With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

One of the G protein-coupled receptors, C-C chemokine receptor 5 (CCR5), is an important regulator for the activation of T and B lymphocytes, dendritic cells, natural killer cells, and macrophages. Upon binding to the ligands, CCR5 activates downstream signaling, which plays critical roles in the innate and adaptive immune response through the promotion of lymphocyte migration and the secretion of pro-inflammatory cytokines. Anti-CCR5 monoclonal antibodies (mAbs) have been developed and evaluated in clinical trials for tumors and inflammatory diseases. In this study, we developed novel mAbs for mouse CCR5 (mCCR5) using the N-terminal peptide immunization. Among the established anti-mCCR5 mAbs, C₅Mab-4 (rat IgG_2a, kappa) and C₅Mab-8 (rat IgG₁, kappa), recognized mCCR5-overexpressed Chinese hamster ovary-K1 (CHO/mCCR5) and an endogenously mCCR5-expressing cell line (L1210) by flow cytometry. The dissociation constant (K_D) values of C₅Mab-4 and C₅Mab-8 for CHO/mCCR5 were determined as 3.5 × 10⁻⁸ M and 7.3 × 10⁻⁹ M, respectively. Furthermore, both C₅Mab-4 and C₅Mab-8 could detect mCCR5 by western blotting. These results indicated that C₅Mab-4 and C₅Mab-8 are useful for detecting mCCR5 by flow cytometry and western blotting and provide a possibility to obtain the proof of concept in preclinical studies.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

Tilapia lake virus (TiLV), a major pathogen of farmed tilapia, is known to be vertically transmitted. Here, we hypothesize that Nile tilapia (Oreochromis niloticus) broodstock immunized with a TiLV inactivated vaccine can mount a protective antibody response and passively transfer maternal antibodies to their fertilized eggs and larvae. To test this hypothesis, three groups of tilapia broodstock, each containing 4 males and 8 females, were immunized with either a heat-killed TiLV vaccine (HKV), a formalin-killed TiLV vaccine (FKV) (both administered at 3.6 ×106 TCID50 per fish), or with L15 medium. Booster vaccination with the same vaccines was given 3-weeks later, and mating took place 1 week thereafter. Broodstock blood sera, fertilized eggs and larvae were collected from 6-14 weeks post-primary vaccination for measurement of TiLV-specific antibody (anti-TiLV IgM) levels. In parallel, passive immunization using sera from the immunized female broodstock was administered to naïve tilapia juveniles to assess if antibodies induced in immunized broodstock were protective. The results showed that anti-TiLV IgM was produced in the majority of both male and female broodstock vaccinated with either the HKV or FKV and that and that these antibodies could be detected in the fertilized eggs and larvae from vaccinated broodstock. Higher levels of maternal antibody were observed in fertilized eggs from broodstock vaccinated with HKV than those vaccinated with FKV. Low levels of TiLV-IgM were detected in some of the 1-3-day old larvae but were undetectable in 7-14-day old larvae from the vaccinated broodstock, indicating a short persistence of TiLV-IgM in larvae. Moreover, passive immunization proved that antibodies elicited by TiLV vaccination were able to confer 85% to 90% protection against TiLV challenge in naïve juvenile tilapia. In conclusion, immunization of tilapia broodstock with TiLV vaccines could be a potential strategy for the prevention of TiLV in tilapia fertilized eggs and larvae, with HKV appearing to be more promising than FKV for maternal vaccination.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

EphB2 is a member of the Eph family tyrosine kinase receptors. EphB2 binds to ephrin-B1, ephrin-B2, and ephrin-B3, which are critical regulators of vascular and nervous development through controlling cell migration and axon guidance. EphB2 is overexpressed in tumors, including glioma, breast cancer, hepatocellular carcinoma, and malignant mesothelioma, and it functions as a tumor promoter. Therefore, the development of monoclonal antibodies (mAbs) against EphB2 is essential for tumor diagnosis and therapy for EphB2-positive tumors. In this study, we developed novel mAbs for human EphB2 using the Cell-Based Immunization and Screening (CBIS) method. One of the established anti-EphB2 mAbs, Eb2Mab-3 (mouse IgG1, kappa), reacted with EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and an endogenously EphB2-expressing cancer cell line (LS174T) by flow cytometry. Using flow cytometry, the dissociation constant (KD) values of Eb2Mab-3 for CHO/EphB2 and LS174T were determined as 1.1 × 10−9 M and 3.6 × 10−10 M, respectively. These results indicated that Eb2Mab-3 possesses a high affinity for detecting EphB2 and could apply to tumor therapy.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

Protection suit is vital for fireman’ safety. Traditional protection suit just physically protects fireman from empyrosis, but can not locate the body injury position from the impact debris. Herein, we present a wearable impact debris positioning system for fireman protection suit alarming based on accelerometer array. The wearable piezoelectric accelerometers with distribute regularly on the suit to detect the vibration on different body parts, which is conducive to positioning injured body parts. In addition, the injured parts can be displayed on the dummy body model on the upper computer with a higher localization accuracy of 4 cm. The positioning alarm system has a rapid response time of 0.11ms attributing to smart signal processing method. This work provides a reliable and smart method for locating and assessing the body injury position from the impact debris, which is significant for fire disaster commander to rescue injured fireman in time.

Background: Ultraviolet (UV) radiation from the sunlight can harm skin cells, causing short-term effects, such as sunburns and long-term effects, such as pigmentation changes, changes in the skin's immune responses, and increased risk of skin cancer. These conditions can be largely prevented with proper sun protection measures and behavioural changes. This study aims to assess the knowledge on sun protection behaviour and baseline knowledge of medical students from the “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania. Methods: Data in this cross-sectional study were collected through a Google Forms questionnaire, which was distributed from November 2023 to December 2023 via digital communication channels to students across all academic years. STROBE guidelines were consulted for data synthesis; Results: A total of 668 stu-dents responded. The student cohort demonstrated a commendable level of awareness of the risks associated with sun exposure and the advantages of employing sun protection factor (SPF); how-ever, the incidence of sunburns remained notably elevated (72.3%). Further analysis revealed cor-relations among gender, academic year, presence of photosensitizing conditions, and adherence to SPF application. Additionally, there is a need to improve understanding of the appropriate appli-cation techniques for SPF, as only 11.5% of the students exhibited proficiency in this regard; Con-clusions: As future healthcare providers, medical students hold significance in promoting healthy behaviours in the broader community. This study indicates that while their knowledge about sun protection is satisfactory, there is scope for enhancement.

Firefighters Protective Clothing consist of several layers of different properties and functions. The layers create barriers against dangerous outer factor. However, they are also barriers to transport of sweat produced by human organism. It causes that very often sweat in the form of vapor is not transferred effectively from the human organism through the FPC to environment. This leads to sweat condensation on the skin of the FPC user causing his discomfort. In order to ensure as good as possible physiological comfort of firefighter while firefighting and other rescue actions it is necessary to take into consideration the transport of condensed sweat in the multilayer textile set creating the FPC. In the presented work four variants of multilayer textile sets for the FPC have been tested in the aspect of liquid moisture transport. Measurement was performed by means of the Moisture Management Tester (MMT290) – innovative instrument manufactured by the SDL Atlas. Obtained results showed that the transfer of sweat in liquid form occurs only in the inner, next to skin layer of the multilayer sets for the FPC.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

Suicide is a public health problem influenced by a variety of biological, psychological, social, and environmental factors. Recognizing the warning signs at each stage is crucial for prevention and helping those at risk. In this context, body awareness, especially interoceptive body awareness, emerges as a potentially relevant and underexplored factor. In this study, binary logistic regression and linear regression analyses were used to examine the relationship between interoceptive body awareness and suicidal orientation in Colombian university students. In addition, the bootstrap technique was used to resample and estimate the distribution of the data. The results support the idea that greater interoceptive awareness may protect against suicidal orientation by improving emotional regulation. An inverse relationship was found between interoceptive awareness and suicidal ideation. These findings are consistent with previous literature on the importance of body awareness for emotional well-being. Further longitudinal research is needed to explore this relationship in depth.

Determination of antibody titre of dogs vaccinated against canine distemper in Jos North and South local Government Areas of Plateau State was carried out by collection of sera of vaccinated dogs and administration of well-structured questionnaires to dog owners. The samples collected were analyzed using the immune-blot ELISA Kit to determining the antibody titre (immunoglobulin G). It indicated that dogs vaccinated against the disease mounted adequate protective immunity. The result revealed that 54 (90.0%) of the sampled dogs have protective immunity, with those given more than one dose having higher level of protective antibody. Statistically, the result showed that the antibody titre did not differ significantly in relation to immunity and sex, breed, age and location but significant difference was seen in relation to number of primary vaccination. The result also revealed that those dogs that received booster doses (secondary vaccination) had more protective antibody. The study was aimed at evaluating the antibody titre of dogs vaccinated against canine distemper in Jos, Plateau State.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

Bio-molecular reagents like antibodies required in experimental biology are expensive and their effectiveness, among other things, is critical to the success of the experiment. Although such resources are sometimes donated by one investigator to another through personal communication between the two, there is no previous study to our knowledge on the extent of such donations, nor a central platform that directs resource seekers to donors. In this paper, we describe, to our knowledge, a first attempt at building a web-portal titled Bio-Resource Exchange that attempts to bridge this gap between resource seekers and donors in the domain of experimental biology. Users on this portal can request for or donate antibodies, cell-lines and DNA Constructs. This resource could also serve as a crowd-sourced database of resources for experimental biology. Further, in order to index donations outside of our portal, we mined scientific articles to find instances of donations of antibodies and attempted to extract information about these donations at the finest granularity. Specifically, we extracted the name of the donor, his/her affiliation and the name of the antibody for every donation by parsing the acknowledgements sections of articles. To extract annotations at this level, we propose two approaches – a rule based algorithm and a bootstrapped relation learning algorithm. The algorithms extracted donor names, affiliations and antibody names with average accuracies of 57% and 62% respectively. We also created a dataset of 50 expert-annotated acknowledgements sections that will serve as a gold standard dataset to evaluate extraction algorithms in the future. Contact: [email protected], [email protected] Database URL: http://tonks.dbmi.pitt.edu/brx Supplementary information: Supplementary data are available at Database online.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

This study reports on the development of bio-based hydrophobic coatings for packaging papers through deposition of polyhydroxybutyrate (PHB) particles in combination with nanofibrillated cellulose (NFC) and plant wax. In a first approach, PHB particles in micrometer range (PHB-MP) were prepared through a phase-separation technique providing internally nanosized structures. The particles were transferred as a coating by dip-coating filter papers in the particle suspension, followed by sizing with a carnauba wax solution. This approach allowed partial to almost full surface coverage of PHB-MP over the paper surface resulting in static water contact angles of 105° to 122° and 129° to 144° after additional wax coating. In a second approach, PHB particles with submicron sizes (PHB-SP) were synthesized by an oil-in-emulsion (o/w) solvent evaporation method, and mixed in aqueous suspensions with 0 to 7 wt% NFC. After dip-coating filter papers in PHB-SP/NFC suspensions and sizing with a carnauba wax solution, static water contact angles of 112° to 152° were obtained. The intrinsic properties of the particles were analyzed by scanning electron microscopy, thermal analysis and infrared spectroscopy, indicating higher crystallinity for PHB-SP than PHB-MP. The chemical interactions between the more amorphous PHB-MP particles and paper fibers were identified as an esterification reaction, while the morphology of the NFC fibrillar network was playing a key role as binding agent in the retention of more crystalline PHB-SP at the paper surface, hence contributing to higher hydrophobicity.

Patients with predominantly antibody deficiencies (PAD) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate their possible contribution to PAD clinical phenotype. Eight CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474) which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD, in order to identify patients with a higher risk for liver disease.

Fine dust causes various disorders, including cardiovascular, neurological, renal, reproductive, motor, systemic, respiratory, and cancerous diseases. Therefore, it is necessary to study functional materials to prevent these problems. In this study we used various methods, including quantitative PCR, flow cytometry, ELISA, and Alizarin O staining, to study the beneficial effects of erucic acid against fine dust. Erucic acid and erucic acid-induced exosomes (EIE) strongly suppress the attenuation of osteocytic differentiation and inflammation induced by fine dust. Erucic acid effectively suppresses inflammation in fibroblasts exposed to fine dust. Notably, despite exposure to fine dust, EIE promoted osteocytic differentiation in adipose-derived stem cells (ASC) and osteogenesis in macrophages, in addition to phagocytosis. Dramatic upregulation of RunX2 and BMP7 by EIE indicates that it is a strong activator of osteocytic differentiation in ASC and protects them from the effects of fine dust. Moreover, EIE induces immune activity and acts as an osteogenic trigger for macrophages. Therefore, this study suggests the potential use of erucic acid and erucic acid-induced exosomes (EIE) as biomaterials to prevent environment-borne diseases.

Background. The Weekly Mortality Cycle among CoViD-19 patients has been studied.Methods. Mortality data obtained from the 'Worldometer' website were analyzed with a comparison of absolute values, percentages, and p-value. Results. For patients suffering from CoViD-19, the most favorable or the safest days of the week were Sundays and Mondays. Conclusion. The weekly cycle with decreased mortality on Sundays and Mondays is a unique phenomenon observed among victims of CoViD-19. Presumably the decreased mortality on certain days of the week related to the optimized therapeutic protocols used on the "safest days".

A novel electrospun nanofiber was developed using polyamide-6 (PA) and ε-poly-L-lysine (PL). PA is a popular textile polymer having desirable mechanical and thermal properties, chemical stability, and biocompatibility. However, PA nanofibers are prone to bacterial growth and user discomfort. PL, a natural homopolyamide, is non-toxic, antimicrobial, and hydrophilic but lacks spinnability due to its low molecular weight. Given its similar backbone structure as PA, with an additional amino side chain, PL was integrated with PA to develop multifunctional nanofibers. This study explores a simple, scalable method to obtain PL nanofibers by utilizing the structurally similar PA as the base. The goal was to enhance the functionality of PA by addressing its drawbacks. The study demonstrates spinnability of varying concentrations of PL with base PA while exploring compositions with higher PL concentrations than previously reported. Electrospinning parameters were studied to optimize the nanofiber properties. The effects of PL addition on morphology, hydrophilicity, thermal stability, mechanical performance, and long-term antimicrobial activity of nanofibers were evaluated. The inclusion of PL in PA-based nanofibers resulted in super hydrophilicity, increased tensile strength, and efficient antimicrobial properties with long-term stability. These enhanced characteristics hold promise for the composite nanofiber’s application in medical and protective textiles.

Nurses have experienced several psychological and work-related issues during the COVID-19 pandemic including pandemic burnout and job burnout. The aim of the study was to examine the impact of social support and resilience on COVID-19 pandemic burnout and job burnout among nurses. We conducted a cross-sectional study in Greece. Study population included 963 nurses. We measured social support, resilience, COVID-19 pandemic burnout, and job burnout with the Multidimensional Scale of Perceived Social Support, Brief Resilience Scale, COVID-19 burnout scale, and single item burnout measure respectively. Nurses received high levels of social support, while their resilience was moderate. Additionally, nurses experienced moderate levels of COVID-19 burnout and job burnout. Increased social support (adjusted beta = -0.075, 95% CI = -0.125 to -0.024) and increased resilience (adjusted beta = -0.399, 95% CI = -0.491 to -0.308) were associated with reduced COVID-19 pandemic burnout. We found a negative relationship between social support and job burnout (adjusted beta = -0.263, 95% CI = -0.405 to -0.121). A similar negative relationship was found between resilience and job burnout (adjusted beta = -0.529, 95% CI = -0.785 to -0.272). Social support and resilience can act as protective factors against COVID-19 pandemic burnout and job burnout among nurses. Policy makers should develop and implement appropriate strategies to improve nurses’ social support and resilience since they are the backbone of healthcare systems worldwide.

Viral diseases represent a major public health concern and an ever-present risk for developing into a future pandemic. Antiviral antibody therapeutics, either alone or in combination with other therapies, have emerged as valuable preventative and treatment options, including during a global emergency. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well suited as therapeutic agents. We will describe the methods of antibody characterization and potency assessment throughout development, highlighting similarities and differences between polyclonal and monoclonal products as appropriate. In addition, we will consider the benefits and challenges of antiviral antibodies when used in combination with other antibodies or other types of antiviral therapeutics. Lastly, we will discuss novel approaches to the characterization and development of antiviral antibodies and identify areas that would benefit from additional research.

A canine population’s immune resistance to canine distemper virus (CDV), canine parvovirus (CPV), and infectious hepatitis virus (CAV-1) was evaluated. In this study, a total of 112 sera were analyzed. Animals were considered as vaccinated if, in the last two years, they had re-ceived at least one dose of a vaccine that provides joint protection against CDV, CPV, and CAV-1. Animals that had never received any dose of these vaccines were designated as non-vaccinated. CDV, CPV, and CAV-1 antibodies were detected via a modified solid-phase enzyme-linked im-munosorbent assay (ELISA), which detects IgG antibody levels in sera and provides semi-quantitative results in less than 30 min. In total, 41.1% of the dogs had been vaccinated, and 58.9% of dogs were designated as non-vaccinated. Overall, 90.2%, 92.0%, and 78.6% of the tested dogs had positive results for the presence of IgG antibodies against CPV, CDV, and CAV-1, re-spectively. CPV antibodies were present in 93.5% (43/46) of the vaccinated and 87.9% (58/66) of the non-vaccinated dogs, while CDV antibodies were present in 95.5% (63/66) of the vaccinated and 87.0% (40/46) of the non-vaccinated dogs. Finally, CAV-1 antibodies were present in 84.8% (56/66) of the vaccinated and of 69.6% (32/46) the non-vaccinated dogs.

Personal protective equipment (P PE) rules must be respected and followed to the letter of healthcare professionals in Cameroon to avoid the transmission of infectious diseases. This research proposes solutions to the problems of non-adherence and non-compliance among healthcare workers in Cameroon towards PPE rules. Inadequate access to suitable PPE, discomfort when wearing PPE during poor quality, and a lack of training on correct PPE use are just a few of these obstacles amongst HCWs in Cameroon. Hospitals and healthcare facilities should prioritize offering thorough instruction on PPE use and pinpoint the need to adhere consistently to PPE rules to remove these obstacles. They should also ensure that all healthcare personnel have access to and a sufficient supply of the proper PPE. Through the organization of impromptu visits by surveillance teams to identify areas of support and training, there is a need for assistance from government bodies and public health groups in creating awareness of the security value of PPE use among healthcare professionals. There is a lack of PPE in health care settings in rural areas in Cameroon, thus a need for an adequate supply. Then can we put appropriate PPE policies and practices for HCWs in Cameroon, as they will keep to it.Healthcare professionals in Cameroon must comprehend that following PPE standards protects not just their selves from diseases but also their patients, coworkers, and communities. We are accountable for ensuring everyone's safety and well-being, and adhering to PPE regulations is an essential first step.

The onset of the Coronavirus 2019 (COVID-19) pandemic has challenged the worldwide healthcare sector, including dentistry. The highly infectious nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and risk of transmission through aerosol generating procedures has profoundly impacted the delivery of dental care services globally for months causing prioritization of critical dental needs and suspension of routine dental procedures. As dental practices with strengthened infection control strategies and preventive measures are re-opening in the “new normal” period, it is the responsibility of healthcare professionals to constantly analyze new data and limit the spread of COVID-19 in dental care settings. With the new variants of SARS-CoV-2 rapidly emerging in different geographic locations, a definite need to comply more than ever with the rigorous public health measures to mitigate COVID -19 transmission exists. The aim of this article is to provide dental clinicians with essential information regarding both the spread of SARS-CoV-2 virus and protective measures against COVID-19 transmission in dental facilities. By compiling guidance and standard protocols recommended by credible national and international organizations, this article serves as an aid to navigating through this unprecedented time with ease. Much to learn about COVID-19 exists and because of constant ongoing research, we are not aware of all of the newly found information. However, in this paper, we reviewed the available literature recommended for the best current practices that must be taken for a dental office to function safely and successfully.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

Carbon monoxide (CO) is a cytoprotective endogenous gas that is ubiquitously produced by the stress response enzyme heme-oxygenase. Being a gas, CO rapidly diffuses through tissues and binds to hemoglobin (Hb) increasing carboxyhemoglobin (COHb) levels. COHb can be formed in the erythrocytes or in plasma from cell-free Hb. Herein, it is discussed whether endogenous COHb is or is not an innocuous and inevitable metabolic waste product and it is hypothesized that COHb has a biological role. In the present review literature data is presented to support this hypothesis based on two main premises: (i) there is no direct correlation between COHb levels and CO toxicity; and (ii) COHb seems to have a direct cytoprotective and antioxidant role in erythrocytes and in hemorrhagic models in vivo. Moreover, CO is also antioxidant by generating COHb, which protects against the pro-oxidant damaging effects of cell free Hb. Up to now COHb has been considered as a sink for both exogenous and endogenous CO generated during CO intoxication or heme metabolism, respectively. Hallmarking COHb as an important molecule with a biological (and eventually beneficial) role is a turning point on CO Biology research, namely in CO intoxication and CO cytoprotection.

Wearable computing is a fast evolving segment of computing that includes smart watches, head mounted wearables such as Magic Leap headsets, Microsoft Hololens, and VR goggles from various vendors. In this report, we present ideas for a smart wearable device that also doubles as a virus protection device. Instead of using the filtering approach that is predominantly used by virus protection equipments such as face masks, we propose to use a computational approach where the device maintains an awareness of the real-time virus spread and use that information to steer the wearer away from the virus. As the wearable has a head enclosing design, viral infection can only happen through the air that is inhaled by the wearer. The objective of the smart wearable is to maintain a repository for clean air and switch the operating modes between stored and fresh air modes depending on the environmental conditions. It can augment this basic operating procedure by recycling the exhaled air to maximize it operating capacity (i.e., time duration for which it could supply the wearer with safe air) and by cleaning the stored air using UVC to further reduces the chance of infection. To maintain an awareness of the virus spread in the environment, the smart wearable will rely on an edge computing framework that will be distributed to cover areas frequented by people. The smart wearable will have modular design so that it can be reconfigured to add or subtract functionality that the wearer wants for a particular situation so that the design remains relevant even after the virus threat recedes.

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Magnesium alloy stents have been extensively studied in the field of biodegradable metal stents due to their exceptional biocompatibility, biodegradability and excellent biomechanical properties. Nevertheless, the specific in vivo service environment causes magnesium alloy stents to degrade rapidly and fail to provide sufficient support for certain time. This paper presents an overview of the development history and protection strategies for magnesium alloy stents. Alloying, optimizing stent structure and preparing protective coating have improved the corrosion resistance of magnesium alloy stents. Based on the corrosion mechanism of magnesium alloy stents, as well as their deformation during use and environmental characteristics, we present some novel solution strategies aiming at reducing the corrosion rate of magnesium alloys and enhancing the comprehensive performance of magnesium alloy stents. These strategies include adapting protective coatings for the deformation of the stents, preparing rapid endothelialization coatings to enhance the service environment of the stent, and constructing coatings with self-healing functions. It is hoped that this review can help to understand the development of magnesium alloy cardiovascular stents and solve the problems related to magnesium alloy stents in clinical applications at the early implantation stage.

Antibody-Drug Conjugates (ADCs) are a powerful therapeutic modality for cancer treatment. ADCs are multi-functional biologics in which a disease-targeting antibody is conjugated to an effector payload molecule through a linker. The success of currently used ADCs has been largely attributed to the development of linker systems which allow targeted release of cytocidal payload drugs inside cancer cells. Many lysosomal proteases are over-expressed in human cancers. They can effectively cleave a variety of peptide sequences, which can be exploited in the design of ADC linker systems. As a well-established linker, valine-citrulline-p-aminobenzyl carbamate (ValCitPABC) is used in many ADCs that are already approved or under preclinical and clinical development. Although ValCitPABC and related linkers are readily cleaved by cathepsins in the lysosome while remaining reasonably stable in human plasma, many studies have shown that they are susceptible to carboxylesterase 1C (Ces1C) in mouse and rat plasma, which hinders preclinical evaluation of the ADCs. Furthermore, neutropenia and thrombocytopenia, two of the most commonly observed dose-limiting adverse effects of ADCs, are believed to result from the premature hydrolysis of ValCitPABC by human neutrophil elastase. In addition to cathepsin-cleavable linkers, there is also growing interest in legumain-sensitive linkers for ADC development. Increasing plasma stability while maintaining lysosomal cleavability of ADC linkers is an objective of intensive current research. This review reports recent advances in the design and structure-activity relationship studies of various peptide/peptidomimetic linkers in this field.

Short chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which significantly restricts is therapeutic activity. Therefore, this study assessed the metabolic stability of the 16 identified naphthoquinone derivatives 1-16 using hepatocarcinoma cells in combination with an optimized reverse-phase liquid chromatography (RP-LC) method. Most of the derivatives showed significantly better stability than idebenone over 6 hours (p < 0.001). By extending the side-chain of SCQs, increased stability for some compounds was observed. Metabolic conversion from the derivative 3 to 5 and reduced idebenone metabolism in the presence of 5 were also observed. These results highlight the therapeutic potential of naphthoquinone-based SCQs and provide essential insights for future drug design, prodrug therapy and polytherapy, respectively.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcome. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNAseq profilings of miRNAs and mRNAs expressed in CD4+ T-lymphocytes upon HIV-1 infection. Our results reveal significant alterations of miRNAs and mRNAs expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T-cells. Addition of miRNA-26a mimics to CD4+ T-cells reduces CD59 at both mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking-out CD59 in CD4+ T-cells renders both HIV-1 infected cells and progeny virions more prone to antibody-dependent CML (ADCML). Addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction of CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.

Monoclonal antibody (mAb) therapy has revolutionized the treatment of various diseases, including cancer and autoimmune disorders. However, the emergence of SARS-CoV-2 variants, as well as other pathogenic variants, poses challenges in maintaining the therapeutic efficacy of mAbs. In this mini review article, we aim to explore the strategies to overcome variants resistance in mAb therapy against viral infections. Firstly, we discuss the mechanisms through which variants can evade the neutralizing effects of mAbs. Understanding these mechanisms is crucial in developing targeted approaches to combat resistance. Next, we delve into the strategies being pursued to address variants resistance. These include developing new mAbs or antibody cocktails that target multiple epitopes, engineering mAbs with improved binding affinities or enhanced neutralizing capabilities, and exploring alternative therapeutic modalities such as bispecific antibodies or antibody-drug conjugates. Furthermore, we highlight the role of computational modeling and artificial intelligence in predicting variant escape mutations and aiding in the design of more effective mAbs. Additionally, we examine the importance of continuous surveillance and monitoring of emerging variants to inform treatment strategies. This article emphasizes the urgent need for proactive approaches to tackle variants resistance in mAb therapy. By combining innovative design strategies, computational modeling, and vigilant surveillance, we can maintain the therapeutic effectiveness of mAbs and stay ahead in the battle against evolving pathogens and viral infections.

Acute ischemic strokes are the third leading cause of death and the leading cause of neurological disability worldwide. The oxygen and glucose deprivation associated with ischemic strokes not only leads to neuronal cell death, but also increases the inflammatory response and decreases functional output of the brain. The only intervention approved by US Federal Drug and Food Administration for treatment of ischemic strokes is tissue plasminogen activator (tPA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its application, and it also might induce detrimental rather than beneficial effects to stroke patients by treatment of the tPA. In order to reduce the infarct volume of an acute ischemic stroke while increasing the time period for treatment, emerging therapies reveal great potential by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors with monoclonal antibody (MAB). With successfully application in the treatment of cancer patient by MAB, in this review, we will focus on recent advances on stroke therapy by using MAB on the treatment of stroke by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors. Therefore, developing specific MAB targeting the signaling pathway of stroke will contribute to stroke therapy.

Gastric inflammation-related disorders are commonly observed digestive system illnesses char-acterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric in-flammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol ex-tract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal GES-1 cells. The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α, to examine the anti-inflammatory properties of Lj extracts. The re-sults indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 ac-tivity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflam-mation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH ex-hibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.

In high-risk railway construction, personal protective equipment monitoring is critical but challenging due to small and frequently obstructed targets. We propose YOLO-EA, an innovative model that enhances safety measure detection by integrating ECA into its backbone's convolutional layers, improving discernment of minuscule objects like hardhats. YOLO-EA further refines target recognition under occlusion by replacing GIoU with EIoU loss. YOLO-EA's effectiveness was empirically substantiated using a dataset derived from real-world railway construction site surveillance footage. It outperforms YOLOv5, achieving 98.9% precision and 94.7% recall, up 2.5% and 0.5% respectively, while maintaining real-time performance at 70.774 fps. This highly efficient and precise YOLO-EA holds great promise for practical application in intricate construction scenarios, enforcing stringent safety compliance during complex railway construction projects.

Myocardial ischemia/reperfusion injury (I/R) and the resulting heart failure is one of the main causes of mortality and morbidity worldwide. Camphene has been shown to have anti-inflammatory and hypolipidemic properties, however, its role in the protection of the heart from ischemia and reperfusion has not been investigated. The cardioprotective role of camphene and the mechanism that mediates its action against I/R injury was evaluated in the present study. A single dose of camphene was administered in adult rats prior to ex vivo I/R induction. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and cardiomyocyte injury was assessed by determining the release of lactate dehydrogenase (LDH) enzyme. Camphene pretreatment provided significant protection reducing myocardial infarct size and cell death after I/R. The effect was correlated with the activation of antioxidant defense mechanisms, namely CAT, MnSOD, GPx and GR, and reduction of oxidative stress as evidenced by determination of protein carbonylation and GSH/GSSG ratio in cardiomyocytes. The results suggest that camphene can protect the heart against I/R injury by maintaining redox homeostasis and can hold therapeutic potential for mitigating the detrimental effects of I/R in the heart.

Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.

The exposure to extreme temperatures in workplaces involves physical hazards for workers. A poorly acclimated worker may have lower performance and vigilance and may therefore be more exposed to accidents and injuries. Due to the incompatibility of the existing standards implemented in some workplaces and the lack of thermoregulation in many protective equipment, thermal stress remains one of the most frequent physical hazards in many work sectors. However, many of these problems can be overcome with the use of smart textile technologies that enable intelligent thermoregulation in personal protective equipment. Smart textiles can detect, react and adapt to many external stimuli. Interconnected sensors and actuators that interact and react to existing risks can provide the wearer with increased safety, protection and comfort. Thus, the skills of smart protective equipment can contribute to the reduction of errors and the number and severity of accidents in the workplace, and thus promote improved performance, efficiency and productivity.This review provides an overview and opinions of authors on the current state of knowledge on these types of technologies by reviewing and discussing the state of the art of commercially available systems and the advances made in previous research works.

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.

Immunohistochemistry is a widely used technique for research and diagnostic purposes that relies on the recognition by antibodies of antigens expressed in tissues. However, tissue processing and particularly formalin fixation affect the conformation of these antigens through the formation of methylene bridges. Although antigen retrieval techniques can partially restore antigen immunoreactivity, it is difficult to identify antibodies that can recognize their target especially in formalin-fixed paraffin-embedded tissues. Most of the antibodies currently used in immunohistochemistry have been obtained by animal immunization; however, in vitro display techniques represent alternative strategies that have not been fully explored yet. This review provides an overview of phage display-based antibody selections using naïve antibody libraries on various supports (fixed cells, dissociated tissues, tissue fragments, and tissue sections) that have led to the identification of antibodies suitable for immunohistochemistry.

Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

Understanding the strength of the associations between perceived risk and individuals’ behavioral intentions to protect their health is important for determining appropriate risk communication strategies in communities impacted by lead contamination. We conducted a survey within communities of northern Idaho, USA (n = 306) near a Superfund megasite with legacy mining contamination. We empirically test a theoretical model based on the Health Belief Model. Survey respondents had higher intentions to practice health protective behaviors when they perceived the risk of lead contamination as severe, recognized the benefits of health protective behaviors, and considered the risks of lead contamination. Women reported higher behavioral intentions than men, but age and mining affiliation did not have an association. Survey comments indicated that perceptions about the long-term environmental remediation in the region influenced risk perceptions. Understanding risk perceptions, behavioral intentions, and related factors can aid public health agencies in tailoring risk communication for increasing protective behaviors in mining-impacted communities internationally.

Studies at the juncture of development economics and public health host considerable responsibility in addressing inequality and related mental health distress. Mental health care in economically marginalized populations requires depicting the linkages between socioeconomic status and psychological distress. In the present work, a sequential mixed-methods design was used to study 190 people in such communities in India. Gender-dependent psychological distress was found according to Kessler Psychological Distress Scale (K-10) with moderate distress in women (M= 26.30, SD= 9.15) and mild distress in men (M= 21.04, SD= 8.35). Regression analysis indicated that gender significantly predicted psychological distress, followed by age, marital status, and education of the head of the family. The Interpretative Phenomenological Analysis of semi-structured interviews to six women who scored the highest on the distress scale unveiled three master themes: (1) Manifestation of Psychological Distress, (2) Contextual Challenges, and (3) Sources of Strength and Resilience. Overall, participants reported lack of resources, community violence, gender discrimination, and widespread substance use as major contributors to the ongoing distress. These findings can pave the way for future studies to expand beyond independent economic indicators and curate clinical interventions for culturally competent mental health care.

Oxidative neurodegeneration causes various neuronal diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease. This study aimed to demonstrate the protective effect of leaf extracts of Allium senescens on 6-hydroxydopamine (6-OHDA)-stressed SH-SY5Y cells, known as an optimal cell for neurotoxic research. Levels of apoptotic markers were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. The localization of apoptotic cells in vivo was analyzed using whole-mount immunochemistry and the terminal deoxynucleo-tidyl transferase dUTP nick end labeling assay. Additionally, reactive oxygen species (ROS) pro-duction was estimated using flow cytometry. 6-OHDA induced ROS production in neuroblast cells and in vivo, but treatment with the extract protected against the 6-OHDA-induced increase in ROS levels. Under oxidative stress, the extract performs three protective functions: decreases ROS production, prevents mitochondrial apoptosis, and protects the central and ventral nervous systems. These results also suggest that the extract can be useful for the development of functional foods for the prevention of neural damage due to oxidative stress.

Richard Peto’s Paradox, first described in 1975 from an epidemiological perspective, established an inverse correlation between the probability of developing cancer in multicellular organisms and the number of cells. Larger animals exhibit fewer tumors compared to smaller ones, though exceptions exist. Mice are more susceptible to cancer than humans, while elephants and whales demonstrate significantly lower cancer prevalence rates than humans. How nature and evolution have addressed the issue of cancer in the animal kingdom remains largely unexplored. In the field of medicine, much attention has been devoted to cancer predisposing genes, as they offer avenues for intervention, including blocking, downregulating, early diagnosis, and targeted treatment. Predisposing genes also tend to manifest clinically earlier and more aggressively, making them easier to identify. However, despite significant strides in modern medicine, the role of protective genes lags behind. Identifying genes with a mild predisposing effect poses a significant challenge. Consequently, comprehending the protective function conferred by genes becomes even more elusive, and their very existence is subject to questioning. While the role of variable expressivity and penetrance defects of the same variant in a family is well-documented for many hereditary cancer syndromes, attempts to delineate the function of protective/modifier alleles have been restricted to a few instances. In this review, we endeavor to elucidate the role of protective genes observed in the animal kingdom and within certain genetic syndromes that appear to act as cancer-resistant/repressor alleles. The ultimate goal is to discern why individuals, like Winston Churchill, managed to live up to 91 years of age, despite engaging in minimal physical activity, consuming large quantities of alcohol daily, and not abstaining from smoking.

Babesia microti (B. microti), is a tick-transmitted protozoan parasite that infects red blood cells. It is the primary cause of human babesiosis in the US. It is also considered an emerging pathogen that continues to expand in terms of both numbers of cases and geograpical range. The severity of babesiosis can range from asymptomatic to fatal. Nevertheless, the mechanisms important for resolution of infection versus pathology remain largely unknown. In the current study we used a mouse model to evaluate factors important in protection from reinfection with B. microti following the clearance of a primary infection. Both B cell and CD4 T cell deficient mice failed to completely eliminate parasitemia 36 days post-infection following primary challenge. In the recall mouse model of infection, wild type or specific gene deleted mice were reinfected with the same strain of B. microti parasites 30-36 days after the initital primary infection, and the development of parasitemia was evaluated. Our results show that wild type mice were protected from reinfection with B. microti. In contrast, B cell and CD4 T cell deficient mice were only modestly impaired in their ability to protect against rechallenge as protection was more similar to reinfected wild type mice than naïve mice. However, one reinfected B cell deficient mice developed parasitemia levels similar to those observed in primary infection. Other factors including IFN-γ, inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88 important for signling via IL-18 and IL-1 had no effect on rechallenge. Thus our study shows that infection with B. microti confers at least short term protection against rechallenge with the same parasite strain. Our data show that CD4 T cells make an important contribution to both primary and rechallenge infection with B. microti. They also suggest that antibody might play an important role in protection against reinfection or persistent infection. However, overall our results Our results suggest that no one aspect of the immune system is solely responsible for adequate protection against reinfection with B. microti.

Wood is very susceptible to the action of biotic agents. There is a growing interest in the protection of wood and wood artworks to extend their life, using environmentally friendly preservatives. The aim of this paper was the study of nano/siliconate impregnation system for wood protection to control biological colonization. The biotic agents studied have been wood decay fungi. In conclusion, this paper has shown that all the treatments have presented an excellent protective performance against biotic agents. Is important to mention that a synergistic effect can be observed when generating the siliconate/nanoparticle mixtures, resulting in protective systems with excellent efficiency for all the degrading agents. Moreover, it presents an easy application, which represents not only a watertight protective system, but also a set of systems that may be used and managed according to the availability of the active components, the costs, and, most importantly, without having to modify the form of application.

The aim of the study was to find the effect of polyethylene (PE) coatings on the short-circuit current of silicon photovoltaic cells covered with glass, in order to improve the short-circuit current of the cells. Various combinations of PE films (thicknesses ranging from 9 to 23 µm, number of layers ranging from 2 to 6) with glasses (greenhouse, float, optiwhite and acrylic glass) were investigated. The best current gain of 4.05% was achieved for the coating combining a 1.5 mm-thick acrylic glass with 2 × 12 µm-thick PE films. This effect can be related to the formation of an array of micro-wrinkles and micrometer-sized air bubbles with a diameter of 50 to 600 µm in the films, which serve as micro-lenses and enhance light trapping.

Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H₂Mab-250/H₂CasMab-2 (IgG₁, kappa). H₂Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H₂Mab-250 did not react with non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H₂Mab-119 (IgG₁, kappa) reacted with both cancer and normal epithelial cells. Furthermore, a core-fucose deleted IgG_2a-type H₂Mab-250 (H₂Mab-250-mG_2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H₂Mab-250-mG_2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H₂Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H₂Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H₂Mab-250. H₂Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

Immunohistochemistry staining is an essential method in pathological diagnoses. Podoplanin (PDPN) is a specific maker of alveolar epithelium, lymphatic vessels, and glomeruli. In this study, we established a novel anti-giraffe PDPN (girPDPN) mAb, PMab-301, using the Cell-Based Immunization and Screening (CBIS) method. PMab-301 (mouse IgG₁, kappa) detected girPDPN in various applications, such as flow cytometry, western blot, and immunohistochemistry. PMab-301 specifically stained type-I alveolar cells using formalin-fixed paraffin-embedded giraffe lung tissues. Our findings suggest the potential usefulness of PMab-301 for the pathophysiological analyses of giraffe tissues.

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.

Thousands of antibodies for diagnostic and other analytical purposes are on the market. However, it is often difficult to identify duplicates, reagent changes, and to assign the correct original publications to an antibody. This slows down scientific progress and might even be a cause of irreproducible research and a waste of resources. Recently, activities were started to suggest the sole use of recombinant antibodies in combination with the open communication of their sequence. In this case, such uncertainties should be eliminated. Unfortunately, this approach seems to be rather a long-term vision since the development and manufacturing of recombinant antibodies remain quite expensive in the foreseeable future. Also, nearly all commercial antibody suppliers may be reluctant to publish the sequence of their antibodies, since they fear counterfeiting. De-novo sequencing of antibodies is also not feasible today for a reagent user without access to the hybridoma clone. Nevertheless, it seems to be crucial for any scientist to have the opportunity to identify an antibody undoubtedly to guarantee the traceability of any research activity using antibodies from a third party as a tool. For this purpose, we developed a method for the identification of antibodies based on a MALDI-TOF-MS fingerprint. To circumvent lengthy denaturation, reduction, alkylation, and enzymatic digestion steps, the fragmentation was performed with a simple formic acid hydrolysis step. Eighty-nine unknown monoclonal antibodies were used for this study to examine the feasibility of this approach. Although the molecular assignment of peaks was rarely possible, antibodies could be easily recognized in a blinded test, simply from their mass-spectral fingerprint. A general protocol is given, which could be used without any optimization to generate fingerprints for a database. We want to propose that in most scientific projects relying critically on antibody reagents, such a fingerprint should be established to prove and document the identity of the used antibodies and to assign a specific reagent to a datasheet of a commercial supplier, a public database record or an antibody ID.

Chili peppers (Capsicum annuum L.) are economically important crop worldwide. Pepper yellow leaf cure Thailand virus (PepYLCTHV), a Begomovirus causing yellow leaf mosaic disease of chili pepper has been reported to damage 95% economic loss under favorable epidemic conditions. Thirty-one chili genotypes were screened for resistance to PepYLCTHV disease through challenge inoculation using 10-15 viruliferous whiteflies per plant. We purified two resistant lines (PEP6 and PEP12) through four generations of selfing and selection through challenged inoculations. At the 28 days after inoculations two chili genotypes showed symptoms less based on disease severity and percentage of disease incidence of 30 plants PEP6 showed a disease severity 3.64 with 69.33 % DI and PEP12 showed a disease severity 3.83 with 77.67 % DI. PEP6 and PEP12 were selected for pure-line development for four cycles.Both varieties showed an increase in percentage of the resistant plant 12.78 % and 16.77 %, respectively. These lines have potential for release as resistant lines for improvement chili pepper resistance to PepYLCTHV and for developing maker associated with the resistant trait.

Plants have been used in alternative medicine for centuries in the treatment of many diseases with the metabolites they contain. The goal of this work was to investigate the phenolic profile, antioxidant capacity and biological activity of I. helenium subsp. pseudohelenium extracts. Phe-nolic (HPLC) substances in leaf ethanol (L-EtOH), leaf pure water (L-PW), root ethanol (R-EtOH), and root pure water (R-PW) extracts of Inula helenium subsp. pseudohelenium plant were investi-gated. Also, in vitro the antimicrobial (hollow agar), antioxidant (DPPH, ABTS.+, FRAP, CU-PRAC), antiproliferative (MTT assay against HT-29, MCF-7 and L-929), and DNA (Agarose gel electrophoresis) protective activities of the samples were examined. Although gallic acid was not detected in the extracts, the presence of curcumin was detected only in EtOH extracts. L-EtOH exhibited the best antimicrobial activity. According to the antioxidant results, it was found that the L-EtOH extract had an activity profile close to the standard antioxidants in general. It was also found that the L-EtOH extract stabilized the DNA by disrupting the scavenging effect of H2O2+DMSO. According to the antiproliferative activity results, EtOH extracts exhibited the strongest effect, especially against MCF7. When evaluated in general terms, it was found that L-EtOH extract showed better activity than other extracts. It is important to conduct more in vivo and in vitro studies after isolating the active components of extracts e.g. L-EtOH, which have good effects in terms of biological activity.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

According to research, we have learned that Mg and TiO2 are new types material of marine protective coatings. We found that the addition of Mg can improve the performance of Zn-Al coating passivation film, and TiO2 has excellent photocatalytic self-cleaning performance. In this paper Zn-Al pseudo alloy coating was prepared by cold spray technique, and Zn-Al-Mg-TiO2 pseudo alloy composite coating was prepared by adding Mg and nano-TiO2. The effects of Mg and TiO2 to the marine protective properties of Zn-Al coatings were studied by friction and wear test, dynamic salt water corrosion test, electrochemical test, scanning electron microscope(SEM), energy dispersive spectrometer(EDS) and super deep scene 3D microscope. The results show that the addition of Mg and nano-TiO2 not only fills the gap of the coating and improves the density of the coating, but also generates grid-like flocculent corrosion products on the surface of the coating which can gather other corrosion products to improve the density of corrosion products, reduce the friction coefficient and corrosion rate of the coating surface, effectively prevent the invasion of Cl- in solution, and improve the wear and corrosion resistance of the coating.

Minerals might have played critical roles for the origin and evolution of possible life forms on Mars. The study of the interactions between “building blocks of life” and minerals relevant to Mars mineralogy under conditions mimicking the harsh Martian environment may provide key insight into possible prebiotic processes. Therefore, this contribution aims at reviewing the most important investigations carried out so far about the catalytic/protective properties of Martian minerals toward molecular biosignatures under Martian-like conditions. Overall, it turns out that the fate of molecular biosignatures on Mars depends on a delicate balance between multiple preservation and degradation mechanisms often regulated by minerals, which may take place simultaneously. Such a complexity requires more efforts in simulating realistically the Martian environment in order to better inspect plausible prebiotic pathways and shed light on the nature of the organic compounds detected both in meteorites and on the surface of Mars through in situ analysis.

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and its binding activity to the EGFR antigen were evaluated. Furthermore, the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the significant accumulation and sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.

Background: In 80% of patients, COVID-19 presents as mild disease^1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia³, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression⁴. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV^5,6 SARS-CoV-1^7-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) ¹¹ demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease³ and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion^{12 13}. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.

The target of an antibody plays a significant role in the success of antibody-based therapeutics and diagnostics, and to an extent, that of vaccine development. This importance is focussed on the target binding site – epitope, where epitope selection as a part of design thinking beyond traditional antigen selection using whole cell or whole protein immunisation can positively impact success. With purified recombinant protein production and peptide synthesis to display limited/selected epitopes, intrinsic factors that can affect the functioning of resulting antibodies can be more easily selected for. Many of these factors stem from the location of the epitope that can affect accessibility of the antibody to the epitope at a cellular or molecular level, direct inhibition of target antigen activity, conservation of function despite escape mutations, and even non-competitive inhibition sites. Through the incorporation of novel computational methods for predicting antigen changes to model-informed drug discovery and development, superior vaccines and antibody-based therapeutics or diagnostics can now be more easily designed to mitigate failures. With detailed examples, this review highlights the new opportunities, factors and methods of predicting antigenic changes for consideration in sagacious epitope selection.

In the aerospace sector, structural and non-structural components are usually subjected to a wide range of environmental conditions. Although lightweight, the use of composite parts for these applications is restricted, due to their poor performance in severe environmental conditions. Specifically, moisture can seriously damage the materials' performance, reducing their mechan-ical, thermal, electrical, and physical properties as well as the service time. A strategy to improve the materials’ resistance in humid environments is the use of protective lightweight barrier coatings to reduce the diffusion of gases and/or liquids in composites. Nanolamellar nanocom-posite characterized by the high in-plane orientation of nanoplatelets effectively works as barrier structures by generating tortuous paths for molecule diffusion. In this work, the effectiveness of protection against water uptake of nanocomposites reinforced with Graphite NanoPlatelets (GNPs) at high filler content (70, 80 and 90%wt) for Kevlar sandwich panels of a nacelle engine of an ATR42 aircraft has been investigated. Moisture uptake and Ground Air Ground (GAG) tests were carried out in an environmental chamber to reproduce temperature and relative humidity profiles representative of a real-scale application for a regional aircraft composite part. The high filler content of the graphene films ensures a high level of tortuosity by delaying and reducing moisture absorption by –71% compared to the unprotected panel, showing good barrier properties.

Abstract: Ultraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Astaxanthin, a ketocarotenoid from Haematococcus pluvialis, has been extensively studied with respect to its possible effect on skin health as well as UV protection. In addition, astaxanthin attenuates increases in the generation of reactive oxygen species (ROS) and capillary regression of skeletal muscle. In the present study, we investigated whether astaxanthin would protect UV-induced photoaging and capillary regression in the skin of HR-1 hairless mice. UV induces wrinkle formation, thickness and capillary regression in dermis of hairless mice and the administration of astaxanthin decreased the UV-induced wrinkle formation, skin thickness, and increase in collagen fibers in skin. Astaxanthin supplementation also inhibited the levels of ROS generation and attenuated the decreases in wrinkle formation, thickness and capillary number in the skin. We also found an inverse correlation between wrinkling and capillary number, and the photoaging associated with capillary regression in skin. These results suggest that astaxanthin can protect against photoaging caused by ultraviolet irradiation and the effects of astaxanthin in photoaging inhibition may be associated with the protection of capillary regression in skin.

Nicotine is a pharmacologically active component of tobacco which adversely affects the male reproductive system and fertility and Icariin (ICA) is the main active ingredient of Epimedium herba which has been used to treat several male reproductive problems. This study was aimed at investigating the protective or ameliorative effect of ICA against reproductive toxicity induced by intraperitoneal injection of nicotine in mice. Forty male mice were randomly divided into 4 groups: control, nicotine (0.75 mg/kg intraperitoneally), icariin (ICA, 75 mg/kg), and icariin plus nicotine (ICA + nicotine) group. After 35 days of treatment, the mice were weighed, sacrificed, and their reproductive organs were collected and examined for further studies. In the nicotine-treated group, epididymal sperm density and serum testosterone concentrations significantly decreased relative to the control group. Nicotine also caused oxidative damage as shown by significant reduction in the activities of antioxidant enzymes and an elevation in Malondialdehyde (MDA) levels. Icariin on the other hand, improved the reduction in sperm characteristics, hormone levels, and activities of antioxidant enzymes alterations observed in the nicotine treated mice. These findings indicate that the nicotine-induced reproductive toxicity and oxidative damages on male reproductive tissues can be effectively attenuated by icariin.

C-C motif chemokine receptor 1 (CCR1/CD191) is a member of G-protein-coupled receptors, and is expressed on myeloid cells, such as neutrophils and macrophages. Because the CCR1 signaling promotes tumor expansion in the tumor microenvironment (TME), the modification of TME is an effective strategy for cancer therapy. Although CCR1 is an attractive target for solid tumors and hematological malignancies, anti-CCR1 therapeutic agents have not been approved. Here, we established a novel anti-mouse CCR1 (mCCR1) monoclonal antibody (mAb), C₁Mab-6 (rat IgG_2b, kappa), using the Cell-Based Immunization and Screening (CIBS) method. Flow cytometry and Western blot analyses showed that C₁Mab-6 recognizes mCCR1 specifically. The dissociation constant of C₁Mab-6 for mCCR1-overexpressed Chinese hamster ovary-K1 was determined as 3.9×10^-9 M, indicating that C₁Mab-6 possesses a high affinity to mCCR1. These results suggest that C₁Mab-6 could be a useful tool for targeting CCR1 in preclinical mouse models.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

Regulatory T cells (Tregs) are major drivers behind immunosuppressive mechanisms and present a major hurdle for cancer therapy. Tregs are characterized by high expression of CD25, which is a potentially valuable target for Treg depletion to alleviate immune suppression. The preclinical anti-CD25 (αCD25) antibody, clone PC-61, has met with modest anti-tumor activity, due to its capacity to clear Tregs from circulation and lymph nodes but not those that reside in the tumor. Optimization of the Fc domain of this antibody clone has been shown to enhance intratumoral Treg depletion capacity. Here, we generated a stable cell line that produces optimized recombinant Treg depleting antibodies. A genome engineering strategy in which CRISPR-Cas9 was combined with homology directed repair (CRISPR-HDR) was utilized to optimize the Fc domain of the hybridoma PC-61 for effector functions by switching it from the original rat IgG1 to a mouse IgG2a isotype. In a syngeneic tumor mouse model the resulting αCD25-m2a antibody mediated effective depletion of tumor resident Tregs leading to a high effector T cell (Teff) to Treg ratio. Moreover, combination of the αCD25-m2a with αPD-L1 treatment augmented tumor eradication in mice, demonstrating the potential for αCD25 as a cancer immunotherapy.

The epithelial cell adhesion molecule (EpCAM) is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. EpCAM is involved in cell adhesion, proliferation, survival, stemness, and tumorigenesis. Therefore, EpCAM is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-EpCAM monoclonal antibodies (mAbs) using the Cell-Based Immunization and Screening (CBIS) method. We characterized them using flow cytometry, western blotting, and immunohistochemistry. One of the established recombinant anti-EpCAM mAbs, recEpMab-37 (mouse IgG1, kappa), reacted with EpCAM-overexpressed Chinese hamster ovary-K1 cells (CHO/EpCAM) or a colorectal carcinoma cell line (Caco-2). In contrast, recEpMab-37 did not react with EpCAM-knocked out Caco-2 cells. The KD of recEpMab-37 for CHO/EpCAM and Caco-2 was 2.0 × 10-8 M and 3.2 × 10-8 M, respectively. In western blot analysis, recEpMab-37 detected EpCAM of CHO/EpCAM and Caco-2 cells. Furthermore, recEpMab-37 could stain formalin-fixed paraffin-embedded colorectal carcinoma tissues by immunohistochemistry. Taken together, recEpMab-37, established by CBIS method, is useful for detecting EpCAM in various applications.

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

Viruses can infect a cell via one or both routes viz. cell-to-cell (c-c) or cell-free (c-f) . Pathogenesis studies of various viruses, including HIV, have shown that c-c transmission yields a significantly higher infection magnitude than the c-f route. Expectedly, potent antibodies inhibited c-f infection more efficiently than with c-cell transmission. To achieve a one-step, synchronous infection cycle that provides amplified infection, we have studied a consistent and efficient c-c HIV infection model since 1992. H9 cells persistently infected with HTLV-IIIB (H3B cells) and uninfected target CD4+ lymphocyte line (HuT78) were mixed in a ratio of 1:4 respectively. We have recently used this model to produce HIV designer antigens that have been shown to elicit monoclonal as well as polyclonal specific antibodies against novel epitopes that are formed post virus-cell engagement, but prior to fusion. The model can be extended for HIV neutralizing antibody assays or drug inhibitors against high multiplicity of infection.

The sulfated polysaccharide (SP) was extracted from Gracilaria edulis and tested for its ability to protect against carbon tetrachloride (CCl4)-induced liver injury in Wistar rats. The chemical composition of the sulfated polysaccharide, documented 12.90% of yield, 83.07% of carbohydrate, 0% of protein, 15.02% of ash, and 2.09% of moisture, and the carbon, hydrogen, nitrogen, and sulfur content were 25.90%, 4.28%, 2.65%, and 3.61%. SP has a molecular weight of 41kDa. The monosaccharide and structural properties of SP were investigated using GC-MS, FT-IR, and 1H-NMR spectral analysis. In rats, CCl4 produced hepatotoxicity, as evidenced by an increase in serum ALT, AST, and ALP levels and a decrease in ALB levels. The SP treated showed decreases in ALT, AST and ALP levels, as well as an increase in ALB levels. SOD, catalase, GPx, and GSH levels were suggestively lower in CCL4-induced rats compared to normal control rats. SOD, catalase, GPx and GSH levels in the SP-treated rats, on the other hand, improved to normal levels. The rat liver tissue treated with SP recovered well from hepatic injury. SP can be considered an alternative in the treatment of liver injury or as preventive medicine.

Inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be an important and timely issue. In this study, we investigated the potential of vitamin D3, turmeric powder and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without supplementation of vitamin D3 (750 IU/kg of body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5±1.3 cm3/h/m3/day) for 30, 60 or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, destruction of the lobular structure and hepato-cytolysis in the liver, shrinkage and fragmentation of glomeruli in the kidneys, and disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately.

It is essential to consider the factors that affect early childhood development because doing so can help identify potential risks and window of opportunity for intervention to improve outcomes for children. However, identifying risk and protective factors in early childhood requires careful consideration of several challenges and an integrated approach that recognises the complex and dynamic nature of development. The purpose of this study was to identify and describe the prevalent psychosocial risk and protective factors in the early childhood development phase, using an ecological perspective. The study employed a quantitative cross-sectional study using a random sampling technique. The final sample consisted of 505 caregivers of children aged 5 years old and younger. This study revealed that the most prevalent protective factors include child self-regulation, parent-child warmth, family management and collective efficacy but more importantly social support. While risk factors may exist this is mitigated by social support as it moderates and buffers against the effects of risk factors, as indicated by the various research studies cited.

Antibody-drug conjugates (ADCs), a groundbreaking advancement in cancer therapy, synergistically combine the precision of monoclonal antibodies with the potent destruction capabilities of cytotoxic drugs, signifying a new era in the targeted oncological treatments. This comprehensive paper delves into the evolving field of antibody-drug conjugates (ADCs) and their pivotal role in cancer therapy. We have conducted an in-depth exploration of the structural components of ADCs, including target antigens, monoclonal antibodies, chemical linkers, and cytotoxic payloads, each playing a crucial role in determining the efficacy and safety profile of these novel therapies. A detailed market analysis reveals the leading pharmaceutical companies shaping the ADC landscape, reflecting the growing interest and potential in this therapeutic approach. We further dissect the engineering intricacies of ADCs, focusing on their ability to target specific cancer cell antigens while minimizing off-target effects, thus offering a more focused treatment with reduced systemic side effects compared to traditional chemotherapy. This approach holds promise in a heightened therapeutic index and decreased toxicity. The mechanisms and effector functions of ADCs are explored, highlight- ing their multifaceted strategy in combating cancer. We include a comprehensive look at how ADCs operate from initial blood circulation to the induction of apoptosis in cancer cells. We also review several key ADCs currently in use or under investigation, offering insights into their unique mechanisms of action, pharmacokinetics, and clinical implications. The discussion extends to drug creation modalities, focusing on innovative conjugation techniques that enhance ADC homogeneity and therapeutic efficacy. In conclusion, the paper underscores the transformative potential of ADCs in the realm of cancer treatment, marking a shift towards more precise and targeted therapeutic approaches. By offering a thorough analysis of ADC technology, this paper sheds light on the prospects of these groundbreaking therapies in the ongoing fight against cancer.

A cell-surface ectonucleotidase CD39 mediates the conversion of extracellular ATP into immunosuppressive adenosine with another ectonucleotidase CD73. The elevated adenosine in the tumor microenvironment (TME) attenuates antitumor immunity, which promotes tumor cell immunologic escape and progression. Anti-CD39 monoclonal antibodies (mAbs), which suppress the enzymatic activity, can be applied to antitumor therapy. Therefore, an understanding of the relationship between the inhibitory activity and epitope of mAbs is important. We previously established an anti-mouse CD39 (mCD39) mAb, C₃₉Mab-1 using the Cell-Based Immunization and Screening (CBIS) method. In this study, we determined the critical epitope of C₃₉Mab-1 using flow cytometry. We performed the PA tag (12 amino acids)-substituted analysis (named PA scanning) and RIEDL tag (5 amino acids)-substituted analysis (named RIEDL scanning) to determine the critical epitope of C₃₉Mab-1 using flow cytometry. By the combination of PA scanning and RIEDL scanning, we identified the conformational epitope, spanning three segments of 275^th to 279^th, 282^nd to 291^st, and 306^th to 323^rd amino acids of mCD39. These analyses would contribute to the identification of the conformational epitope of membrane proteins.

To increase the prediction accuracy of positive oral food challenge (OFC) outcome during stepwise slow oral immunotherapy (SS-OIT) in children with hen’s egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding-avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFC with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding-avidity of OVM-sIgE defined as the level of 1/ IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/ IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE and binding-avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p<0.01). Among them, the variable with greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFC during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT

Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative such as Escherichia coli and Salmonella enterica serovar Typhimurium. Grape seeds, wine industry by-products, have antioxidant, antimicrobial, and anti-inflammatory activities. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damages has been studied in a model of Caco-2 cells. The in vitro activity of prGSE against formation of biofilm of S. Typhimurium and E. coli, has been investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results showed that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by LPS treatment of Caco-2 cells has been demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In in vivo activity, increased survival of infected G. mellonella larvae after treatment with prGSE has been demonstrated. In conclusion, grape seed extracts could be used in the reduction of GI damage caused by bacterial endotoxin and biofilm of Gram-negative bacteria.

The COVID-19 crisis has resulted in a shortage of personal protective equipment (PPE) [1]. COVID-19 is currently the leading cause of death in the United States[2]. Health care providers caring for COVID-19 patients or at high risk of being exposed to the SARS-CoV-2 virus benefit from a face shield to protect against aerosol droplets that could hit the face and minimize the chance of inadvertently touching the face with contaminated hands, and air filtration to filter out aerosolized SARS-CoV-2. Adapting commercially available full-faced snorkel masks has been proposed as an alternative to narrow the gap in PPE [3]. Here we explore a full-faced snorkel mask with commercially available particulate filters.

Krill oil (KO) shows promise as a natural marine-derived ingredient for improving skin health. This study investigated its antioxidant, anti-inflammatory, anti-wrinkle, and moisturizing effects on skin cells and UVB-induced skin photoaging in hairless mice. In vitro assays on HDF, HaCaT, and B16/F10 cells, and in vivo experiments on 66 hairless mice, were conducted. Mice received oral KO administration (100, 200, or 400 mg/kg) once a day for 15 weeks and UVB radiation three times a week. In vitro, KO significantly countered UVB-induced oxidative stress, reduced wrinkles, and prevented skin water loss by enhancing collagen and hyaluronic synthesis. In vivo, all KO dosages showed dose-dependent inhibition of oxidative stress-induced inflammatory photoaging-related skin changes. Skin mRNA expressions for hyaluronan synthesis and collagen synthesis genes also increased dose-dependently after KO treatment. Histopathological analysis confirmed that Krill Oil (KO) ameliorated the damage caused by UVB-irradiated skin tissues. These findings suggest that KO may be a valuable intervention to mitigate UVB-induced skin photoaging and address various skin concerns.

Diabetes mellitus (DM) comprises a range of metabolic disorders characterized by high blood glucose levels caused by defects in insulin release, insulin action, or both. DM is a widespread condition that affects a substantial portion of the global population, causing high morbidity and mortality rates. The prevalence of this major public health crisis is predicted to increase in the forthcoming years. Although, several drugs are available to manage DM, these are associated with adverse side effects, which limits their use. In underdeveloped countries, where such drugs are often costly and not widely available, many people continue to rely on alternative traditional medicine, including medicinal plants. The latter serve as a source of primary healthcare and plant-based foods in many low and middle-income countries. Interestingly, many of the phytochemicals they contain have been demonstrated to possess antidiabetic activity such as lowering blood glucose levels, stimulating insulin secretion and alleviating diabetic complications. Therefore, such plants may provide protective effects that could be used in the management of DM. The purpose of this article was to review the medicinal plant-based foods traditionally used for the management of DM, including their therapeutic effects, pharmacologically-active phytoconstituents and antidiabetic mode of action at the molecular level. It also presents future avenues for research in this field.

Teacher burnout has been shown to be one of the most common negative consequences of the COVID-19 pandemic. This study aimed to identify distinct psychological resources and burnout risk profiles of teachers and examine their association with Kolb’s educator roles and their professional experience. Methods: The survey data were collected from 330 preschool and primary school (84 males, Mage = 38.3, SD = 9.14) teachers using a convenience sampling method. Results: The two-step cluster analysis revealed two distinct profiles. The first profile, “high psychological resources, no burnout risk,” was characterized by absent symptoms of burnout and increased levels of well-being, self-control, and positive emotionality. The second profile, “moderate psychological resources, mild burnout,” was associated with medium levels of well-being, self-control, and positive emotionality accompanied by mild burnout. Our findings highlighted that cluster one had a significantly higher score for the facilitator role and cluster two for the expert and coach roles. Additionally, teachers with less professional experience were more likely to belong to cluster one, considering their adequate skills in digital literacy. Conclusions: These findings provide new insights into the explanation of teacher burnout and the design of intervention programs.

Numerous studies have established the link between ADHD and antisocial behavior, one of the most serious functional impairments caused by the disorder. However, research on protective factors that mitigate this link is still lacking. The Salutogenic Model of Health offers the “Sense of Coherence” (SOC), establishing that individuals who see their lives as logical, meaningful, and manageable are more resistant to various risk factors and diseases. The present study examines for the first time whether SOC is also a protective factor against ADHD-related different types of antisocial behaviors (severe/mild violent behavior, verbal violence, property crimes, public disorder, and drug abuse). 2260 participants aged 15-50 completed online questionnaires assessing the level of ADHD symptoms, antisocial behaviors, and SOC. An interaction between ADHD and SOC was found in predicting each type of antisocial behavior. The link between ADHD and antisocial behavior was significantly weaker for high than low SOC participants, regardless of age group. The current study found that people with high SOC are protected against the effect of ADHD on one of the most serious functional impairments, antisocial behavior. These findings suggest that SOC is a protective factor from the adverse effects of ADHD, justifying further prospective and intervention studies.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Background: Oenothera biennis (evening primrose) produces bioactive substances with a diverse range of pharmacological functions. However, it is currently unknown whether extract prepared from the aerial parts of O. biennis (APOB) can protect the skin against oxidative stress. To investigate the protective effects of APOB against oxidative stress-induced damage in human skin keratinocytes (HaCaT) and elucidate the underlying mechanisms. Methods: We pretreated HaCaT cells with various concentrations of APOB or the antioxidant N-acetyl-L-cysteine before applying H2O2. We then compared the cell viability, intracellular reactive oxygen species (ROS) production, and DNA and mitochondrial damage between pretreated and untreated control cells using a range of assays, flow cytometry, and Western blot analysis and also examined the reducing power and DPPH free radical-scavenging activity of APOB. Results: APOB pretreatment significantly increased cell viability, effectively attenuated H2O2-induced comet tail formation, and inhibited H2O2-induced phosphorylation of the histone γH2AX, as well as the number of apoptotic bodies and Annexin V-positive cells. APOB was found to have a high reducing power and DPPH radical-scavenging activity and also exhibited scavenging activity against intracellular ROS accumulation and restored the loss of mitochondrial membrane potential caused by H2O2. APOB pretreatment almost totally reversed the enhanced cleavage of caspase-3, the degradation of poly (ADP-ribose)-polymerase (PARP), DNA fragmentation that usually occurs in the presence of H2O2 and increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme that is associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). Conclusions: APOB can protect HaCaT cells from H2O2-induced DNA damage and cell death by blocking cellular damage related to oxidative stress via a mechanism that affects ROS elimination and by activating the Nrf2/HO-1 signaling pathway.