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Abstract Hepatocellular carcinoma (HCC) is characterized by high incidence and fatality rates worldwide. In our exploration of prognostic factors in HCC, the 26s proteasome subunit, non-ATPase 1 (PSMD1) protein emerged as a significant contributor, demonstrating its potential as a therapeutic target in this aggressive cancer. PSMD1 is a subunit of the 19S regulatory particle in the 26S proteasome complex; the 19S particle controls the deubiquitination of ubiquitinated proteins, which are then degraded by the proteolytic activity of the complex. Proteasome-targeting in cancer therapy has received significant attention because of its practical application as an established anticancer agent. We investigated whether PSMD1 plays a critical role in cancer owing to its prognostic significance. PSMD1 depletion induced cell cycle arrest in G2/M phase, DNA damage and apoptosis of cancer cells, irrespective of the p53 status. PSMD1 depletion-mediated cell death was accompanied by an increase in overall protein ubiquitination. These phenotypes occurred exclusively in cancer cells, with no effects observed in normal cells. These findings indicate that PSMD1 depletion-mediated ubiquitination of cellular proteins induces cell cycle arrest and eventual death in cancer cells, emphasizing PSMD1 as a potential therapeutic target in HCC.

This study proposes a deep learning-based long short-term memory (LSTM) model to predict the state of charge (SOC) of lithium-ion batteries. The purpose of the research is to accurately model the complex nonlinear behavior that occurs during the charging and discharging processes of batteries to predict the SOC. The LSTM model was trained using battery data collected under various temperature and load conditions. To evaluate the performance of the artificial intelligence model, measurement data from the CS2 lithium-ion battery provided by the University of Maryland College of Engineering was utilized. The LSTM model excels in learning long-term dependencies from sequence data, effectively modeling temporal patterns in battery data. The study trained the LSTM model based on battery data collected from various charge and discharge cycles and evaluated the model’s performance by epoch to determine the optimal configuration. The proposed model demonstrated high SOC estimation accuracy for various charging and discharging profiles. As training progressed, the model’s predictive performance improved, with the predicted SOC moving from 14.8400% at epoch 10 to 12.4968% at epoch 60, approaching the actual SOC value of 13.5441%. Simultaneously, the mean absolute error (MAE) and root mean squared error (RMSE) decreased from 0.9185% and 1.3009% at epoch 10 to 0.2333% and 0.5682% at epoch 60, respectively, indicating continuous improvement in predictive performance. In conclusion, this study demonstrates the effectiveness of the LSTM model for predicting the SOC of lithium-ion batteries and its potential to enhance the performance of battery management systems.

Abstract Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof‐of‐principle evidence is presented that a cell‐penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene‐addicted cancer cells through transcription activity‐independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2‐p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome‐wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C‐resistant cancers. This study enhances the understanding of ACP52C‐induced cancer‐specific apoptosis induction and supports the use of ACP52C in anticancer drug development.

Abstract Background Postoperative pneumonia (POP) is a devastating complication that can frequently occur after hip fracture surgery. This study aimed to quantitatively and comprehensively summarize the risk factors for POP following hip fracture surgery. Methods PubMed, Embase, and Cochrane Library were systematically searched for studies assessing risk factors for POP following hip fracture surgery. The pooled odds ratio (OR) and standardized mean difference (SMD) between patients with and without POP were calculated. Evidence was assessed using the Newcastle–Ottawa scale. Results Ten studies including 37,130 patients with hip fractures were selected. POP occurred in 1768 cases with an accumulated incidence of 7.8% (95% confidence interval [CI]: 0.061–0.094). Advanced age (SMD: 0.50, 95% CI: 0.10–0.90), male sex (OR: 1.50, 95% CI: 1.12–2.01), American Society of Anesthesiologists physical status scale ≥3 (OR: 3.17, 95% CI: 1.25–8.05), chronic obstructive pulmonary disease (OR: 2.05, 95% CI: 1.43–2.94), coronary heart disease (OR: 1.82, 95% CI: 1.27–2.60), arrhythmia (OR: 1.49, 95% CI: 1.04–2.15), congestive heart failure (OR: 1.41, 95% CI: 1.14–1.75), chronic kidney disease (OR: 2.09, 95% CI: 1.28–3.41), and cerebrovascular accident (OR: 2.14, 95% CI: 1.60–2.85) were risk factors for POP. Hemoglobin (SMD: -0.14, 95% CI: − 0.25 to − 0.03), albumin (SMD: -0.97, 95% CI: − 1.54–-0.41), blood urea nitrogen (SMD: 0.20, 95% CI: 0.03–0.37), alanine aminotransferase (SMD: 0.27, 95% CI: 0.10–0.44), arterial oxygen pressure (SMD: -0.49, 95% CI: − 0.71–-0.27), time from injury to surgery (SMD: 0.13, 95% CI: 0.08–0.17), and surgery within 48 h (OR: 3.74, 95% CI: 2.40–5.85) were associated with the development of POP. Conclusion Patients with the aforementioned risk factors should be identified preoperatively, and related prophylaxis strategies should be implemented to prevent POP following hip fracture surgery.

Background and Objectives: Patients experience severe pain after surgical correction of ankle fractures. Although their exact mechanism is unknown, dexamethasone and epinephrine increase the analgesic effect of anesthetics in peripheral nerve blocks. This study aimed to compare the postoperative pain control efficacy of peripheral nerve blocks with ropivacaine combined with dexamethasone/epinephrine and peripheral nerve blocks with only ropivacaine and added patient-controlled analgesia in patients with ankle fractures. Materials and Methods: This randomized, controlled prospective study included patients aged 18–70 years surgically treated for ankle fractures between December 2021 and September 2022. The patients were divided into group A (n = 30), wherein pain was controlled using patient-controlled analgesia after lower extremity peripheral nerve block, and group B (n = 30), wherein dexamethasone/epinephrine was combined with the anesthetic solution during peripheral nerve block. In both groups, ropivacaine was used as the anesthetic solution for peripheral nerve block, and this peripheral nerve block was performed just before ankle surgery for the purpose of anesthesia for surgery. Pain (visual analog scale), patient satisfaction, and side effects were assessed and compared between the two groups. Results: The patients’ demographic data were similar between groups. Pain scores were significantly lower in group B than in group A postoperatively. Satisfaction scores were significantly higher in group B (p = 0.003). There were no anesthesia-related complications in either group. Conclusions: Dexamethasone and epinephrine as adjuvant anesthetic solutions can effectively control pain when performing surgery using peripheral nerve blocks for patients with ankle fractures.

Background One in five patients with mechanical alignment (MA) after total knee arthroplasty (TKA) was reportedly dissatisfied. As constitutional varus knees are common, restoring the patients’ natural residual varus (RV) alignment is as an appealing alternative to neutral MA. This meta-analysis aimed to evaluate the effects of RV alignment on the functional outcomes compared with those of MA in TKA for the knees with varus osteoarthritis. Methods The MEDLINE/PubMed, Cochrane Library, and EMBASE databases were comprehensively searched for papers comparing the effects of RV alignment and MA on the functional outcomes from the time of inception of the databases to July 2020. Studies comparing the functional outcomes in the knees subjected to TKA with RV alignment (case group) and MA (control group) were included. The Knee Society knee and functional scores (KSKS and KSFS, respectively), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Oxford knee score (OKS), and forgotten joint score (FJS) were compared. Results Seven studies were finally included; all studies showed a low risk of selection bias and provided detailed demographic data. The pooled mean difference in the KSKS (0.06, 95% confidence interval [CI]: −0.14 to 0.27; p = 0.55) and KSFS (0.08, 95% CI: −0.08 to 0.35; p = 0.56) between RV alignment and MA did not significantly differ. The pooled mean differences in the WOMAC (−0.25, 95% CI: −0.57 to 0.07; p = 0.12), OKS (0.06, 95% CI: −0.15 to 0.27; p = 0.56), and FJS (0.41, 95% CI: −0.18 to 1.00; p = 0.18) between the groups were not significant. Conclusion The beneficial effects of RV alignment on the functional outcomes are limited compared to those of MA in TKA for varus osteoarthritis to date. Currently, TKA with neutral MA should be considered as the gold standard.

Mallet hallux injury typically occurs due to trauma from forced hyperflexion. The injury is commonly an avulsion fracture of the extensor hallucis longus tendon at the distal end of the great toe, but the extensor tendon can also rupture around its insertion into the first distal phalanx. It is rare for both types of injury to occur simultaneously. A mallet toe occurring in the hallux is rarely reported, and there is no established standard treatment method. Here, we present our therapeutic strategy for a case of traumatic avulsion fracture and tendon rupture of the distal phalanx of the hallux.

Abstract Supplementation of appropriate probiotics can improve the health and productivity of ruminants while mitigating environmental methane production. Hence, this study was conducted to determine the effects of Enterococcus faecium SROD on in vitro rumen fermentation, methane concentration, and microbial population structure. Ruminal samples were collected from ruminally cannulated Holstein–Friesian cattle, and 40:60 rice straw to concentrate ratio was used as substrate. Fresh culture of E. faecium SROD at different inclusion rates (0, 0.1%, 0.5%, and 1.0%) were investigated using in vitro rumen fermentation system. Addition of E. faecium SROD had a significant effect on total gas production with the greatest effect observed with 0.1% supplementation; however, there was no significant influence on pH. Supplementation of 0.1% E. faecium SROD resulted in the highest propionate (P = 0.005) but the lowest methane concentration (P = 0.001). In addition, acetate, butyrate, and total VFA concentrations in treatments were comparatively higher than control. Bioinformatics analysis revealed the predominance of the bacterial phyla Bacteroidetes and Firmicutes and the archaeal phylum Euryarchaeota. At the genus level, Prevotella (15–17%) and Methanobrevibacter (96%) dominated the bacterial and archaeal communities of the in vitro rumen fermenta, respectively. Supplementation of 0.1% E. faecium SROD resulted in the highest quantities of total bacteria and Ruminococcus flavefaciens, whereas 1.0% E. faecium SROD resulted in the highest contents of total fungi and Fibrobacter succinogenes. Overall, supplementation of 0.1% E. faecium SROD significantly increased the propionate and total volatile fatty acids concentrations but decreased the methane concentration while changing the microbial community abundance and composition.

Objective Dairy cattle nutrient requirement systems acknowledge amino acid (AAs) requirements in aggregate as metabolizable protein (MP) and assume fixed efficiencies of MP used for milk protein. Regulation of mammary protein synthesis may be associated with AA input and milk protein output. The aim of this study was to evaluate the effect of nanoemulsified methionine and cysteine on the in-vitro expression of milk protein (casein) in bovine mammary epithelial cells (MAC-T cells). Methods Methionine and cysteine were nonionized using Lipoid S 75 by high-speed homogenizer. The nanoemulsified AA particle size and polydispersity index were determined by dynamic light scattering correlation spectroscopy using a high-performance particle sizer instrument. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the cytotoxicity effect of AAs with and without nanoionization at various concentrations (100 to 500 μg/mL) in mammary epithelial cells. MAC-T cells were subjected to 100% of free AA and nanoemulsified AA concentration in Dulbecco’s modified Eagle medium/nutrient mixture F-12 (DMEM/F12) for the analysis of milk protein (casein) expression by the quantitative reverse transcription polymerase chain reaction method. Results The AA-treated cells showed that cell viability tended to decrease (80%) in proportion to the concentration before nanogenesis, but cell viability increased as much as 90% after nanogenesis. The analysis of the expression of genetic markers related to milk protein indicated that; αs2-casein increased 2-fold, κ-casein increased 5-fold, and the amount of unchanged β-casein expression was nearly doubled in the nanoemulsified methionine-treated group when compared with the free-nanoemulsified methionine-supplemented group. On the contrary, the non-emulsified cysteine-administered group showed higher expression of genetic markers related to milk protein αs2-casein, κ-casein, and β-casein, but all the genetic markers related to milk protein decreased significantly after nanoemulsification. Conclusion Detailed knowledge of factors, such nanogenesis of methionine, associated with increasing cysteine and decreasing production of genetic markers related to milk protein (casein) will help guide future recommendations to producers for maximizing milk yield with a high level of milk protein casein.

Background: During total knee arthroplasty (TKA) for osteoarthritis, the sagittal gap imbalance (SGI) with a relatively large extension gap is an important surgical challenge. We determined the predictors of SGI with a relatively large extension gap and evaluated the surgical outcomes of knees with SGI. Methods: 551 consecutive cases of primary TKA for osteoarthritis were retrospectively reviewed. The cohort was divided into two groups according to the SGI and statistically matched according to baseline characteristics via the inverse probability of treatment weighting method. Multiple linear and logistic regression analyses were performed to determine the predictors of sagittal gap difference (SGD) and SGI. Intergroup differences in clinical and radiological outcomes were analyzed. Results: Of all the knees included, 8.5% (n = 45) presented with SGI with a relatively large extension gap and required femoral sagittal balancing to manage SGI. The hyperextension angle (HA), preoperative joint line convergence angle (JLCA), and the change in posterior tibial slope (PTS) significantly correlated to SGD and predicted SGI with a relatively large extension gap. SGI group showed significant changes in femoral posterior condylar offset and joint line height compared to those without SGI (1.48 vs −0.45, 1.37 vs −0.51, respectively). Postoperative ROM and knee society knee scores were lower in SGI group. Conclusion: Knees requiring sagittal balancing to manage SGI with a relatively large extension gap is not uncommon in TKA for osteoarthritic knees. The change in PTS is an independent and modifiable predictor of SGI.

Abstract Background Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer’s disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for treating neurodegenerative diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells and are involved in the neuroinflammatory response. Thus, we recently developed and synthesized a non-self-polymerizing analog of DA (CA140) and examined the effect of CA140 on neuroinflammation. Methods To determine the effects of CA140 on the neuroinflammatory response, BV2 microglial cells were pretreated with lipopolysaccharide (LPS, 1 μg/mL), followed by treatment with CA140 (10 μM) and analysis by reverse transcription-polymerase chain reaction (RT-PCR). To examine whether CA140 alters the neuroinflammatory response in vivo, wild-type mice were injected with both LPS (10 mg/kg, intraperitoneally (i.p.)) and CA140 (30 mg/kg, i.p.), and immunohistochemistry was performed. In addition, familial AD (5xFAD) mice were injected with CA140 or vehicle daily for 2 weeks and examined for microglial and astrocyte activation. Results Pre- or post-treatment with CA140 differentially regulated proinflammatory responses in LPS-stimulated microglia and astrocytes. Interestingly, CA140 regulated D1R levels to alter LPS-induced proinflammatory responses. CA140 significantly downregulated LPS-induced phosphorylation of ERK and STAT3 in BV2 microglia cells. In addition, CA140-injected wild-type mice exhibited significantly decreased LPS-induced microglial and astrocyte activation. Moreover, CA140-injected 5xFAD mice exhibited significantly reduced microglial and astrocyte activation. Conclusions CA140 may be beneficial for preventing and treating neuroinflammatory-related diseases, including AD.

Sphingosine kinase (SK) enzyme, a central player of sphingolipid rheostat, catalyzes the phosphorylation of sphingosine to the bioactive lipid mediator sphingosine 1 phosphate (S1P), which regulates cancer cell proliferation, migration, differentiation, and angiogenesis through its extracellular five G protein-coupled S1P receptors (S1PR1–5). Recently, several research studies on SK inhibitors have taken place in order use them for the development of novel anticancer-targeted therapy. In this study, we designed and synthesized analog derivatives of known SK1 inhibitors, namely RB005 and PF-543, by introducing heteroatoms at their tail structure, as well as investigated their anticancer activities and pharmacokinetic parameters in vitro. Compounds 1–20 of RB005 and PF-543 derivatives containing an aliphatic chain or a tail structure of benzenesulfonyl were synthesized. All compounds of set 1 (1–10) effectively reduced cell viability in both HT29 and HCT116 cells, whereas set 2 derivatives (11–20) showed poor anticancer effect. Compound 10, having the highest cytotoxic effect (48 h, HT29 IC50 = 6.223 µM, HCT116 IC50 = 8.694 µM), induced HT29 and HCT116 cell death in a concentration-dependent manner through the mitochondrial apoptotic pathway, which was demonstrated by increased annexin V-FITC level, and increased apoptotic marker cleaved caspase-3 and cleaved PARP. Compound 10 inhibited SK1 by 20%, and, thus, the S1P level decreased by 42%. Unlike the apoptosis efficacy, the SK1 inhibitory effect and selectivity of the PF-543 derivative were superior to that of the RB005 analog. As a result, compounds with an aliphatic chain tail exhibited stronger apoptotic effects. However, this ability was not proportional to the degree of SK inhibition. Compound 10 increased the protein phosphatase 2A (PP2A) activity (1.73 fold) similar to FTY720 (1.65 fold) and RB005 (1.59 fold), whereas compounds 11 and 13 had no effect on PP2A activation. Since the PP2A activity increased in compounds with an aliphatic chain tail, it can be suggested that PP2A activation has an important effect on anticancer and SK inhibitory activities.

The incorporation of metal oxide nanoparticles (NPs) in fiber filters is an effective approach to enhance the specific surface area and surface roughness of the fiber, hence improving their efficiency for fine dust capture and other gas treatment or biological applications. Nevertheless, uneven distribution of NPs limits their practical applications. In this study, a commercial silane coupling agent (3-methacryloxypropyltrimethoxysilane) was used to improve the dispersion of zinc oxide (ZnO) NPs in thin polyacrylonitrile fibers. Scanning electron microscopy (SEM) revealed that the fibers incorporating the silane-modified NPs exhibited better distribution of NPs than those prepared with pristine ZnO NPs. The silane modification enhanced the specific surface area, surface roughness, and fiber porosity. In particular, the nanofiber filter incorporating 12 wt% ZnO NPs modified with 0.5 g silane per g of ZnO NPs maintained a filtration efficiency of 99.76% with a low pressure drop of 44 Pa, excellent antibacterial activity, and could decompose organic methylene blue dye with an efficiency of 85.11% under visible light.

Abstract Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol–cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real‐time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC tissues (46.8%, based on 2.1‐fold cutoff). UQCRH overexpression was observed in HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan–Meier analysis revealed significantly shorter overall (P = 0.005) and recurrence‐free survival (P = 0.027) in patients with tumors overexpressing UQCRH. The prognostic impact of UQCRH was significant in subgroups of patients divided according to the α‐fetoprotein (AFP) level. The patient subgroup with higher AFP levels (≥20 ng/mL) exhibited significant differences in 5‐year overall (18.5% vs. 67.9%) and recurrence‐free survival rates (11.1% vs. 46.4%) between groups with and without UQCRH overexpression. In contrast, no marked survival differences were observed between subgroups with lower AFP levels (

Summary: The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP. : Nam et al. demonstrate that activation of hippocampal astrocytic μ-opioid receptor causes glutamate release, which increases the release probability by neuronal presynaptic mGluR1 activation and potentiates synaptic plasticity at the SC-CA1 pathway. This enhanced synaptic transmission and synaptic plasticity account for the acquisition of memory associated with CPP. Keywords: astrocyte, hippocampus, μ-opioid receptor, conditioned place preference, long-term potentiation opioid

According to the previous research, proper demand forecasting could help construction-related firms in effective planning for future market changes. However, existing market demand forecasting models are somewhat limited, and most of them bear some critical shortcomings. This research aims to develop a forecasting model for the Korean residential construction industry using system dynamics. In developing the market forecasting model, this research uses variables that significantly impact future construction market change. Many of the existing models do not include as many variables as this model, and none of them have considered complex interlocking effects among these variables. This model is also the first model using a system-based approach by looking at the target industry as a ‘one complex system’ rather than focusing on individual variables’ impact on future market changes. By employing system dynamics, it is possible to consider qualitative and quantitative aspects and produce long-term market forecasting results. The developed market forecasting model consists of two main modules, the first being a prediction module for the grassroots construction market and the second for operation and maintenance (O&M) and the demolition market. Sixteen input variables are grouped into four categories: social, economy, regulation, and past market size among over 25 identified variables. The model utilizes a mathematical function system using the designed feedback loops in producing future market forecasts. Based on the validation tests with past market data, it turns out that the model is reliable, with the determination coefficient (R2) being over 0.7 on all tested occasions. According to the model’s forecasting results, the Korean construction market’s size is expected to be 231 billion won in 2015 and 286 billion won in 2030. However, the O&M market’s growth rate is expected to be higher than 180%, which is much bigger than those of the grass-root and demolition markets. Thus, this research model is realistic according to the construction paradigm change. This research is considered one of the pioneering studies in construction market forecasting by employing dynamic inter-relationships among various input variables. Therefore, the market forecasting results can be interpreted as more practical and can provide more insights to the construction industry stakeholders. The model is envisioned to provide the public sector with useful guidelines in preparing future public market supply strategies such as construction budget allocations. It would also be helpful for the private sector to develop more proactive and accurate demand strategies for timely decision-making.

Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability.

The microbial community within the rumen can be changed and shaped by heat stress. Accumulating data have suggested that different breeds of dairy cows have differential heat stress resistance; however, the underlying mechanism by which nonanimal factors contribute to heat stress are yet to be understood. This study is designed to determine changes in the rumen microbiome of Holstein and Jersey cows to normal and heat stress conditions. Under heat stress conditions, Holstein cows had a significantly higher respiration rate than Jersey cows. Heat stress increased the rectal temperature of Holstein but not Jersey cows. In the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, Jersey cows had a significantly higher proportion of genes associated with energy metabolism in the normal condition than that with other treatments. Linear discriminant analysis effect size (LEfSe) results identified six taxa as distinguishing taxa between normal and heat stress conditions in Holstein cows; in Jersey cows, 29 such taxa were identified. Changes in the rumen bacterial taxa were more sensitive to heat stress in Jersey cows than in Holstein cows, suggesting that the rumen mechanism is different in both breeds in adapting to heat stress. Collectively, distinct changes in rumen bacterial taxa and functional gene abundance in Jersey cows may be associated with better adaptation ability to heat stress.

In this paper, we propose an intelligent battery control system that incorporates an active balancing technique and a fuzzy controller to manage and extend the life of an agricultural drone battery efficiently. The control system includes the following key features: A battery pack balancing algorithm based on a bidirectional DC/DC converter; a cell balancing system to prevent overcharge/discharge and ensure equal control of the cell voltages; and a monitoring system and wireless link to track the real-time status of the battery, temperature, and acceleration while the drone is in operation. Each battery pack consists of six lithium polymer batteries, one fuzzy controller per cell, and supports active balancing using the developed balancing technique. The capacity of each of the battery packs in the system is 11,000 mAh, and two can be combined to provide a total capacity of 22,000 mAh.

PF-543, the most potent sphingosine kinase (SK) inhibitor, does not demonstrate effective anticancer activity in some cancer cells, unlike other known SK1 inhibitors. PF-543 has a non-lipid structure with a unique toluene backbone; however, the importance of this structure remains unclear. Therefore, the purpose of this study was to investigate changes in SK inhibitory and anticancer activities and to explore the role of the tolyl group structure of PF-543 through various modifications. We transformed the methyl group of PF-543 into hydrogen, fluorine, and hydroxy. PF-543 derivatives in which the methyl group was substituted by hydrogen and fluorine (compound 5) demonstrated SK1 inhibitory and anticancer activities similar to PF-543. Moreover, we performed molecular modeling studies of PF-543 and compound 5. To assess the metabolic stability of PF-543 and compound 5, we determined their degree of degradation using the liver microsomes of four different animal species (human, dog, rat, and mouse). However, both PF-543 and compound 5 showed poor microsomal stability. Therefore, for the medical applications of PF-543, the structural modifications of its other parts may be necessary. Our results provide important information for the design of additional PF-543 analogs.

In this study, we prepared stabilized vitamin A and C nanoemulsions, and investigated their efficacy on milk-specific proteins in bovine mammary epithelial cells (MAC-T). Emulsions of vitamin A (vit-A) and C (vit-C) were prepared using Lipoid S 75 and microfluidization. The particle size and polydispersity index (PDI) of nanoemulsified vit-A and vit-C were studied. The cytotoxic effect of nanoemulsion-free and nanoemulsified vit-A and vit-C was determined by an MTT assay. In addition, the efficacy of nanoemulsified vit-A and vit-C on the in vitro expression pattern of milk-specific proteins in MAC-T cells was investigated by quantitative RT-PCR. The results showed that the efficacies of stabilized nanoemulsions of vit-A and vit-C were 100% and 92.7%, respectively. The particle sizes were around 475.7 and 225.4 nm, and the zeta potentials were around −33.5 and −21.3 mV, respectively. The expression changes of αs2-, β- and κ-casein were higher in the presence of a stabilized nanoemulsion of vit-A, compared with nanoemulsion-free vit-A. Furthermore, the expression changes of αs2- and β-casein were lower and that of κ-casein was higher in the presence of a stabilized nanoemulsion of vit-C, compared with nanoemulsion-free vit-C. Thus, our findings demonstrate the efficacy of nanoemulsified vit-A and vit-C in changing the expression of milk-specific proteins in MAC-T cells.

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

GSK5182 (4) is currently one of the lead compounds for the development of estrogen-related receptor gamma (ERRγ) inverse agonists. Here, we report the design, synthesis, pharmacological and in vitro absorption, distribution, metabolism, excretion, toxicity (ADMET) properties of a series of compounds related to 4. Starting from 4, a series of analogs were structurally modified and their ERRγ inverse agonist activity was measured. A key pharmacophore feature of this novel class of ligands is the introduction of a heterocyclic group for A-ring substitution in the core scaffold. Among the tested compounds, several of them are potent ERRγ inverse agonists as determined by binding and functional assays. The most promising compound, 15g, had excellent binding selectivity over related subtypes (IC50 = 0.44, >10, >10, and 10 μM at the ERRγ, ERRα, ERRβ, and ERα subtypes, respectively). Compound 15g also resulted in 95% transcriptional repression at a concentration of 10 μM, while still maintaining an acceptable in vitro ADMET profile. This novel class of ERRγ inverse agonists shows promise in the development of drugs targeting ERRγ-related diseases.