Real-imaginary spectrum decomposition of the transparency spectra in microwave dressed Rydberg systems.

To distinguish the contributions of electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) in their applications in precision laser spectroscopy, we propose a real-imaginary spectrum decomposition method to investigate the transparency spectra in a four-level microwave (MW) dressed Rydberg system. We show that the opening transparency windows in the absorption spectra of probe field is a prominent character by EIT, EIT-ATS crossover, and ATS when the MW field is turned off and the intensity of the control field is adjusted. When the MW field is turned on and gradually increased, the EIT is destroyed and disappears. In addition, the most prominent characters that open a transparency window are the EIT-ATS crossover and the ATS. Then, if we further increase the intensity of the MW field, we find that the transparency windows open mainly due to the ATS. Compared to the previous considerations of this issue, which were limited to three-level systems, our four-level scheme reported here is useful for understanding the features of quantum interference in multilevel atomic systems, and has potential applications to study enhanced sensitivity, measurement spectroscopic, quantum processing, quantum communication, and transmission.

High-precision multi-spectral radiation thermometry method based on the improved grey wolf optimization algorithm inversion.

In this paper, in order to rapidly measure the temperature of a high-temperature target in real time without emissivity data, a high-precision multispectral radiation temperature measurement method based on the improved grey wolf optimization (IGWO) algorithm is proposed. The method can automatically identify the emissivity models of different trends and realize the simultaneous estimation of temperature and emissivity without the emissivity hypothesis model. The IGWO algorithm is applied to the temperature test of a silicon carbide and tungsten material. The temperature test results show that the absolute and relative errors of the silicon carbide (the tungsten) are less than 3 K (4.5 K) and 0.25% (0.18%), respectively. The average time of the algorithm is 0.28 s. The IGWO algorithm can be expected to be applied to some high-precision temperature measurement scenarios.

Fat accumulation in striped hamsters (Cricetulus barabensis) reflects the temperature of prior cold acclimation.

BACKGROUND: Proper adjustments of metabolic thermogenesis play an important role in thermoregulation in endotherm to cope with cold and/or warm ambient temperatures, however its roles in energy balance and fat accumulation remain uncertain. Our study aimed to investigate the effect of previous cold exposure (10 and 0 °C) on the energy budgets and fat accumulation in the striped hamsters (Cricetulus barabensis) in response to warm acclimation. The body mass, energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST), serum thyroid hormone levels (THs: T3 and T4), and the activity of brown adipose tissue (BAT), indicated by cytochrome c oxidase (COX) activity and uncoupling protein 1 (ucp1) expression, were measured following exposure to the cold (10 °C and 0 °C) and transition to the warm temperature (30 °C). RESULTS: The hamsters at 10 °C and 0 °C showed significant increases in energy intake, RMR and NST, and a considerable reduction in body fat than their counterparts kept at 21 °C. After being transferred from cold to warm temperature, the hamsters consumed less food, and decreased RMR and NST, but they significantly increased body fat content. Interestingly, the hamsters that were previously exposed to the colder temperature showed significantly more fat accumulation after transition to the warm. Serum T3 levels, BAT COX activity and ucp1 mRNA expression were significantly increased following cold exposure, and were considerably decreased after transition to the warm. Furthermore, body fat content was negatively correlated with serum T3 levels, BAT COX activity and UCP1 expression. CONCLUSION: The data suggest that the positive energy balance resulting from the decreased RMR and NST in BAT under the transition from the cold to the warm plays important roles in inducing fat accumulation. The extent of fat accumulation in the warm appears to reflect the temperature of the previous cold acclimation.

Hypoxia preconditioning increases Notch1 activity by regulating DNA methylation in vitro and in vivo.

BACKGROUND: Our previous research has demonstrated that hypoxic preconditioning (HPC) can improve spatial learning and memory abilities in adult mice. Adult hippocampal neurogenesis has been associated with learning and memory. The Neurogenic locus notch homolog protein (Notch) was involved in adult hippocampal neurogenesis, as well as in learning and memory. It is currently unclear whether the Notch pathway regulates hippocampal neuroregeneration by modifying the DNA methylation status of the Notch gene following HPC. METHOD: The HPC animal model and cell model were established through repeated hypoxia exposure using mice and the mouse hippocampal neuronal cell line HT22. Step-down test was conducted on HPC mice. Real-time PCR and Western blot analysis were used to assess the mRNA and protein expression levels of Notch1 and hairy and enhancer of split1 (HES1). The presence of BrdU-positive cells and Notch1 expression in the hippocampal dental gyrus (DG) were examined with confocal microscopy. The methylation status of the Notch1 was analyzed using methylation-specific PCR (MS-PCR). HT22 cells were employed to elucidate the impact of HPC on Notch1 in vitro. RESULTS: HPC significantly improved the step-down test performance of mice with elevated levels of mRNA and protein expression of Notch1 and HES1 (P < 0.05). The intensities of the Notch1 signal in the control group, the H group and the HPC group were 2.62 ± 0.57 × 107, 2.87 ± 0.84 × 107, and 3.32 ± 0.14 × 107, respectively, and the number of BrdU (+) cells in the hippocampal DG were 1.83 ± 0.54, 3.71 ± 0.64, and 7.29 ± 0.68 respectively. Compared with that in C and H group, the intensity of the Notch1 signal and the number of BrdU (+) cells increased significantly in HPC group (P < 0.05). The methylation levels of the Notch1 promoter 0.82 ± 0.03, 0.65 ± 0.03, and 0.60 ± 0.02 in the C, H, and HPC groups, respectively. The methylation levels of Notch1 decreased significantly (P < 0.05). The effect of HPC on HT22 cells exhibited similarities to that observed in the hippocampus. CONCLUSION: HPC may confer neuroprotection by activating the Notch1 signaling pathway and regulating its methylation level, resulting in the regeneration of hippocampal neurons.

Multiplying Oxygen Permeability of a Ruddlesden-Popper Oxide by Orientation Control via Magnets.

Ruddlesden-Popper-type oxides exhibit remarkable chemical stability in comparison to perovskite oxides. However, they display lower oxygen permeability. We present an approach to overcome this trade-off by leveraging the anisotropic properties of Nd2 NiO4+δ . Its (a,b)-plane, having oxygen diffusion coefficient and surface exchange coefficient several orders of magnitude higher than its c-axis, can be aligned perpendicular to the gradient of oxygen partial pressure by a magnetic field (0.81 T). A stable and high oxygen flux of 1.40 mL min-1 cm-2 was achieved for at least 120 h at 1223 K by a textured asymmetric disk membrane with 1.0 mm thickness under the pure CO2 sweeping. Its excellent operational stability was also verified even at 1023 K in pure CO2 . These findings highlight the significant enhancement in oxygen permeation membrane performance achievable by adjusting the grain orientation. Consequently, Nd2 NiO4+δ emerges as a promising candidate for industrial applications in air separation, syngas production, and CO2 capture under harsh conditions.

Limits to sustained energy intake. XXXIII. Thyroid hormones play important roles in milk production but do not define the heat dissipation limit in Swiss mice.

The limits to sustained energy intake set physiological upper boundaries that affect many aspects of human and animal performance. The mechanisms underlying these limits, however, remain unclear. We exposed Swiss mice to either supplementary thyroid hormones (THs) or the inhibitor methimazole during lactation at 21 or 32.5°C, and measured food intake, resting metabolic rate (RMR), milk energy output (MEO), serum THs and mammary gland gene expression of females, and litter size and mass of their offspring. Lactating females developed hyperthyroidism following exposure to supplementary THs at 21°C, but they did not significantly change body temperature, asymptotic food intake, RMR or MEO, and litter and mass were unaffected. Hypothyroidism, induced by either methimazole or 32.5°C exposure, significantly decreased asymptotic food intake, RMR and MEO, resulting in significantly decreased litter size and litter mass. Furthermore, gene expression of key genes in the mammary gland was significantly decreased by either methimazole or heat exposure, including gene expression of THs and prolactin receptors, and Stat5a and Stat5b. This suggests that endogenous THs are necessary to maintain sustained energy intake and MEO. Suppression of the thyroid axis seems to be an essential aspect of the mechanism by which mice at 32.5°C reduce their lactation performance to avoid overheating. However, THs do not define the upper limit to sustained energy intake and MEO at peak lactation at 21°C. Another, as yet unknown, factor prevents supplementary thyroxine exerting any stimulatory metabolic impacts on lactating mice at 21°C.

Late lactation in small mammals is a critically sensitive window of vulnerability to elevated ambient temperature.

Predicted increases in global average temperature are physiologically trivial for most endotherms. However, heat waves will also increase in both frequency and severity, and these will be physiologically more important. Lactating small mammals are hypothesized to be limited by heat dissipation capacity, suggesting high temperatures may adversely impact lactation performance. We measured reproductive performance of mice and striped hamsters (Cricetulus barabensis), including milk energy output (MEO), at temperatures between 21 and 36 °C. In both species, there was a decline in MEO between 21 and 33 °C. In mice, milk production at 33 °C was only 18% of that at 21 °C. This led to reductions in pup growth by 20% but limited pup mortality (0.8%), because of a threefold increase in growth efficiency. In contrast, in hamsters, MEO at 33 °C was reduced to 78.1% of that at 21 °C, yet this led to significant pup mortality (possibly infanticide) and reduced pup growth by 12.7%. Hamster females were more able to sustain milk production as ambient temperature increased, but they and their pups were less capable of adjusting to the lower supply. In both species, exposure to 36 °C resulted in rapid catastrophic lactation failure and maternal mortality. Upper lethal temperature was lowered by 3 to 6 °C in late lactation, making it a critically sensitive window to high ambient temperatures. Our data suggest future heat wave events will impact breeding success of small rodents, but this is based on animals with a long history in captivity. More work should be performed on wild rodents to confirm these impacts.

A Pre-Grasping Motion Planning Method Based on Improved Artificial Potential Field for Continuum Robots.

Secure and reliable active debris removal methods are crucial for maintaining the stability of the space environment. Continuum robots, with their hyper-redundant degrees of freedom, offer the ability to capture targets of varying sizes and shapes through whole-arm grasping, making them well-suited for active debris removal missions. This paper proposes a pre-grasping motion planning method for continuum robots based on an improved artificial potential field to restrict the movement area of the grasping target and prevent its escape during the pre-grasping phase. The analysis of the grasping workspace ensures that the target is within the workspace when starting the pre-grasping motion planning by dividing the continuum robot into delivery and grasping segments. An improved artificial potential field is proposed to guide the continuum robot in surrounding the target and creating a grasping area. Specifically, the improved artificial potential field consists of a spatial rotating potential field, an attractive potential field incorporating position and posture potential fields, and a repulsive potential field. The simulation results demonstrate the effectiveness of the proposed method. A comparison of motion planning results between methods that disregard and consider the posture potential field shows that the inclusion of the posture potential field improves the performance of pre-grasping motion planning for spatial targets, achieving a success rate of up to 97.8%.

Dyeing Properties, Color Gamut, and Color Evaluation of Cotton Fabrics Dyed with Phellodendron amurense Rupr. (Amur Cork Tree Bark).

The application of plant dyes in the textile industry has been very limited due to their limited sources, incomplete color space, and narrow color gamut, etc. Therefore, studies of the color properties and color gamut of natural dyes and the corresponding dyeing processes are essential for completing the color space of natural dyes and their application. In this study, water extract from the bark of Phellodendron amurense (P. amurense) was used as a dye. Dyeing properties, color gamut, and color evaluation of dyed cotton fabrics were studied, and optimal dyeing conditions were obtained. The results showed that the optimal dyeing process was pre-mordanting with liquor ratio at 1:50, P. amurense dye concentration at 5.2 g/L, mordant concentration (aluminum potassium sulfate) at 5 g/L, dyeing temperature at 70 °C, dyeing time of 30 min, mordanting time of 15 min, and pH 5. Through the optimization of the dyeing process, a maximum color gamut range was obtained with lightness L* value from 74.33 to 91.23, a* value from -0.89 to 2.96, b* value from 4.62 to 34.08, chroma C* value from 5.49 to 34.09, and hue angle h° value from 57.35° to 91.57°. Colors from light yellow to dark yellow were obtained, among which 12 colors were identified according to the Pantone Matching Systems. The color fastness against soap-washing, rubbing, and sunlight on the dyed cotton fabrics all reached grade 3 level or above, further expanding the applicability of natural dyes.

Evaluation of Cryogen-Free Thermal Modulation-Based Enantioselective Comprehensive Two-Dimensional Gas Chromatography for Stereo-Differentiation of Monoterpenes in Citrus spp. Leaf Oils.

This study evaluates the applicability of enantioselective gas chromatography (eGC) and enantioselective comprehensive two-dimensional gas chromatography (eGC×GC) coupled with flame ionization detection for the stereospecific analysis of designated chiral monoterpenes within essential oils distilled from the leaves of Citrus hystrix (CH), C. limon (CL), C. pyriformis (CP), and C. microcarpa (CM). A cryogen-free solid-state modulator with a combination of enantioselective first-dimension and polar second-dimension column arrangements was used to resolve potential interferences in Citrus spp. leaf oils that can complicate the accurate determination of enantiomeric compositions. Interestingly, considerable variations were observed for the enantiomeric fractions (EFs) of the chiral terpenes. (+)-limonene was identified as the predominant enantiomer (60.3-98.9%) in all Citrus oils, (+)-linalool was the major enantiomer in CM (95.9%), (-)-terpenin-4-ol was the major isomer in CM (66.4%) and CP (61.1%), (-)-α-pinene was the dominant antipode in CL (55.5%) and CM (92.1%). CH contained (-)-citronellal (100%) as the pure enantiomer, while CL and CP have lower proportions (9.0-34.6%), and citronellal is absent in CM. The obtained enantiomeric compositions were compared and discussed with results from eGC using the same enantioselective column. To our knowledge, this work encapsulates the first report that details the EFs of these chiral monoterpenes in Citrus spp. leaf oil.

IKAROS and CK2 regulate expression of BCL-XL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia.

High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the IKAROS (encoded by the IKZF1 gene) tumor suppressor. Here, we report that IKAROS regulates expression of the BCL2L1 gene (encodes the BCL-XL protein) in human B-ALL. Gain-of-function and loss-of-function experiments demonstrate that IKAROS binds to the BCL2L1 promoter, recruits histone deacetylase HDAC1, and represses BCL2L1 expression via chromatin remodeling. In leukemia, IKAROS' function is impaired by oncogenic casein kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces IKAROS binding and recruitment of HDAC1 to the BCL2L1 promoter. This results in a loss of IKAROS-mediated repression of BCL2L1 and increased expression of BCL-XL. Increased expression of BCL-XL and/or CK2, as well as reduced IKAROS expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, increases binding of IKAROS to the BCL2L1 promoter and enhances IKAROS-mediated repression of BCL2L1 in B-ALL. Treatment with CX-4945 increases sensitivity to doxorubicin in B-ALL, and reverses resistance to doxorubicin in multidrug-resistant B-ALL. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia. These data lay the groundwork for clinical testing of a rationally designed, targeted therapy that combines the CK2 inhibitor, CX-4945, with doxorubicin for the treatment of hematopoietic malignancies.

Electrical stimulation enhancing anaerobic digestion under ammonia inhibition: A comprehensive investigation including proteomic analysis.

Microbial electrolysis cell (MEC) coupled anaerobic digestion (AD), named as MEC-AD system, can effectively promote methane production under ammonia inhibition, but the inherent mechanism is still poorly understood. This study comprehensively explored the MEC-AD performance and mechanism under high-concentration ammonia stress including using proteomic analysis. It was found that the methane generation rates in MEC-AD systems were 2.0-2.7 times that of AD ones under 5.0 g/L ammonia stress. Additionally, the experimental conditions for methane generation in MEC-AD systems were optimized using response surface methodology. Further analysis indicates that the activities of acetate kinase and F420 were improved, and particularly the direct interspecies electron transfer (DIET) was promoted in MEC-AD systems, as indicated by increased electroactive extracellular polymeric substance, decreased charge transfer resistance, and enrichment of electroactive microbes such as Geobacter on the bioelectrodes. Moreover, proteomic analysis reveals that the DIET associated proteins such as Cytochrome C was up-regulated, and ammonia transfer-related proteins were down-regulated and ammonium detoxification-related proteins were up-regulated in MEC-AD systems. This work provides us a better understanding on the MEC-AD performance especially for the treatment of wastewater containing high-concentration ammonia.

Geospatial epidemiology of Toxoplasma gondii infection in livestock, pets, and humans in China, 1984-2020.

Undercooked or raw meat containing cyst-stage bradyzoites and oocyst-contaminated pets are presumed to constitute a major source of human toxoplasmosis. As the geospatial epidemiology of Toxoplasma gondii (T. gondii) infection in livestock, pets, and humans is rarely studied in China, we undertook a geospatial analysis using GIS visualization techniques. The present study retrieved information from the PubMed, China National Knowledge Infrastructure, and Baidu Scholar databases from 1984 up to 2020. All the data about the seroprevalence of T. gondii in livestock (sheep and goats, pigs, cattle and yaks), pets (cats, dogs), and humans in China were collected. Geospatial epidemiology of T. gondii infection in these hosts was performed using GIS. Results revealed that the estimated pooled seroprevalence of T. gondii was ranged from 3.98 to 43.02% in sheep and goats in China, 0.75 to 30.34% in cattle and yaks, 10.45 to 66.47% in pigs, 2.50 to 60.00% in cats, 0.56 to 27.65% in dogs, and 0.72 to 23.41% in humans. The higher seroprevalences of T. gondii were observed in sheep and goats in the districts of Chongqing, Zhejiang, and Beijing. The infection rates of T. gondii in cattle and yaks were higher in Guizhou, Zhejiang, and Chongqing. Also, the pigs from Chongqing and Guizhou were most severely infected with T. gondii. For cats, the districts of Shanxi, Hebei, and Yunnan had higher seroprevalences of T. gondii and, the infections among dogs were higher in Yunnan and Hebei as well. Furthermore, higher infection pressure of T. gondii exists in the districts of Taiwan and Tibet in humans. The geographical and spatial distribution of toxoplasmosis indicated that infection with T. gondii was widely spread in China, with a wide range of variations among the different hosts and regions in the country. Our results suggested that livestock and pets are not only a reservoir for the parasite but also a direct source of T. gondii infection for humans. It is important to control T. gondii infections in these animals that would reduce the risk of toxoplasmosis in humans.

The thermal neutral zone is shifted during lactation in striped hamsters.

The thermoneutral zone (TNZ), one of the most well-recognized concepts of thermal physiology of homeothermic organisms, is observed to differ between animal species, and may be associated with energy expenditure. However, the characteristics of the TNZ of lactating females, the stage of life history with typically the highest energy demands, remain unclear. In this study, we examined body mass, metabolic rate, TNZ and body composition, and milk energy output, in striped hamsters (Cricetulus barabensis, mean body mass: 29.1 ± 4.4g ranging from 20.0 to 36.6g) at peak lactation, and in hamsters raising small, medium, and large litter sizes throughout lactation. There was a significant downward shift in the lower critical temperature (LCT) of the TNZ in lactating hamsters (TNZ = 22.5-35 °C), resulting in a wider TNZ compared to non-reproductive females (TNZ = 27.5-32.5 °C). At peak lactation, hamsters raising large litter sizes had a considerably lower LCT and a wider TNZ compared to hamsters raising medium and small sized litters, whose upper critical temperature of the TNZ remain fixed. Compared to virgin hamsters, hamsters at peak lactation consumed 2.5 times more food, and had significantly higher energy expenditure corresponding to a significantly higher resting metabolic rate and milk output to meet the requirements of their offspring, which increased with litter size. The organs with the highest oxygen consumption rates, such as the liver, kidneys, and digestive tracts, were considerably heavier in lactating hamsters, particular in those raising large litter sizes, compared to virgin hamsters. The data show that the increased energy expenditure during lactation induces a substantial downward shift of the LCT, consequently resulting in a wider TNZ. The morphological plasticity of organs with high energy requirements is likely involved in this TNZ shift.

A Study of Type II ɛ-PL Degrading Enzyme (pldII) in Streptomyces albulus through the CRISPRi System.

ε-Poly-L-lysine (ε-PL) is a widely used antibacterial peptide polymerized of 25-35 L-lysine residues. The antibacterial effect of ε-PL is closely related to the polymerization degree. However, the mechanism of ε-PL degradation in S. albulus remains unclear. This study utilized the integrative plasmid pSET152-based CRISPRi system to transcriptionally repress the ε-PL degrading enzyme (pldII). The expression of pldII is regulated by changing the recognition site of dCas9. Through the ε-PL bacteriostatic experiments of repression strains, it was found that the repression of pldII improves the antibacterial effect of the ε-PL product. The consecutive MALDI-TOF-MS results confirmed that the molecular weight distribution of the ε-PL was changed after repression. The repression strain S1 showed a particular peak with a polymerization degree of 44, and other repression strains also generated ε-PL with a polymerization degree of over 40. Furthermore, the homology modeling and substrate docking of pldII, a typical endo-type metallopeptidase, were performed to resolve the degradation mechanism of ε-PL in S. albulus. The hydrolysis of ε-PL within pldII, initiated from the N-terminus by two amino acid-binding residues, Thr194 and Glu281, led to varying levels of polymerization of ε-PL.

Clinical Characteristics, Antimicrobial Resistance, and Outcomes of Patients with Invasive Pneumococcal Disease in Ningxia Hui Autonomous Region, China, 2013-2021.

Objectives: This study aimed to analyze the clinical features, antibiotic susceptibility profiles, and outcomes of patients with invasive pneumococcal disease (IPD) at a hospital in Ningxia Hui Autonomous Region, to provide the basis for improving the clinical treatment effect. Methods: Patients with IPD were retrospectively collected from 2013 to 2021. Clinical manifestations, laboratory tests, antimicrobial susceptibility, antibiotic treatment, and outcomes of the disease were analyzed. Results: In this study, we identified 127 IPD cases, of whom 49 (38.6%) had meningitis and 78 (61.4%) had bacteremia. The median ages of pediatric cases and adult cases were 2 years (IQR: 0-5) and 52.5 years (IQR: 35-62), respectively. There were 27 and 45 males in the pediatric and adult groups, and no significant gender difference in the different age groups (p = 0.584) was found. Of 75 cases with underlying diseases, pneumonia (11%), malignancy (11%), hypertension (9.4%), and hepatic cirrhosis (7.9%) were the most common. The incidence of underlying diseases was even higher in the adult group (67.1%) than in the pediatric group (47.1%) (p = 0.028). The frequency of fever, cough, and seizures was significantly higher in the pediatric group than in the adult group, with p-values of 0.004, 0.004, and 0.001, respectively. The percentage of neutrophils in the blood was significantly higher in the adult cases than in the pediatric cases (p < 0.001). Furthermore, there was a significantly higher WBC count (p < 0.001), percentage of neutrophils (p = 0.012), and protein level (p = 0.019) in the CSF samples in the adult patients compared to pediatric patients. The susceptibility rates of S. pneumoniae isolates to vancomycin, linezolid, and levofloxacin were 100%. The susceptibility rates of penicillin were 98.7% and 34.1% in bacteremia and meningitis patients, respectively. Most isolates were resistant to erythromycin, clindamycin, tetracycline, and azithromycin. The most common antibiotic treatment was ß-lactams. Seven (5.5%) patients died during hospitalization, and 38 (29.9%) patients' health deteriorated. Conclusion: These results may provide a reference basis for the diagnosis and empiric treatment of IPD in the region.

The effect of aggression II: Acclimation to a high ambient temperature reduces territorial aggression in male striped hamsters (Cricetulus barabensis).

Thyroid hormones have a profound influence on development, cellular differentiation and metabolism, and are also suspected of playing a role in aggression. We measured territorial aggression, body temperature (Tb) and serum thyroid hormones levels of male striped hamsters (Cricetulus barabensis) acclimated to either cold (5 °C), cool (21 °C) or hot (34 °C) ambient temperatures. The effects of methimazole on territorial aggression, food intake, metabolic rate and serum thyroid hormone levels, were also examined. Territorial aggression was significantly lower in male hamsters acclimated to the hot temperature compared to those acclimated to the cool or cold temperatures. Tb significantly increased during aggressive territorial interactions with intruders but did not significantly differ among the three temperature treatments. Serum T3, T4 and cortisol levels of hamsters acclimated to 34 °C were significantly lower than those acclimated to 21 °C. In addition to significantly reducing territorial aggression, treatment with methimazole also significantly reduced serum T3 and T4 levels, Tb and metabolic rate. These results suggest that exposure to high temperatures reduces the capacity of hamsters to dissipate heat causing them to lower their metabolic rate, which, in turn, causes them to reduce territorial aggression to prevent hyperthermia. The lower metabolic rate mediated by down-regulated thyroid hormones inhibits territorial aggression and could thereby determine the outcome of territorial conflicts.

Chemical Fingerprinting of HULIS in Particulate Matters Emitted from Residential Coal and Biomass Combustion.

Identification of humic-like substances (HULIS) structures and components is still a major challenge owing to their chemical complexity. This study first employed a complementary method with the combination of two-dimensional gas chromatography-time-of-flight mass spectrometry and liquid chromatography-quadrupole-time-of-flight mass spectrometry to address low-polarity and polar components of HULIS in PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm), respectively. The combination method showed a significant correlation in identifying overlapping species and performed well in uncovering the chemical complexity of HULIS. A total of 1246 compound species in HULIS (65.6-81.0% for each sample), approximately 1 order of magnitude more compounds than that reported in previous studies, were addressed in PM2.5 collected in real-world household biomass and coal combustion. Aromatics were the most abundant compounds (37.4-64.1% in biomass and 34.5-70.0% in coal samples) of the total mass in all HULIS samples according to carbon skeleton determination, while the major components included phenols (2.6-21.1%), ketones (6.0-17.1%), aldehydes (1.1-6.8%), esters (2.9-20.0%), amines/amides (3.2-8.5%), alcohols (3.8-17.0%), and acids (4.7-15.1%). Among the identified HULIS species, 11-36% mass in biomass and 11-41% in coal were chromophores, while another 22-35 and 23-29% mass were chromophore precursors, respectively. The combination method shows promise for uncovering HULIS fingerprinting.

Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC), the most common form of oesophageal malignancies in the Asia-Pacific region, remains a major clinical challenge. In this study, we found that ivermectin, an effective antiparasitic drug that has been approved for patients to orally treat onchocerciasis for over 30 years, displayed potent antitumour activity against ESCC cells in vitro and in nude mice. We demonstrated that ivermectin significantly inhibited cell viability and colony formation, and induced apoptosis through a mitochondrial-dependent manner in ESCC cells. Ivermectin also abrogated ESCC cell migration, invasion, as well as the protein levels of MMP-2 and MMP-9. Mechanistically, ivermectin strongly inhibited the expression of PAK1; by further gain- and loss-of-function experiments, we confirmed that PAK1 played a crucial role in ivermectin-mediated inhibitory effects on ESCC cells. In addition, the data indicated that ivermectin promoted PAK1 degradation through the proteasome-dependent pathway. Additionally, ivermectin synergized with chemotherapeutic drugs including cisplatin and 5-fluorouracil to induce apoptosis of ESCC cells. Interestingly, the in vivo experiments also confirmed that ivermectin effectively suppressed tumour growth and lung metastasis of ESCC. Collectively, these results indicate that ivermectin exerts a potent antitumour activity against ESCC and is a promising therapeutic candidate drug for ESCC patients, even those carrying metastasis.

Benzophenanthridine alkaloids suppress lung adenocarcinoma by blocking TMEM16A Ca2+-activated Cl- channels.

An increasing amount of evidence suggests that transmembrane member 16A (TMEM16A)-encoded Ca2+-activated Cl- channels play a crucial role in regulating tumorigenesis. Therefore, specific and potent TMEM16A inhibitors have been proposed to potentially be useful for the treatment of cancer. During drug screening, we found that benzophenanthridine alkaloids (sanguinarine, sanguinarium chloride, sanguinarine nitrate, ethoxysanguinarine, chelerythrine, and dihydrosanguinarine) potently inhibited the recombinant TMEM16A current. The IC50 and Emax values for TMEM16A inhibition of six tested benzophenanthridine alkaloids were 5.6-12.3 µM and 77-91%, respectively. These benzophenanthridine alkaloids also significantly inhibited the endogenous TMEM16A currents and proliferation, migration, and induced apoptosis in LA795 lung adenocarcinoma cells. These data demonstrate that benzophenanthridine alkaloids are novel TMEM16A inhibitors and are potentially useful in specific cancer therapies. These findings also provide new insight for the development of TMEM16A inhibitors.