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BackgroundNormothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP.MethodsSix human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student’s t-test.ResultsWithin circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion.ConclusionsTime-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.

Here authors report intraoperative sampling of blood entering and leaving the lung allowing direct assessment of nutrient use by lung cancer.

We performed intraoperative arteriovenous sampling in participants undergoing surgical resection for non-small cell lung cancer (NSCLC) to characterize in situ tumor metabolism, directly measuring metabolite consumption and secretion in tumor-bearing lung versus normal lung and the systemic circulation. Healthy lung tissue secreted lower levels of lactate, pyruvate, and tricarboxylic acid (TCA) intermediates and consumed less glucose compared to the systemic circulation. In contrast, tumor-bearing lung demonstrated elevated lactate secretion, along with increased efflux of succinate, fumarate, glycine, and aspartate, despite similar glucose uptake. Lactate secretion correlated with tumor PET avidity but not size, and overall metabolic profiles distinguished cancerous from normal lung tissue. These findings confirm enhanced glycolysis in NSCLC in vivo, while also revealing context-dependent patterns of TCA metabolite accumulation and amino acid secretion. Our results demonstrate the utility of intraoperative sampling to uncover metabolic features of human tumors.

The misuse of antibiotics has led to antibiotic-resistant bacterial strains, making it even harder to combat and eliminate their infections. Staphylococcus aureus causes various adverse infections and diseases, including skin abscesses, bloodstream infections, pneumonia, and joint infections. In this study, we aimed to test the cytotoxic and antibacterial effects of bee venom-loaded chitosan nanoparticles (BV-loaded CS-NPs) in comparison to gamma-irradiated BV and native BV from Apis mellifera. The physiochemical characterizations of our treatments were determined by Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscope (TEM), zeta-potential, release rate, and Encapsulation Efficiency (EE). Our study was conducted on both levels, in-vitro and in-vivo. For the in-vitro study, a bacterial model of Staphylococcus aureus with an ATCC number of 6538 was grown in tryptic soy agar (TSA) medium, and the inhibition zones of our drug candidates were measured with the appropriate statistical analysis performed. For the in-vivo study, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Creatinine, Urea, and interleukin 6 (IL-6) were analyzed. BV-loaded CS-NPs showed relatively better results than the other alternatives, which are native BV and gamma-irradiated BV. The results showed that the antibacterial effect of BV-loaded CS-NPs was greater than the alternatives. Furthermore, its cytotoxic effect was far less than the native and irradiated bee venom. These outcomes ensure that loading BV on CS-NPs makes it a promising drug candidate for an antibiotic alternative with minimal cytotoxicity and enhanced antibacterial activity.

In contrast to traditional designs that place actuators within the body, which makes replacement a demanding task, ZTUNA features a fully modular structure where each subsystem can be easily detached, reattached, and replaced for maintenance or reconfiguration. The fish consists of four independently designed modules: the head, middle, pectoral fins, and tail. These modules were developed with waterproofing and hydrodynamic behavior in mind. ZTUNA employs bio-inspired kinematics in the design of the pectoral fins and tail, enabling 3D maneuvers, and a buoyancy engine situated in its middle section to control depth. It operates in two swimming modes: a biomimetic swimming mode, which utilizes only the tail, and a faster pectoral-tail mode, achieving a maximum forward velocity of 14.6 cm/s and a vertical ascent rate of 6.31 cm/s. The motion analysis of the tail oscillations reveals a close similarity to that of real fish, demonstrating that the modularity of the design can be achieved without compromising its effectiveness.

Diabetic peripheral neuropathy (DPN) is one of the most common and disabling complications of DM. Many studies documented the prevalence of clinical and subclinical hypothyroidism (SCH) in diabetic patients but not in the particular group of patients with DPN. The present study aimed to determine the prevalence of SCH in DPN patients and to evaluate its association with severity of DPN. The present cross-sectional study was conducted on 300 consecutive patients with DPN. The clinical manifestations of DPN were documented according to the validated Arabic version of the Michigan Neuropathy Screening Instrument. Severity of DPN was categorized into mild (6-8 points), moderate (9-11 points) or severe (12+ points) according to the Toronto Clinical Scoring System. All patients were submitted to careful history-taking and full clinical and neurological examination. Patients were diagnosed with SCH if they had TSH level above the upper limit of the normal reference range in association with normal free thyroxine (FT4) level. SCH was prevalent in 53 patients (17.7%, 95% CI: 13.5%-22.5%). Patients with SCH had significantly higher frequency of severe DPN (52.8% versus 28.3%, =0.003). It was also shown that patients with SCH had significantly higher HbA1c (8.4 ± 1.0 versus 7.3 ± 1.2%, <0.001) and HOMA-IR (3.7 ± 0.8 versus 2.7 ± 0.9, <0.001) when compared with patients without SCH. Logistic regression analysis identified patients' age [OR (95% CI): 1.06 (1.03-1.08), <0.001], HbA1c [OR (95% CI): 2.2 (1.7-2.9), <0.001] and SCH [OR (95% CI): 7.7 (3.6-15.5), <0.001] as independent predictors of DPN severity. The present study showed that SCH is highly prevalent in DPN patients and is independently related to its severity.

The goal of the present study was to investigate the biochemical and histological changes in dog’s kidney, liver, heart, and skeletal muscles within 72 h after death. Ten male mongrel dogs aged from 1 to 2 years old were subjected to this study. Dogs were euthanized by the rapid intravenous injection of a lethal dose of sodium thiopental, and then the liver, kidney, heart, and skeletal muscle samples were collected from the whole carcasses at different time intervals 4, 12, 24, 48, and 72 h postmortem. Samples were divided into two parts; one part was used for measuring tissue levels of lactate dehydrogenase (LDH), lactate, creatine phosphokinase (CPK), and aspartate aminotransferase (AST). The other part was subjected to histopathological examinations. On the biochemical level, LDH in the liver, kidney, and cardiac and skeletal muscles showed a significant increase at 4 h followed by significant decrease at 48 and 72 h in all the studied tissues. Lactate level showed variable degrees of increase and decrease in kidney and liver tissues while muscles showed increased lactate concentration during the first 48 h then decreased at 72 h. CPK in cardiac and skeletal muscles showed similar changes; it increased from 4 to 48 h then decreased at 72 h. AST level decreased in liver tissue at 4 until 72 h, while in muscular tissue it showed a delayed reduction in concentration which started at 12 and 24 h in the cardiac and skeletal muscles respectively. Similar changes of AST levels in both skeletal and cardiac muscles were observed; it increased at 4 h and then decreased at 24, 48, and 72 h. Histopathological changes in the kidneys were the earliest changes seen in tissue. The changes in the hepatic tissue were earlier than those of heart and skeletal muscle. We concluded that LDH enzyme showed regular changes in all examined tissues; the biochemical changes in cardiac and skeletal muscles were regular and can be useful in estimation of the time of death. The histopathological changes in the kidney, liver, and cardiac and skeletal muscles were very clear and can be used for estimating the postmortem intervals in dogs.

Super-thermites can offer large amount of energy up to 16736 J/g. Flares based on super-thermites can offer superior thermal signature to countermeasure infrared (IR) guided missile seekers. This study reports on the sustainable fabrication of mono-dispersed Fe 2 O 3 nanoparticles of 3 nm average particle size. Colloidal Fe 2 O 3 nanoparticles were harvested from their synthesis medium and re-dispersed in acetone. Fluorocarbon polymers (teflon and viton) as well as aluminum metal fuel were integrated into Fe 2 O 3 /acetone colloid. The colloid mixture was granulated and mold pressed to develop the desired grain. The impact of Fe 2 O 3 nanoparticles on thermal signature was assessed using (FT-MIR 1–6 µm) spectrometer. Flame propagation was investigated by video imaging of combustion wave. Combustion zones were quantified using image analysis. Quantification of flame temperature and main IR emitting species was performed using ICT thermodynamic code (virgin 2008). Nanocomposite flare with 12 wt% Fe 2 O 3 offered an increase in the intensity of β band by 230% to that of reference formulation. The primary reaction zone was extended by 164%. Super-thermite particles not only offered superior spectral performance but also altered the combustion mechanism.

The role of histamine H3 receptors (H3Rs) in the regulation of gastroprotection and production of prostaglandin E2 (PGE2) as well as somatostatin remains contradictory. Therefore, the effects of the H3R antagonist/inverse agonist M39 on in vivo acidified ethanol-induced gastric ulcers and gastric acid secretion in the C57BL/6 mice were assessed. Results showed that acute systemic administration of H3R agonist ( R )-α-methylhistamine (RAMH, 100 mg/kg, i.g.) significantly reduced the severity of ulcer index, increased gastric acid output, and increased mucosal PGE2 production without any alteration of somatostatin concentration in gastric juice. However, only acute systemic administration of the H2R agonist dimaprit (DIM, 10 mg/kg, p.o.) significantly decreased the level of somatostatin measured in gastric juice. Moreover, acute systemic administration of M39 (0.3 mg/kg, i.g.) abrogated the RAMH-induced increase of acid output as well as PGE2 production, but not the DIM (10 mg/kg, i.g.)-stimulated acid secretion, indicating that RAMH as well as M39 modulate the gastroprotective effects through interactions with histamine H3Rs. The present findings indicate that agonistic interaction with H3Rs is profoundly involved in the maintenance of gastric mucosal integrity by modulating PGE2 as well as gastric acid secretion, with no apparent role in the regulation of the inhibitory influence of somatostatin.

Let \\(f \\in \\mathbb Q[x]\\) be a square-free polynomial of degree at least \\(3\\), \\(m_i\\), \\(i=1,2,3\\), odd positive integers, and \\(a_i\\), \\(i=1,2,3\\), non-zero rational numbers. We show the existence of a rational function \\(D\\in\\mathbb{Q}(v_1,v_2,v_3,v_4)\\) such that the Jacobian of the quadratic twist of \\(y^2=f(x)\\) and the Jacobian of the \\(m_i\\)-twist, respectively \\(2m_i\\)-twist, of \\(y^2=x^{m_i}+a_i^2\\), \\(i=1,2,3\\), by \\(D\\) are all of positive Mordell-Weil ranks. As an application, we present families of hyperelliptic curves with large Mordell-Weil rank.