Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma.

Purpose: This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed Imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, Version 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19-14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05-8.93; p=0.04), and the absence of arterial phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18-18.47; p<0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors. Conclusion: In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

Rosarugosides A and D from Rosa rugosa Flower Buds: Their Potential Anti-Skin-Aging Effects in TNF-α-Induced Human Dermal Fibroblasts.

This present study investigated the anti-skin-aging properties of Rosa rugosa. Initially, phenolic compounds were isolated from a hot water extract of Rosa rugosa's flower buds. Through repeated chromatography (column chromatography, MPLC, and prep HPLC), we identified nine phenolic compounds (1-9), including a previously undescribed depside, rosarugoside D (1). The chemical structure of 1 was elucidated via NMR, HR-MS, UV, and hydrolysis. Next, in order to identify bioactive compounds that are effective against TNF-α-induced NHDF cells, we measured intracellular ROS production in samples treated with each of the isolated compounds (1-9). All isolates reduced the level of ROS at a concentration of 10 µM. Particularly, two depsides-rosarugosides A and D (2 and 1)-significantly inhibited ROS expression in TNF-α-induced NHDFs compared to the other phenolic compounds. Subsequently, the production of MMP-1 and procollagen type Ι α1 by these two depsides was examined. Remarkably, rosarugoside A (2) significantly decreased MMP-1 secretion at all concentrations. In contrast, rosarugoside D (1) regulated the expression of procollagen type Ι α1. These findings collectively suggest that Rosa rugosa extracts and their isolated compounds, rosarugosides A (2) and D (1), hold significant potential for protecting against aging and skin damage. Overall, these findings suggest that Rosa rugosa extracts and their isolated compounds, rosarugosides A (2) and D (1), have the potential to prevent and protect against aging and skin damage, although more specific quantitative analysis is needed.

Unveiling interatomic distances influencing the reaction coordinates in alanine dipeptide isomerization: An explainable deep learning approach.

The present work shows that the free energy landscape associated with alanine dipeptide isomerization can be effectively represented by specific interatomic distances without explicit reference to dihedral angles. Conventionally, two stable states of alanine dipeptide in vacuum, i.e., C7eq (ß-sheet structure) and C7ax (left handed α-helix structure), have been primarily characterized using the main chain dihedral angles, φ (C-N-Cα-C) and ψ (N-Cα-C-N). However, our recent deep learning combined with the "Explainable AI" (XAI) framework has shown that the transition state can be adequately captured by a free energy landscape using φ and θ (O-C-N-Cα) [Kikutsuji et al., J. Chem. Phys. 156, 154108 (2022)]. In the perspective of extending these insights to other collective variables, a more detailed characterization of the transition state is required. In this work, we employ interatomic distances and bond angles as input variables for deep learning rather than the conventional and more elaborate dihedral angles. Our approach utilizes deep learning to investigate whether changes in the main chain dihedral angle can be expressed in terms of interatomic distances and bond angles. Furthermore, by incorporating XAI into our predictive analysis, we quantified the importance of each input variable and succeeded in clarifying the specific interatomic distance that affects the transition state. The results indicate that constructing a free energy landscape based on the identified interatomic distance can clearly distinguish between the two stable states and provide a comprehensive explanation for the energy barrier crossing.

Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury.

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

Adjunctive recombinant human parathyroid hormone agents for the treatment of medication-related osteonecrosis of the jaw: a report of three cases.

Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.

Genetic Structure and Diversity of Hatchery and Wild Populations of Yellow Catfish Tachysurus fulvidraco (Siluriformes: Bagridae) from Korea.

Yellow catfish Tachysurus fulvidraco is an important commercial fish species in South Korea. However, due to their current declines in its distribution area and population size, it is being released from hatchery populations into wild populations. Hatchery populations also produced from wild broodstocks are used for its captive breeding. We reported 15 new microsatellite DNA markers of T. fulvidraco to identify the genetic diversity and structure of its hatchery and wild populations, providing baseline data for useful resource development strategies. The observed heterozygosity of the hatchery populations ranged from 0.816 to 0.873, and that of the wild populations ranged from 0.771 to 0.840. Their inbreeding coefficient ranged from -0.078 to 0.024. All populations experienced a bottleneck (p < 0.05), with effective population sizes ranging from 21 to infinity. Their gene structure was divided into two groups with STRUCTURE results of K = 2. It was confirmed that each hatchery population originated from a different wild population. This study provides genetic information necessary for the future development and conservation of fishery resources for T. fulvidraco.

Fulfilling the Role of a Parent While Undergoing Treatment for Cancer: A Review of the Literature and the Potential Impact of Childcare Support on Cancer Outcomes.

Breast cancer is the most prevalent malignancy among adolescents and young adults (AYAs). Despite the efficacy of chemotherapy, AYA patients contend with psychosocial challenges, including psychological distress and financial toxicity, exacerbated further by those with dependent children. Parenting responsibilities intersect with cancer care, impacting both family dynamics and treatment adherence. Despite recognized needs, however, the impact of parenting concerns or even parenting status and the presence of dependents has not been systematically addressed and there is a paucity of interventional research regarding patients with cancer as concomitant caregivers. A feasibility study conducted by the Brown University Oncology Cooperative Group demonstrated the potential benefits of providing financial assistance for childcare, both improving treatment adherence and reducing distress among participants. Similar interventions have shown promise in addressing financial hardships for AYA patients with cancer who are concomitant caregivers. Ultimately, parenting concerns have a significant impact on medical decision-making, and further interventional research on childcare support is required to examine the ways in which health systems can improve family stability, stress, and quality of life.

Scale Separation of Shear-Induced Criticality in Glasses.

In a sheared steady state, glasses reach a nonequilibrium criticality called yielding criticality. We report that the qualitative nature of this nonequilibrium critical phenomenon depends on the details of the system and that responses and fluctuations are governed by different critical correlation lengths in specific situations. This scale separation of critical lengths arises when the screening of elastic propagation of mechanical signals is not negligible. We also discuss the determinant of the impact of screening effects from the viewpoint of the microscopic dissipation mechanism.

Outcomes of Liver Resection and Transarterial Chemoembolization in Patients with Multinodular BCLC-A Hepatocellular Carcinoma.

Background: This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. Methods: We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Results: Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (p <0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS <0.05). Conclusion: In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Progression-free survival is a weakly predictive surrogate end-point for overall survival in follicular lymphoma: A systematic review and meta-analysis.

Although progression-free survival (PFS) is a commonly used surrogate end-point for clinical trials of follicular lymphoma (FL), no analyses have evaluated the strength of surrogacy for PFS with overall survival (OS). A systematic review was performed and 20 studies (total participants, 10 724) met final inclusion criteria. PFS was weakly associated with OS (correlation coefficient; 0.383, p < 0.001). The coefficient of determination was 0.15 (95% CI: 0.002-0.35) suggesting 15% of OS variance could be explained by changes in PFS. This challenges the role for PFS as a surrogate end-point for clinical trials and drug approvals.

Simulation of a Multistaggered Baffle Scrubber to Enhance the Efficiency of Simultaneous Desulfurization and Denitrification.

In this study, we conduct simulation research on simultaneous desulfurization and denitrification in a multistaggered baffle spray scrubber. By employing two-phase flow simulations within the Euler-Lagrange framework and calculating the gas-liquid mass transfer rate with user-defined functions, we comprehensively analyzed the effects of various operational parameters. Initially, we validated our simulation model by comparing the simulation results with experimental data. Under conditions of a 0.2 mm droplet diameter, a liquid-to-gas ratio (L/G) of 12 L/m3, and a gas flow rate of 5 CMM using a full cone nozzle, the simulation indicated a desulfurization efficiency of 99.90 versus 99.84% obtained experimentally and a denitrification efficiency of 92.01 versus 90.67% obtained experimentally. This comparison confirmed the reliability of the simulation model. Our findings indicate that a droplet size of 2 mm is optimal, enhancing the desulfurization efficiency from 99.90 to 99.98% and the denitrification efficiency from 92.01 to 99.76%. However, when the droplet size exceeds 2 mm, efficiencies marginally decrease. Increasing the liquid-to-gas ratio to 16 L/m3 further improves desulfurization and denitrification efficiencies to 99.98 and 99.80%, respectively. In contrast, higher inlet flue gas flow rates reduce these efficiencies, with a decline observed from 100% to as low as 93.90% for denitrification with 2 mm droplets. Additionally, the use of a swirl cone nozzle, compared to full or hollow cone nozzles, better disperses droplets, enhancing the gas-liquid contact and achieving efficiencies of 99.99% for desulfurization and 99.81% for denitrification with 2 mm droplets. These insights are valuable for optimizing operational conditions in industrial-scale spray scrubbers, significantly contributing to mitigating the environmental impacts of industrial emissions.

Thrombocytopenia after Aortic Valve Replacement Using Sutureless Valves.

Background: Sutureless valves are widely used in aortic valve replacement surgery, with Perceval valves and Intuity valves being particularly prominent. However, concerns have been raised about postoperative thrombocytopenia with Perceval valves (Corcym, UK). We conducted a comparative analysis with the Intuity valve (Edwards Lifesciences, USA), and assessed how thrombocytopenia affected patient and transfusion outcomes. Methods: Among 595 patients who underwent aortic valve replacement from June 2016 to March 2023, sutureless valves were used in 53 (Perceval: n=23; Intuity: n=30). Platelet counts were monitored during hospitalization and outpatient visits. Daily platelet count changes were compared between groups, and the results from patients who underwent procedures using Carpentier Edwards Perimount Magna valves were used as a reference group. Results: Compared to the Intuity group, the Perceval group showed a significantly higher amount of platelet transfusion (5.48±1.64 packs vs. 0.60±0.44 packs, p=0.008). During the postoperative period, severe thrombocytopenia (<50,000/µL) was significantly more prevalent in the Perceval group (56.5%, n=13) than in the Intuity group (6.7%, n=2). After initial postoperative depletion, daily platelet counts increased, with significant differences observed in the extent of improvement between the Perceval and Intuity groups (p<0.001). However, there was no significant difference in early mortality or the incidence of neurological complications between the 2 groups. Conclusion: The severity of postoperative thrombocytopenia differed significantly between the Perceval and Intuity valves. The Perceval group showed a significantly higher prevalence of severe thrombocytopenia and higher platelet transfusion volumes. However, thrombocytopenia gradually recovered during the postoperative period in both groups, and the early outcomes were similar in both groups.

Ultra-thin flexible rectenna integrated with power management unit for wireless power harvester/charging of smartwatch/wristband.

This paper proposes a circularly polarized ultra-thin flexible antenna with a flexible rectifier and power management unit (PMU) for smartwatch/wristband applications. The flexible antenna is compact (0.17λ0 × 0.20λ0 × 0.0004λ0) and has a stepped ground plane. A parasitic element is used at the substrate bottom to reduce the specific absorption rate (SAR) and enhance the gain up to 3.2 dBi, at the resonating frequency of WLAN/Wi-Fi (2.45 GHz). The SAR of the proposed design is also analysed at the resonating frequency, and it satisfies the guidelines of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and IEEE C95.1-2019 human safety standards. An impedance matching circuit is used between the antenna and the RF energy harvester to improve conversion efficiency. Polarization mismatch is avoided with the help of circular polarization, achieved by tuning stubs of size 0.02λ0 × 0.044λ0. The integration of the antenna and rectenna results in a good conversion efficiency of 78.2% at - 5 dBm of input power with a load resistance of 2 KΩ. The availability of RF signals allows the user to charge the smartwatch/wristband by connecting the PMU circuit with the RF energy harvester.

Acute type A aortic dissection features and outcomes in octogenarians: a propensity score analysis.

OBJECTIVES: The clinical characteristics and early outcomes of surgical repair in octogenarians with acute type A aortic dissection were compared with those in nonoctogenarians. METHODS: All patients who underwent emergency surgical repair for acute type A aortic dissection in our institution between 2003 and 2022 were included in this study. The patients were divided into an octogenarian group and a nonoctogenarian group. The patients in the 2 groups were propensity score matched at a ratio of 1:1. Before matching, the baseline characteristics were compared between 2 groups. The major complication and 30-day mortality rates were compared in the matched population. RESULTS: A total of 495 patients were screened, and 471 were included in the analysis, with 48 in the octogenarian group and 423 in the nonoctogenarian group. Before matching, DeBakey type II dissection was significantly more prevalent in the octogenarians (42% vs 14% in the octogenarians and nonoctogenarians, respectively, P < 0.001). Additionally, intramural haematomas (39.6% vs 14.4%, P < 0.001) were more prevalent in the octogenarians. However, severe aortic regurgitation (4.2% vs 15.4%, P = 0.046) and root enlargement (0% vs 13.7%, P = 0.009) were less prevalent in the octogenarians. After matching (36 pairs), the incidence of postoperative delirium was higher in the octogenarians (56% vs 25%, P = 0.027). However, there were no significant differences in 30-day and in-hospital mortality rates, intensive care unit stay or major complications, including stroke, paraplegia, respiratory complications, mediastinitis and haemodialysis. CONCLUSIONS: The octogenarians with acute type A aortic dissection had higher incidences of DeBakey type II dissection and intramural haematomas and lower incidences of severe aortic regurgitation and aortic root enlargement than the nonoctogenarians. Being an octogenarian was not associated with an increased risk of early major complications or mortality after surgery for acute type A aortic dissection.

Influence of Preoperative COVID-19 Vaccination on Outcomes After Coronary Artery Bypass Grafting-A Propensity Score-Matched Analysis.

BACKGROUND: Reports of intravascular thrombosis and cardiac complications have raised concerns about the safety of COVID-19 vaccinations, particularly in patients with high cardiovascular risk. Herein, we aimed to analyze the impact of preoperative COVID-19 vaccination on outcomes after coronary artery bypass grafting (CABG). METHODS AND RESULTS: Among 520 patients who underwent isolated CABG from 2020 to 2022, 481 patients (mean±SD age: 67±11 years, 86 women) whose COVID-19 vaccination status could be confirmed were included. A total of 249 patients who had not received any COVID-19 vaccine before CABG (never vaccinated group) and 214 patients who had completed primary vaccination (fully vaccinated group) were subjected to 1:1 propensity score matching, and 156 pairs of patients were matched. There was no significant difference in early mortality between the 2 groups after matching. After matching, overall survival (P=0.930) and major adverse cardiovascular and cerebrovascular event-free survival (P=0.636) did not differ between the 2 groups. One-year graft patency also did not differ significantly between the 2 groups; all patent grafts in 85/104 patients (82%) and 62/73 patients (85%) in the never vaccinated and fully vaccinated groups, respectively (P=0.685). Subgroup analysis showed equivalent overall and major adverse cardiovascular and cerebrovascular event-free survival among AstraZeneca and Pfizer vaccine recipients and between those with ≤30 days versus >30 days from vaccination to CABG. CONCLUSIONS: Despite the very high cardiovascular risk for patients undergoing CABG, COVID-19 vaccination did not affect major outcomes after CABG. Therefore, there is no reason for patients with coronary artery disease requiring CABG to avoid preoperative COVID-19 vaccination.

The Hepatokine Orosomucoid 2 Mediates Beneficial Metabolic Effects of Bile Acids.

Bile acids (BAs) are pleiotropic regulators of metabolism. Elevated levels of hepatic and circulating BAs improve energy metabolism in peripheral organs, but the precise mechanisms underlying the metabolic benefits and harm still need to be fully understood. In the current study, we identified orosomucoid 2 (ORM2) as a liver-secreted hormone (i.e., hepatokine) induced by BAs and investigated its role in BA-induced metabolic improvements in mouse models of diet-induced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared with C57BL/6J control, partly due to the increased energy expenditure. However, when challenged with a HFD supplemented with cholic acid, Orm2-KO eliminated the antiobesity effect of BAs, indicating that ORM2 governs BA-induced metabolic improvements. Moreover, hepatic ORM2 overexpression partially replicated BA effects by enhancing insulin sensitivity. Mechanistically, ORM2 suppressed interferon-γ/STAT1 activities in inguinal white adipose tissue depots, forming the basis for anti-inflammatory effects of BAs and improving glucose homeostasis. In conclusion, our study provides new insights into the molecular mechanisms of BA-induced liver-adipose cross talk through ORM2 induction.

Improving the hepatitis C virus care cascade with the in-hospital Reflex tEsting ALarm-C (REAL-C) model.

BACKGROUND: The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in-hospital Reflex tEsting ALarm-C (REAL-C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. METHODS: We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti-HCV between March 2020 and June 2023. Three distinct periods were defined: pre-REAL-C (n = 696), incomplete REAL-C (n = 515) and complete REAL-C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. RESULTS: The rate of HCV RNA testing increased significantly from 51.0% (pre-REAL-C) to 95.6% (complete REAL-C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL-C model. The treatment rate among treatment-eligible patients was 92.4% during the study period. The mean interval from anti-HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti-HCV positivity to direct-acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL-C model. CONCLUSION: The REAL-C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection.

Enhancing Loop-Mediated Isothermal Amplification through Nonpowered Nanoelectric Preconcentration.

The global threat posed by the COVID-19 pandemic has catalyzed the development of point-of-care (POC) molecular diagnostics. While loop-mediated isothermal amplification (LAMP) stands out as a promising technique among FDA-approved methods, it is occasionally susceptible to a high risk of false positives due to nonspecific amplification of a primer dimer. In this work, we report an enhancing LAMP technique in terms of assay sensitivity and reliability through streamlined integration with a nonpowered nanoelectric preconcentration (NPP). The NPP, serving as a sample preparation tool, enriched the virus concentration in samples prior to the subsequent LAMP assay. This enrichment enabled not only to achieve more sensitive assay but also to shorten the assay time for all tested clinical samples by ∼10 min compared to the conventional LAMP. The shortened assay time suppresses the occurrence of nonspecific amplification by not providing the necessary incubation time, effectively suppressing misidentification by false positives. Utilizing this technique, we also developed a prototype of the POC NPP-LAMP kit. This kit offers a streamlined diagnostic process for nontrained individuals, from the sample enrichment, transfer of the enriched sample to LAMP assays, which facilitates on-site/on-demand diagnosis of SARS-CoV-2. This development holds the potential to contribute toward preventing not only the current outbreak but also future occurrences of pandemic viruses.

Cryopreservation of sperm from the gudgeon, Microphysogobio rapidus (Cyprinidae): Effects of cryoprotectant, diluents, and dilution ratio.

We investigated methods for cryopreserving sperm from the endangered gudgeon, Microphysogobio rapidus, by examining the effects of cryoprotective agent (CPA) concentration, diluent, and dilution ratio on post-thaw sperm quality. The quality of frozen sperm was evaluated in terms of motility and kinematic parameters, viability, DNA damage, and fertilization rate. We evaluated methanol, glycerol, dimethyl sulfoxide (DMSO), and ethylene glycol as CPAs. Sperm motility, velocity, and viability were significantly higher when methanol was used as the CPA (p < 0.05). The diluents tested were Ringer's solution, Kurokura's Extender, Common Carp Sperm Extender (CCSE), and buffered sperm motility-inhibiting saline solution (BSMIS); post-thaw motility was highest when Ringer's solution was used as the diluent. Next, various quantities of methanol were combined with Ringer's solution to identify the optimal dose of methanol. The dilution ratios tested ranged from 1:1 to 1:7. Cryopreserved sperm was thawed at 20 °C for 15 s. The use of 10% methanol with Ringer's solution at a dilution ratio of 1:5 resulted in the highest post-thaw sperm motility, viability, and velocity including VAP, VCL, and VSL. Post-thaw sperm showed significantly greater DNA damage than the control (fresh sperm) (p < 0.05). The fertilization rate was highest with fresh sperm (p < 0.05), followed by sperm frozen with 10% methanol + Ringer's solution. We recommend that the best way to preserve sperm in the studied species is to use a combination of Ringer's solution and 10% methanol at a 1:5 dilution ratio. Our findings will facilitate the artificial fertilization of M. rapidus.

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice.

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids associated with autoimmune disease in SF mice, many of which were downregulated by DSM 17938. The upregulated lipids in SF mice demonstrated a significant correlation with gut bacteria known to be implicated in the pathogenesis of various autoimmune diseases. Chronic hepatitis in SF livers responded to DSM 17938 treatment with a reduction in hepatic inflammation. Altered gene expression associated with lipid metabolism and the positive correlation between lipids and inflammatory cytokines together suggest that autoimmunity leads to dyslipidemia with impaired fatty acid oxidation in SF mice. Probiotics are presumed to contribute to the reduction of lipids by reducing inflammatory pathways.