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Red swamp crayfish, Procambarus clarkii, is the most cultured freshwater crayfish species. It attracts significant research attention due to its considerable economic importance. However, the limited availability of genome information has impeded further genetic studies and breeding programs. By utilizing Illumina, PacBio, and Hi-C sequencing technologies, we present a more comprehensive and continuous chromosome-level assembly for P. clarkii than the published one. The final genome size is 4.03 Gb, consisting of 2,358 scaffolds with a N50 of 42.87 Mb. Notably, 3.68 Gb, corresponding to 91.42% of the genome, was anchored to 94 chromosomes. The assembly comprises 70.64% repetitive sequences, including 5.21% tandem repeats and 65.40% transposable elements. Additionally, a total of 4,456 non-coding RNAs and 28,852 protein-coding genes were predicted in the P. clarkii genome, with 96.26% of the genes were annotated. This high-quality genome assembly not only represents a significant improvement for the genome of P. clarkii and provides insights into the unique genome evolution, but also offers valuable information for developing freshwater aquaculture and accelerating genetic breeding. [ABSTRACT FROM AUTHOR]

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]

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]

Cadmium (Cd), a non-biodegradable contaminant in freshwater ecosystems, can pose a serious threat to aquatic animals at high levels. In this study, the Cd toxicokinetics and the immune and antioxidant defense were explored in Procambarus clarkii exposed to different levels of Cd (0, 0.1, 1.0 mg Cd/L) or treated with 1.0 mg Cd/L and dietary Bacillus subtilis supplementation (1 × 107 cfu/g). Results from the 21-day uptake and depuration experiment revealed that Cd exposure elicited a dose- and time-dependent uptake in all crayfish tissues, and the rank order of Cd concentration was gill > hepatopancreas > exoskeleton > muscle. The one-compartment model demonstrated that gills had the highest uptake rate (ku) value after Cd aqueous exposure and the ku and elimination rate (kd) values in gill, hepatopancreas, and exoskeleton of the group with 1.0 mg Cd/L were higher than those of the group at alow Cd concentration (0.1 mg Cd/L). However, B. subtilis could decrease Cd ku and increase Cd kd in hepatopancreas, resulting in the reduction of bioconcentration factors (BCF), steady-state concentrations (Css), and biological half-life (Tb1/2). A positive correlation was found between aqueous Cd concentration and the severity of hepatopancreas histopathological injury, while B. subtilis could ameliorate the pathological damage in the high Cd group. Similarly, aqueous exposure to Cd elevated malonaldehyde (MDA) content and suppressed the activities of lysozyme (LZM), acid phosphatase (ACP) in hepatopancreas and alkaline phosphatase (AKP) in hemolymph. The activities of superoxide dismutase (SOD) and catalase (CAT) in hepatopancreas were also inhibited. Nevertheless, they were all recovered with the dietary addition of B. subtilis. In conclusion, our results indicated that exposure to Cd significantly increased Cd accumulation and toxic damages in crayfish hepatopancreas, while dietary administration of B. subtilis to crayfish significantly decreased Cd accumulation and improved the immune and antioxidant defense, leading to the prevention in toxic effects of Cd. [ABSTRACT FROM AUTHOR]

Contamination with heavy metals in wild red swamp crayfish (Procambarus clarkii) from 7 different geographical areas in six provinces of China (Hubei, Hunan, Jiangxi, Anhui, Jiangsu, and Shandong) was evaluated. Concentrations of chromium (Cr), arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg) in the abdominal muscle, gonad, and hepatopancreas were determined by inductively coupled plasma mass spectrometry (ICP-MS) and atomic fluorescence spectrometer (AFS). Except for the Cd content in the hepatopancreas, the contents of selected heavy metals in three different tissues were significantly lower than the proposed limits provided by United States Environmental Protection Agency (USEPA). The maximum accumulations of Cd and Pb were in the hepatopancreas, while the maximum accumulation of As was in the gonad, and the maximum accumulations of Hg and Cr were in the abdominal muscle. The highest contents of Cr, Hg, and Pb were all detected in Dongting Lake, Hunan, which was consistent with the trend of the metal pollution index (MPI). Risk value of the target hazard quotient (THQ) was below 1.0, suggesting that the intake of selected heavy metals through crayfish consumption would not pose a significant health risk to consumers. [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]

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]

The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB. [ABSTRACT FROM AUTHOR]

Phase-pure nanostructured WB ceramics are hot pressed at ultrahigh pressures of 1.0 to 3.0 GPa and high temperatures of 700 to 1000 °C (UHPHT) for 60 min. The UHPHT samples are nanograin size from 15 to 40 nm. Our experimental observation shows that ultrahigh pressure could improve densification, and the density of WB samples could reach 99.4% of theoretical. The comparative experiments carried out at ambient pressure and temperatures of 550 to 1100 °C for 60 min indicate that the external pressure was favorable for phase-pure and highly dense WB formation. In addition, the UHPHT samples give a high hardness value of 28.9 ± 0.8 GPa. [ABSTRACT FROM AUTHOR]

Nanostructured bulk NiAl materials were prepared at high pressure and temperature (0–5.0 GPa and 600–1500 °C, respectively). The sintered samples were characterized by x-ray diffraction, scanning electron microscope, density, and indentation hardness measurements. The results show that NiAl nanoparticles may have a compressed surface shell, which may be the reason why NiAl nanomaterials were difficult to densify sintering using conventional methods and why high-pressure sintering was an effective approach. We also observed that B2-structured NiAl could undergo a temperature-dependent phase transition and could be transformed into Al0.9Ni4.22 below 1000 °C for the first time. It is interesting to note that Vickers hardness decreased as grain size decreased below ∼30 nm, indicating that the inverse Hall-Petch effect may be observed in nano-polycrystalline NiAl (n-NiAl) samples. Moreover, a tentative interpretation was developed for high-pressure nanosintering, based on the shell-core model of nanoparticles. [ABSTRACT FROM AUTHOR]

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.

Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing neurotoxicity, but the exact mechanisms of action still remain unclear. Using proteomic analysis, forty-five proteins were identified to be significantly altered in hippocampal neurons of rats treated with MCLR. Among them, Ca2+-activated phosphatase calcineurin (CaN) and the nuclear factor of activated T-cells isoform c3 (NFATc3) were up-regulated remarkably. Validation of the changes in CaN and NFATc3 expression by Western blotting demonstrated CaN cleavage and subsequent NFATc3 nuclear translocation were generated, suggesting that exposure to MCLR leads to activation of CaN, which in turn activates NFATc3. Activation of CaN signaling has been reported to result in apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member Bad. In agreement with this, our results revealed that treatment of neurons with the CaN inhibitor FK506 blocked the reduction in Bad dephosphorylation and cytochrome c (cyt c) release triggered by MCLR. Consistent with these biochemical results, we observed a marked decrease in apoptotic and necrotic cell death after MCLR exposure in the presence of FK506, supporting the hypothesis that MCLR appeared to cause neuronal toxicity by activation of CaN and the CaN-mediated mitochondrial apoptotic pathway. [ABSTRACT FROM AUTHOR]