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Introduction: Cadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. This study aimed to identify the biomarkers of clinical response and explore the immune response within the tumor microenvironment upon the AK104 therapy in advanced solid tumors. Material and methods: Gene expression profiles of paired pre- and post-treatment tumor tissues from twenty-one patients were analyzed. The association of gene expression levels with either clinical efficacy or prognosis was evaluated and subsequently validated with published datasets using log-rank for Kaplan–Meier estimates. Comparative immune profile analyses of tumor microenvironment before and after AK104 treatment were conducted. The visualization of tumor-infiltrating lymphocytes was performed using multiplex immunohistochemistry. The predictive value of CD74 was further validated with protein expression by immunohistochemistry. Results: Baseline CD74 gene expression was associated with favorable patient outcomes (overall survival [OS], HR = 0.33, 95% CI 0.11–1.03, p = 0.0463), which was further confirmed with the published datasets. Tumors with high CD74 gene expression at baseline were more likely to exhibit an immune-inflamed microenvironment. AK104 efficiently enhanced the infiltration of immune cells in the tumor microenvironment. Additionally, high CD74 protein expression (≥ 10% of the tumor area occupied by CD74 stained immune cells) at baseline was associated with better progressive-free survival (HR = 0.21, 95% CI 0.06–0.68, p = 0.0065) and OS (HR = 0.35, 95% CI 0.12–1.08, p = 0.0615). Conclusions: Our findings demonstrate that CD74 is a promising predictive biomarker for AK104 therapeutic response in advanced solid tumors. Trial registration number NCT03261011. [ABSTRACT FROM AUTHOR]

This study explored the potential of granite stone powder (GSP) as a supplementary cementitious material (SCM). The 72 h early hydration process stages of GSP-mixed slurry were analyzed in depth, and the mechanical properties of manufactured sand concrete (MSC) mixed with GSP were investigated. Physical phase types, morphological characteristics, and pore structure evolution were investigated using an X-ray diffractometer, scanning electron microscope, and mercury intrusion approach (MIP). Atomic force microscopy was used to show the interface transition zone between aggregate and slurry in phase images, height images, and 3D images, allowing quantification of ITZ and slurry by calculating the roughness. Gray entropy analysis was used to evaluate the significance of the effect of pore size distribution parameters on mechanical strength, and the GSP-content-mechanical-strength gray model GM (1, 1) was established to predict mechanical strength. The results indicate that, compared with the reference group, the GSP cement slurry system exhibited a delayed hydration process acceleration rate, with a 1.04% increase in cumulative heat of hydration observed in the 5% test group and an 11.05% decrease in the 15% test group. Incorporating GSP in MSC led to decreased mechanical properties at all ages, with significant decay observed when incorporation ranged from 10% to 15%. Although the type of hydration products remained unchanged, there was a decrease in the number of C-S-H gels and gel pores, while large pores increased, resulting in increased porosity and roughness of the interface transition zone and slurry. Large pores (>1000 nm) were found to have the greatest influence on mechanical strength, with gray correlation above 0.86. The GM (1, 1) model yielded accurate predictions, showing good agreement with measured data and thus it can be identified as belonging to a high-precision prediction model category. These findings provide theoretical support and a reference for applying GSP as an SCM, laying the groundwork for data-based specification development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nitrogen-doped carbon dots (N-CQDs) with high fluorescence quantum yield were synthesized using a green and simple method. • Two modes of fluorescence emission displacement method and fluorescence internal filtering effect detection method were used to detect quinoline yellow, and their detection limits were 0.18 μM and 2.6 nM respectively. • The constructed fluorescent sensor has high sensitivity and excellent selectivity. • The sensor can actually measure the content of quinoline yellow in common beverages. • A fluorescent test strip was constructed for the visual detection of quinoline yellow. Quinoline yellow (QY), as a food coloring agent, will consume a large number of detoxifying substances in the body after being ingested by the human body, interfering with the normal metabolic functions of the human body, and may cause allergies, diarrhea and other symptoms, as well as a certain degree of carcinogenicity, posing a great threat to human health. As a result, it is critical to develop a fast, sensitive, and effective approach to determining quinoline yellow in food. In this study, carbon dots (N-CQDs) with high fluorescence quantum yield were prepared and used to determine the QY content using the dual mode of internal filtering effect and fluorescence emission shift detection. Both methods showed good linearity in the range of QY concentration of 0.3–3.2 μM, and the detection limits were classified as 2.6 nM and 0.18 μM. In addition, in order to achieve visual detection of QY, fluorescent test strips were constructed using the carbon dots and non-fluorescent qualitative filter paper to make the detection of QY more convenient. This probe presents a novel way for detecting quinoline yellow in food analysis. [ABSTRACT FROM AUTHOR]

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-β with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer. [ABSTRACT FROM AUTHOR]

The metacestode stage of Echinococcus granulosus can cause cystic echinococcosis (CE), which still widely occurs around the world. Since the early 1970s, benzimidazoles have been shown to inhibit the growth of cysts and used to treat CE. However, benzimidazoles are still ineffective in 20%-40% of cases. In order to explore the new agents against CE, we have investigated the therapeutic effect of the recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) on protoscoleces-infected mice. In our study, we successfully established the model mice which infected with protoscoleces intraperitoneally. At 18 weeks post-infection, the mice received rAd-mIL-28B (1×107 PFU) weekly by intramuscular injection for 6 weeks. Compared with the untreated control (13.1 ± 2.2 g), there was a significant reduction in cysts wet weight in rAd-mIL-28B group (8.3 ± 3.5 g) (P < 0.05), especially in Albendazole (ABZ) + rAd-mIL-28B group (5.8 ± 1.4 g) (P < 0.01). We also observed the severe damage of the germinal layer and the laminated layer of cysts after treatment. rAd-mIL-28B group showed a prominent increase in the level of Th1 type cytokines (such as IFN-γ, IL-2 and TNF-α). Meanwhile, the frequency of Foxp3+ T cells was decreased in the rAd-mIL-28B group (4.83 ± 0.81%) and ABZ + rAd-mIL-28B group (4.60 ± 0.51%), comparing with the untreated group (8.13 ± 2.60%) (P < 0.05). In addition, compared with the untreated control (122.14 ± 81.09 pg/ml), the level of IFN-γ significantly increased in peritoneal fluid in the rAd-mIL-28B group (628.87 ± 467.16 pg/ml) (P < 0.05) and ABZ + rAd-mIL-28B group (999.76 ± 587.60 pg/ml) (P < 0.001). Taken together, it suggested that ABZ + IL-28B may be a potential therapeutic agent against CE. Author summary: Echinococcosis is a chronic zoonotic parasitic disease, which is caused by the larval stage of Echinococcus granulosus (E. granulosus) and Echinococcus multiocularis (E. multiocularis). This disease is still widely prevalent in the world and seriously endangers human health and life, causing heavy burdens and economic losses to agriculture and animal husbandry. China is also one of the high incidence areas of the disease. At present, the preferred treatment is surgical excision of the parasitic mass, but patients with multiple cysts appear in multiple organs have to receive drug therapy. The approved chemotherapeutic drugs in clinic, such as albendazole (ABZ) and mebendazole, often do not work expectedly with a high rate of recurrence. Therefore, it is urgent to develop the new anti-echinococcal drug. IL-28B is an important member of type-III IFNs, which is equipped with the capacity of anti-viral activity and anti-tumor. In our previous study, we found that IL-28B could inhibit the proliferation of cervical cancer cells via down-regulating Treg cells in mice. This study mainly studied the therapeutic effect of rAd-mIL-28B on E. granulosus-infected mice, and the results showed that rAd-mIL-28B could relieve the parasitic burden and inhibit Treg cells meanwhile improve the Th1 and Th17 immune responses. It may contribute to another choice for the anti-echinococcal treatment. [ABSTRACT FROM AUTHOR]

Nanovaccines have attracted booming interests in vaccinology studies, but the profound impacts of their delivery mode on immune response remain unrealized. Herein, immunostimulatory CpG‐modified tumor‐derived nanovesicles (CNVs) are used as a nanovaccine testbed to initially evaluate the impacts of three distinct delivery modes, including mono‐pulse CNVs, staggered‐pulse CNVs, and gel‐confined CNVs. Fundamentally, delivery mode has enormous impacts on the immunomodulatory effects, altering the spatiotemporal distribution of nanovaccine residence and dendritic cell–T cell interaction in lymph nodes, and finally affecting subsequent T cell‐mediated immune performance. As a result, the gel‐confined delivery mode offers the best therapeutic performance in multiple tumor models. When extending evaluation to examine how the various delivery modes impact the performance of liposome‐based nanovaccines, similar trends in intralymph node distribution and antitumor effect are observed. This work provides a strong empirical foundation that nanovaccine researchers should position delivery mode near the top of their considerations for the experimental design, which should speed up nanovaccine development and facilitate efficient selection of appropriate delivery modes in the clinic. [ABSTRACT FROM AUTHOR]

Background: Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date. Methods and Results: Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy. Conclusion: An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance. [ABSTRACT FROM AUTHOR]

Diamond and gold powders were compressed nonhydrostatically in a diamond anvil cell and examined by x-ray diffraction using a radial geometry to evaluate the evolution of stresses and strains in these materials to ultrahigh pressure. We found that near isostrain continuity developed across diamond and gold grains under uniaxial compression. The observed mean pressure of diamond powder reached to 360(40) GPa while it was only 31(1) GPa for the polycrystalline gold under the highest load. Polycrystalline diamond can support a microscopic deviatoric stress of 160(18) GPa at about 360 GPa. Due to the deformation of the diamond anvil culet, the macroscopic differential stress of the diamond sample was limited to about 43(8) GPa. There is no evidence that the diamond grains have yielded in our experimental pressure range. [ABSTRACT FROM AUTHOR]

Background and Aim: Results obtained from different hepatitis E virus (HEV) tests are usually inconsistent. The detection of serum HEV antigen (Ag) has been suggested to be more sensitive for the diagnosis of genotypes 1 and 3 HEV. Methods: We compared the diagnostic accuracies of serum HEV Ag and HEV RNA by using 202 serum samples from patients suspected acute viral hepatitis. Results: The HEV Ag assay was 100% specific. The lower detected levels of viremia ranged from 102 to 103 copies/mL. The sensitivity of the HEV Ag test was 90.5%. One of the 42 cases was negative for anti‐HEV IgM, but HEV Ag was still detectable. The detectable period of HEV Ag was in concordance with the detectable period of HEV RNA. Serum HEV Ag was persistently detected in two cases of chronic hepatitis E, confirmed by the persistent presence of HEV RNA despite being negative for anti‐HEV IgM. HEV Ag demonstrated good consistency with positive HEV RNA (k = 0.938, P < 0.001). Receiver operating characteristic analysis of HEV Ag suggested a second cut‐off value of >0.095 to predict HEV patients with 95.24% sensitivity and 98.75% specificity, and the area under the curve was 0.9887, which was higher than that of three commercial anti‐HEV IgM ELISA tests. Conclusions: The presence of HEV Ag has good consistency with HEV RNA in both acute and chronic genotype 4 hepatitis E. HEV Ag is a more promising serum marker to identify active genotype 4 HEV infection than anti‐HEV IgM and HEV RNA. [ABSTRACT FROM AUTHOR]

In this study, for the purpose of finite-time tracking control of quad-rotor Unmanned Aerial Vehicle (UAV) system under modeling uncertainties and external disturbances, an adaptive command-filtered backstepping sliding mode control scheme is presented. At first, a state-space model of quad-rotor's system is considered in the existence of bounded model uncertainties and exterior perturbations. Then, a command-filter according to the virtual control input is planned to reduce the computing complications. Subsequently, the output of command filter is considered instead of high-order derivative of virtual input. Besides, in order to remove the differential signals which are obtained during design of command-filter, the compensation error is used. Afterward, the sliding surfaces are designed according to tracking errors which are defined between actual states of the quad-rotor, desired values and compensation error system. Furthermore, backstepping control procedure combined with Lyapunov stability theory is used for finite-time convergence of switching surface. Besides, the adaptive control strategy is applied to estimate the upper bound of uncertainty and disturbance which is unknown in advance. At last, in order to validate the high efficacy of the designed control scheme, simulation results based on the actual parameters of quadrotor are provided. In addition, the comparison outcomes are provided to show proficiency and validity of the recommended technique compared with the existing method. [ABSTRACT FROM AUTHOR]

A PCR array, based on expression of genes along the hypothalamic–pituitary–gonadal–liver (HPGL) axis of fish, has been suggested as a useful method for screening of endocrine-disrupting chemicals (EDCs). However, effects of circadian rhythm on responses of the HPGL axis to exposure to chemicals were unknown. In this study, profiles of expression of genes along the HPGL axis and concentrations of 17β-estradiol (E2) in blood plasma of female zebrafish were compared at two sampling times of day (8:00 AM and 7:00 PM). Prochloraz (PCZ) was selected as a model chemical to evaluate differences in responses of the HPGL axis at these two times of day. Profiles of responses of concentrations of E2 in plasma and expressions of genes along the HPGL axis genes were different between the two times of sampling. Concentrations of E2 were less, and abundances of mRNA for several genes along the HPGL axis were significantly greater or lesser when samples were collected at 7:00 PM than they were when samples were collected at 8:00 AM. Exposure to three concentrations of PCZ (3, 30 or 300 μg/L) for 48 h resulted in significantly lesser concentrations of plasma E2 and caused compensatory up-regulation of genes included in hypothalamus, pituitary and ovary. Expressions of genes along the HPGL were more responsive to PCZ at 8:00 AM than they were when samples were collected at 7:00 PM. Correlations among parameters in samples collected at the two times indicated the effects might be due to different concentrations of E2 in plasma due to exposure to PCZ. [ABSTRACT FROM AUTHOR]

Objective. Interferon (IFN)-γ-induced protein-10 (IP-10) serum level has been shown be associated with viral response in chronic hepatitis C (CHC) patients. However, little is known in Chinese population. We determined IP-10 serum levels in Chinese CHC patients undergoing PEG-IFN-based therapy. Predictive role of IP-10 level for virological responses was accessed. Material and methods. IP-10 serum levels were determined in 165 hepatitis C virus (HCV) genotype 1 and 33 genotype 2 patients. Multivariate analysis was performed to screen independent factors for sustained virological response (SVR) prediction. Predictive value of IP-10 level in combination with interleukin 28B ( IL28B) genotype or rapid virological response was further investigated. Results. Our study showed that pretreatment IP-10 level was significantly higher in HCV genotype 1 patients. IP-10 levels were independently predictive for SVR with cut-off values of 250.60 pg/ml at baseline or 407.40 pg/ml at week 4. Positive predictive value (PPV) for SVR of low IP-10 level at baseline and IL28B CC genotype was 96.15% and negative predictive value (NPV) was 50.00%. PPV for SVR of low IP-10 level at week 4 and rapid viral response (RVR) was 95.24% and NPV was 50.00%. Conclusion. Together our study indicated that higher IP-10 serum levels were associated with HCV genotype 1 CHC Chinese patients. IP-10 levels at baseline and week 4 were both predictive of SVR and improved predictive performances of IL28B genotype and RVR for SVR. [ABSTRACT FROM AUTHOR]

In this work, rhodamine 6G (Rh 6G) was modified on the surface of carbon quantum dots (CQDs) synthesized by a hydrothermal method via a microwave reaction and Rh 6G-CQDs (R-CQDs) with obvious double emission peaks were obtained. UV-visible (UV-vis), fluorescence, and Fourier transform infrared (FTIR) spectra showed that Rh 6G was successfully modified on the surface of CQDs. Rh 6G modification on the surface of CQDs is more stable than simple mixing dependent on electrostatic adsorption, avoids desorption and degradation of the dye, and further improves the quantum yield of CQDs. The broader emission spectrum of R-CQDs effectively increases the overlap with the absorption spectrum, R-CQDs with ratio fluorescence properties achieve selective detection of doxorubicin (DOX) by the inner filter effect (IFE) and fluorescence resonance energy transfer (FRET), and it has a good linear response in the range of 8 × 10−7–4.28 × 10−5 M with a recovery of 93.29–109.51% and a minimum detection limit of 5.31 × 10−7 M. [ABSTRACT FROM AUTHOR]

Highlights: [•] MCLR significantly impaired LTP in a concentration-dependent manner. [•] GSK-3β inhibitors prevents the effects of MCLR on hippocampal LTP in vivo. [•] MCLR increased the activity of GSK-3β via regulating phosphorylation at Ser9 site. [Copyright &y& Elsevier]

Abstract: Objective: The present study evaluated differences in gene expression associated with age and gender in the human parotid gland. Design: Parotid gland tissue was analysed using the Affymetrix® GeneChip® HGU133plus2.0 array. Results: Differential gene expression, defined as a statistically significant difference with a 1.5-fold or greater change, was detected in 787 gene probe sets; 467 (∼59%) showed higher expression in females. Several genes associated with saliva secretion were differentially expressed in male and female parotid glands including vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated protein SNAP23, RAS oncogene family member RAB1A and the syntaxin binding protein STXBP1. Evaluation of gene expression in the youngest and the oldest female subjects revealed that the expression of 228 probe sets were altered during aging; 155 genes were up-regulated in the aged female parotid gland. However, of the genes that were altered during aging, 22 of the 30 probes (73%) classified as being associated with immune responses were down-regulated in the aged parotid gland. A panel of differentially expressed, age- and gender-related genes was selected for validation by quantitative, real-time RT-PCR. Comparable differences in gene expression were detected by both Affymetrix® array and quantitative, real-time RT-PCR methods. Conclusions: Our data suggest that salivary gland function may be adversely affected in the aged population due, at least in part, to the altered regulation of several categories of genes. Moreover, the gender specific differences in gene expression identified in the present study correlate with the previously observed sexual dimorphism in salivary gland function. [Copyright &y& Elsevier]

Demonstrates that the thermal maximum in the Holocene climate lasted from 7200 to 2700 aBP, with several abrupt ephemeral vibrations occurring between 7250-120 aBP and at around 4460, 3850 and 270 aBP in the Hainan Island, China. Distinct environmental change indicating an important climate transition in the tropical eastern Asia; High-resolution algae record.

The frequency with which the hybrid vector AdLTR-luc mediates genomic integration [Nat. Biotech. 18 (2000) 176–180] is unknown. To address this, we constructed AdLTR-red, using the AdLTR-luc backbone and the enhanced red fluorescence protein cDNA. Kinetic studies showed that AdLTR-red and a conventional adenoviral vector, AdCMV-red, entered and transduced epithelial cells comparably. AdLTR-red integration frequency in vitro, i.e., the percentage of red clones after 10–12 doubling times from limiting dilutions, was 8.0% (36/450; at 67 particles/cell). With AdCMV-red, 0/549 clones were integration-positive. Seven days after AdLTR-luc or AdCMV-luc (1011 particles) femoral vein administration to adult rats splenocytes were prepared, stimulated with concanavalin A, and examined by FISH. AdLTR-luc integration occurred in 5–11% of mitotic rat splenocytes, while no unequivocal integration was found with AdCMV-luc. These data provide the first quantitative evidence of the frequency for genomic integration with this hybrid vector. [Copyright &y& Elsevier]

Presents a study which examined the use of the Raman difference spectroscopic techniques to obtain the myosin S1. magnesium (Mg) adenosine diphosphate (ADP).vanadate complex (Vi), with reference to the vanadate solution model compound. Suggestion of a normal mode analysis; Preparation of the myosin; Concentration of the complexes.

The cover image is based on the Original Article I Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance i by Xianbo Wang, Jianghua Wang, Dong Jiang et al., https://doi.org/10.1111/liv.14241 GLO:Q18/01jan20:liv14317-toc-0001.jpg PHOTO (COLOR): . gl. [Extracted from the article]

The red swamp crayfish (Procambarus clarkii) has become one of China’s most important freshwater aquaculture species. As the epicenter of crayfish cultivation, Hubei province provides the majority of germplasm resources for breeding applications. However, the genetic diversity and population structure of P. clarkii in this area remains largely incomplete, hindering the effective utilization of these germplasm resources. In this study, 20 polymorphic microsatellites were developed and used to investigate genetic diversity and differentiation in representative P. clarkii populations from five cultivated and five wild populations in Hubei province. A total of 169 alleles were discovered at these loci, and the average polymorphic information content was calculated as 0.584. Diversity index of expected heterozygosity (He) indicated a relatively medium genetic diversity across all populations (0.431 ~ 0.565), while wild populations exhibited higher genetic diversity (He = 0.542) compared to that in cultured populations (He = 0.478). The average value of pairwise population differentiation index (Fst) was 0.108, manifesting a moderate level of genetic differentiation among populations. Analysis of molecular variance between ten populations revealed that genetic variation mostly resided within individuals (79.4%), with slightly higher variation observed in cultured populations (84.79%) compared to that in wild populations (80.52%). Bayesian assignment, dendrogram, and principal component analysis grouped the genotypes into three clusters with wide variation among the accessions. These results reflected substantial genetic differentiation presented in P. clarkii populations. Our findings shed light on the diversity status of P. clarkii in Hubei province and will be great value for genetic improvement through selective breeding. [ABSTRACT FROM AUTHOR]

• There is a similarity in PV potential within similar urban block types in the same types. • A significant difference exists between the three different types of urban blocks in regards to PV potential. • The highest PV potential is exhibited by commercial blocks, followed by residential and then industrial blocks. • Different block types exhibit different proportions of PV potential in terms of rooftops and facades due to variation in urban form. Due to the ever increasing energy demand, PV utilisation in the urban scale has become an attractive solution. The purpose of this paper is to demonstrate the effect of urban block type on solar potential. There exists a requirement to analyse solar potential in the real urban context of Wuhan based on block function and type. Therefore, this paper studies a real case in Wuhan's urban context by selecting 15 cases of real urban industrial, commercial and residential blocks. The PV output was calculated for roofs and façades respectively. The results obtained showed obvious differences between the three type of blocks, where commercial blocks received the most total solar irradiation, followed by residential blocks, and then industrial blocks. Similarly, the distribution of solar irradiation on roofs and façades for each block was vividly different based on the block type, owing to differences in building forms based on block function. [ABSTRACT FROM AUTHOR]

An abstract of the article "Long-Term Rapamycin Control of Transgene Expression in Mouse Salivary Glands in a Single AAV Vector," by Jianghua Wang, Antonis Voutetakis, Milton Papa, Victor M. Rivera, Tim Clackson, Beatrijs M. Lodde, Fumi Mineshiba and Bruce J. Baum is presented.

An abstract of the article "Microvessel Injury and Irradiation Damage in Salivary Glands," by Ana Paola P. Cotrim, Jianghua Wang, Antonis Voutetakis, Anastasia L. Sowers, James B. Mitchell and Bruce J. Baum is presented.

The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice. [Display omitted] • An antibody-PET probe targeting PD1/CTLA4 was radiolabeled. • High affinity to PD1/CTLA4 in vitro and in vivo. • This tracer can noninvasively demonstrate the presence of PD1/CTLA4-positive infiltrating T cells at the tumor site in humanized mice using an imaging method. [ABSTRACT FROM AUTHOR]

Compensation responses and adaptability of hypothalamic-pituitary-gonadal (HPG) axis have been reported in fish exposed to model chemicals, however due to its importance in predictive toxicology further study was needed to elucidate details of the integrated responses to model chemicals. Transcriptional profiles of the hypothalamic-pituitary-gonadal (HPG) axis and concentrations of 17β-estradiol (E2) in plasma were measured in male and female zebrafish that had been exposed to one of seven concentrations of the fungicide, prochloraz: low (1, 3 or 10 μg/L), medium (30 or 100 μg/L) or high concentrations (300 or 1000 μg/L) for 4 days. In zebrafish exposed to the low and medium concentrations of prochloraz, compensation responses of the HPG axis through transcription, occurred in brain (up-regulation of gnrh , gnrhr and lhβ ) and both brain and gonad (up-regulation of steroidogenic genes), respectively. Concentrations of E2 in plasma and expression of estrogen receptor 1 ( er1 ) and vitellogenins ( vtgs ) in liver did not change. This result suggested that compensatory responses were successful in maintaining homeostasis. In zebrafish exposed to the two greatest concentrations, compensatory responses occurred in brain, gonad and liver through up-regulation of er2β , but it failed to maintain concentration of E2 in blood plasma and expression of er1 and vtgs in liver. Collectedly, the results observed in this study allowed characterization of dose-dependent compensatory responses along the HPG axis and liver and identified key linkages between compensatory responses occurring in brain, gonad and liver after exposure to prochloraz. [ABSTRACT FROM AUTHOR]

Polycrystalline ruby (α-AlO:Cr), a widely used pressure calibrant in high-pressure experiments, was compressed to 68.1 GPa at room temperature under non-hydrostatic conditions in a diamond anvil cell. Angle-dispersive X-ray diffraction experiments in a radial geometry were conducted at beamline X17C of the National Synchrotron Light Source. The stress state of ruby at high pressure and room temperature was analyzed based on the measured lattice strain. The differential stress of ruby increases with pressure from ~3.4 % of the shear modulus at 18.5 GPa to ~6.5 % at 68.1 GPa. The polycrystalline ruby sample can support a maximum differential stress of ~16 GPa at 68.1 GPa under non-hydrostatic compression. The results of this study provide a better understanding of the mechanical properties of this important material for high-pressure science. From a synthesis of existing data for strong ceramic materials, we find that the high-pressure yield strength correlates well with the ambient pressure Vickers hardness. [ABSTRACT FROM AUTHOR]

Linear polyglycidol (LPG) has emerged as a polyethylene glycol (PEG) alternative in novel surfactant development due to its unique advantages, such as high bioavailability and multiple functionalization sites. In this study, a series of LPG based acylhydrazones, including copolymers CLPG1–3 with different length (n = 7–11) of alkyl chains and a curcumin (CUR) drug conjugate CLPG4 were synthesized for the first time. CLPG1 - 4 exhibited a decreasing trend in their surface-active properties as the molecular hydrophobicity increased. Among them, CLPG1 revealed the most powerful foaming ability, emulsion stability than the other analogs and tested commercial references, attributing to its optimal hydrophilic/hydrophobic balance. On the other hand, the drug conjugate CLPG4 revealed significantly enhanced selective tumor cell inhibition and cellular uptake than free CUR in the in vitro experiments. The established structure-property profile in this study provides a useful reference for their practical applications in the chemical and pharmaceutical fields. [Display omitted] • Novel LPG acylhydrazones (CLPG 1 - 3) and CUR-LPG conjugate (CLPG 4) were synthesized. • Structure-activity profile was established for CLPG1 - 3 as potent surfactants. • Enhanced drug loading and stability were observed for CLPG4 compared to physically encapsulated complexes. • CLPG4 revealed improved permeability and selective cancer cell inhibition. [ABSTRACT FROM AUTHOR]

Selenium (Se), an indispensable micronutrient for living organisms, has been extensively studied for its heavy metal-detoxifying properties in diverse biological systems and tissues. Nevertheless, it is not entirely certain whether Se can effectively protect against Cadmium (Cd)-induced gut inflammation, especially in aquatic animals. In this study, we employed various approaches, including transcriptome profiling, histological examinations, assessment of antioxidant enzyme activities, and analysis of gut microbiota composition to investigate the effects on crayfish growth and intestinal health after exposure to dietary Cd (15 mg kg−1 diet) and Se (15 mg kg−1 diet) individually or in combination for 8 weeks. The results revealed that dietary Cd exposure resulted in reduced body weight and survival rates, along with an increased occurrence of intestinal inflammation. Nevertheless, Se supplementation proved effective in mitigating the adverse effects of Cd on growth and gut health. Se exhibited a remarkable ability to counteract the disruption of gut antioxidant abilities induced by dietary Cd, as evidenced by the observed increases in ROS and MDA contents, decrease in GSH levels, and inhibition of antioxidative enzyme activities. At the concentration of 6 mg kg−1 in the diet, Se was found beneficial for maintaining gut microbiota richness and diversity. Among them, Flavobacterium , Thermomonas , and Chloronema displayed a weak negative correlation with the rate of gut inflammation. Meanwhile, the levels of short chain fatty acids (SCFAs), including acetic acid (AA) and butanoic acid (BA), showed a significant increase in the Se–Cd group compared to the Cd-only group. Furthermore, transcriptome analysis exhibited significant responses of the PI3K/Akt and NF-κB pathways following crayfish exposure to dietary Se and Cd, either separately or in combination. In short, this study provides a new evidence regarding the molecular mechanisms through which Se could regulate the PI3K/Akt and NF-κB pathways, either directly or indirectly via ROS and SCFAs, thereby alleviating Cd-induced gut inflammation in crayfish. [Display omitted] • Chronic Cd exposure (15 mg/kg) markedly induced gut inflammation and apoptosis. • Cd decreased crayfish weight and survival, but Se supplementation mitigated this. • Se countered the disruption of gut antioxidant capabilities induced by dietary Cd. • Se antagonized Cd-induced gut inflammation by boosting SCFA content. • PI3K/Akt/NF-κB pathways mediated Se's counteraction of Cd toxicity in the gut. [ABSTRACT FROM AUTHOR]

Objective To investigate the feasibility and safety of laparoscopic reoperation combined with choledochoscope in the treatment of intra - and extrahepatic bile duct stones. Methods The 35 patients wiih intra - and extrahepatic bile duct stones who underwent laparoscopic bile duct reoperation from January 2008 to May 2012 were selected as a laparoscopic treatment group; 50 patients with recurrent intra - and extrahepatic bile duct stones who underwent open surgery in the same period were selected as an open surgery group. The t - test was used to compare the two groups in terms of off - bed activity early after operation, recovery of intestinal function, and length of hospital stay ; the chi - square test was used to compare the incision infection rate between the two groups. Results Among the 35 cases of intra - and extrahepatic bile duct stones, 32 completed laparoscopic surgery, 2 had the procedure converted to open surgery due to severe adhesion, and 1 had the procedure converted to open surgery due to subcutaneous emphysema. In the laparoscopic treatment group, the mean operative time of laparoscopic bile duct reoperation was 148 min (range, 105 -200 min) ; there were no bleeding and bile leak in the perioperative period. All patients underwent T - tube drainage ; postoperative peritoneal drainage was performed for 2 - 5 d ; the mean length of hospital stay after operation was 5 - 8 d. No case of incision infection occurred in the laparoscopic treatment group. The laparoscopic treatment group had a significantly better outcome than the open surgery group in terms of time to off - bed activity early after operation, time to recovery of intestinal function, length of hospital stay after operation, and incision infection rate (? <0.05). In the laparoscopic treatment group, 3 cases had retained bile duct stones, and the stones were taken out through the sinus tract using a fiber choledochoscope at 2 months after operation. All cases were followed up for 6-24 months after operation, and no recurrence was found in the laparoscopic treatment group. Conclusion Laparoscopic bile duct reoperation is minimally invasive and causes few complications, and the patients have rapid recovery after this procedure. Laparoscopic bile duct reoperation is safe and effective in the patients with intra - and extrahepatic bile duct stones who have the indications for this procedure. [ABSTRACT FROM AUTHOR]

It has been reported that monoclonal antibodies (MAbs) to the E1E2 glycoproteins may have the potential to prevent hepatitis C virus (HCV) infection. The protective epitopes targeted by these MAbs have been mapped to the regionsencompassing amino acids 313–327 and 432–443. In this study, we synthesized these two peptides and tested the reactivity of serum samples from 336 patients, 210 of whichwere from Chronic Hepatitis C (CHC) patients infected with diverse HCV genotypes.The remaining 126 samples were isolated from patients who had spontaneously clearedHCV infection.In the chronic HCV-infected group (CHC group), the prevalence of human serum antibodies reactive to epitopes 313–327 and 432–443was 24.29%(51 of 210) and4.76%(10 of 210),respectively. In thespontaneousclearance group (SC group),the prevalence was 0.79%(1 of 126) and 12.70%(16 of 126), respectively.The positive serum samples that contained antibodies reactive to epitope 313–327 neutralizedHCV pseudoparticles (HCVpp) bearing the envelope glycoproteins of genotypes 1a or 1b and/or 4, but genotypes 2a, 3a, 5 and 6 were not neutralized. The neutralizing activity of these serum samples could not be inhibited by peptide 313–327. Six samples (SC17, SC38, SC86, SC92, CHC75 and CHC198) containing antibodies reactive to epitope 432–443 had cross-genotype neutralizing activities. Theneutralizing activityof SC38, SC86, SC92 and CHC75waspartiallyinhibited by peptide 432–443. However,the neutralizing activity of sample SC17 for genotype 4HCVpp and sample CHC198 for genotype 1b HCVppwere notinhibited by the peptide.This study identifies the neutralizing ability of endogenous anti-HCV antibodies and warrants the exploration of antibodies reactive to epitope432–443as sources for future antibody therapies. [ABSTRACT FROM AUTHOR]

Abstract: The effects of puerarin on behaviour and brain neuronal activity in animal studies have been described previously. However, molecule mechanisms underlying these effects were poorly understood. Here, we examined the regulation of puerarin on the Ca2+ signals in primary rat hippocampal neurons using Fura-2 based calcium imaging techniques. Application of puerarin had no effect on the basal intracellular calcium concentration ([Ca2+]i), but potentiated the KCl-evoked [Ca2+]i transient in 87% of recorded neurons. Dantrolene or ruthenium red, the inhibitors of ryanodine receptors, completely blocked this potentiation induced by puerarin. Moreover, in Ca2+-free solution, pre-application of puerarin significantly augmented the elevation of [Ca2+]i evoked by caffeine (3 mM), which is a specific agent to activate the ryanodine receptors. In contrast, nifedipine failed to prevent the potentiation induced by puerarin. Similarly, in the experiments of whole-cell patch-clamp recording, puerarin did not show any effect on calcium currents generated by depolarization pulses. These data demonstrated that the potentiation induced by puerarin was attributed to the facilitation of Ca2+-induced Ca2+ release (CICR) via ryanodine receptors, rather than extracellular Ca2+ influx. Using estrogen receptor antagonist ICI 182780 and tamoxifen, we further demonstrated that the potentiation induced by puerarin was mediated by the estrogen receptor. Furthermore, the membrane-permeant inhibitor of protein kinase A (PKA) H89 completely inhibited this potentiation. However, U-73122, the inhibitor of phospholipase C (PLC) had no effect, indicating that the cyclic AMP/PKA signaling pathway was involved in the activation of CICR by puerarin. [Copyright &y& Elsevier]

Directing the local or systemic expression of therapeutic proteins is a potentially important clinical application of gene transfer technology. Gene-based therapeutics theoretically offer many advantages over protein therapeutics. Numerous tissues have been evaluated for this purpose in animal models, most commonly the liver and skeletal muscle. Based on pre-clinical studies, we suggest that salivary glands are a valuable, yet under-appreciated, target tissue for both systemic and upper gastrointestinal tract gene therapeutic applications. [Copyright &y& Elsevier]

This paper describes a technique for computing lower bound limit bearing capacity of rectangular surface footings. A perfectly rigid plastic model is adopted to describe the property of soil materials. The bearing capacity of footing is regarded as the objective function in this method, subject to the stress boundary condition, stress discontinuity equilibrium condition, stress equilibrium condition and yield condition. By solving a non-linear optimization problem, i.e., searching the maximum value of objective function, the bearing capacity of smooth surface rectangular footing and the corresponding 3D stress field are obtained. [Copyright &y& Elsevier]

Examines the implications of phosphoryl group bonding for phosphoryl transfer and enzymatic catalysis. Effect of dimethyl sulfoxide on the bond length of phosphoryl; Process of enzymatic catalysis; Bonding properties of phosphoryl groups.

The purpose of our study was to elucidate the functions of miR-30c-5p on adenomyosis for exploring novel treatment strategies. We first detected the expression of miR-30c-5p in clinical adenomyotic tissues and isolated endometrial cells from adenomyotic tissues. Next, gain and loss-of-function assays were performed to detect the effect of miR-30c-5p on adenomyotic endometrial cells. Further, luciferase assay and real-time polymerase chain reaction as well as western blot were conducted to investigate the potential target of miR-30c-5p; and transwell assay, wound-healing assay and CCK-8 assay were used to evaluate the effects of miR-30c-5p and its target on regulating biological functions of adenomyotic endometrial cells. Our results found that miR-30c-5p was down-regulated in both adenomyosis tissues and adenomyotic epithelial cells, which correlated with dysmenorrhea, longer duration of symptoms and more menstrual bleeding. Moreover, the overexpression of miR-30c-5p inhibited the proliferation, migration and invasion of adenomyotic epithelial cells, where miR-30c-5p knockdown had an opposite effect. Furthermore, we confirmed mitogen-activated protein kinase 1 (MAPK1) was one of the direct targets of miR-30c-5p, indicating its important role in miR-30c-5p-mediated suppression of proliferation, invasion and migration in adenomyotic epithelial cells. This study showed that the interaction of miR-30c-5p with MAPK1 can regulate the proliferation, invasion and migration in adenomyotic epithelial cells. [ABSTRACT FROM AUTHOR]

Several mechanisms regarding the developmental and reproductive toxicity of l -selenomethionine (SeMet) in freshwater fish have been widely reported. However, limited information was available on endocrine-disrupting effects of SeMet. In this study, zebrafish larvae (day 24 post-fertilization) were exposed to environmentally-relevant levels of dietary SeMet (control, 1.11 ± 0.11, 3.59 ± 0.20, 10.80 ± 0.52, 29.19 ± 0.46, and 58.63 ± 0.70 μg Se/g d.w. diet) for 90 days until sexual maturity. For the first time, a gender difference in the effect of SeMet on body mass of zebrafish was observed. The lowest observed adverse effect level (LOAEL) in male was 10.80 ± 0.52 μg Se/g d.w., while it was 29.19 ± 0.46 μg Se/g d.w. in female. Chronic exposure to dietary SeMet reduced the percentage of early vitellogenic oocyte in female and the percentage of spermatid in male by inhibiting the growth hormone/insulin-like growth factors (GH/IGFs) and hypothalamus-pituitary-gonad (HPG) systems, which was characterized by significant decreases in the transcriptional levels of gh , igf1 , era , and ar. Se content in the liver of male was significantly higher than that in female when dietary Se level reached 10.80 ± 0.52 μg Se/g d.w.. Furthermore, the zinc content in the livers and gonads of both female and male treated with 29.19 ± 0.46 and 58.63 ± 0.70 μg Se/g d.w. diets was significantly reduced. Reduction of zinc ion not only led to the significantly upregulated transcriptional levels of zip1 and znt2 , but also downregulated transcriptional levels of znf219l and sp7. In summary, this study provides a new evidence that chronic exposure to high level of dietary SeMet (≥10.80 μg Se/g d.w.) could impair the development and reproduction of zebrafish with gender difference by interfering the GH/IGFs and HPG systems. Moreover, disruption of zinc ion homeostasis might exacerbate the toxicity of Se to zebrafish. Image 1 • The LOAEL in male was 10.80 μg Se/g, while it was 29.19 μg Se/g in female. • SeMet impaired growth and reproduction by interfering GH/IGFs and HPG systems. • Chronic exposure to high level of dietary SeMet disrupted zinc ion homeostasis. [ABSTRACT FROM AUTHOR]

Pure-phase polycrystalline cadmium tetraphosphide (CdP4) has been successfully synthesized under high pressures in a large volume cubic press, and the pressure-temperature (P-T) formation boundary of CdP4 from the Cd-P binary system has been determined. The equation of state of monoclinic CdP4 has also been evaluated by synchrotron-radiation angle-dispersive X-ray diffraction (ADXRD) under quasihydrostatic compression up to 26.4 GPa in a diamond-anvil cell. The ADXRD data yield a bulk modulus B0 = 94 ± 9 GPa with a pressure derivative B0′ = 8.0. The experimental data are discussed and compared to the results of first-principles calculations. [ABSTRACT FROM AUTHOR]

The alveolar echinococcosis of human is a severe helminthic disease caused by the larva of Echinococcus multilocularis tapeworms. Novel compounds or therapy strategies for the treatment of alveolar echinococcosis are urgently needed due to the limitation of the widely used albendazole. Magnetic microspheres as drug carriers in magnetically targeted therapy of tumor have gained growing interests advantaged by delivering the drug to the aimed site, achieving localized therapeutic effect effectively under the influence of an external magnetic field. In this study, we formulated magnetic microspheres loaded with E2-a (PLGA-Fe-E2-a) and identified the activity in E. multilocularis-infected mice which infected with 3,000 protoscoleces intraperitoneally. Compared with the untreated control, with the help of a magnet, there was a significant reduction in parasite burden with PLGA-Fe-E2-a treatment and similar reduction observed with albendazole. PLGA-Fe-E2-a treatment group also showed a significant increase in the IFN-γ level and impaired morphological and ultrastructural alterations. Most importantly, one-third concentrations of E2-a from PLGA-Fe-E2 based on the release profile of E2-a was equally effective in inhibiting metacestode growth as E2-a treated group, supporting efficacy and bioavailability of a drug. It will be an alternative treatment for alveolar echinococcosis using magnetic microspheres as drug carriers. [ABSTRACT FROM AUTHOR]

• The Protective effects of astragalus polysaccharide nanoparticles on LPS-treated H9c2 cell in morphology and anti-apoptosis. • The down-regulating effects of astragalus polysaccharide nanoparticles on bacterial loads, cardiac troponin I and inflammatory cytokines in septic mice. • Protective effects of astragalus polysaccharide nanoparticles on septic cardiac dysfunction through inhibition of TLR4/NF-κB signaling pathway. Sepsis-induced myocardial dysfunction was the leading cause of morbidity and mortality in hospitalized patients and yet there were no effective therapies. With excessive released inflammatory mediators through the TLR4-trigger NF-κB signaling pathway being implicated as key players in sepsis-induced myocardial injury, we prepared astragalus polysaccharide (APS) nanoparticles as an TLR4-responsive drug for alleviating sepsis-induced myocardial injury. Firstly, treatment with APS nanoparticles in LPS-treated H9c2 cells to evaluate the direct effect demonstrated that this drug maintained the cell viability, cell morphology and exerted anti-apoptotic effects. Additionally, animal studies using cecal ligation and puncture (CLP) in C57BL/6 mice revealed that APS nanoparticles were much more efficacious in attenuating sepsis-induced myocardial injury by down-regulating the bacterial loads, inhibiting serum C-reactive protein (CRP), white blood cells (WBC) levels, alleviating myocardial histopathologic abnormalities, remarkably reducing the cardiac troponin I (cTnI). Moreover, APS nanoparticles significantly decreased the myocardial inflammatory cytokine expression and inhibited the activity of TLR4/NF-κB pathway. In conclusion, APS nanoparticles could protect the sepsis-induced cardiac dysfunction. The mechanism of the protective action of APS nanoparticles seems to involve its ability to reduce inflammatory response and to suppress TLR4/NF-κB pathway. This drug may be a potential candidate strategy for septic cardiac dysfunction treatment. [ABSTRACT FROM AUTHOR]

The compression behavior and stress state of nanocrystalline tungsten boride (WB) were investigated using radial x-ray diffraction (RXRD) in a diamond-anvil cell under non-hydrostatic compression up to 60.4 GPa. The compression properties and stress state are analyzed using lattice strain theory. Experiments were conducted at beamline X17C of the National Synchrotron Light Source. The radial x-ray diffraction data yield a bulk modulus that is qualitatively consistent with density functional theory calculations and demonstrate that WB is a highly incompressible material. A maximum differential stress, t, of about 14 GPa can be supported by nanocrystalline WB at the highest pressure. This corresponds to about 5% of the shear modulus, G, which is smaller than the values of t/G (∼8%-10%) observed for BC2N, B6O, TiB2, and γ-Si3N4 at high pressures. Thus, while WB is highly incompressible, its strength is relatively low at high pressures compared to other hard ceramics. [ABSTRACT FROM AUTHOR]

Abstract Pentachlorophenol (PCP) and its byproduct hexachlorobenze (HCB) are two co-existing persistent environmental chemicals, but their combined toxicity remains unclear. In this study, adult zebrafish were exposed to 5 (low dose) and 25 μg·L−1 (high dose) of PCP, HCB or their combination for 21 days, and the impact on endocrine and reproduction was investigated. Results showed that combined exposure to 25 μg·L−1 PCP and 25 μg· L−1 HCB significantly increased the plasma estradiol (E2) and testosterone (T) levels, altered the expressions of genes along the hypothalamic-pituitary-gonadal-liver (HPGL) axis, inhibited gonadal development, and eventually lead to decreased egg production of F0 zebrafish as well as inhibited development of F1 eggs/larvae. Compared to the combined exposure of high doses, significantly lower levels of plasma E2 and T were observed for either the high PCP or high HCB alone exposure, indicating a synergistic effect of the two chemicals on endocrine disruption after combination. Furthermore, the high PCP alone exposure inhibited the gonadal development in both the males and females, while the HCB alone exposure did not. Comparison of exposure effects indicated a greater decrease of mature gametes levels and egg production in the high combined group when compared to the high HCB alone group, but no significant difference was observed between the high combined group and the high PCP alone group. Taken together, the results suggested that combined exposure to PCP and HCB may synergistically affect endocrine of zebrafish, and result in reproduction impairments, with PCP being the primary contributor. Highlights • Combined exposure to PCP and HCB resulted in reproductive impairments in zebrafish. • Combined exposure to PCP and HCB may synergistically affect endocrine of zebrafish. • Decreased GSI value and inhibited gonadal development in females might be associated with the decrease of egg production. • Reproductive impairments in the high combined group may be more attributable to the PCP toxicity. [ABSTRACT FROM AUTHOR]

Abstract Tris (2-butoxyethyl) phosphate (TBOEP) is a ubiquitous environmental contaminant due to its overuse. TBOEP has been found to cause reproductive toxicity and endocrine disruption during acute toxic experiment. In this study, we examined the effects of TBOEP on growth in initial generation (F0) zebrafish and transgenerational effects on growth of first generation (F1) larvae after parental long-term exposure (120 d) to environmentally relevant concentrations (0, 0.1, 1, 10 and 100 μg/L). Exposure to TBOEP resulted in significantly less growth as measured by body length, body weight and gonadosomatic index (GSI) in F0 females but not F0 males. Furthermore, the bioaccumulation of TBOEP in gonad, the alteration of the gene transcriptions in the hypothalamic-pituitary-gonadal (HPG) axis, and the delay in gonadal development in both female and male zebrafish were demonstrated. In addition, the residues of TBOEP were detected in F1 larvae after parental exposure, resulting in lower survival and shorter body length, as well as faster heart rate. And no significant changes in gene expressions along the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis were found in F1 larvae. In conclusion, these results indicated that long-term parental exposure to environmentally relevant concentrations of TBOEP could inhibit the development of progeny by parental gonadal impairment and by TBOEP transfer to offspring, instead of gene transcription in GH/IGF and HPT axes. Highlights • TBOEP caused significantly less growth in F0 females but not F0 males. • TBOEP at environmentally relevant concentrations caused gonadal impairment. • The residues of TBOEP were detected in F1 larvae after exposure of parents. • Long-term parental exposure to TBOEP inhibited the development of progeny. [ABSTRACT FROM AUTHOR]

In order to study the effect of reed and cattail on the bacterial community structure of surface sediments of wetland in winter, high-throughput sequencing technology was used to analyze the bacterial composition. The results showed that 134 228 high-quality gene sequences were obtained by high-throughput sequencing in sediments of natural wetland in winter, and there were 13 866 OTUs, in which the number of OUT in sediments of reed wetland and cattail wetland was 6 677 and 7 189 respectively. The richness and diversity of bacterial communities in sediments of cattail wetland in winter were higher than those in sediments of reed wetland. Relative abundance of Proteobacteria in sediments of reed wetland and cattail wetland was 0.54 and 0.52, respectively. The dominant classes of bacteria were Betaproteobacteria, Deltaproteobacteria, Gammaproteobacteria and Epsilonproteobacteria, which belonged to gram-negative bacteria, indicating that the rhizosphere of wetland was easier to enrich gram-negative bacteria. Under the genus level, the dominant bacteria in the sediments were not obvious. [ABSTRACT FROM AUTHOR]

Abstract Tris (2-butoxyethyl) phosphate (TBOEP), as one of the most widely used organophosphate flame retardants (OPFRs), is applied in nearly all manufactured items and materials. It has been reported that TBOEP could cause developmental impairments and disrupt the endocrine regulation of fish growth during acute toxic experiments. However, concentrations to which fish were exposed in these studies were greater than environmentally relevant concentrations ever reported. This study examined effects on growth associated with exposure of zebrafish to 0, 0.1, 1 and 10 μg/L TBOEP during 20–90 days post fertilization (dpf). The changes in growth indicators and bioaccumulation of TBOEP were examined along with the transcription of related genes in the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis. The average body contents of TBOEP were higher in females than in males in all the exposure groups. Exposure to environmentally relevant concentrations of TBOEP significantly decreased body length and body mass and down-regulated expression of several genes involved in the GH/IGF and HPT axes. Exposure to TBOEP decreased plasma thyroxine (T4) content accompanied by decreased mRNA level of thyrotropin β-subunit (tshβ) in females at 60 dpf, but no effects were observed at 90 dpf. These results suggested that bioaccumulation of TBOEP and down-regulation of genes involved in the GH/IGF axis might be responsible for the observed growth inhibition in zebrafish exposed to TBOEP. Highlights • Growth of zebrafish was inhibited by environmentally relevant levels of TBOEP. • TBOEP had no persistent effect on concentrations of THs. • Bioaccumulation of TBOEP contributed to the growth inhibition. • Disruption of GH/IGF axis was induced by environmentally relevant levels of TBOEP. [ABSTRACT FROM AUTHOR]

• TDCIPP could selectively inhibited the growth of female zebrafish. • TDCIPP altered the microbial communities in the intestine of zebrafish. • TDCIPP induced an increase in α-diversity of the gut microbiome in male zebrafish. • TDCIPP induced histological injury and inflammation responses in female intestine. • Abundances of pathogenic bacteria were negatively correlated with female growth. Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is ubiquitous in aquatic environment, but its effect on intestinal health of fish has yet not been investigated. In the present study, the AB strain zebrafish embryos were exposed to environmentally realistic concentrations (0, 30, 300, and 3000 ng·L−1) of TDCIPP for 90 days, after which the fish growth and physiological activities were evaluated, and the intestinal microbes were analyzed by 16S rRNA gene high-throughput sequencing. Our results manifested that the body length and body weight were significantly reduced in the female zebrafish but not in males. Further analyses revealed that TDCIPP resulted in notable histological injury of intestine, which was accompanied by impairment of epithelial barrier integrity (decreased tight junction protein 2), inflammation responses (increased interleukin 1β) , and disruption of neurotransmission (increased serotonin) in female intestine. Male intestines maintained intact intestinal structure, and the remarkably increased activity of glutathione peroxidase (GPx) might protect the male zebrafish from inflammation and intestinal damage. Furthermore, 16S rRNA sequencing analysis showed that TDCIPP significantly altered the microbial communities in the intestine in a gender-specific manner, with a remarkable increase in alpha diversity of the gut microbiome in male zebrafish, which might be another mechanism for male fish to protect their intestines from damage by TDCIPP. Correlation analysis revealed that abnormal abundances of pathogenic bacteria (Chryseobacterium, Enterococcus, and Legionella) might be partially responsible for the impaired epithelial barrier integrity and inhibition in female zebrafish growth. Taken together, our study for the first time demonstrates the high susceptibility of intestinal health and gut microbiota of zebrafish to TDCIPP, especially for female zebrafish, which could be partially responsible for the female-biased growth inhibition. [ABSTRACT FROM AUTHOR]

Tris (2-butoxyethyl) phosphate (TBOEP) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. Recently, the reproductive and developmental toxicology of TBOEP has been reported. However, fewer studies have assessed the neurotoxic effects in zebrafish ( Danio rerio ) larvae. In this study, zebrafish embryos were subjected to waterborne exposure of TBOEP at 0, 50, 500, 1500 and 2500 μg/L from 2 to 144-h post-fertilization (hpf). Behavioral measurements showed that TBOEP exposure reduced embryonic spontaneous movement and decreased swimming speed of larvae in response to dark stimulation. In accordance with these motor effects, TBOEP treatment reduced neuron-specific GFP expression in transgenic Tg ( HuC -GFP) zebrafish larvae and inhibited the growth of secondary motoneurons, as well as decreased expression of marker genes related to central nervous system development in TBOEP treated group. Furthermore, increased concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as reduction of SOD activity were detected in TBOEP exposure group. The present results showed that the alteration in motor neuron and oxidative stress could together lead to the motor behavior alterations induced by TBOEP. [ABSTRACT FROM AUTHOR]

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) could have neurotoxic effects and alter motor behaviors in zebrafish ( Danio rerio ) larvae, however, the underlying mechanisms are still unknown. In this study, zebrafish embryos were subjected to waterborne exposure of TDCIPP at 100, 300, 600, 900 μg/L from 2 to 120-h post-fertilization (hpf). Behavioral measurements indicate that TDCIPP exposure significantly elevated spontaneous movement, and altered swimming behavior response of larvae to both light and dark stimulation. Interestingly, in accordance with these motor effects, TDCIPP significantly decreased expression of the neuron-specific GFP in transgenic ( HuC -GFP) zebrafish larvae as well as decreased expression of the neural marker genes elavl3 and ngn1 , inhibited the axonal growth of the secondary motoneurons and altered the expressions of axon-related genes ( α1-tubulin , shha and netrin2 ) in zebrafish larvae. Furthermore, TDCIPP exposure at 900 μg/L significantly increased the activity of acetylcholinesterase (AChE) enzyme, and decreased the total acetylcholine (ACh) concentration. Our data indicate that the alteration in motor neuron and inhibition of cholinergic system could together lead to the TDCIPP induced motor behavior alterations in zebrafish larvae. [ABSTRACT FROM AUTHOR]

Tris (2-butoxyethyl) phosphate (TBOEP), is used as a flame retardant worldwide. It is an additive in materials and can be easily discharged into the surrounding environment. There is evidence linking TBOEP exposure to abnormal development and growth in zebrafish embryos/larvae. Here, using zebrafish embryo as a model, we investigated toxicological effects on developing zebrafish ( Danio rerio ) caused by TBOEP at concentrations of 0, 20, 200, 1000, 2000 μg/L starting from 2 h post-fertilization (hpf). Our findings revealed that TBOEP exposure caused developmental toxicity, such as malformation, growth delay and decreased heart rate in zebrafish larvae. Correlation analysis indicated that inhibition of growth was possibly due to down-regulation of expression of genes related to the growth hormone/insulin-like growth factor (GH/IGF) axis. Furthermore, exposure to TBOEP significantly increased thyroxine (T4) and 3,5,3′-triiodothyronine (T3) in whole larvae. In addition, changed expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis was observed, indicating that perturbation of HPT axis might be responsible for the developmental damage and growth delay induced by TBOEP. The present study provides a new set of evidence that exposure of embryo-larval zebrafish to TBOEP can cause perturbation of GH/IGF axis and HPT axis, which could result in developmental impairment and growth inhibition. [ABSTRACT FROM AUTHOR]

The binary tungsten boride, WB, has potential industrial applications as it not only has a high melting point but is generally harder and less compressible than the pure metals. Here, the physical and mechanical properties (phase stability, bulk modulus and compressibility) of WB were investigated by in situ high-pressure x-ray diffraction and theoretical calculations. Its crystal structure still remains stable even at the highest pressure of 63.7 GPa and room temperature for the diamond-anvil cell experiments. The pressure-volume ( P-V ) data were fitted using the Birch-Murnaghan EOS and the Vinet EOS to obtain the isothermal bulk modulus, K 0 = 452 (4) GPa and 451(3) GPa and its pressure derivative, K 0 ′ = 4 (fixed) in the two sets of experiments with two different pressure transmitting mediums (PTMs), respectively. The excellent bulk modulus ( K 0 ) is attributed to the high valence electron density of W atom, the layered and chain-like crystal structure of WB and the strong chemical bonds formed by W and B atoms. Besides, anisotropic compression behavior of the unit-cell axes ( a - and c -axes) of WB is manifested by experimental observations and theoretical calculations. This remarkably elastic property is closely related to the strongly directional bonding between W and B atoms. [ABSTRACT FROM AUTHOR]