Development of new neurotherapeutics is strongly depending on appropriate animal model chosen in preclinical studies. A cuprizone model is an effective tool for studying demyelination and re-myelination processes in the brain, but BBB integrity in cuprizone model is still a topic for debate. Several publications claim that BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could be explained by the increased BBB permeability. In our work we aim to analyze permeability of BBB for different macromolecules, particularly, antibody-conjugates in cuprizone-intoxicated mice. We compared the traditional approach using Evans blue injection with following dye extraction and detection of antibody-conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in cuprizone model. First, we validated our model of demyelination by detecting changes in gene expression of myelin basic protein and proteolipid protein, and by performing MRI and histological analysis. Our results suggest that the methods with better sensitivity were able to detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that ques-tioned BBB integrity in cuprizone model and demonstrate possibility for delivery of anti-body-conjugates to demyelinated corpus callosum

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.

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.

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.

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.

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.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

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.

The Yixian Formation (Lower Cretaceous) of China is famous worldwide for its fossils of early angio-sperms, but there is only one record of flower bud hitherto. A previous fossil record of flower bud just showed the appearance and lacked any internal details. Such a lacuna in knowledge of flower buds hin-ders our understanding of the evolution of flowers. Our new specimen was collected from an outcrop of the Yixian Formation (the Barremian-Aptian, Lower Cretaceous) near Dawangzhangzi, Lingyuan, Liao-ning, China. The specimen was observed and photographed using a Sony ILCE-7 digital camera and a Nikon SMZ1500 stereomicroscope, and details were observed using a TESCAN MAIA3 SEM. Our ob-servations document a fossil flower bud, Archaebuda cretaca sp. nov, from the Lower Cretaceous of China. The occurrence of two species of Archaebuda in the Yixian Formation not only confirms the ex-istence of the expected gynoecium (and possible androecium) in a flower bud, but also underscores the occurrence of typical flowers in the Early Cretaceous.

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.

A new generalized definition of Mersenne numbers is proposed of the form (a^n - (a-1)^n), called Global Generalized Mersenne numbers, or simply Generalized Mersenne numbers and noted GM_{a,n} where a is the base and n is the exponent, both being positive integers. The properties are investigated for prime exponents n and several theorems on Mersenne numbers regarding their congruence properties are generalized and demonstrated. In particular, it is found that, for any base a, Generalized Mersenne numbers are in general such that (GM_{a,n} - 1) are even and divisible by n, a and (a-1) for any odd prime exponent n and by (a(a-1)+1) for any prime exponent n > 5. The remaining factor is a function of triangular numbers of (a-1), specific to each prime exponent n. Four theorems on Mersenne numbers are generalized and four new theorems are demonstrated, allowing to show first, that (GM_{a,n} - 1) are divisible by 6, and more precisely GM_{a,n} are congruent to 1(mod 12) or 7(mod 12) depending on the congruence of the base a(mod 4); second, that (GM_{a,n} - 1) are divisible by 10 if n == 1(mod 4) and, if n == 3(mod 4), GM_{a,n} == 1(mod 10), or 7(mod 10) or 9(mod 10) depending on the congruence of the base a(mod 5); third, that all factors c_{i} of GM_{a,n} are of the form (2nf_{i}+1) with f_{i} natural integers such that c_{i} is prime itself or the product of primes of the form (2nj+1) with j natural integer; fourth, that for odd prime exponents n, all GM_{a,n} are periodically congruent to either +/-1\(mod 8) or +/-3(mod 8) depending on the congruence of the base a(mod 8); and fifth, that the factors of a composite GM_{a,n} is of the form (2nf_{i}+1) with f_{i} == u(mod 4) and u being either 0, 1, 2 or 3 depending on the congruence of the exponent n(mod 4) and on the congruence of the base a(mod 8). The potential use of Generalized Mersenne primes in cryptography is shortly addressed.

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.

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H₂Mab-250/H₂CasMab-2. In flow cytometry and immunohistochemistry, H₂Mab-250 reacted with HER2-positive breast cancer cells but did not show the reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG₁ version of H₂Mab-250 (H₂Mab-250-hG₁) possesses compatible in vivo antitumor effects against breast cancer xenografts with trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H₂Mab-250-hG₁ and trastuzumab. Both H₂Mab-250-hG₁ and trastuzumab showed ADCC activity against CHO/HER2 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed that trastuzumab showed a more significant ADCC effect compared to H₂Mab-250-hG₁. Importantly, H₂Mab-250-hG₁ exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in mouse IgG_2a types of both H₂Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H₂Mab-250-hG₁ and trastuzumab and indicate the future direction for the clinical development of H₂Mab-250-hG₁ against HER2-positive tumors.

Iron (Fe), the main component of non-exhaust particulates, is known to have variable health effects that depend on the chemical species of iron. This study characterized the possible contribution of iron oxides and hydroxides to airborne brake-wear particles under realistic vehicle driving and braking conditions with different brake-pad friction materials. We found significant differences in wear coefficients and PM₁₀ emissions between non-asbestos organics (NAO) and European performance (ECE) brake pads. Iron was the dominant contributor to PM₁₀ and PM_2.5 brake-wear particles for both NAO and ECE. The iron concentration ratio in the particle mass were comparable to the disc to pads ratio measured by wear mass. The fact that magnetite, which is of interest with respect to health effects, was less abundant in NAO than in ECE suggested that tribo-oxidations occurred in NAO. Metallic iron is generated not only from abrasive wear but also from tribo-chemical reduction with magnetite as the starting material. We found differences not only in PM emissions between brake friction materials but also that the phase transformations of iron differed between friction materials. These differences were apparent in the distribution of iron oxides and hydroxides. Heat, tribo-oxidation, and tribo-reduction are intricately involved in these reactions.

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.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

Pneumonic plague outbreaks are relatively infrequent in modern times but in the early part of the 20th century, they were commonplace including several well-documented epidemics responsible for the deaths of thousands. The transmissibility of this disease seems to be discontinuous since in some outbreaks few transmissions occur, while in others, the progression of the epidemic is explosive. Modern epidemiological studies explain that transmissibility within populations is heterogenous with relatively few subjects likely to be responsible for most transmissions and that ‘super spreading events’, particularly at the start of an outbreak, can lead to a rapid expansion of cases. These findings concur with outbreaks observed in real-world situations. It is often reported that pneumonic plague is rare and not easily transmitted but this view could lead to unnecessary complacency since future risks such as the spontaneous incidence of anti-microbial strains, climate change leading to a disruption of natural cycles within plague foci and use of plague as a bioweapon cannot be discounted. Carers and first responders are vulnerable, particularly in poorer countries where access to medicines may be limited, out-breaks occur in inaccessible areas or where there is a lack of surveillance due to a paucity of funds.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterized by brain damage, particularly affecting the white matter tracts of the pontine region. This damage arises due to rapid correction of metabolic imbalances, primarily cases of hyponatremia. Noteworthy triggers encompass severe burns, liver transplantations, anorexia nervosa, hyperemesis gravidarum, and hyperglycaemia, all linked to the development of CPM. Clinical manifestations encompass a spectrum of signs and symptoms, including dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, disorientation, catatonia, and, in severe instances, locked-in syndrome and coma. A recent case involving a 45-year-old woman illustrates these complexities. Upon admission to the Medicine Intensive Care Unit, she presented with symptoms indicative of diminished responsiveness and bilateral weakness in upper and lower limbs. Of significance, the patient had a pre-existing medical history of hyperthyroidism. Extensive diagnostic investigations were undertaken, revealing compelling evidence of profound hyponatremia through blood analyses. Furthermore, magnetic resonance imaging (MRI) was performed, unveiling conspicuous areas of abnormal hyperintensity located in the central pons, intriguingly accompanied by spared peripheral regions. These radiological findings align with the characteristic pattern associated with osmotic demyelination syndrome, illuminating the underlying pathology.

Exergy analysis evaluates the efficiency of system components by quantifying the rate of entropy generation. In general, the exergy destruction rate or irreversibility rate was directly obtained through the exergy-balance equation. However, this method cannot determine the origin of the component's entropy generation rate, which is a very important factor in system design and improvement. In this study, a thorough energy, exergy thermoeconomic analysis of a proton exchange membrane fuel cell (PEMFC) was performed, providing the heat transfer rate, entropy generation rate and cost loss rate of each component. The irreversibility rate of each component is obtained by the Gouy-Stodolar theorem. Detailed and extensive exergy and thermoeconomic analyses of PEMFC system have determined that water cooling units experience the greatest heat transfer among the components in the studied PEMFC system, resulting in the greatest irreversibility and thus the greatest monetary flow loss.

Introduction The climate crisis is essentially a public health crisis. Response is imperative to prevent economic and social crises associated with the growing burden of climate impacts on human health and the health care sector. Green Podiatry Pillars By adopting the three pillars of Exercise, Evidence, and Everyday changes, podiatrists can contribute to more sustainable health and health care. Discussion Educating our patients to use their feet for low carbon active transport, eliminating interventions not supported by evidence, and reducing fossil fuel driven supply chains and energy use, are three impactful measures that all podiatrists, and indeed, all health and medical personnel, need to adopt. The avoidable suffering, enormous and costly use of resources for diabetic foot disease, is a scourge that must realise its preventable potential. It is too late, too costly, too polluting, and too sad, to continue to direct health care and research efforts and budgets, to an expensive modifiable diabetes disease process, potentiated by poor food and physical inactivity. Affected patients require skilled support, to avert such chronic disease processes, often not of their making. Conclusions Healthcare contributes 5 to 8% of green house gases (GHG), and non-communicable diseases (NCD) are increasing, so healthcare must lead on primary health. As citizens and health professionals, we must advocate for better community health, and educate our patients. Future Directions All health and medical personnel need to consider planetary health and sustainable healthcare within their daily work. Healthcare must act to address climate change, and realise benefits for people and planet.

The construction of optimized biological fuel cells requires a cathode which combines the longevity of a microbial catalyst with the power density of an enzymatic catalyst. Laccase secreting fungi were grown directly on the cathode of a biological fuel cell to facilitate the exchange of inactive enzymes with active enzymes with the goal of extending the lifetime of laccase cathodes. Additionally, a functionally graded coating was developed to increase enzyme loading at the cathode. Directly incorporating the laccase producing fungus at the cathode extends the operational lifetime of laccase cathodes while eliminating the need for frequent replenishment of the electrolyte. Additionally, the hybrid microbial-enzymatic cathode addresses the issue of enzyme inactivation by using the natural ability of fungi to exchange inactive laccases at the cathode with active laccases. Finally, enzyme adsorption was increased through the use of a functionally graded coating containing an optimized ratio of titanium dioxide nanoparticles and single walled carbon nanotubes. The hybrid microbial-enzymatic fuel cell combines the higher power density of enzymatic fuel cells with the longevity of microbial fuel cells and demonstrates the feasibility of a self-regenerating fuel cell in which inactive laccases are continuously exchanged with active laccases.

Considerable attention has been given to the research field of bioorganometallic chemistry, which is a hybrid chemistry field between biology and organometallic chemistry. The introduction of biomolecules, which have hydrogen bonding sites and chiral centers, into organometallic compounds is considered to be a promising strategy to construct chirality-organized bioorganometallic conjugates. This feature paper sketches an outline of induction of helical chirality into bioorganometallic conjugates. Topics covered include control of the helical chirality of 1,n’-disubstituted ferrocene moieties in ferrocene-dipeptide conjugates and the chirality induction of the Au(I)–Au(I) axis in the dinuclear organogold(I)-uracil conjugates.

Twelve clinically healthy and sexually mature New Zealand White rabbits were studied. The non-contrast imaging included T1-weighted and T2-weighted spin echo and gradient echo sequences in transverse, sagittal and dorsal planes. Transverse MRI (Т2-weighted image) through L1 demonstrated only the right kidney. The transverse T2-weighted image through L2 showed both kidneys. The cranial part of the urinary bladder on T1-weighted transverse scans through L4 was flexed to the left. The T2-weighted sagittal image 30 mm to the right of the median plane showed the right kidney, the right ureter and the urinary bladder. The T2-weighted sagittal image 30 mm to the left of the median plane showed part of the left kidney, the left ureter and the urinary bladder. The T2-weighted sagittal image 45 mm to the left of the median plane presented the lateral part of the left kidney. The dorsal MRI image (Т2-weighted sequence) through the horizontal plane 30 mm ventral to the spine demonstrated the whole organs. The data will be useful in imaging anatomy and diagnostic studies of various pathologies of the excretory system in rabbits and other mammalian species.

Fatigue is a recognized concern in air traffic management, prompting international bodies like ICAO and EASA to advocate for Fatigue Risk Management Systems (FRMS). EU Regulation 2017/373, effective since January 2020, imposes specific requirements on air traffic service providers regarding controllers' fatigue, stress, and rostering systems, as part of safety management protocols. Despite active campaigns promoting fatigue awareness in air traffic control (ATC), there remains a need for standardized operational requirements. Eurocontrol recently published "Guidelines on fatigue management in ATC rostering systems" (April 23), aiming to facilitate the adoption of common fatigue operational standards. However, neither EU Regulation 2017/373 nor existing documentation specifies exact rostering criteria. Air Navigation Service Providers (ANSPs) typically derive these criteria from scientific literature, best practices, historical data, and legal and operational necessities. Yet, assessing and monitoring fatigue in operational settings can be complex and require long-term studies due to its multifaceted nature, spanning factors such as sleep quality, circadian rhythms, psychosocial influences, individual traits, and environmental conditions. The case studies reported in this paper represent an attempt to create an evidence-based protocol for fatigue risk monitoring in ATC operations, utilizing a non-invasive approach and collecting multidimensional data. The two case studies involved en-route and tower controllers from different ATC Centers, and the results underscore the importance of fatigue assessment in ATC and elucidates challenges in implementing fatigue monitoring within operational contexts.

We study the brain segmentation by dividing the brain into multiple tissues. Given possible brain segmentation by deep, machine learning can be efficiently exploited to expedite the segmentation process in the clinical practice. To accomplish segmentation process, a MRI and tissues transfer using generative adversarial networks is proposed. Given the better result, we propose the transfer model using GAN. For the case of the brain tissues, white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) are segmented. Empirical results show that this proposed model significantly improved segmentation results compared to the stat-of-the-art results. Furthermore, a dice coefficient (DC) metric is used to evaluate the model performance.

In the present work report, the MgAl₂O₄and the Ag/MgAl₂O₄ samples were successfully synthesized by the modified hydrothermal and the isovolumetric impregnation methods, respectively. The structural properties of the prepared samples were systematically characterized by XRD, SEM, TEM, DRS, XPS and et al techniques. The photocatalytic degradation of methylene blue by the Ag/MgAl₂O₄ and MgAl₂O₄ samples was comparatively studied under UV lamp irradiation. The results revealed that the prepared Ag/MgAl₂O₄ (pH=6) samples were the most active among the samples in photocatalytic of methylene blue. Under UV lamp irradiation, the Ag/MgAl₂O₄ (pH=6) photodegradation of methylene blue reached to 89.6% within 120 min. And the Ag/MgAl₂O₄ (pH=6) complex photocatalysts displayed a high photochemical stability under repeated irradiation. Repeated irradiate the Ag/MgAl₂O₄ (pH=6) compound, which indicated it had a high photochemical stability.

Abstract: Tumor-targeting and blood-brain barrier (BBB)-penetrating are highly desirable for the treatment of glioma. In this study, we developed Pep-1&borneol-bifunctionalized carmustin-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting to IL-13 receptor-overexpressed glioma and penetrating the brain microvascular endothelial cells-associated physiologic barriers. Pep-1/Bor/CMS-M were nearly spherical particles with a dimeter of 32.6 ± 1.1 nm and zeta potential of -21.3 ± 3.1 mV. Carmustine (CMS) released from Pep-1/Bor/CMS-M in pH 7.4 was significantly faster than in acidic environments. In human glioma BT325 cellular studies, Pep-1/Bor/CMS-M remarkably increased the cytotoxicity, notably improved the internalization and effectively induced the cell apoptosis. Likewise, in human brain microvascular endothelial cells (HBMEC) cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance (TEER) and thereby of enhancing the ability of penetration. In orthotopic Luc-BT325 glioma tumor-bearing nude mouse models, the stronger fluorescence signal and longer retention were observed in brain tissues compared with other controls, after single administration of DiD-labelled Pep-1/Bor/M (DiD/Pep-1/Bor/M). Importantly, Pep-1/Bor/CMS-M displayed the strongest inhibition of tumor growth, the longest survival period and low systemic toxicity in treating orthotopic glioma tumor-bearing nude mice. Simultaneous functionalization of Pep-1 and borneol offers a novel strategy for designing CMS-based nanomedicine and precisely treating glioma.

Snow parameters have traditionally been retrieved using discontinuous, multi-band sensors; however, continuous hyperspectral sensor are now being developed as an alternative. In this paper we investigate the performance of various sensor configurations using machine learning neural networks trained on a simulated dataset. Our results show improvements in accuracy of retrievals of snow grain size and impurity concentration for continuous hyperspectral channel configurations. Retrieval accuracy of snow albedo was found to be similar for all channel configurations.

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by the demyelination of neural fibers in the central nervous system. Understanding the impact of demyelination on neural network efficiency is crucial for elucidating the pathophysiological mechanisms underlying MS. This study aims to model the effects of demyelination on neural network efficiency, specifically focusing on how increased resistance and path lengths due to demyelination correlate with the clinical symptoms of MS. We employed a graph-theoretical approach to simulate neural networks, introducing varying degrees of demyelination. The demyelination was represented by increasing the resistance (weights) of selected edges within the network, affecting both random and clustered distributions of network connections. The primary metric analyzed was the average shortest path length, indicative of network efficiency. The models demonstrated a significant increase in the average shortest path length in demyelinated networks compared to intact ones. Specifically, networks with clustered demyelination exhibited localized inefficiencies, correlating with the focal nature of MS lesions. The increase in path length was associated with reduced signal transmission efficiency, providing insights into a range of MS symptoms including motor and sensory impairments, cognitive dysfunction, visual disturbances, and fatigue. The graph-theoretical model of neural network demyelination offers a novel perspective on how structural changes in the brain's connectivity due to MS can lead to diverse clinical manifestations. While the model simplifies the complexity of neural networks, it underscores the potential of computational approaches in understanding and predicting the course of neurological disorders like MS.

Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South American has caused severe human congenital and neurologic disorders. Thus, it is vitally important to figure out inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost ability to inhibit the infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.

Necrotic enteritis (NE) is an intestinal disease that results in poor performance, inefficient nu-trient absorption, and has a devastating economic impact on poultry production. This study evaluated the effects of a saponin-based product (Clarity Q [CQ]) during a NE challenge. A to-tal of 1,200 male chicks were randomly assigned to four dietary treatments (10 pens/treatment; 30 birds/pen): treatment 1 (NC): a non-medicated corn-soybean basal diet; treatment 2 (PC) NC + 50 g/metric ton (MT) of Bacitracin methylene disalicylate (BMD); treatments 3 (CQ15) and 4 (CQ30) NC + 15 and 30 g/MT, respectively. On day (d) of placement, birds were challenged by a coccidia vaccine to induce NE. On d 8, 14, 28, and 42, performance parameters were measured. On d 8, three birds/pen were necropsied for NE lesions. On d 8 and d 14, jejunum samples from one bird/pen were collected for mRNA abundance of tight junction proteins and nutrient trans-porter genes. Data were analyzed in JMP (JMP Pro, 16) and significance (P ≤ 0.05) between treatments identified by Fisher’s least significant difference (LSD) test. Compared to PC and NC, CQ15 had higher average daily gain (ADG), while CQ30 had lower average daily feed in-take (ADFI) and feed conversion ratio (FCR). NE lesions in the duodenum were lower in CQ15 compared to all other treatments. On d 8, mRNA abundance of CLDN1, CLDN5, AMPK, PepT2, GLUT2, and EAAT3 were significantly greater in CQ30 (P < 0.05) compared to both PC and NC. On d 14, mRNA abundance of ZO2 and PepT2 was significantly lower in PC when compared to all treatments, while that of ANXA1, JAM3, and GLUT5 was comparable to CQ15. In summary, adding Clarity Q to broiler diets has the potential to alleviate adverse effects caused by this enteric disease by improving performance, reducing intestinal lesions, and positively modulating the mRNA abundance of various tight junction proteins and key nutrient transporters during peak NE infection.

The manufacturing parameters influence the properties of thermo-mechanically processed met-als such as Mg alloys. This paper presents how the mechanical properties, the microstructure and the degradation rate of extruded Mn-containing Mg-Gd-alloys can be modified. Gd as repre-sented REE-element is particularly interesting due to the influence on the texture development in Mg and therefore studied as a base alloy system. The contents of Gd were investigated be-tween 2 to 9 wt.% with Mn-addition of 0.5 and 1.0 wt.%. The grain sizes and the corresponding textures were modified by the extrusion parameters and the alloy content. It was shown that modification by Mn can decrease the grain size, but increase the degree of recrystallization and decrease the degradation rate in the biological medium compared to the binary Mg-Gd system from previous studies. The results suggest that the binary Mg-Gd system can be produced more efficiently by adding Mn and that the resulting properties are more robust.

The antioxidant potential (capacity and activity) of aqueous fullerene dispersions (AFD) of non-functionalized C₆₀, C₇₀, and Gd@C₈₂ endofullerene (in micromolar concentration range) was estimated based on chemiluminescence measurements of the model of luminol and generation of organic radicals by 2,2’-azobis(2-amidinopropane) dihydrochloride (ABAP). The antioxidant capacity was estimated by the TRAP method, from the concentration of half-suppression, and from the suppression area in the initial period. All three approaches agree and show that the antioxidant capacity of AFDs increased in the row Gd@C₈₂ < C₇₀ < C₆₀. Mathematical modeling of the long-term kinetics data was used for antioxidant activity estimation. The effect of C₆₀ and C₇₀ is found to be quenching of the excited product of luminol with ABAP-generated radical and not an actual antioxidant effect; quenching constants differ insignificantly. Apart from quenching with a similar constant, the AFD of Gd@C₈₂ exhibits actual antioxidant action. The antioxidant activity in Gd@C₈₂ is 300-fold higher than quenching constants.

Transparent conductive electrodes (TCEs) are of enormous significance to the emergence of flexible and wearable electronics and continued growth of modern devices. Versatile and tunable TCEs, featuring with not only high optical transmittance but also intriguing features of electrochemical energy-storage capability, remain a significant challenge. Here we develop capacitive active films comprised of graphene-conjugated V2O5@poly (3,4-ethylene dioxythiophene) ternary composite (V2O5@PEDOT/rGO) on silver nanowire coated substrates as solid-state super/pseudocapacitors. The constructed electrodes exhibit improved electrolyte ions interaction with effective graphene layer, achieving high areal capacitance 0.6-1.2 mF.cm−2 with 0.5M LiCl electrolytes at optical transparency >60% with record durability. As demonstrated, the kinetic blocking of PEDOT layer and anchoring capability of graphene upon amphoteric soluble vanadium ions from layered V2O5 nanoribbons/nanobelts contribute synergistically to the unusual electrochemical stability, also shown using scanning electrochemical microscopy (SECM) providing electroactivity sites and ion transportation rates. As-fabricated symmetric solid-state supercapacitors delivered broad potential window >1.4 V under two different electrolyte environments (aqueous LiCl and LiCl/PVA gel) and demonstrated higher power and energy density (0.27 μWh.cm−2) outperforming previously reported devices at <0.1 μWh.cm−2. The electrochemical properties are also discussed in terms of solvation in polymer gel electrolyte ions.

Most of the mid-high permeability sandstone oilfields in China have entered the ultra-high water cut stage, accompanied with the highly-dispersed residual oil, and the control effect of mi-cro-heterogeneity on the residual oil is increasingly prominent. Understanding the microscopic characteristics of pore structural and its evolution during the long-term waterflooding is critical for enhancing the accuracy and efficiency of oil field exploitation. While the previous insights paid more attention to the geometrical and morphological features of pore structure and ignores the relation of pore structure with the fluid flow capacity. In this study, we propose a microscopic pore structure classification method considering pore size and local permeable capacity, which realizes the physical classification and quantitative evaluation of pore structure characteristics for different permeability rocks. The micro-pore structure is classified into 6 types based on the key evaluation parameters of pore diameter and flow flux area. By taking six mid-high permea-bility sandstone core samples from Daqing oilfield in China, a series of long-term waterflooding experiments are carried out and the interior pore structure was captured using high precision CT scanning technique. The results reveals that high-permeability reservoirs exhibit concentrated pores diameters and finer throats, whereas mid-permeability reservoirs exhibit smaller pores and throats in greater quantity. With the increase of water injection volumes, the permeable ca-pacity and connectivity of the high-connectivity pore space in ultra-high- and high-permeability reservoirs are enhanced, and in mid-permeability reservoirs, the micro-heterogeneity intensifies the increase in low-connectivity small pores. These findings provide new insights for the micro-scopic heterogeneity and a solid theoretical basis for investigating the occurrence of microscopic residual oil and optimising enhanced oil recovery strategies at the late stage of ultra-high water cut.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

Infrastructure development is rapidly increasing, driving up demand for concrete, a key construction material. Cement and aggregate are essential constituents, with global cement production reaching 4.1 billion metric tons in 2011 and CO2 emissions hitting 1.7 billion metric tons by 2024, a significant contributor to carbon emissions. To address this, alternative constituents like Rice Husk Ash (RHA) and Animal Bone Powder (ABP) are proposed. With rice husk comprising 20% of rice weight and a substantial cattle population in Bangladesh, RHA and ABP offer promising alternatives. This study examines the benefits and limitations of incorporating RHA and ABP into cement, focusing on concrete strength and permeability. By replacing varying percentages of cement with RHA and ABP simultaneously, experiments evaluate their impact on concrete properties after 28 days of curing. The research aims to identify the optimal combination for sustainable concrete production, reducing environmental impact by curbing waste generation and pollution. Results show that compressive strength increases and permeability decreases with up to 5% replacement of RHA and ABP, highlighting their potential for enhancing concrete performance while mitigating environmental concerns.

Nanocomposites of TiO₂ Degussa P25 nanoparticles/activated carbon (TiO₂/AC ) were prepared at various mass ratios of (4:1), (3:2), (2:3), and (1:4) by a facile process. The effects of TiO₂/AC mass ratios on the structural, morphological, and photocatalytic properties were systematically studied in comparison with bare TiO₂ and bare AC. TiO₂ nanoparticles exhibited dominant anatase and minor rutile phases, and a crystallite size of approximately 21 nm; while AC had XRD peaks of graphite and carbon, and a crystallite size of 49 nm. The composites exhibited tight decoration of TiO₂ nanoparticles on micron-/submicron AC particles, and uniform TiO₂/AC composites were obtained as evidenced by the uniform distribution of Ti, O, and C in an EDS mapping. Moreover, Raman spectra show the typical vibration modes of anatase TiO₂ (e.g., E_1g⁽¹⁾, B_1g⁽¹⁾, E_g⁽³⁾) and carbon materials with D and G bands. The TiO₂/AC with (4:1), (3:2), and (2:3) possessed higher reaction rate constants (k) in photocatalytic degradation of methylene blue (MB) than that of either TiO₂ or AC. Among the investigated materials, TiO₂/AC = 4:1 achieved the highest photocatalytic activity with a high k of 55.2×10^-3 min^-1 and an MB removal efficiency of 96.6% after 30 min treatment under UV-Vis irradiation (120 mW/cm²). The enhanced photocatalytic activity for TiO₂/AC is due to the synergistic effect of the high adsorption capability of AC and the high photocatalytic activity of TiO₂. Furthermore, TiO₂/AC promotes the separation of photoexcited electron/hole (e^-/h⁺) pairs to reduce their recombination rate and thus enhance photocatalytic activity. The optimal TiO₂/AC composite in this study can be used for treating industrial or household wastewater with organic pollutants.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), some defects prevent its clinical application, such as severe side effects and loss of anticancer activity due to lack of selectivity to cancer cells and hydrolysis of ring E, respectively. To address the issue, herein a multifunctional SN38 derivative (compound 9) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound 9 exhibited superior cytotoxicity as irinotecan against human cervical cancer HeLa cells, albeit inferior to SN38. More significantly, compound 9 significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound 9 had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that compared with irinotecan, compound 9 induced similar apoptosis of cancer cells. Consequently, compound 9 can not only improve its tumor-targeting ability mediated by biotin but also exert the potent anticancer activity through the synergism of SN38 and valproic acid, indicating that the design concept is an effective strategy for structural modification of SN38.

Gas-water relative permeability curve is the foundation of gas reservoir dynamic analysis and numerical simulation. It is generally obtained through gas displacing water experiment. Referring to the existing national standards, gas-water relative permeability test is carried out for low-permeability and tight sandstone. The flow is discontinuous and the curve smoothness is poor, which affects the application of gas-water relative permeability curve. Based on the comparative analysis of a large number of mercury injection and NMR experimental results of low-permeability and tight sandstone, a method to characterize the throat radius distribution of low-permeability tight sandstone based on NMR T2 spectrum is explored. Combined with high-speed centrifugal experiment, the calculation formulas of core water saturation, phase relative permeability of gas-water under different centrifugal force are established. A new method of "nuclear magnetic resonance + high-speed centrifugation" for gas-water relative permeability curve test of low-permeability and tight sandstone is formed, and the test is carried out on Sulige low-permeability tight sandstone core. The results show that: (1) The shape of cumulative distribution curve of throat radius by mercury injection method is basically consistent with that of T2 relaxation time by NMR, and there is a good corresponding relationship between them. (2) The centrifugation process is similar to the gas displacing water process. With the decrease of water saturation, water centrifugation in rock core becomes more and more difficult until it become irreducible. (3) The test process of the new method is unified and standard and up to 6 cores can be tested at the same time. The calculation results of water saturation and relative permeability curve are reliable and the integral curve is smooth, which greatly improves the test efficiency of gas-water relative permeability curve in low-permeability and tight sandstone. The new method can be widely used to study the gas-water two-phase seepage law in low-permeability and tight sandstone gas reservoir.

Recent advances in synthetic membranes allow their use in fields as diverse as food and agriculture, biotechnology, industrial wastewater treatment, and potable water production. Among the newly developed technologies, nanofiltration for liquids and more particularly for desalination of seawater or saline aquifers are actively pursued. However, current solid-state membranes performance is limited, which calls for the development of novel formulations for membranes offering both high permeability (ion and water flux) and ion differentiation (selectivity), usually considered antagonist features. We report the development of hybrid nanoporous membranes made of solid-state polymeric carbonate track-etched (PCTE) thin films in which biological ion channels such as Gramicidin A (GA), alpha-hemolysin (α-HL), and outer-membrane protein F (OmpF) aquaporin are confined and graphene oxide (GO) conjugated cobalt ion selective binding peptide motifs (Copep) are adsorbed, referring as bioinspired and biomimetic approaches, respectively. These solid-state nanoporous membranes are attracting widespread attention since they offer scalability, mechanical robustness, selectivity, controlled pore dimension and shape, for water sustainability. The ion permeability, ion diffusion coefficient and selective ion recognition are evaluated via nanofiltration, cell diffusion kinetics, and UV-Visible absorption spectroscopy to gain insights into the role of key performance parameters including effective ion confinement in track-etched pores, rich surface chemistry, and peptide-induced channel for selective ion transport. These findings provide new avenues for artificial ion channels by synergistic combination of eco-friendly material design such as GO enabled by bio-molecular recognition chemistry.

Ni1-xGdxFe2O4 (x=0.02, 0.04, 0.06 & 0.08) (NGF) nanoparticles were synthesized via hydrothermal method. The X-ray diffraction study confirmed the single-phase cubic spinel structure. The morphology indicated the stones (approximately nanocubes) like structures in the FESEM images. The mass loss, and thermal transition temperatures were evaluated as a function of Gd-content using TG-DTG, and TG-DSC measurements. The M-H loops evidenced the high magnetization values for NGFO as compared to pure nickel ferrite. Cation distribution showed the preferred occupancy of cations in the magnetic spinel system. Frequency dependence of dielectric, conductivity, and impedance parameters was elucidated with increase in Gd-content.

Polymer inclusion membranes (PIMs), which contained cellulose tri-acetate used as a polymer base, a plasticizer in the form of o-NPOE, and meso-tetra methyl tetrakis-[methyl-2-(4-acetlphenoxy)] calix[4]pyrrole (KP) used as a carrier, were prepared and tested for the effective purification of aqueous solutions of methylene blue dye. The scanning electron microscope (SEM), thermogravimetric analysis (TGA), and attenuated total reflection Fourier transform infrared (ATR-FTIR) were used to define the microstructure and surface of PIMs. Experimental results showed that with the increased concentration of methylene blue in an aqueous solution, the removal percentage also increased. Further observation also showed that the flux increased with the rise of the source phase pH values from 3 to 10. The carrier and plasticizer content in the membrane significantly influenced the membrane’s transport properties. The optimal composition of the membrane in per cent by weight was for KP: 74% plasticizer; 18% support; 8% carrier. It was shown that the membrane with optimal composition showed good reusability and enabled the easy and spontaneous separation of methylene blue from aqueous solutions.

The rapid transmission of COVID-19 in school communities has been a major concern. To ensure that mitigation systems were in place and support was available, a digital intervention to encourage and facilitate infection control behaviours was rapidly adapted and optimised for implementation as a whole school intervention. Using the person-based approach, ‘Germ Defence’ was iteratively adapted, guided by relevant literature, co-production with Patient and Public Involvement representatives, and think aloud interviews with forty-five school students, staff, and parents. Suggested infection control behaviours deemed feasible and acceptable by the majority of participants included handwashing/hand-sanitising and wearing a face covering in certain contexts such as crowded public spaces. Promoting a sense of collective responsibility was reported to increase motivation for the adoption of these behaviours. However, acceptability and willingness to implement recommended behaviours seemed to be influenced by participants’ perceptions of risk. Barriers to the implementation of recommended behaviours in school and at home primarily related to childcare needs and physical space. We conclude that it was possible to rapidly adapt Germ Defence to provide an acceptable resource to help mitigate against infection transmission within and from school settings. Adapted content was considered acceptable, persuasive, and accessible.

Desertification and dune progression over vegetation is quantified using remote sensing data, but vegetation, eventually temporarily, buried under sand blowout may escape such assessment, and to estimate the extent of buried vegetation, a GPR campaign was conducted over the coastal sand-dune of Tottori Prefecture (Japan) in combination with a high-resolution topographic UAV-based survey of the topography. The result shows that buried vegetation exists underneath sand-blowout, especially near the dune ridges, and that this vegetation can extend 20 – 30 m further than the estimation made from airborne remote sensing. Furthermore, the presence of palaeo-vegetation in palaeodune layers also provide information on the long-term evolution of sand dunes (with periods of stability vs rapid change), which can be used to reconstruct Quaternary coastal environments.

We have an unprecedented ability to map the Earth’s surface as deep learning technologies are applied to an abundance of high-frequency Earth observation data. Simple, free, and effective methods are needed to enable a variety of stakeholders to use these tools to improve scientific knowledge and decision making. Here we present a trained U-Net model that can map and delineate ground mounted solar arrays using publicly available Sentinel-2 imagery, and that requires minimal data pre-processing and no feature engineering. By using label overloading and image augmentation during training, the model is robust to temporal and spatial variation in imagery. The trained model achieved a precision and recall of 91.5% each and an intersection over union of 84.3% on independent validation data from two distinct geographies. This generalizability in space and time makes the model useful for repeatedly mapping solar arrays. We use this model to delineate all ground mounted solar arrays in North Carolina and the Chesapeake Bay watershed to illustrate how these methods can be used to quickly and easily produce accurate maps of solar infrastructure.

The Safe Drinking Water Act Amendments of 1996 require community water systems in the United States to send consumers Consumer Confidence Reports (CCRs). CCRs contain information on detected contaminants and required educational information about drinking water. The authors of this study developed a survey to evaluate how utilities track consumer feedback, understanding, and the role of the CCR in shaping consumer perceptions about water quality. Responses from this survey indicate it is common for utilities to indirectly track the effectiveness of their CCRs, but few utilities indicated directly evaluating consumer understanding or the effect of CCRs on consumer perceptions.

Polyethylene terephthalate (PET) is one of the most produced plastic materials in the world. The emer-gence of microplastics and nanoplastics (MPs/NPs) as a significant environmental contaminant has become a matter of increasing concern. While the toxicological effects of PET NPs have been widely re-searched, there is a lack of methodologies for studying their accumulation. The present study introduces a novel method to monitor the distribution of PET NPs in germinating wheat (Triticum aestivum L.) seeds. This involves the functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with PET NPs (PET-fSPION) coupled with magnetic resonance microimaging (µMRI) to provide insight into their distribution within the seed. The present study has demonstrated that PET-fSPION accumulates in specific regions of germinating wheat seeds, including the shoot apical meristem, the radicle, the cole-optile, the plumule, and the scutellum. Furthermore, the accumulation of PET-fSPION has been shown to exert a discernible effect on spin-spin relaxation, as observed via MRI and quantitative T2 relaxation time analysis. The accumulation of PET NPs in embryo regions was also confirmed by SEM. Diffu-sion-weighted magnetic resonance imaging (DW-MRI) and non-invasive chemical shift imaging analyses demonstrated that PET NPs resulted in restricted diffusion within the highlighted areas, as well as an impact on lipid content. Our study reveals that using µMRI with fSPION provides a non-invasive method to monitor the biodistribution of PET nanoparticles in wheat seeds. Additionally, it offers valuable in-sights into the microstructural interactions of PET.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

Uganda possesses natural rainforests that serve enormous environmental ecosystems and biodiversity services. Moreover, the country is known for its various tropical rainforest hardwoods, birds, and animal species. Over the years, the trend in the natural forest land has declined at an alarming rate; hence need to investigate the possible drivers. The loss of such biodiversity and ecosystems risks desertification and extreme climatic condition. As the world moves towards Zero Deforestation 2030, understanding the determinants of deforestation and forest degradation is paramount. Therefore, the main objective of this study was to understand the impact and relationships between net forest conversion, energy emission, agriculture, and forest production of Roundwood. We used data from FAO for the period 2004-2016. Using the ADF and KPSS test, we checked for the unit root presence in the variables. Also, the study used two different regression models: multiple linear regression and dynamic linear model. To analyze the determinants of deforestation, we used net forest conversion in Uganda. There was 94 % variation in the dependent variable (Net Forest conversion). The outcome of the dynamic linear regression showed that agriculture and energy emission positively impact net forest conversion. Based on our findings, this study recommended the modernization of agriculture by the government of Uganda to stop cutting down the forests on a big scale. Also, the study suggested that the government strictly legislate Roundwood and wood fuels/charcoal and firewood to reduce huge dependency on forests toward Zero-Deforestation by 2030. If well-structured and implemented, government policies could solve the unnecessary over dependency on the rainforest, the heart of the region's climatic conditions.

Carnivorous waterbirds have been reported to enhance wetlands diversities, control pests, bio-indicators of ecological conditions, and act as indicators of potential disease outbreaks. They also provide important ecosystem services to indigenous communities residing along wetlands. Regardless of their importance, global waterbirds populations are declining. Despite their ecological contribution to wetlands functions and ecosystem services, piscivore waterbirds have been re-ported to compete with piscivorous fish and fishermen. The aim of this study was to compare piscivorous waterbirds species and functional diversity between fish protected areas (FPA) and non-fish protected area (NFPA) in two tributaries of Zambezi River in Namibia. We also measured the degree to which patterns of guild structure between piscivore waterbirds and fish were similar between FPA and non-FPA. Species diversities were determined by calculating the Shannon Diversity Index. We calculated taxonomic diversity, functional diversity and community-based trait diversity indices for each tributary. Generally, species diversities were not significantly different between FPA and NFPA (P > 0.05). However, all functional diversities indices calculated were significantly different between FPA an NFPA (P < 0.05 for all comparisons). This was partly due to food item, weight and movement type that were associated with each site.

(1) Background: After the discovery and application of Chlamydomonas reinhardtii channelrhodopsins, the optogenetic toolbox has been greatly expanded with engineered and newly discovered natural channelrhodopsins. However, channelrhodopsins of higher Ca2+ conductance or more specific ion permeability are still in demand. (2) Methods: In this study, we mutated the conserved aspartate of the transmembrane helix 4 (TM4) within Chronos (Stigeoclonium helveticum channelrhodopsin = ShChR) and PsChR (Platymonas subcordiformis channelrhodopsin) and compared them with published ChR2 (C. reinhardtii channelrhodopsin-2) aspartate mutants. (3) Results: We found that the ChR2 D156H mutant (XXM) showed enhanced Na+ and Ca2+ conductance, which was not noticed before, while the D156C mutation (XXL) influenced the Na+ and Ca2+ conductance only slightly. Furthermore, the D173H mutant of PsChR showed a much improved photocurrent, compared to wildtype, and even higher Na+ selectivity to H+ than XXM. PsChR D173H also showed a strongly enhanced Ca2+ conductance, more than 2-fold that of the calcium translocating L132C of ChR2 (CatCh). (4) Conclusions: We found that mutating the aspartate of the TM4 to histidine influences the ion selectivity of channelrhodopsins. With the large photocurrent and enhanced Na+ selectivity and Ca2+ conductance, XXM and PsChR D139H are promising powerful optogenetic tools, especially for Ca2+ manipulation.

Heterodimeric approach has emerged as a promising method for simultaneously targeting multiple receptors on tumor cells using a single molecule. Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) holds the potential to improve the accuracy of prostate cancer diagnosis. This study aimed to develop and compare six alternative routes for stereoselective synthesis of heterobivalent conjugates designed to deliver the chelating agent DOTA to PSMA/GRPr receptors. The comparison of these alternative synthetic approach, considered such factors as efficiency, complexity, synthesis and purification characteristics, as well as yields of the target compounds has been made. Optimal conditions for the stereoselective synthesis of heterobivalent ligands to PSMA and GRP, which could serve as molecular platforms for the targeted delivery of therapeutic and/or diagnostic agents to these receptors, were determined. For synthesized heterobivalent ligand 26^x and heterobivalent conjugate with DOTA 27 complete signal assignment in ¹H, ¹³C, and ¹⁵N NMR spectra was achieved using 2D NMR techniques. Based on these data, comprehensive signal assignments were provided for all final compounds in their NMR spectra.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

This study aims to investigate the interfacial tension, emulsion stability, and the impact on oil displacement effectiveness of mixed systems containing nonionic surfactants and amphoteric surfactants at different ratios. To achieve this, three different emulsion stability formulations were prepared by mixing betaine and nonionic surfactants in ratios of 1:1, 3:2, and 3:1 respectively. By adjusting the proportions of betaine and nonionic surfactants, variations in interfacial tension and emulsion formation among the three mixed systems were studied to analyze the mechanism of interaction between betaine and nonionic surfactants and evaluate their effects on crude oil displacement and enhanced oil recovery in reservoirs. Subsequently, microscopic and macroscopic oil displacement experiments were conducted on the three mixed systems, along with experiments on emulsion flow resistance. The aim was to verify the oil displacement effectiveness of different mixed systems and further understand their potential applications in reservoirs. By comprehensively analyzing the experimental results, optimal ratios and conditions for the mixed systems were determined. The experimental results indicate that the emulsification system formed by mixing betaine and nonionic surfactants at a ratio of 3:1 achieves molecular synergies through electrostatic interactions and mixed adsorption with betaine, resulting in a compact arrangement of interface membranes and demonstrating a synergistic effect in reducing interfacial tension to an ultra-low value of 10 -4 mN/m. Additionally, as the proportion of betaine surfactant increases, the viscosity of the aqueous phase liquid film increases, the rate of thinning of the liquid film slows down, the rate of water release slows down, and the stability of the emulsion increases. Microscopic oil displacement experiments verified that the three mixed systems increase oil washing efficiency through low interfacial tension and emulsification stripping action, thereby increasing the oil displacement mechanism's coefficient. Emulsion flow resistance experiments demonstrated that as the proportion of betaine surfactant increases, the system exhibits better plugging ability. However, macroscopic oil displacement experiments revealed differences in compatibility between different emulsion stability solutions and rocks with different permeabilities. The mixed system of betaine and nonionic surfactants at a ratio of 3:1 exhibits the best emulsification plugging ability in rocks with a permeability of 109mD, while the 1:1 mixed system performs best in rocks with a permeability of 12mD. This holds significant theoretical and practical significance for reservoir development and enhanced production.

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.

Brain magnetic resonance imaging (MRI) offers a unique lens to study neuroanatomic support of human neurocognition and intelligence. A core mystery is the MRI explanation of individual differences in neurocognition and intelligence. The past four decades have seen great advancement in studying this century-long mystery, but the sample size and population-level studies limit the explanation at the individual level. The recent rise of big data and artificial intelligence offers novel opportunities. Yet, data sources, harmonization, study design, and interpretation need to be carefully considered. This review aims to summarize past work, discuss rising opportunities and challenges, and facilitate further investigations on machine intelligence inferring human intelligence.

Medical brain image analysis is a necessary step in the Computers Assisted /Aided Diagnosis (CAD) systems. Advancements in both hardware and software in the past few years have led to improved segmentation and classification of various diseases. In the present work, we review the published literature on systems and algorithms that allow for classification, identification, and detection of White Matter Hyperintensities (WMHs) of brain MRI images specifically in cases of ischemic stroke and demyelinating diseases. For the selection criteria, we used the bibliometric networks. Out of a total of 140 documents we selected 38 articles that deal with the main objectives of this study. Based on the analysis and discussion of the revised documents, there is constant growth in the research and proposal of new models of deep learning to achieve the highest accuracy and reliability of the segmentation of ischemic and demyelinating lesions. Models with indicators (Dice Score, DSC: 0.99) were found, however with little practical application due to the uses of small datasets and lack of reproducibility. Therefore, the main conclusion is to establish multidisciplinary research groups to overcome the gap between CAD developments and their complete utilization in the clinical environment.

Aquaporins (AQPs; AQP0-AQP12) are water channels expressed in many and diverse cell types, participating in various functions of cells, tissues and systems, including the central nervous system (CNS). AQP dysfunction and autoimmunity to AQPs are implicated in several diseases. The best-known example of autoimmunity against AQPs is the antibodies to AQP4 which are involved in the pathogenesis of Neuromyelitis Optica spectrum disorder (NMOSD), a demyelinating disease of the CNS. The present review focuses on the discovery and the potential role of antibodies against AQP1 in the CNS, and their potential involvement in CNS demyelination and specifically in NMOSD. We describe (a) the several techniques developed for the detection of the AQP1-antibodies, with emphasis on methods that specifically identify antibodies targeting the extracellular domain of AQP1, i.e., those of potential pathogenic role, and (b) the available evidence supporting the pathogenic relevance of AQP1-antibodies.

Cardiotonic glycoside toxins, originally isolated from plants or amphibians, have been proposed as mammalian cardiotonic hormones. This paper is a review and update of the discovery of [i] a new class of steroid hormones, [ii] the path for their biosynthesis and [iii] some preliminary data on their function. The compounds are phosphoester conjugates and share a characteristic structural feature, a lactone ring, with [a] one class of synthetic potassium sparing diuretics and with [b] plant and amphibian cardiotonic steroids. Purification was initially monitored by cross reaction with steroid sulfate assays and later with digoxin-specific assays. Six compounds were purified by HPLC to near homogeneity and characterized by Tandem mass spectroscopy (MS-MS) and 31P-NMR. Three were digoxin-like materials (DLM) with 23 carbon atoms. The two extra carbon atoms form a spiral lactone E-ring. Several additional spiral lactones have been identified by MS-MS. In a pilot study, based on MS analysis, we evaluated phosphocholine steroid levels in individual serum samples in patients with pre-eclampsia (n=20). The control group of normotensive pregnant women (n=20) was used to estimate the mean and standard deviation. Twelve of the women with pre-eclampsia had a z-score over 2 for at least one of the four phosphocholine steroids. In contrast, only 1 sample from the normotensive women had a z-score over 2. The observation that there are two patterns, one with elevated phosphocholine steroid levels and one without the elevation, suggests that there may be two different underlying causes of pre-eclampsia. We now need to extend the study to determine which pattern predicts progression to life-threatening hypertension in pregnant women. This pilot study illustrates that it is possible to evaluate individual endogenous cardiotonic hormones without relying on antibodies developed to plant or amphibian toxins.

The advent of deep learning (DL) has revolutionized medical imaging, offering unprecedented avenues for accurate disease classification and diagnosis. DL models have shown remarkable promise for classifying brain tumor from Magnetic Resonance Imaging (MRI) scans. However, despite their impressive performance, the opaque nature of DL models poses challenges in understanding their decision-making processes, particularly crucial in medical contexts where interpretability is essential. This paper explores the intersection of medical image analysis and DL interpretability, aiming to elucidate the decision-making rationale of DL models in brain tumor classification. Leveraging state-of-the-art DL frameworks with transfer learning, we conduct a comprehensive evaluation encompassing both classification accuracy and interpretability. Using state-of-the-art DL frameworks with transfer learning, we conduct a thorough evaluation covering both classification accuracy and interpretability. We employ adaptive path-based techniques to understand the underlying decision-making mechanisms of these models. Grad-CAM and Grad-CAM++ highlight critical image regions where the tumors are located.

Objective: The purpose of this study was to investigate the effects of Crocin on brain neuroterophins, cognition, sensory and motor dysfunction and compare to fingolimod effects in experimental model of demyelination with Ethidium Bromide EB in female Wistar rats. Methods: Animals were assigned in to 8 groups; Sham, Sham operated (ShOp), EAE, crocin treated (Cr5,10,20 mg/kg), Vehicle, Fingolompd (Fing) and fingolimod + crocin (Cr+Fing). Demyelination was induced by single dose injection of 10 μl of EB 0.1% into the fourth ventricle of the brain. Crocin and fingolimod were applied for 21 days, daily, oral gavage. BDNF, NGF1, nerve conduction velocities, tail flake latency, balance and behavioral variables were sampled and analyzed by paired t-test and ANOVA test with repeated post hoc measurements. Results: The results showed that crocin improves all studied factors, but remarkable imrovments were observed in dosage of 10 mg/kg. Crocin (10mg/kg) and fingolimod (1mg/kg) significantly improved cognition variables in open field test, sensory and motor nerve conduction velocity, tail flick latency and clinical signs (p<005). In addition, applying of crocin co-administered with fingolimod led to significant increases in all assessed factors, greater than crocin or fingolimod intervention alone (α≤0.001). Conclusion: Based on the current findings, crocin can improve the level of brain neurotrophins, exploratory behavior and nerve conduction after demyelination as close as fingolimod results. So, crocins can be considered as a neuro supportive agent in the management of degenerative diseases maybe similar to fingolimod mechanism.

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).

Gadolinium-based contrast agents (GBCA) are complexes, highly stable in vivo, used in Magnetic Resonance Imaging (MRI), administered in patients and then eliminated via renal, passing through wastewater treatment plants (WWTP) before being discarded in the receiving medium, without apparent removal. In this study, it was studied if different exposure periods to several environmental parameters (solar radiation, different salinities, temperatures and pH) will influence the stability of these complexes, namely, the Gd-DOTA. Gd-DOTA solutions were processed in a seaFAST-pico saline matrix pre-concentration and elimination system and Gd concentrations were determined by ICP-MS. Results showed that the complex remained stable in fresh, brackish and saline water environments, even when exposed to extreme temperatures (40ºC) or slightly acidic to basic conditions (6-10), for an exposure period of 96h. A small increase in the free Gd concentration was observed after 18 days when exposed to pH&lt;4, in all tested salinities (0, 18 and 36 PSU), with a degradation increase of up to 29%, after 5 weeks of exposure in freshwater. When exposed to direct solar radiation a low Gd-DOTA degradation (4%) was observed after 24h at salinity 18 PSU and remained constant until the end of the exposure period (96h), while the remaining salinities showed negligible values.

Cobalt ferrite nanoparticles (NPs) doped with rare earth (RE) metals with general formula CoFe_2-xRE_xO₄ (RE=Yb, Dy, Gd; x = 0.0 - 0.3) were synthesized by the co-precipitation method followed by post thermal treatment. The influence of RE doping on structural, magnetic and thermal properties and potential biomedical applications like magnetic hyperthermia has been investigated. In the as-prepared samples RE cations enter the spinel lattice as detected by X-ray diffraction. Thermal treatment leads to thermodynamically stable and relaxed single-phase spinel structures only for lower RE content, x = 0.01-0.05. However, annealed samples present higher mass magnetization values (M_S), up to 83 Am²/kg. RE content also affects M_S, especially in the case of annealed samples where it decreases linearly with x from about 80 Am²/kg (x = 0.01) to about 60 Am²/kg (x = 0.30). Thermal treatment induces a reduction in coercivity from 60-100 mT for as-prepared samples to 18-33 mT for annealed samples, in a nonlinear manner with respect to RE content. Heating efficiency, i.e., Specific Loss Power (SLP), of all samples has been studied using both magnetometric and calorimetric method to deeper examine the energy loss mechanisms involved.

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.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

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

Visible light photography diagnostic images are coloured ex vivo medical images popularly used in Dermatology and Endoscopy for diagnosis and monitoring. The need to protect the integrity of these images as well as associated patient data calls for techniques such as image steganography and watermarking. This research explores and compares the effect of watermarking on the YIQ and YCbCr colour transforms used in processing digital coloured images and video in recent times. Using a new spread spectrum watermarking algorithm, it was found that YIQ has better distortion performance than YCbCr in the order of 3dB while YCbCr had lower BER for accurate watermark retrieval and tamper detection in the order of 1.3 x 10-3.

Landform Evolution Modelling (LEM) provides an avenue for simulating how a landscape may evolve over extended time periods of thousands of years. The CAESAR-Lisflood LEM that includes a hydrologic model (TOPMODEL) and a hydraulic model (Lisflood) can be used to assess the proposed final landform morphology of a mine site by simulating how the mine landform and the landscape would evolve over a 1,000-year period. The accuracy of future simulations depends on the calibration and validation of the model to the past and present events. Calibration and validation of the model involves finding a combination of parameters of the model which when applied and simulated gives model outputs similar to those observed for the real site scenario for corresponding input data. Calibrating the sediment output of the CAESAR-Lisflood model at the catchment level and using it for studying the equilibrium conditions of the landform is an area yet to be explored. Therefore, the aim of this study was to calibrate the CAESAR-Lisflood model and then validate it. To achieve this, the model was run for a rainfall event with a set of parameters, plus discharge and sediment data for the input point of the catchment, to analyze how similar the model output would behave when compared with the discharge and sediment data for the output point of the catchment. The model parameters were then adjusted until the model closely approximate the real site values of the catchment. It was then validated by running the model for a different set of events and checking that the model gave similar results to the real site values. The outcomes demonstrated that while the model can be calibrated to a greater extent for hydrology (discharge output) throughout the year, the sediment output calibration may be slightly improved by having the ability to change parameters to take into account the seasonal vegetation growth during the start and end of the wet season. This study is important for designing and testing post-mining rehabilitated landscape systems that assess hydrology and sediment movement in seasonal biomes.

Many pilot-based initiatives have been developed to promote awareness and use of climate information services among vulnerable smallholder farmers in Africa through million-dollar investments. However, despite their experimental nature, these pilot projects have been successful in raising participating farmers’ awareness and use of climate information services and they can inform transferrable good practices. Through a systematic literature review approach, this review sought to understand ways in which these past pilot projects have contributed to climate risk management in the context of smallholder farming and the factors that led to their success. Results showed that climate information services main contribution to climate risk management has been through facilitating farm level decision making. Factors that led to success of the pilots include: use of downscaled information; building institutional partnerships to add value to climate information; involving farmers through the co-designing and co-developing process; face-to-face way of communication; embedding pre-seasonal workshops in the activities of local institutions for sustainability; using diversity of communication channels to enhance reach among others. These factors can be borrowed as good practices to inform future efforts focused on increasing adoption of climate information services among a wider population beyond pilot project reach.

With growing urbanisation the sustainability of cities has become increasingly important. Although cities have been using indicators for a long time it is only in the last decades that attempts have been made to collate indicators into indicator sets with the aim of reflecting the many different aspects that need to be covered to assess the sustainability of a city. The aim of this paper is to review how indicators for monitoring sustainable urban development have evolved over time and compare them to the indicators suggested by the UN Sustainable Development Goals (SDGs). The review reveals that previous indicator sets emphasised environmental sustainability, health and economic growth. It is also shown that indicator sets that pre-date the SDGs lacked dimensions such as gender equality and reduced inequalities. In all, the SDG indicators provide the possibility of a more balanced and integrated approach to urban sustainability monitoring. At the same time, a methodology is needed to facilitate the adaptation process of localising the SDGS, targets and indicators. Challenges of local application include their large number, their generic characteristics and the need to complement them with specific indicators that are more relevant at the city level.

Objective biomarkers have been a critical challenge for the field of psychiatry, where diagnostic, prognostic and theranostics assessments are still based on subjective narratives. Psychopathology operates with idiographic knowledge and subjective evaluations incorporated into clinical as-sessment inventories, but is considered to be a medical discipline and, as such, uses medical in-tervention methods (e.g., pharmacological, ECT; rTMS; tDCS), and therefore is supposed to oper-ate with the language and methods of nomothetic networks. The idiographic assessments are pro-visionally “quantified” into “structured clinical scales” to in some way resemble nomothetic measures. Instead of fostering data merging and integration, this approach further encapsulates the clinical psychiatric methods, as all other, biological tests (molecular, neuroimaging) are per-formed separately, only after the clinical assessment has provided diagnosis. Translational cross-validation of clinical assessment instruments and fMRI is an attempt to address the gap. The aim of this approach is to investigate whether there exist common and specific neural circuits, which underpin differential item responses to clinical self-rating scales during fMRI session in pa-tients suffering from the two main spectra of mental disorders: schizophrenia and major depres-sion. The current status of this research program and future implications to promote the devel-opment of psychiatry as a medical discipline are discussed.

Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, closo-dodecaborate anion represents a high-boron containing residue with remarkable chemical stability and low toxicity, suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5'-, 3'-, or both terminal positions of DNA, RNA, 2'-O-Me RNA, and 2'-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3'-end of all oligomers stabilized their complementary complexes, while analogous 5'-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2'-O-methyl and 2'-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized DNA/DNA duplex but gave a strong stabilization of the duplex with RNA target. According to CD spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

Background: HIV poses a threat to global health. With effective treatment options available, education and testing strategies are essential in preventing transmission. Text messaging is an effective tool for health promotion and can be used to target higher risk populations. This study reports on the design, delivery and testing of a mobile text messaging SMS intervention for HIV prevention and awareness, aimed at adults in the construction industry and delivered during the COVID-19 pandemic. Method: Participants were recruited at Test@Work workplace health promotion events (21 sites, n=464 employees), including health checks with HIV testing. Message development was based on a participatory design and included a focus group (n=9) and message fidelity testing (n=291) with assessment of intervention uptake, reach, acceptability, and engagement. Barriers to HIV testing were identified and mapped to the COM-B behavioural model. 23 one-way push SMS messages (19 included short web links) were generated and fidelity tested, then sent via automated SMS to two employee cohorts over a 10-week period during the COVID-19 pandemic. Engagement metrics measured were; opt-outs, SMS delivered/read, number of clicks per web link, and four two-way pull messages exploring repeat HIV testing, learning new information, perceived usefulness and behaviour change. Results: 291 people participated (68.3% of eligible attendees). A total of 7,726 messages were sent between March and June 2020, with 91.6% successfully delivered (100% read). 12.4% of participants opted out over 10 weeks. Of delivered messages, links were clicked an average of 14.4%, max 24.1% for HIV related links. The number of clicks on web links declined over time (r= -6.24, p=0.01). Response rate for two-way pull messages was 13.7% of participants. Since the workplace HIV test offer at recruitment, 21.6% reported having taken a further HIV test. Qualitative replies indicated behavioural influence of messaging on exercise, lifestyle behaviours and intention to HIV test. Conclusion: SMS messaging for HIV prevention and awareness is acceptable to adults in the construction industry, has high uptake, low attrition and good engagement with message content, when delivered during a global pandemic. Data collection methods may need refinement for audience and effect of COVID-19 on results is yet to be understood.

The application potential of cellulosic materials in natural composites and other fields needs to be explored to develop innovative, sustainable, lightweight, functional biomass materials that are also environmentally friendly. This study investigated Typha augostifolia (Typha sp.) as a potential new raw material for extracting cellulose nanocrystals (CNCs) for application in wastewater treatment composites. Alkaline treatments and bleaching were used to remove cellulose from the stem fibers. The CNCs were then isolated from the recovered cellulose using acid hydrolysis. The study showed a few distinct functional groups (O-H, -C-H, =C-H and C-O, and C-O-C) in the Fourier Transform Infrared (FTIR) spectra. Scanning electron microscope (SEM) revealed the smooth surface of CPC and CNCs that resulted from removing lignin and hemicellulose from powdered Typha augostifolia. Based on the crystalline index, the powdered Typha augostifolia, CPC, and CNCs were 42.86%, 66.94% and 77.41%. The loss of the amorphous section of the Typha sp. fiber resulted in a decrease in particle size. It may be inferred from the features of a Typha sp. CNC that CNCs may be employed as reinforcement in composites for wastewater treatment.

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5 % of the mass of GOn dispersion (at a concentration of 1 mg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, GOn potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

Evaluation of drug permeability using cell monolayers is an important in vitro assay in the process of drug development, to identify compounds with favourable pharmacokinetics that may proceed to in vivo studies. When allowed to differentiate on permeable filters for at least 21 days, monolayers of Caco-2 cells develop morphological and functional properties similar to those of the intestinal epithelium. Permeability through Caco-2 monolayers is thus particularly relevant to assess drug absorption after oral administration. The major drawback of this assay is its very low throughput, with the cell monolayers being used in a single permeability assay. We have previously proposed a protocol to allow the re-use of the Caco-2 monolayer on additional permeability assays during the stable period and shown that cell monolayer integrity is maintained. In this work we evaluate the effect of re-use on the permeability of several reference compounds that permeate through passive pathways and show that the cell monolayers can be re-used twice in additional permeability assays. Preliminary results were also obtained regarding active transport pathways, and a new methodology is proposed to quantify the contribution from passive and active transport. This is a major step towards the full validation of the re-use methodology proposed, which at least triplicates the throughput of this important in vitro assay.

Appling the controlling relative permittivity and permeability in the equations for the gravitational-magnetic-electric field interaction, a very large variation of the gravitational acceleration of the Earth by electric/magnetic field could be arrived at. This conclusion may be supported by some of the experiments for the gravitational effect of superconductivity.

The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

In this study, the relationship between air diffusivity and permeability in cementitious materials was investigated. First, we derived an equation to correlate air diffusivity and permeability in a straight circular tube. Then, we reviewed existing studies that measured both air diffusivity and permeability and compared reported data and calculated values to verify the applicability of the derived equation to cementitious materials. Although a correction factor was not used, the two sets of data showed good agreement quantitatively. This indicates that the derived equation can be applied to cementitious materials including concrete, and measured air diffusivity can be converted to permeability of concrete and vice versa using the derived equation.

This study is part of a project designed to simulate the long-term landform equilibrium of a rehabilitated mine site. The project utilizes event fine suspended sediment (FSS) fluxes in a receiving stream following a rainfall event as an indicator of landform stability. The aim of this study was to use HEC-HMS to determine sediment and discharge quantity upstream to determine how it affects the downstream development of the catchment landform, in terms of sediment changes and geomorphology. Thus, the study focused on hydrology and sediment modelling of the upper catchment with HEC-HMS (Hydrologic Engineering Center-Hydrologic Modeling System) to determine daily discharge and sediment output at the catchment outlet. HEC-HMS was used to calibrate the stream discharge and FSS quantities at the catchment outlet to observed continuous discharge and FSS values. Calibration of the HEC-HMS model was done for two water years and then the same model parameters were used to validate the model for a third water year. Catchment discharge and FSS were calibrated and validated for continuous rainfall events against observed discharge and FSS data at the catchment outlet. The model was then run for a projected rainfall of 50 years. The denudation rate predicted by the model falls in the range previously determined for the region. The simulated sediment output was compared to the rainfall trends over the years. As a result, the sediment spikes following a rainfall-runoff event gradually decreased over time. Reducing FSS spikes indicate that the landform gradually attains stability. This modeling study can be used for long-term simulations to determine erosion equilibrium over the years and to quantify sediment yield in catchments for projected wet and dry rainfall scenarios.

In this work, Gd-filled skutterudite GdxCo4Sb12 has been prepared in one-step method under high-pressure conditions in a piston-cylinder press at 3.5 GPa and moderate temperature of 800 °C. A detailed structural characterization was performed using synchrotron X-ray diffraction (SXRD), revealing a filling fraction of x = 0.066(4) and an average &lt;Gd–Sb&gt; bond length of 3.3499(3) Å. The lattice thermal expansion accessed via temperature-dependent SXRD led to a precise determination of a Debye temperature of 322(3) K, from the fitting of the unit-cell volume expansion using the second order Grüneisen approximation. Such parameter, when evaluated from the mean square displacements of Co and Sb, displayed a value of 265(2) K, meaning that the application of the harmonic Debye theory underestimates the Debye temperature in skutterudites. Regarding the Gd atom, its intrinsic disorder value is ~5× and ~25× higher than those of Co and Sb, respectively, denoting that Gd has a strong rattling behavior with an Einstein temperature of θE = 67(2) K. As a result, an ultra-low thermal conductivity of ~0.89 W/m·K at 773 K was obtained, leading to a thermoelectric efficiency zT of ~0.5 at 673 K.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination in considered the only sustainable method for global trypanosomosis control. Unfortunately, not a single field applicable vaccine solution has been successful so far. Active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here we show Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and diminazene diaceturate anti-parasite treatment scheme, our result demonstrate that while the latter ensured the full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-pertussis vaccine recall response. DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-pertussis antibody ratio in favor of the latter, and a striking impact on all spleen immune cell populations. Interestingly, an increased plasma IFNy level in DTPa vaccinated trypanosome infected mice did result in a temporary antibody-independent improvement of early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome inflicted immune damage is permanent, and is not restored by successful anti-parasite treatment.

Incorporating ChatGPT into the classroom has several benefits that improve the educational experience for both teachers and students. ChatGPT seems useful in preparing students for success in the digital age, from personalized learning and increased instructional content to fostering collaboration, enabling bilingual classrooms, and encouraging creativity. This review offers insights regarding the perks of using ChatGPT in education as a tool for students. Among the many benefits of implementing ChatGPT in the classroom are enhanced accessibility, enhanced personalized learning, development of critical thinking skills, administrative support for educators, promotion of collaborative learning, and preparedness for a technologically advanced future. These advantages demonstrate how AI technologies have the capacity to drastically change teaching strategies and outcomes. While problems remain, the benefits of integrating ChatGPT in teaching are enormous. By integrating AI technology, educators may develop more dynamic and individualized learning environments that respond to the demands of 21st-century learners.

Mass crises are disruptive to people's mental health. The study aimed to explore mental distress during COVID-19 quarantine in a sample of university workers in Brazil. The survey included sets of questions about demographics, health, and support, an open question about major concerns, and the Clinical Outcome Routine Evaluation (CORE-OM), a measure of mental distress. 407 professionals participated in the study: mean age of 40 years (SD = 11.2), mostly female (67.8%), married (64.8%) and fulfilling social distancing to avoid COVID-19 infection (99%). Using the Consensual Qualitative Research for simple qualitative data (CQR-M) the main areas of concern were grouped into six domains, as follows: Work, Health, Isolation, Personal life and routine, Social environment, and Future. Many responses were multiple. They form categories indicating specific concerns within these domains. Quantitative data were analyzed by identifying the simple effects of potential predictors of mental distress. The results indicated medium effects of help with household chores, psychiatric treatment, age and physical exercise. Having someone available to listen was the only variable with a large effect in reducing mental suffering. The hybrid approach showed that the psychological experience during the pandemic is quite multifaceted and complex pointing new clues for public mental health.

The development effect of water flooding in ultra-low permeability reservoir was poor due to its poor physical property and high shale content, the experimental study of air flooding which help to complement producing energy was carried out. Based on the Accelerating Rate Calorimeter experimental results, the crude oil of N block in L oilfield can produce low-temperature oxidation reaction, which was the basic condition of air flooding. Three groups of experiment natural cylinder core were designed for oil displacement, water flooding and air flooding were used respectively, and the relationship of differential pressure, oil recovery, injection capacity with injection volume was investigated. It has been showed on the result that the recovery efficiency improved sharply than water flooding, the effect of depressurization and augmented injection was obvious, and the air displacement was validation.

The protein TRPM8, a non-selective, calcium (Ca2+) permeable ion channel is implicated in several pathological conditions, including neuropathic pain states. In our previous research endeavors, we have identified β–lactam derivatives with high hydrophobic character that exhibit potent and selective TRPM8 antagonist activity. This work describes the synthesis of novel derivatives featuring C-terminal amides and diversely substituted N’-terminal monobenzyl groups, in an attempt to increase the total polar surface area (TPSA) in this family of compounds. The primary goal was to assess the influence of these substituents on the inhibition of menthol-induced cellular Ca2+ entry, thereby establishing critical structure-activity relationships. While the substitution of the tert-butyl ester by isobutyl amide moieties improved the antagonist activity, none of the N’-monobencyl derivatives, regardless of the substituent on the phenyl ring, achieved the activity of the model dibenzyl compound. The antagonist potency of the most effective compounds was subsequently verified using Patch-Clamp electrophysiology experiments. Furthermore, we evaluated the selectivity of one of these compounds against other members of the TRP ion channel family and some receptors connected to peripheral pain pathways. This compound demonstrated specificity for TRPM8 channels. To better comprehend the potential mode of interaction, we conducted docking experiments to uncover plausible binding sites on the functionally active tetrameric protein, which come upon four main poses by the pore zone, differents from those described for other known antagonists. Finally, in vivo experiments, involving a couple of selected compounds, revealed significant antinociceptive activity within a mice model of cold allodynia induced by oxaliplatin.

Potentially, such an approach would significantly increase the effectiveness of therapy for a number of infectious and other diseases, reduce the dosage of antibiotics, shorten the duration of treatment, and reduce the risk of developing resistance. Moreover, the use of a polymer carrier with covalently bound organic molecules of different structures avoids problems with different (suboptimal) solubility and bio-distribution, which would be almost inevitable when using the same compounds separately. It would be very difficult to find antibiotic/adjuvant pairs that simultaneously achieve optimal concentrations in the same target cells. In our case, terpenoids and alkylbenzenes used as adjuvants are practically insoluble as individual compounds and their unacceptable pharmacological properties would not allow them to be used as efflux pump inhibitors.

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.

Rectal cancer presents significant diagnostic and therapeutic challenges, with neoadjuvant therapy playing a pivotal role in improving resectability and patient outcomes. MRI serves as a critical tool in assessing treatment response. However, differentiating viable tumor tissue from therapy-induced changes on MRI remains a complex task. In this comprehensive review, we explore treatment options for rectal cancer based on resectability status, focusing on the role of MRI in guiding therapeutic decisions. We delve into the nuances of MRI-based evaluation of treatment response following neoadjuvant therapy, with particular attention to emerging techniques like radiomics. Drawing from current literature and insights, we provide essential recommendations for post-neoadjuvant therapy management in rectal cancer, all within the context of MRI-based findings.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

Appropriate governance structures are extremely important for the fishery dependent communities to develop integrated territorial development strategies and adaptive capacity to change, including the climate one. This paper assesses to what extent fisheries co-management schemes (e.g Fisheries LAGs, being regional/local governance instruments in fishing communities) are strengthening sustainability. The latter includes improving energy efficiency, promoting renewable energy sources (RES), coping with climate crisis, minimizing environmental impacts, and promoting sustainable blue economy. For detecting policy aspects of aligning climate neutrality and sustainable blue economy, the research lens focuses on the Greek Fisheries Local Action Groups (FLAGs) given that these are mostly located in coastal/marine and insular territories with significant blue growth potential. To map and assess their capacity and efficiency in pursuing Green Deal objectives, a co-development process with FLAG managers was put in place. The results and findings of this process reveal the scarcity of sustainability and blue economy related strategies. Key conclusion is that transition to a post-carbon blue economy on a local level, requires the understanding of the evolutionary dynamics of fisheries co-management schemes. The latter, being multi-sectoral structures, may boost dialogue and cooperation to harmonize local development strategies and EU policies. Maritime Spatial Planning (MSP) as an evolutionary governance process itself, can be a driver for making FLAGs evolve, and strengthen commonization and blue justice and equity for fishers.

This study aligns with the 2030 United Nations Sustainable Development Goals- 3 which aim to “ensure healthy lives and promote well-being for all at all ages”. It contributes to the nascent literature stream on energy-health dynamics by introducing a holistic theoretical model to empirically examine the mediation effect of carbon emissions on the relationship between nonrenewable energy and infant mortality rates. Using an unbalanced panel data on 42 Asia and the Pacific countries from 2005 to 2015 and deploying the structural equation modeling approach, the empirical results are surmised as follows: (i) in regard to the full sample of countries, nonrenewable energy indirectly increases infant mortality rates through increasing carbon emissions. In other words, carbon emissions play a partial mediation role between nonrenewable energy and infant mortality rates; and (ii) for the different income groups, carbon emissions show varying mediation effects. For example, the mediation effects of carbon emissions in lower-middle and upper-middle income countries are found to be similar to those of the full sample of countries. Therefore, based on these findings, we conclude that nonrenewable energy is an essential determinant of infant mortality rates. Policy recommendations are put forward.

A non-negligible fraction of quasars are red at optical wavelengths, indicating (in the vast majority of cases) that the accretion disc is obscured by a column of dust which extinguishes the shorter-wavelength blue emission. In this paper we summarise recent work by our group, where we find fundamental differences in the radio properties of SDSS optically selected red quasars. We also present new analyses, using a consistent colour-selected quasar parent sample matched to four radio surveys (FIRST, VLA Stripe 82, VLA COSMOS 3 GHz and LoTSS DR1) across a frequency range 150 MHz-3 GHz and four orders of magnitude in radio flux. We show this enhancement is driven by systems with small-scale radio emission (∼kpc) and peaks around the radio-quiet threshold (defined as the ratio of 1.4 GHz luminosity to 6μm luminosity) across the four radio samples. Exploring the potential mechanisms behind this enhancement, we rule out star-formation and propose either small-scale jets or dusty winds interacting with the interstellar medium; this will be tested in detail using new multi-band uGMRT data. Overall our results cannot be explained with a simple viewing angle hypothesis, and so may point towards red quasars representing a key phase in the evolution of galaxies.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.