may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF was utilized as an adjuvant to deplete Tregs and paired with GMI-HBVac as a unique therapeutic vaccine regimen against established CHB mice to produce a functional cure, as seen by the remarkable clearance of HBsAg.

The carbohydrate antigen Sda is expressed on cells and secretions of the vast majority of Caucasians. The epitope is formed by a terminal GalNAc residue β4-linked to a α3-sialylated galactose. Different carbohydrate chains N- or O-linked to glycoproteins can be terminated by this epitope. The final step of Sda biosynthesis is catalyzed by the GalNAc transferase B4GALNT2. In this review, we will discuss the multifaceted aspects of B4GALNT2/Sda biology. In particular, we will see its implications in fertility and pregnancy, in susceptibility to infectious diseases, in chronic kidney diseases and in Duchene muscular dystrophy. In particular, we will show its regulation and prognostic implications in cancer.

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

This study investigates the stochastic dynamics of hepatitis B virus (HBV) infection using a newly proposed stochastic model. Contrary to deterministic models that fail to encapsulate the inherent randomness and fluctuations in biological processes, our stochastic model provides a more realistic representation of HBV infection dynamics. It incorporates random variability, thereby acknowledging the changes in viral and cellular populations and uncertainties in parameters such as infection rates and immune responses. We examine the solution's existence, uniqueness, and positivity for the proposed model, followed by a comprehensive stability analysis. We provide the necessary and sufficient conditions for local and global stability, offering deep insight into the infection dynamics. Furthermore, we utilize numerical simulations to corroborate our theoretical results. This research provides a robust tool for understanding the complex behavior of HBV dynamics, contributing significantly to the ongoing quest for more effective HBV control and prevention strategies.

It is well known that the event of hepatitis B virus reactivation can occur among patients undergoing treatment for hematological malignancies. In this paper we will present the available data regarding the risk of hepatitis B virus reactivation in this special population of immunosuppressed patients and explore the relevance of an accurate prevention and management of this condition. A computerized literature search was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. The evaluation of hepatitis B reactivation risk is a multidimensional process, which includes conducting an accurate clinical and physical history, considering the virological categories, the knowledge of the medication chosen to treat these hematological malignancies and the induced grade of immunosuppression. Adopting adequate preventive strategies and surveillance according to the current international recommendations is crucial to prevent HBVr and its dire clinical consequences (hepatitis, liver failure, interruption of lifesaving anti-neoplastic treatments). Universal HBV screening of patients scheduled to undergo treatment for hematological malignancies should be the chosen policy, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and the classes of immunosuppressive drugs.

Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

The variation of aerosols, especially dust aerosol, in time and space plays an important role in climate forcing studies. Aerosols can effectively reduce land surface longwave emission and re-emit energy at a colder temperature, making estimation of downwelling surface longwave radiation (DSLR) with satellite data difficult. Using the latest atmospheric radiative transfer code (MODTRAN 5.0), we simulate the outgoing longwave radiation (OLR) and DSLR under different land surface and atmospheric profile conditions. The results show that dust aerosol has an obvious “warming” effect to longwave radiation compared with other aerosols, that aerosol longwave radiative forcing (ALRF) increased with increasing aerosol optical depth (AOD), and that the atmospheric water vapor content (WVC) is critical to the understanding of ALRF. A method is proposed to improve the accuracy of DSLR estimation from satellite data for the skies under heavy dust aerosols. The AOD and atmospheric WVC under cloud-free conditions with a relatively simple satellite-based radiation model that yields the high accurate DSLR under heavy dust aerosol are used explicitly as model input to reduce the effects of dust aerosol on the estimation of DSLR. Validations of the proposed model with satellites data and field measurements show that it estimates the DSLR accurately under heavy dust aerosol skies. The root mean square errors (RMSEs) are 20.4 W/M² and 24.2 W/M² for Terra and Aqua satellites, respectively, at the Yingke site, and the biases are 2.7 W/M² and 9.6 W/M², respectively. For the Arvaikheer site, the RMSEs are 23.2 W/M² and 19.8 W/M² for Terra and Aqua, respectively, and the biases are 7.8 W/M² and 10.5 W/M², respectively. The proposed method is especially applicable to acquire relatively high accurate DSLR under heavy dust aerosol using MODIS data with available WVC and AOD data.

Axial resolution is one of the most important characteristics of a microscope. In all microscopes, a high axial resolution is desired in order to discriminate information efficiently along the longitudinal direction. However, when studying thick samples that do not contain laterally overlapping information, a low axial resolution is desirable as information from multiple planes can be recorded simultaneously from a single camera shot instead of plane-by-plane mechanical refocusing. In this study, we increased the focal depth of an infrared microscope non-invasively by introducing a binary axicon fabricated on barium fluoride substrate close to the sample. Preliminary results of imaging thick and sparse silk fibers showed an improved focal depth with a slight decrease in lateral resolution and increase in background noise.

We aimed to investigate the relationship between membrane material and development of membrane fouling in a membrane bioreactor (MBR) using membranes with different pore sizes and hydrophilicities. Batch filtration tests were performed using submerged single hollow fiber membrane ultrafiltration (UF) modules with different polymeric membrane materials including cellulose acetate (CA), polyethersulfone (PES), and polyvinylidene fluoride (PVDF) with activated sludge taken from a municipal wastewater treatment plant. The three UF hollow fiber membranes were prepared by a non-solvent-induced phase separation method and had similar water permeabilities and pore sizes. The results revealed that transmembrane pressure (TMP) increased more sharply for the hydrophobic PVDF membrane than for the hydrophilic CA membrane in batch filtration tests, even when membranes with similar permeabilities and pore sizes were used. PVDF hollow fiber membranes with smaller pores had greater fouling propensity than those with larger pores. In contrast, CA hollow fiber membranes showed good mitigation of membrane fouling regardless of pore size. The results obtained in this study suggest that the surface hydrophilicity and pore size of UF membranes clearly affect the fouling properties in MBR operation when using activated sludge.

In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted, and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x10^4 – 2x10^7 CFU per ml and has a sensitivity of S = 1.655x10^5 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10^-9 grams (g), which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

BACKGROUND: Chronic hepatitis B infected with Hepatitis B virus remains a major health concern worldwide. Despite standard interferon-α and nucleotide analogues have been shown to reduce the deterioration of liver disease among chronic hepatitis B patients, covalently closed circular DNA was still difficult to eradicate. METHODS: A literature search of Pubmed and Web of science was performed with the following key words: ‘CRISPR’, ‘CRISPR/Cas9’, ‘hepatitis B’, ‘HBV’, ‘chronic hepatitis B’ and ‘HBV cccDNA’. The information about CRISPR/Cas9 for the treatment of HBV cccDNA or hepatitis B was reviewed. RESULTS: CRISPR/Cas9 could treat hepatitis B through suppressing or clearing HBV cccDNA with different gRNAs. CONCLUSION: With the emergence of CRISPR/Cas9 (the RNA-guided clustered regulatory interspaced short palindromic repeats, CRISPR) editing technology, clearance of hepatitis B virus and better prevention of liver carcinoma seemed to be possible.

In the case of a Cu-Mo-W polymetallic ore, the wastewater from the scheelite cleaning flowsheet contains large amounts of residual flocculants and metal ions, and the separation of chalcopyrite and molybdenite require a large number of environmentally harmful depressants. Therefore, it is necessary to find new methods to reduce the environmental and cost pressures of wastewater treatment and the use of depressants. In this work, the flotation wastewater from scheelite cleaning flowsheet for the separation of chalcopyrite and molybdenite by selective surface passivation was investigated for the first time. Flotations of single minerals and artificially mixed minerals with or without immersion pretreatment in the presence and absence of aeration were performed. The results showed that pulp pH had no effect on the flotation of either mineral, and a molybdenite recovery of 93.22% with chalcopyrite recovery of 10.77% was achieved under the conditions of 10 days of immersion pretreatment with aeration, 350 mg/L of kerosene, and 100 mg/L of MIBC. By combining the electrochemical cyclic voltammetry analysis and characterization by XRD and SEM, the selective surface passivation mechanism of chalcopyrite was discussed, which could be due to the coverage of the insoluble oxidation products, especially jarosite. This work has simultaneously achieved the depressant-free flotation separation of molybdenite and chalcopyrite and the reuse of scheelite flotation wastewater, which is of great significance for environmental protection and cost saving.

This study aimed to learn disturbance information to effectively control multiple small unmanned surface vehicles (USVs) for marine research purposes at sea. The learned disturbance information was used to investigate the control of multiple USV swarms based on the leading–following formation technique. Numerous studies have already been conducted on swarm control using drones in the air; however, there has been a paucity of studies on swarm control in the sea. Contrary to swarm control in aviation, the fluid density of the sea is high, and the environment is constantly changing; thus, a robot system would be significantly affected by disturbances. This ultimately influences the maintenance of swarm formations and the accomplishment of missions [1,2]. Therefore, it is difficult to control numerous moving objects while maintaining a formation at sea by using the existing aerial drone swarm control technology. To solve this problem, we learned a long short-term memory (LSTM) model with time-series marine environmental data to predict maritime disturbances. Thereafter, the model was applied to a mission-based position control algorithm of each USV constituting the swarm to design a marine unmanned floating vessel swarm control system that can be applied to various marine environments. Specifically, to effectively control numerous small USVs for marine research purposes, ocean currents are learned using the LSTM algorithm, and the predicted ocean currents are used to generate a swarm USV control system for USV formations. In this study, a control system model of several small USVs equipped with two rear thrusters and a front lateral thruster was designed. The LSTM algorithm was learned using the previous ocean current data, and the velocity of the following ocean currents was predicted. The predictions were then used as a system disturbance to determine the thrust of the controller. To measure ocean currents in the sea when each USV moves, the velocity, azimuth, and position (latitude, longitude) data from the GPS mounted on the USV were used to measure the velocity and direction of the hull's movement. Further, the flow rate was measured using a flow rate sensor on a small USV. The USV movement and position were controlled using an artificial neural network-PID (ANN-PID) controller. This study entailed a comparative analysis of the designed USV model results and those generated by the simulator, including the behavior control rule of the USV swarm and the path of the actual USV swarm at sea. It was verified that the effectiveness of the USV mathematical model and behavior control rules. By comparing the movement path of the swarm USV with and without the disturbance learning algorithm and ANN-PID control algorithm applied to the designed simulator, the position error and maintenance performance of the swarm formation were analyzed, and the application results were compared.

Water quality assessment in pastoral of Tibetan Plateau, which is water sources for about 40% of world's population and the runoff-yield area of Yellow rivers, is very important. In this paper, Xiahe county which belongs to Tibetan Plateau pastoral was investigated. Six parameters(via, chloride, COD, ammonia nitrogen, nitrate, fluoride, sulfate) were selected to assess the water quality and health degree by using fuzzy comprehensive evaluation methods. The hydrochemical type in surface water was of HCO3--Mg2+-Ca2+ type. The cations and anions in surface water were mainly from weathering and dissolution of carbonate rock. Results showed that the water quality in all 69 sampling sites was all of class Ⅰ. The integrated health degree reached more than 0.85 and the health rate were 100%. Although ammonia nitrogen was regarded as the main contamination factor, but it had a little effect on the entire body of water. Overall, the surface water qualities of most samples in Xiahe County was good condition.

Introduction: The trophoblast derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. The aim of this study was to establish relationship between concentrations of soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of the fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices were determined in 41 uncomplicated singleton pregnancies. Results: The sHLA-G levels were unchanged both in amniotic fluid and in serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β=0.63, p<0.01). Significant correlation was found between serum sHLA-G level and abdominal measurement (β=0.41, p<0.05) and estimated fetal weight (β=0.41, p<0.05). The amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p<0.01 and VFI: β = -0.44, p<0.01, respectively) were negatively interrelated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p<0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator for placental function, whereas the sHLA-G level in serum can be a prognostic modality for feto-placental insufficiency.

This research was devoted to study the effect of the tacticity of PMMA on the surface physicochemical properties such as the London dispersive component of the surface energy of the polymer, the polar and dispersive free energies, the Lewis’s acid-base surface parameters, and the Lewis acid and base surface energies of atactic, isotactic and syndiotactic PMMAs as a function of the temperature. Inverse gas chromatography (IGC) at infinite dilution was used to determine the surface thermodynamic properties of PMMA at different tacticities. The experimental values of the net retention time and volume of model organic molecules adsorbed on the atactic, isotactic and syndiotactic PMMAs, were obtained by IGC technique at infinite dilution. The London dispersion interaction energy was used for the separation of the polar and dispersive energy of the different n-alkanes and polar solvents adsorbed on the different PMMA surfaces. The London dispersive surface energy γ_s^d (T) of PMMAs was determined by applying the Hamieh thermal model that took into account the effect of the temperature on the surface area of adsorbed molecules. The obtained results showed non-linear variations of γ_s^d (T) of atactic, isotactic, and syndiotactic PMMAs with three maxima characterizing the three transition temperatures of PMMAs, T_g, T_g and T_(liq-liq) with a shift of these temperatures with the isotactic and syndiotactic PMMAs. It was showed that the polar interaction free energy ∆G_a^p (T) also showed the presence of the three above transition temperatures of the polymers. The study showed an important non-linearity variation of the different acid-base parameters in the various polymer surfaces proving the highest effect of the temperature and the tacticity on these parameters. The determination of the enthalpic and entropic Lewis’s acid-base parameters showed an amphoteric character for the different PMMAs. The basicity of the atactic PMMA was about four times larger than its acidity outside the neighborhood of the transition temperatures of the polymer. Whereas, the isotactic PMMA was about 2 to 2.5 times more basic than acid, while the syndiotactic PMMA exhibited the highest basicity by showing a surface 5 to 8 times more basic than acid. However, the Lewis acid-base parameters strongly depended on the temperature and sudden variations of these surface parameters were observed around the transition temperatures largely depending on the PMMA tacticity. The determination of the polar acid and base surface energies of the three PMMAs led to the same previous transition temperatures with an important effect of the tacticity of PMMA on the values of these acid-base surface energies.

Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent outbreak in several countries around the world. A 39-year-old male with HIV-HBV coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox infection, presented to our hospital with disseminated dermatosis (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for Mpox. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. After 65 days of Mpox PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox infection because it could be related to higher mortality.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Environmental monitoring programs rely on periodic spot sampling at specific locations, followed by laboratory analysis, aiming at the evaluation of water quality at a catchment scale. For this purpose, automatic telemetric stations for specific parameters have been installed by the Institute of Marine Biological Resources and Inland Waters of Hellenic Centre for Marine Research (IMBRIW-HCMR) within several Greek rivers and lakes, providing continuous and temporal monitoring possibilities. Nevertheless, the employment of unmanned surface vehicles (USV) equipped with integrated sensors represents a tool valuable to several monitoring strategies, offering enhanced temporal and spatial coverage over specific timeframes, allowing for targeted examination of sites or events of interest. The USVs have been deployed by Athens Water and Sewerage Company (EYDAP) as a cost-effective tool for the environmental monitoring of surface water bodies of interest, with emphasis on the spatial fluctuations of chlorophyllα, electrical conductivity, dissolved oxygen and pH, observed in Koumoundourou Lake and rivers Acheloos, Asopos and Kifissos. The effectiveness of an innovative heavy metal (HM) system installed in the USV for thein situ determination of copper and lead was also evaluated herewith. The results obtained demonstrate that both the timely detection of potential pollution from both anthropogenic activities and natural processes as well as the monitoring of inland waters are made feasible through the employment of USV.

Objective: The aim of this study was to optimize the fermentation process of Radix Ranunculi ternate via microbial fermentation and analyze the changes in the contents of the main components, the antioxidant and hypoglycemic capacities of the extract before and after fermentation. Methods: The solid-state fermentation process was optimized using single-factor tests and the response surface method, with the yield of the alcohol extract of R. ternate as an evaluation index. Results: The best fermentation process was optimized using solid-state endophytic fungus fermentation technology as follows: strain addition ratio of Chaetomium globosum/Fusarium equiseti =1:1, fermentation for 5 d, sieve size of 40 mesh, liquid/material ratio of 0.8:1 mL·g−1, fermentation temperature of 31 °C, and inoculation amount of 7.5%. Under the optimized conditions, the contents of the water-soluble extract and total polysaccharides decreased by 12.71% and 12.95%, respectively, in the fermentation, The contents of ethanol-soluble-extract, flavonoids, saponins, polyphenols, organic acids, and total amino acids of fermented R. ternate increased by 19.77%, 57.14%, 79.67%, 14.29%, 17.63% and 3.82%, respectively, and the scavenging rate for DPPH, ABTS+, ·OH free radicals and inhibitory rate for α-amylase also increased by 19.02%, 14.17%, 7.53% and 34.54%, respectively, compared with unfermented R. ternate. Conclusions: Solid-state fermentation opens new avenues for the development and application of R. ternate as natural antioxidant and hypoglycemic food.

According to the guidelines of the European Association of Urology (EAU), it is recommended to exclude PSA testing when the expected remaining lifespan is less than 10 years. In this study, we provide a comprehensive analysis of the impact of prostate-specific antigen (PSA) testing on the quality of life of elderly men who are frail. We conducted a comprehensive literature review to identify publications that examine the use of PSA as a screening and prognostic tool for prostatic illnesses in frail men. Our search included the following keywords: Prostate-specific antigen, Frailty, Prostate cancer screening, Hypogonadism, and Benign Prostatic Obstruction (BPO). Prostate-specific antigen (PSA) testing can be used to identify prostate cancer in its early and treatable stages in fragile men with a life expectancy of over 15 years. Additionally, PSA testing allows for the evaluation of the effectiveness of various prostate cancer treatments and the monitoring of testosterone replacement therapy for hypogonadism. PSA is also indicative of the clinical development of patients with benign prostatic obstruction (BPO). Nevertheless, PSA is being extensively provided without individualised patient assessment, contributing to the economic strain on healthcare systems. Conducting a frailty evaluation on men to determine the potential advantages of PSA tests on their quality of life will help minimise avoidable expenses.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

In light of the critical and emerging global challenge posed by the increasing frequency and severity of heatwaves in recent decades, this study demonstrates a practical and robust workflow that bridges the gap in understanding how the effective integration of remote sensing data with ground-based observations can facilitate a comprehensive assessment of spatiotemporal heatwave patterns and trends in the central region of Thailand. This research transcends traditional methods, utilizing air temperature (Tair) and satellite-derived land surface temperature (LST) data from 1981 to 2019. Results exhibit that an analysis of Tair indicates increasing daytime heatwaves in peri-urban areas, with significant trends in heatwave number (HWN), heatwave frequency (HWF), and heatwave duration (HWD), heatwave amplitude (HWA) rises in urban settings while nighttime heatwaves significantly intensify in rural locales. Notably, LST trends reveal varied patterns, with peri-urban areas showing marked daytime increases in heatwave magnitude (HWM), HWA, and HWF. Correlation analysis (p=0.05) highlights strong daytime associations between Tair and LST in rural (HWN, HWF, HWD, r&gt;0.90) and peri-urban (HWM, HWA, r&gt;0.65) regions. Overall, this study advances approaches to the adaptable measurement and spatial-temporal pattern of heatwave-related risk areas, providing insights for decision-makers to develop sustainable practices and strategies for climate change adaptation.

Coinfection of B virus (HBV) and hepatitis Delta virus (HDV) lead to severe forms of progressive liver diseases. However, commercially available antiviral drugs have shown considerable adverse effects and low efficacy in managing these patients. Thus, there is a pressing need to develop new, innovative, and evidence-based therapies for these pathological entities. In line with this, some investigators have attempted to develop anti-viral drugs targeting HBV/HDV coinfection. In another development, investigators have also attempted to establish immune therapy targeting for HBV infection as recovery or effective control of HBV infection also lead to efficient control of HDV infection. This review has discussed an account of the evolving antiviral and immune therapeutic drugs for HBV/HDV infection. Also, based on current scientific knowledge how we have described the pros and cons of these drugs as no suitable drug has been developed during the last forty years for treating HBV infection except the availability of two” repurposed drugs”; interferons and its derivatives and nucleoside analogs, for managing HBV or HBV/HDV coinfection. It seems that an evolving and innovative therapeutic regimen that combines both antiviral drugs and immune modulators may be the best and realistic option for management of HBV/HDV coinfection.

The poly lactic acid (PLA) is one of the most used bio-derived thermoplastic polymers in 3D and 4D printing applications. The determination of PLA surface properties is of capital importance in 3D/4D printing technology. (1) Background: The surface thermodynamic properties of PLA polymer were determined by using the inverse gas chromatography (IGC) technique at infinite dilution. The determination of the retention volume of polar and non-polar molecules adsorbed on the PLA particles filling the column allowed us to obtain the dispersive, polar, and Lewis’s acid-base surface properties at different temperatures from 40 °C to 100 °C. (2) Methods: the applied surface method was based on our recent model that used the London dispersion equation and the new chromatographic parameter function of the deformation polarizability and the harmonic mean of the ionization energies of the PLA polymer and organic molecules. (3) Results: The application of this new method led to the determination of the dispersive and polar free surface energy of adsorption of molecules on the polymeric material, as well as the glass transition and the Lewis acid-base constants. (4) Conclusions: four interval temperatures were distinguished showing four zones of the variations of the surface properties of PLA as a function of the temperature before and after the glass transition.

In the last decades, technological advances related to RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle employed. Among the systems, yeasts emerge as a new approach to a natural delivery platform. The presence of β-glucans and mannans in its wall is responsible for the adjuvant action of this system. Yeasts are already employed to deliver protein antigens, with success and efficacy demonstrated through pre-clinical and clinical trials. Yeast β-glucan capsules, microparticles, and nanoparticles are capable of modulating host immune responses and have a high capacity to carry RNA and small molecules, with bioavailability upon oral immunization and with targeting to receptors present in anti-gen-presenting cells (APCs). Besides, yeasts are interesting vehicles for the protection and specific delivery of therapeutic vaccines based on shRNA or dsRNA. In this review, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing their current challenges and prospects for using this promising strategy.

This study was designed for the first time to improve phenolic yield and antioxidant activity of ultrasonic-assisted extraction from Acer truncatum leaves (ATL) using response surface methodology, and phenolic composition in ATL extracted under the optimized condition were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol: water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent /100 g d.w. and a maximal DPPH• antioxidant activity of 74241.61 μmol Trolox equivalent/100 g d.w.. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic composition in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloyl-glucoside was interpreted. All these results provided practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

Antigen-based rapid diagnostic tests for Lymphatic filariasis do not come with quality control (QC) materials, and research and disease control programmes rely on stored positive plasma samples. This study was undertaken to evaluate the use of freeze-dried Wuchereria bancrofti antigen positive plasma samples to serve as QC materials for LF RDTs. 10 well characterized W. bancrofti positive samples were lyophilized and stored at 4°C, 28°C and 40°C. The samples were evaluated using the Filaria Test Strips before lyophilization and after one and three (3) months of storage. The sensitivity and stability of the lyophilized samples were evaluated. The results revealed a loss of sensitivity and stability with increasing temperature and duration of storage. The results are further discussed in terms of the use of Dried Blood Spot (DBS) in diagnostics studies on LF requiring quantitative assessments, and the need for thoughtful DBS preparation and storage.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modified putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 to 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common.

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

(1) Background: A simple approach to map irrigated landcover has been introduced by using measures derived from optical spectral range as an alternative to thermal range. It has been demonstrated that substituting surface temperature (Ts, ‘thermal approach’) with SWIR transformed reflectance (STR, ‘optical approach’) to detect surface moisture is feasible with comparable results. (2) Methods: Using an iterative thresholding procedure to minimize within-class variance, the bilevel segmentation of variables derived from Landsat-8 representing surface moisture and vegetation cover was achieved for the 2020-21 summer for a key irrigation district in Australia. (3) Results: The results of irrigated landcover by optical approach found to be comparable with those by thermal approach. The classification accuracy was assessed using water delivery records at farm level. Though the overall accuracy is high in both cases, the optical approach (97.6%) performed slightly better than the thermal approach (93.9%). (4) Conclusions: The feasibility of using STR to map irrigated landcover has been confirmed by a high-level overall accuracy assessment. This has broader implications in terms of irrigated landcover assessment, as the use of satellite imagery in these applications may not necessarily be limited to microwave or thermal sensors.

Autoantibodies against specific lung cancer-associated antigens have been suggested for lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of anti-gen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, NGAL, and NSE in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9G DNA chip method. The ratios of AICs to their antigens and combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than their free antigens in all participants. The levels of each free antigen distinguished patients with NSCLC from HCs. The ratios of AIC to its antigen and seven combinations consisting of two to four ratios were significantly higher in patients with NSCLC than those in HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at cutoff 3.51. Higher sensitivity was observed in the very early stages (0–I) and adenocarcinoma than in stages II–IV and other pathological types. The combination of all ratios of AICs and their antigens for all four markers is useful in the diagnosis of NSCLC.

Buckling defect will appear on the outer surface of the deformed ring during constrained ring rolling (CRR) of aluminum alloy thin wall conical ring with inner high ribs (AATWCRIHR), if the geometrical dimension of the ribs doesn't match the wall thickness. To avoid the buckling defect, a quantitative method for characterizing the degree of the buckling defect is proposed using the area of buckling profile. Then an orthogonal experimental scheme was designed taking the width of the middle rib, thickness of wall, and height of the middle rib as design variables and defining the area of buckling profile as optimization objective. Subsequently, a quadratic polynomial response surface model was established by combining the optimization algorithm with the finite element method (FEM), and the geometrical dimension of the middle ribs of the deformed AATWCRIHR is optimized. Also the optimal parameter combination to minimize the area of buckling profile is obtained and verified using FE simulation. Results show that the AATWCRIHR after optimization doesn’t generate the buckling defect during constrained ring rolling, and it is proved that the quantitative buckling defect representation method and the optimization design method based on the response surface model and the finite element simulation results are feasible for the constrained ring rolling process of the AATWCRIHR.

Displacement mapping is a computer graphics technique that enables the design of components with regularly or randomly textured surfaces that can be quickly materialized on a three-dimensional (3D) printer when needed. This approach is in principle more flexible, faster and more economical compared to conventional texturing methods, but the accuracy of the texture depends heavily on the parameters used. The purpose of this study is to demonstrate how to produce a surface-textured part using polygonal (mesh) modeling software and a photopolymerizable resin, and to develop a universal methodology to predict the dimensional accuracy of the model file log combined with a resin 3D printer. The printed components were characterized on a scanning confocal microscope. In the setup used in this study, the mesh size had to be reduced to 10% of the smallest feature size and the textured layer had to be heavily (x4) overexposed to achieve the desired accuracy. As a practical application, two functional stamps with a regular (honeycomb) and a random texture, respectively, were successfully manufactured. The insights gained will be of great benefit in quickly and cost-effectively producing components with innovative patterns and textures for a variety of hobby, industrial and biomedical applications.

Viral integration within the host genome plays a pivotal role in carcinogenesis. Various disruptive mechanisms are involved, leading to genomic instability, mutations, and DNA damage. With next-generation sequencing (NGS), we can now precisely identify viral and host genomic breakpoints and chimeric sequences, which are useful for integration site analysis. In this study, we evaluated a commercial hybrid-capture NGS panel specifically designed for detecting three key viruses: HPV, HBV, and HIV-1. We also tested workflows for Viral Hybrid Capture (VHC) and Viral Integration Site (VIS) analysis, leveraging customized viral databases in CLC Microbial Ge-nomics. By analyzing sequenced data from virally infected cancer cell lines (including SiHa, HeLa, CaSki, C-33A, DoTc2, 2A3, SCC154 for HPV; 3B2, SNU-182 for HBV; and ACH-2 for HIV-1), we precisely pinpointed viral integration sites. The workflow also highlighted disrupted and neigh-boring human genes that may play a crucial role in tumor development. Our results included in-formative virus-host read mappings, genomic breakpoints, and integration circular plots. These visual representations enhance our understanding of the integration process. In conclusion, our seamless end-to-end workflow bridges the gap in understanding viral contributions to cancer development, paving the way for improved diagnostics and treatment strategies.

Mutations within the hepatitis B virus (HBV) genome have been associated with rapid progres-sion to hepatocellular carcinoma (HCC); however, there is limited information regarding the prevalence and impact of these mutations in most of sub-Saharan Africa, including Botswana. We aimed to determine the prevalence of HBV mutations known to be associated with progression to HCC using a retrospective, cross-sectional analysis of 48 previously generated HBV sequences from adults with concomitant HBV/HIV initiating HIV antiretroviral therapy in Botswana. The sequences were aligned with reference sequences, and HCC-associated mutations were manually identified using BioEdit. Sixteen (33.3 %) of 48 participant samples had 20 HCC-associated mu-tations. Seven HCC mutations were present in the core region, 4 in the preCore region, 7 in the X region, and one mutation in the surface region, as well as deletions within the preSurface 1 region. Seven of the 16 participants (43.8%) had multiple HCC-associated mutations. There were also previously uncharacterized mutations at positions with known HCC-associated mutations. HCC-associated mutations were common in this cohort; hence, some participants may require close clinical monitoring as they might be more prone to rapid disease progression. Other functionally uncharacterized polymorphisms were also detected and require characterization in future studies.

Detection of virus in sample is an actual problem in biotechnology, virology, medicine using biosensor. History of problem dates back to middle of last century and is associated with development of an ion-sensitive solid-state device for neurophysiological measurements. Aim of work is theoretical investigation process of detection antibody+antigen (AB+AG) complexes using SOI-FET biosensor. On example of crystal with ten biosensors, estimates of probability detection AB+AG complexes influenza virus are made. In detection process, following four results are possible: – target complex is present in test sample, and it was correctly detected; – target complex is present in sample, but it was not detected; – target complex is absent in sample, but background particles are mistakenly detected as target complex; – target complex is absent in sample, background particles present in sample and are correctly detected as noise.

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shape nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a non-coding ssRNA template. The PapMV nanoparticle induces innate immunity through stimulation of the toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, either at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the CTL epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C) using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate the TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

The urbanization effects on land surface phenology (LSP) have been investigated by many studies, but few studies focused on the temporal variations of urbanization effects on LSP. In this study, we used the MODIS EVI, MODIS LST data and China’s Land Use/Cover Datasets (CLUDs) to investigate the temporal variations of urban heat island intensity and urbanization effects on LSP in Northeast China during 2001–2015. Land surface temperature (LST) and phenology differences between urban and rural areas represented the urban heat island intensity and urbanization effects on LSP, respectively. Mann-kendall nonparametric test and Sen's slope were used to evaluating the trends of urbanization effects on LSP and urban heat island intensity. The results indicated that the average land surface phenology (LSP) during 2001–2015 was characterized by high spatial heterogeneity. The start of the growing season (SOS) in old urban area had become earlier and earlier than rural area and the differences of SOS between urbanized area and the rural area changed greatly during 2001–2015 (−0.79 days/year, p < 0.01). Meanwhile, the length of the growing season (LOS) in urban and adjacent areas had become increasingly longer than rural area especially in urbanized area (0.92 days/year, p < 0.01), but the differences of the end of the growing season (EOS) between urban and adjacent areas did not change significantly. Next, the UHII increased in spring and autumn during the whole study period. Moreover, the correlation analysis indicated that the increasing urban heat island intensity in spring contributed greatly to the increases of urbanization effects on SOS, but the increasing urban heat island intensity in autumn did not lead to the increases of urbanization effects on EOS in Northeast China.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially under influence of oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted previously introduced clinical model of host-virus interaction (i.e. infectious process in immunodeficiency) for analysis of B cells and specific IgG role (observational study of a CVID patient who received intravenous immunoglobulin (IVIG)) Suddenly, the patient deteriorated with positive result of HBs, HBV-DNA (369x106copies). In spite of lamivudine therapy and IVIG escalation (from 0.3 to 0.4g/kg), CT showed 11cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs had been positive in time-lapse analysis (range 111-220 IU/ml). Replacement therapy intensification was complicated by immune complex disease with renal failure. The fulminant HCC in CVID and the development of the tumor as the first sign is interesting. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HBs substitution has not been proven to be effective, oncoprotective nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, patient selection more precise with the exclusion of HBV-positive donors. Our clinical model show HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g. chronic hepatitis). Lack of cell cooperation, B cell deficiency observed in CVID plays a crucial role in high HBV replication, especially in carcinogenesis.

Multiple sclerosis is an autoinflammatory condition that results in damage of myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing remittent disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting opportunity to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, and many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes, including proteins, metabolites, nucleic acids, and lipids. Consequently, it is argued that exosomes may serve as unconventional secretory vesicles, playing a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses both qualitatively and quantitatively. Thus, the analysis of EVs from multiple biofluids, due to its ease of implementation, has become a booming tool for monitoring various pathologies, particularly cancer, as we shall outline further on. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Indeed, during a viral infection, the production of EVs and circulating exosomes is often enhanced to signal danger, stimulate immunity, and possibly serve as pathological biomarkers. Conversely, viruses can disrupt or hijack the exosome content and production. In this review, we discuss the particular and ambiguous functions of exosomes in infectious contexts. Furthermore, we explore the vectoring capacity of exosomes in light of the extensive literature examining their function in mounting adaptive immune responses. Exosomes provide an interesting platform for antigen presentation and could therefore serve as novel therapeutic targets or be used in vaccine strategies.

Presence of lipopolysaccharides (LPSs) in the outer layer of outer membranes (OMs) is an almost universal molecular signature of Gram-negative bacteria. The O-antigen or O-polysaccharide (OPS) chains attach to millions of LPS molecule to form a continuous layer on the surface of most of Escherichia coli strains. OPS structure is one of the most variable features of bacteria, with about 200 E. coli O-serotypes currently described. In this review a analyze accumulating evidence suggesting that a vast majority of these OPS types provide robust shields that restrict the access of large molecules to the OM surface. Sophisticated mechanisms employed by bacteriophages to penetrate the OPS barrier are also considered. These are initiated with specific recognition of OPS molecules by phage receptor-binding proteins (RBP), or of other cell-surface molecules that are exposed above the OPS layer. Only after can virions gain access to secondary receptors found closer to the OM surface. The mechanisms of breaking through OPS in most if not all cases appear to rely on mechanical force generated by molecular motors of processive depolymerization or deacetylation of cell surface polysaccharides by enzymatically active RBPs, or by internal rearrangement of the virion.

Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by RT-PCR using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and 51Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

Background and Aim: Spontaneous bacterial peritonitis is a common infection in liver cirrhosis. This systematic review and meta-analysis provides detailed information on the prevalence of SBP among HBV and HCV-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV, and HCV related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1,713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7 – 21.0%; I2= 96.13%; p < 0.001)], followed by SBP in HCV associated liver cirrhosis [4.0% (95% CI, 1.3% – 11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1 – 66.3%), the USA (50.0%, CI: 34.6 – 65.4%), and Holland (31.1%, CI: 21.6 – 42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV+HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P<0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed an increase in the incidence of SBP in viral hepatitis over the last decade, the latter could be due to the global increase in Bacterial resistance. This indicates a possible future rise in the global prevalence of SBP among HBV, and HCV-related liver cirrhosis.

Despite the remarkable success of SARS CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS CoV-2 challenge. The SARS CoV-2 MAPS vaccine generated robust neutralizing antibodies as well as Th1, Th17 and cytotoxic CD8 T-cell responses in NHPs. Furthermore, MAPS-immunized NHPs had significantly lower viral loads in the nasopharynx and lung compared to control animals. Taken together, these findings support the use of the MAPS platform to make a SARS CoV-2 vaccine. The nature of the platform also could enable its use for the inclusion of different variants in a single vaccine.

Helicobacter pylori is the most common human gastric infection. H. pylori stool antigen lateral flow immunochromatography assay (HpSA-LFIA) is considered one of the most cost-effective and rapid non-invasive assays (active tests). The evaluation of this test is crucial for accuracy and utility assurance. This study aimed to evaluate the polyclonal antibody-based HpSA-LFIA in comparison to a monoclonal antibody-based ELISA kit. Methodology: Stool samples were collected from 200 gastric patients for HpSA-LFIA and semi-quantitative HpSA-ELISA. Statistical analysis of the diagnostic values was performed using MedCalc software. Chi-square tests were used to determine the effects of gender and age. Results: The obtained results found that HpSA-LFIA achieved promising sensitivity (93.75%) and NPV (98.00%). However, it had poor specificity, PPV, and accuracy, respectively, 59.76%, 31.25%, and 65.31%. LR+ & LR- were 2.33% & 0.1%, respectively. Gender had no significance on the di-agnostic parameters of HpSA-LFIA. Age groups had irrelevant sensitivity; however, specificity was significantly higher in patients over 45 years. Conclusion: It was concluded that HpSA-LFIA was not accurate enough to be the sole test for di-agnosis and needs other confirmatory tests in case of positive conditions

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.

Determination of the presence in the blood of antibodies specific to the causative agent of a particular disease (serodiagnosis) is an effective approach in medical analytical chemistry. Serodiagnostics performed in the lateral flow immunoassay format (immunochromatography) meet the modern requirements for point-of-care testing and are supported by existing technologies of large-scale diagnostic tests production—thus raising increased attention in a tense epidemiological situation. For traditional lateral flow serodiagnostics formats, a large number of nonspecific immunoglobulins in the sample significantly reduces the degree of detectable binding. To overcome these limitations, an assay based on the formation of immobilized antigen— specific antibody—labeled antigen complexes detection was proposed. However, the requirements for its implementation, providing maximum sensitivity, have not been established. This article describes the mathematical model for the above assay. The influence of the ratio of reagent concentrations on the analysis results is considered. It is noted that the formation of specific antibody complexes with several labeled antigens is the main limiting factor in reducing the detection limit, and methods are proposed to minimize this factor. Recommendations for the choice of the assay conditions, following from the analysis of the model, are confirmed experimentally.

Cancer has been considered one of the most serious diseases in recent decades. Early diagnosis of cancer is a crucial step for an expedited treatment. Ideally, detection of cancer biomarkers, which are usually elevated because of cancer, is the most straightforward approach to detect cancer. Consequently, the accurate, effective, and prompt detection of these compounds is an insistent need for the medical diagnosis of the disease in order to start an early therapy plan for the patients. Among these biomarkers, Carcinoembryonic antigen (CEA) is considered one of the most important tumor markers for colorectal cancer, but it has been also used as a biomarker for other types of cancers, including breast, gastric, ovarian, pancreatic, and lung cancers. Typically, conventional CEA testing depends on immunoassay approaches, which are known to be complex, highly expensive, and time-consuming. In this context, many biosensors were designed for the aim of detecting cancer biomarkers. The main prerequisites of these biosensors are high sensitivity, fast response, and low cost. Many nanostructures have been involved in the design of biosensors. Metal organic frameworks (MOFs) were found to be one of the most potential and promising materials for biosensing. MOFs are highly porous and crystalline materials that consist of metal clusters surrounded by organic linkers, where the assembly of these components gives rise to the exquisite geometric 3D structures of MOFs. Moreover, the unique structure and geometry of MOFs allow for a better tailoring of their design to provide properties that are needed by different categories of biosensors. In the past few years, researchers have extensively considered MOFs for their fabrication of biosensors that can be used for the early detection of cancer biomarkers. In this regard, MOFs were used solely or were further decorated with other nanostructures to introduce more accurate signals and lower limits of detection. This review briefly classifies and describes MOFs-based biosensors trials that have been published recently for the aim of detecting CEA.

Findings of new targeted treatments with adequate safety evaluations is essential for better cancer cures and mortality rates. Immunotherapy holds promise for patients with relapsed disease, with the ability to elicit long-term remissions. Emerging promising clinical results in B-cell malignancy using gene-altered T-lymphocytes uttering chimeric antigen receptors have sparked a lot of interest. This treatment could open the path for a major difference in the way we treat tumors that are resistant or recurring. Genetically altered T cells used to produce tumor-specific chimeric antigen receptors are resurrected field of adoptive cell therapy by demonstrating remarkable success in the treatment of malignant tumors. Because of the molecular complexity of chimeric antigen receptors -T cells, a variety of engineering approaches to improve safety and effectiveness are necessary to realize larger therapeutic uses. In this study, we investigate at new strategies for enhancing chimeric antigen receptors-T cell therapy by altering chimeric antigen receptors proteins, T lymphocytes, and their relations with other solid tumor microenvironment (TME) aspects.

Multiple Myeloma (MM) is one of the incurable types of cancer in plasma cells. While immense progress has been made in the treatment of this malignancy, a large percentage of patients were unable to adapt to such therapy. Additionally, these therapies might be associated with significant diseases and are not always tolerated well in all patients. Since cancer in plasma cells has no cure, patients develop resistance to treatments, resulting in R/R MM. BCMA is primarily produced on mature B cells. Its up-regulation and activation are associated with multiple myeloma in both murine and human models, indicating that this might be an effective therapeutic target for this type of malignancy. Additionally, BCMA's predictive value, association with effective clinical trials, and capacity to be utilized in previously difficult to observe patient populations, imply that it might be used as a biomarker for multiple myeloma. Numerous kinds of BCMA-targeting medicines have demonstrated antimyeloma efficacy in individuals with refractory/relapsed MM, including CAR T-cell treatments, ADCs, bispecific antibody constructs. Among these medications, CART cell-mediated BCMA therapy has shown significant outcomes in multiple myeloma clinical trials. This review article outlines CAR T cell mediated BCMA medicines have the efficiency to change the therapeutic pattern for multiple myeloma significantly.

Successful fertilization treatments targeted to improve stand productivity while reducing operational complexities and cost depend on a clear understanding of soil nutrient availability under varying environmental conditions. Soil nutrient data collected from 154 forest sites throughout the Inland Northwest, USA were analyzed to examine soil nutrient characteristics on different geologic soil parent materials and to rank soil fertility. Results show that soil parent material explains significant differences in soil nutrient availability. Soils developed from volcanic rocks have the highest CEC and are relatively high in P, K, S, Mg, Cu, Ca, and B, but generally poor in N. Forest soils developed from plutonic rocks exhibit the lowest CEC and are low in N, S, K, Mg, Cu, and Ca, but higher in P. Some soils located on mixed glacial till are low only in K, Cu, Mg, and Ca, but many glacial soils are relatively rich in other nutrients, albeit the second lowest CEC. Soils developed from metasedimentary and sedimentary rocks are among those with lowest soil nutrient availability for P and B. Sulfur was found to have the highest concentrations in metasedimentary influenced soils and the least in sedimentary derived soils. Our results should be useful in designing site-specific fertilizer and nutrient management prescriptions for forest stands growing on soils developed from these major geologies within the Inland Northwest region of the United States.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

Developing prolonged antigen delivery systems that mimick the long-term exposure to pathogens appears as a promising, still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which his-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system, and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been done by taking, as building blocks, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.

Preferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis and is overexpressed in various cancers. PRAME family proteins are leucine rich repeat proteins, that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcome in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.

For marine vessels, a propeller shaft system, also known as a propulsion shaft system, is an essential changer in engine torque and propeller thrust. The propeller shaft system is subjected to transverse, longitudinal, and torsional excitations during operation. These sources of excitations originate from alternating thrust generated by the propeller, operation of a propeller in a stern flow field which is non-uniform in time and space, misalignment of components such as shafts, bearings, and keyholes in the assembly, excitations in the form of rotational motion, and the whirling motion of the shafts. These dynamic excitations posed a challenging issue for the integrity and reliability of a marine vehicle. Thus, it is crucial to analyze the dynamic response of the propulsion shaft system. The dynamic analysis of the propulsion shaft system is typically conducted using numerical /analytical models. At present, Finite Element Model (FEM) as a numerical model plays a vital role in analyzing the dynamic response of the structure. The computed response and the modal parameters from the FE model are reliable only if accurate boundary conditions, such as stiffness, can be imposed on the model. However, the numerical FE model deviates from the experimental results because of uncertainties in the stiffness values of the bearings and other connectors. This paper uses the Response Surface Optimization (RSO) technique to estimate the unknown stiffness of the bearings used in the propulsion shaft system. The experimental model of the propeller shaft system is constructed from the steady-state response of the system using the step sine excitation. The natural frequencies and the amplitude of vibrations in the FE model are updated using the parametric RSO technique. The updated model shows that the difference in natural frequencies and vibration amplitude is less than 10% between the optimized and experimental models. Propeller Shaft, Vibrations, Optimization, Response Surface

In the recent years, biochar has emerged as a remarkable biosourced material for addressing global environmental, agricultural, biomedical, and energy challenges. However, the performances of biochar rest in part on finely tuning its surface chemical properties, intended to obtain specific functionalities. In this review, we tackle surface treatment of biochar with silane and other coupling agents such as diazonium salts, titatantes, ionic/non-ionic surfactants, as well as nitrogen-containing (macro)molecules. We summarize the recent progress achieved mostly in the last five years, and correlate the nature and extent of functionalization to eye catchy end applications of the surface engineered biochar.

Various methods of polymer surface tailoring have been studied to control the changes in wetting behavior. Polymers having precisely controlled wetting behavior in a specific environment are blessed with a wealth of opportunities and potential applications exploitable in biomaterial engineering. The controlled wetting behavior can be obtained by combining surface chemistry and morphology. Plasma assisted polymer surface modification technique have played a significant part to control surface chemistry and morphology. This review focuses on plasma polymerization and investigations regarding surface chemistry, surface wettability, coating kinetics, as well as coating stability. We begin with brief overview of plasma polymerization; these include growth mechanisms of plasma polymerization and influence of plasma parameters. Next, surface wettability and theoretical background structures and chemistry of superhydrophobic and superhydrophilic surfaces. In this review, overview of recent work on tunable wettability by tailoring surface chemistry and physical appearance (i.e. substrate texture) is also described. The formation of smart polymer coatings, which adjust their surface wettability by according to outside environment, including, pH, light, electric field and temperature. Finally, the applications of tunable wettability and pH responsiveness of polymer coatings in real life are addressed. This review should be of interest to plasma surface science communality specifically focused controlled wettability of smart polymer surfaces.

Myr47 lipopeptide consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2-48 peptide) is a commercialized effective anti-HBV drug, preventing the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, of which the activity requires both N-myristoylation residue and specific amino acid sequence. Meanwhile, we recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression (Somiya; et al. Virology 2016, 497, 23–32). In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner whereas in an amino acid sequence-independent manner. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, N-myristoyl residue of lipopeptides generally could interfere the LPs/HBsAg-ApoE3 complex formation, thereby reducing the cellular uptake of LPs/HBsAg. When lipid nanoparticles are used as a DDS (drug delivery system) nanocarrier, the surface modification with lipopeptides may be a new method to inhibit unwanted cellular uptake of DDS nanocarriers by non-target cells.

Rocky Mountain or Brazilian spotted fever, caused by Ricketsia ricketssi, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Rapid detection are essential for a better prognosis and survival rate of the infected individual. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. Therefore, this review aimed to identify methods for antibody or antigen detection, its gaps, and evolution over time. A search was conducted to find all studies in the Pubmed database that described antibody or antigen detection for Ricketsia ricketsii infection. Initially, a total of 403 articles were screened. Of these articles, only 19 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as low specificity using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective Ricketsia ricketssi infection diagnosis.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

In this study, we investigated the effects of three surface treatment techniques on 316L stainless steel, low-temperature immersion corrosion, shot peening followed by immersion corrosion, and electrochemical corrosion. Surface alterations were analyzed using scanning electron microscopy, Raman spectroscopy, and α-step thin-film thickness profiling. Human osteoblast adhesion was evaluated using Liu’s stain and metallographic optical microscopy. The results revealed weak cell adhesion after low-temperature immersion and shot peening followed by immersion corrosion. By contrast, electrochemical corrosion, particularly with a high current density and low corrosive solution concentration, resulted in a uniformly corroded surface, thus promoting dense cell adhesion. All three techniques resulted in porous oxide layers. Overall, our experimental findings highlighted shot peening (1 kg/cm2 for 20 s) and electrochemical corrosion (0.5 M HCl) as effective processes. Electrochemical corrosion produced uniformly dense corrosion pits, whereas shot peening produced semicircular grooves with small corrosion pits, both favorable for cell adhesion. Electrochemical corrosion also yielded excellent cell adhesion, emphasizing its suitability for biomedical activity. We developed a process for creating a porous surface layer and thereby enhancing the cell adhesion to 316L stainless steel for potential biomedical implant applications.

Abstract: A prevalence boundary (PB) marks the point in prevalence where the false omission rate, RFO=FN/(TN+FN), exceeds the tolerance limit for missed diagnoses. Objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise: Tier-1) 90%, 95%; Tier-2) 95%, 97.5%; and Tier-3) 100%, ≥99%, respectively. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-university-commercial evaluation, RAgTs generated sensitivity of 34.4%, which improved to 55.3% when repeated, then 68.5% with the third test. With RFO=5%, PBs were 7.37/10.46/14.22%, respectively. PB analysis suggests RAgTs should achieve clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links to diseases such as type 2 diabetes and obesity. It has severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and portal hypertension that can lead to liver transplantation in some cases. To better prevent and treat this pathology, it is important to understand its underlying physiology. Here, we identify three main factors that play a crucial role in the physiopathology of NAFLD: oxidative stress, insulin resistance, and the key role of carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). We discuss the pathophysiology linking these factors to NAFLD pathophysiology.

Persistent land subsidence or uplift can cause serious latent hazards to urban infrastructure. To thoroughly investigate the causes and impacts of land surface deformation, this study examines the case of Wuxi City, focusing on the land fluctuation patterns in the region following the enforcement of the groundwater abstraction prohibition policy in 2005. This research utilizes the PS-InSAR technique to quantify land surface deformations in the Wuxi region from November 2015 to June 2023 and analyzes 100 SAR images to obtain comprehensive spatiotemporal evolution data of the land surface. Furthermore, this study conducts an in-depth analysis of the effects of various factors, including groundwater, precipitation, and soil geology, on the characteristics of land surface deformation. It pioneers the application of the GARCH (Generalized Autoregressive Conditional Heteroskedasticity) model to analyze the time-series displacement in the study area and innovatively introduces the "amplitude factor" index to assess land surface fluctuations. This study investigates the recent land surface deformation patterns and mechanisms in Wuxi City. By integrating the "amplitude factor", it provides a scientific foundation for future urban development and disaster mitigation strategies in Wuxi City, offering valuable insights for related research.

Firstly, a new set of Quasi-Cubic Trigonometric Bernstein basis with two tension shape parameters is constructed, and we prove that it is an optimal normalized totally basis in the framework of Quasi Extended Chebyshev space. And the Quasi-Cubic Trigonometric Bézier curve is generated by the basis function and the cutting algorithm of the curve are given, the shape features (cusp, inflection point, loop and convexity) of the Quasi-Cubic Trigonometric Bézier curve are analyzed by using envelope theory and topological mapping; Next we construct the non-uniform Quasi-Cubic Trigonometric B-spline basis by assuming the linear combination of the optimal normalized totally positive basis have partition of unity and continuity, and its expression is obtained. And the non-uniform B-spline basis is proved to have totally positive and high-order continuity. Finally, the non-uniform Quasi Cubic Trigonometric B-spline curve and surface are defined, the shape features of the non-uniform Quasi-Cubic Trigonometric B-spline curve are discussed, and the curve and surface are proved to be continuous.

Blood has certain significant physical properties, which the authors investigated. This paper provides values of surface tension and viscosity of blood at 37 °C, as well as relationship between them plotted on a cross-plot. By applying Hagen- Poiseuille equation and Jurin's law to the experimentally obtained data, the authors calculated with great accuracy viscosity and surface tension of blood. Evaluating both of the properties using described methods required from the authors to know the density of investigated liquid, which was found to be on average $\rho=1063,56 \frac{kg}{m^3}$. The authors took blood samples from 30 healthy subjects and determined aforementioned physical properties. There has been made a distinction in regard of a sex of the blood donor. Results indicate that both surface tension and viscosity are independent from sex of a subject, as well as indicate that there is no correlation between viscosity and surface tension of blood at 37\degree C. Average values of surface tension and viscosity were found to be $\sigma=5,241\pm 0,262 \cdot 10^{-2}\frac{J}{m^2}$ and $\eta=3,352\pm0,360 \cdot 10^{-3} Pa \cdot s$, respectively.

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro by protein chemical methods, mass-spectrometry, circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in large amounts as secreted and folded proteins in mammalian cells. Antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG levels induced by the different vaccines were comparable but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were 7- and 2-fold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively and 6-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Background: Single nucleotide polymorphisms (SNPs) in the SLC10A1 gene, coding for a functional receptor of hepatitis B virus (HBV), sodium taurocholate co-transporting polypeptide (NTCP), may influence the susceptibility, the outcome, and disease course of HBV infection in some populations. Aim: to determine the prevalence of SNPs of NTCP gene, rs2296651 and rs943277, and their relationship with chronic HBV infection in a group of Egyptian patients. Methods: 137 patients with HBV and 65 healthy controls were enrolled, and the patients were divided into two groups; group I chronic HBV infection (68 patients with normal ALT and minimal or no liver necroinflammation or fibrosis) and group II chronic hepatitis B (69 patients with elevated ALT and moderate or severe liver necroinflammation). They were subjected to full history taking, clinical examination, laboratory investigations, abdominal ultrasound, and liver stiffness measurement using both Echosens® Fibroscan and acoustic radiation force impulse (ARFI). Real time PCR TaqMan 5’ allelic discrimination assay was applied to detect the SNPs in NTCP gene, rs2296651 and rs943277. Results: On studying the rs2296651 variant, all controls and patients had genotype GG without any significant association with HBV infection or disease progression. However, the rs943277 variant in all controls and 98% of patients had genotype GA, except for two chronic HBV infection patients who had genotype AA, but no significant difference between patients and controls was found. The non-invasive methods for liver fibrosis assessment ARFI, AST/platelet's ratio (APRI), and fibrosis-4 score (FIB-4) could predict the stages of fibrosis in agreement with Fibroscan with AUCOR 0.8, 0.79, and 0.76, respectively. Conclusion: These findings may suggest that there is no relation between these SNPs of the NTCP gene and susceptibility or chronicity of HBV infection in the Egyptian population. We also suggest that the use of the non-invasive methods for liver fibrosis assessment, ARFI, FIB-4, and APRI may decrease the need for liver biopsies in prediction of significant hepatic fibrosis in chronic HBV patients.

: Since the COVID-19 pandemic, people have become aware that materials (products) can transmit infection and have begun to focus on questions such as how bacteria and germs, the sources of in-fection, maintain their infectivity on material surfaces, and the extent to which materials can or cannot prevent this. and to what extent materials can and cannot prevent it. The SIAA, a non-profit organization of many Japanese companies, had created an entirely separate interna-tional standard for materials' antibacterial, antiviral, and antibiofilm properties (products). The authors have studied the academic basis for the operation of the standards and were deeply in-volved as researchers in establishing one of the standards. This paper describes the interna-tional standards and some representative examples of the authors' actual use of these standards and explains the current status and future problems.

It is estimated that almost 4% of all neonatal intensive care unit admissions are attributed to Candida spp. infections. Clinical diagnosis of invasive fungal infection (IFI) is not easy as signs and symptoms are commonly vague. Mannan antigen (MA) in neonates is not well studied and the aim of this study was to evaluate the use of MA (Platelia™ Candida Ag Plus kit, Bio-Rad) in a neonatal unit. This is a prospective case-control study, which compared the performance of MA between neonates who had rectal Candida colonization with non-colonized controls. We cultured 340 rectal swabs of neonates and 39 of them were positive for Candida albicans colonization. MA was checked in 25 C. albicans colonized and in 30 non-colonized neonates with similar postnatal age and gender distribution. During the hospitalization period there was not any IFI in the neonatal population. MA was negative in all non-colonized neonates (30/30, 100% specificity) and in 24 out of 25 colonized neonates (96% specificity). However, the one infant with positive rectal colonization and MA had recent Candida mucositis. The results indicate a high specificity of the assay even in neonates colonized with Candida. Further investigation in neonates with IFI is required in order to determine the sensitivity of the method.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment are considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments are inadequate due to improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co- polyethylenimine (PEI)(PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, non-toxic and enhanced intracellular uptake in immature dendritic cells. In murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and also enhance the antitumor immune response against melanoma tumor in the future clinical trials.

Mn-promoted bulk iron catalysts with high specific surface area (82-211 m2.g-1) were synthesized by coprecipitation followed by drying under supercritical conditions. The catalysts were tested in the CO2 hydrogenation reaction. The Mn-promoted iron catalysts showed better textural properties than the bare Fe2O3 catalyst, allowing better dispersion of the active phase, easier reduction of iron oxide, better carburization of iron oxides and higher catalytic activity than the bare Fe2O3 catalyst. The best activity results were obtained by catalyst promotion with a very low amount of Mn (Mn/Fe ratio of 0.05). Upon steady-state conditions (T=340 ºC, total pressure of 20 bar and H2/CO2=3), this catalyst showed high CO2 conversion (44.2%) and selectivity to C2-C4 hydrocarbons (68%, olefin to paraffin ratio of 0.54), while the selectivity to C5+ hydrocarbons, CH4 and CO was about 3.2, 38.5 and 5%, respectively. A close correlation was found between catalyst textural properties and CO2 conversion. The most active MnFe-0.05 catalyst shows high stability during 72 h of reaction related to low amount of soft coke formation and catalyst activation through the formation of χ-Fe5C2 phase during the on-stream reaction.

Helicobacter Pylori (H. Pylori) is a common pathogen with high prevalence of infection in human populations. Diagnosis of H. Pylori infection is critical for its treatment, eradication, and prognosis. Biosensors have been demonstrated to be powerful for rapid onsite detection of pathogens, particularly for point-of-care test (POCT) scenarios. In this work, we propose a novel optical biosensor, based on nanomaterial porous silicon (PSi) and photonic surface state Tamm Plasmon Polariton (TPP), for detection of cytotoxin-associated antigen A (CagA) antigen of H. Pylori bacterium. We fabricated the PSi TPP biosensor, analysed its optical characteristics and demonstrated through experiments towards sensing of CagA antigen, that TPP biosensor has sensitivity of 100 pm/(ng/ml), limit of detection of 0.01 ng/ml, and specificity in terms of positive-to-negative ratio of more than six. From these performance factors, it can be concluded that TPP biosensor can serve as an effective tool for diagnosis of H. Pylori infection, either in analytical labs or in POCT applications.

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

Therapeutics antibodies have increasingly shifted the paradigm of disease treatments, from small molecules to biologics, especially in cancer therapy. Despite the increasing number of antibody candidates, much remains unknown about the antibody and how its various regions interact. In fact, the constant region can govern effects that might be useful in reducing the unwanted consequences resulted from systemic circulation. For this reason, apart from the commonly used IgG isotypes, IgA antibodies are promising therapeutics drugs, given its localized mucosal effects. While the antibody Fc effector cell activity has been well explored, recent research has shown evidences that the constant region of the antibody can also influence antigen binding, challenging the conventional idea of region-specific antibody functions. To further investigate this, we analyzed the IgA antibody constant and its allosteric effects onto the antigen binding regions, using recombinant Pertuzumab IgA1 and IgA2 variants. We found mutations in the C-region to reduce Her2 binding, and our computational structural analysis showed that such allosteric communications were highly dependent on the antibody hinge, providing the evidence to consider antibodies as a whole protein rather than a sum of functional regions.

(1) Background: We aimed to determine the prevalence of hepatitis B virus (HBV) resistance-associated mutations (RAMs) in people with HBV and human immunodeficiency virus (HBV/HIV) in Botswana. (2) Methods: We sequenced HBV from participants with HBV/HIV from the Botswana Combination Prevention Project study (2013-2018) using the Oxford Nanopore GridION platform. Consensus sequences were analyzed for genotypic and mutational profiles. (3) Results: Overall, 98 HBV sequences had evaluable reverse transcriptase region coverage. The median participant age was 43 years (IQR: 37, 49) and 66/98 (67.4%) were female. Most participants, 85/97 (87.6%) had suppressed HIV viral load (VL). HBV RAMs were identified in 61/98 (62.2%) participants. Most RAMs were in positions 204 (60.3%), 180 (50.5%) and 173 (33.3%), mostly associated with lamivudine resistance. The triple mutations, rtM204V/L180M/V173L and was the most predominant (17/61 [27.9%]). Most participants (96.7%) with RAMs were on antiretroviral therapy for a median duration of 7.5 years (IQR: 4.8, 10.5). Approximately 27.9% (17/61) of participants with RAMs had undetectable HBV VL, 50.8% (31/61) had VL &lt;2000IU/mL and 13/61 (21.3%) had VL ≥2000 IU/mL. (4) Conclusions: The high prevalence of lamivudine RAMs discourages the use of ART regimens with 3TC as the only HBV-active drug in people with HIV/HBV.

The present work proposes a novel manufacturing technique based on the combination of Laser Metal Deposition, Laser Beam Machining and Laser Polishing processes for the complete manufacturing of complex parts. Therefore, the complete process is based on the application of a laser heat source both for the building of the preform shape of the part by additive manufacturing and for the finishing operations. Their combination enables to manufacture near-net-shape parts and afterwards, remove the excess material via laser machining, which has resulted to be capable of eliminating the waviness resulting from the additive process. Besides, surface quality is improved via laser polishing to reduce the roughness of the final part. Therefore, conventional machining operations are eliminated, what results in a much cleaner process. In order to validate the capability of this new approach, the dimensional accuracy and surface quality of the resulting parts are evaluated. The process has been validated on an Inconel 718 test part, where a previously additively built up part has been finished by means of laser machining and laser polishing.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Haemonchus contortus (H. contortus) is a gastrointestinal parasite affecting small ruminants, leading to a significant decline in animal productivity. In this study, we developed a nanovaccine by encapsulating the recombinant protein rHcES-15, derived from the excretory/secretory products of H. contortus, within biodegradable poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). To construct the nanovaccine, PLGA NPs were prepared using a modified double emulsion solvent evaporation technique. Scanning electron microscopy (SEM) illustrated successful encapsulation of rHcES-15 within PLGA NPs, with a size ranging between 350-400 nm. The encapsulation efficiency (EE) of the antigen in the nanovaccine was determined to be 72%. A total of forty experimental mice were divided into five groups, receiving the nanovaccine on day 0 and being humanely sacrificed at the end of the 14-day trial. The stimulation index (SI) from mice vaccinated with the nanovaccine indicated an amplified lymphocyte proliferation and a significant increase in anti-inflammatory cytokines (IL-4, IL-10, and IL-17). Furthermore, the percentages of T-cells (CD4+, CD8+) and dendritic cell phenotypes (CD83+, CD86+) were substantially upregulated in mice immunized with the nanovaccine compared to control groups and the rHcES-15 group. Similarly, higher levels of antigen-specific serum immunoglobulins (IgG1, IgG2a, IgM) were observed in response to the nanovaccine compared to both the antigenic (rHcES-15) and control groups. In conclusion, the data strongly supports the notion that encapsulation of rHcES-15 within PLGA NPs effectively stimulates immune cells in vivo, ultimately augmenting antigen-specific adaptive immune responses against H. contortus. This discovery highlights the promising potential of the nanovaccine, justifying additional investigations to ascertain its efficacy finally.

Rapid antigen detection tests (RAD) are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC) presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One-hundred and twenty samples were selected and tested with both RT-qPCR and five commercial RAD commonly sold in Belgian pharmacies. Of these, direct whole genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron. Sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) were comparable and ranged from 70.0% to 77.1% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct &gt; 25), poor performances were observed for the Delta strains (20.0 to 40.0%) and, even more so, for Omicron strains (0.0 to 23.1%). Two devices failed to detect all samples (n = 13) containing Omicron strains with a low viral load. The poor performance observed with low viral loads is an important limitation of RAD, which is not sufficiently highlighted in the instruction for use of these devices.

The use of bacteriophage is reemerging as a tool for combatting multi-drug resistant bacterial infections. In our previous study, we showed that colistin resistant carbapenem-resistant Klebsiella pneumoniae (ColR-CRKP) is more susceptible to killing by lytic tailed phages, including ФNJS1 specific for nonmucoid K. pneumoniae. Although we demonstrated that alteration on surface charges of ColR-CRKP promotes phage adherence and infection, the receptor for ФNJS1 was still unknown. In current study, we identified O-antigen was involved in the reversible adsorption, and outer membrane protein (OMP) FepA may be served as one of the irreversible receptors for ФNJS1. We firstly found accelerated reversible phage adsorption to ColR-CRKP cells, and that periodate treatment of bacteria inhibited the phage binding, indicating LPS may be involved in phage reversible adsorption. ФNJS1-resistant bacterial mutants screening revealed that mutants in ∆wecG(mTn5) and ∆wecA(mTn5), two genes responsible for LPS biosynthesis, affected phage adsorption capacity and phage infectivity. The loss of wzyE encoding O-antigen polymerase showed no significant difference in phage adsorption but increased phage infectivity, suggesting the long chain length of O-antigen may also be a barrier for bacteriophage infection. Among four OMP mutants including ∆fepA, ∆fhuA, ∆ompA and ∆ompC, only ∆fepA slowed phage lysis rate, suggesting FepA may be as one of irreversible receptors for ФNJS1. The results are helpful to better understand why ColR-CRKP sensitizes phage infection and to combat multi-drug resistant K. pneumoniae infections in the future.

At present, nanomaterials (NMs) show extreme potential for a wide range of applications ranging from aerospace to energy storage applications owing to a number of properties which, in a number of contexts have been reported to be superior as compared to those of bulk counterparts. However, the high surface area to volume ratio which yields extraordinary properties to NMs also turns out to be the major limitation in a number of different contexts. For instance, the high surface area to volume ratio in these materials leads to a high reactivity, especially in electrochemical environments which are prevalent during energy storage applications. In this context, it is worthwhile mentioning that processing of NMs play a crucial role in influencing their mechanical properties. On the other hand, surface engineering has emerged as a powerful tool to deconvolute bulk properties from surface characteristics and has been reported to exhibit tremendous potential for overcoming the aforementioned limitation of NMs. The present review therefore, is aimed at highlighting the present status of research in the field of processing and applications of surface engineered NMs. Moreover, challenges and future perspectives in the aforementioned avenue have been discussed.

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).