Genetically engineered membrane-based nanoengagers for immunotherapy of pancreatic cancer.

Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive "cold" pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane.

Micro and Macro Flooding Mechanism and Law of a Gel Particle System in Strong Heterogeneous Reservoirs.

To address the issue of ineffective injection resulting from the consistent channeling of injected water through highly permeable channels in ultra-deep, high-temperature, high-salinity, and strongly heterogeneous reservoirs during the production process, a gel particle profile control agent suitable for high-temperature and high-salinity conditions was chosen. With the help of the glass etching visual microscopic model and the heterogeneous long core model, the formation mechanism of a water flooding channeling path and the distribution law of the remaining oil were explored, the microscopic profile control mechanism of the different parameters was clarified, and the profile control effect of macroscopic core displacement was analyzed. The research shows that the formation mechanism of a water flooding channeling path is dominated by the distribution law of the permeability section and the connection mode between different penetration zones. The remaining oil types after water flooding are mainly contiguous block, parallel throats, and multi-branch clusters. The profile control effect of gel particles on reservoir vertical heterogeneity is better than that of reservoir lateral heterogeneity. It was found that 10 wt% submicron particles with a median diameter of 600 nm play a good role in profiling and plugging pores of 5-20 µm. In addition, 10 wt% micron-sized particles with a median diameter of 2.63 µm mainly play a strong plugging role in the pores of 20-30 µm, and 5 wt% micron-sized particles with a median diameter of 2.63 µm mainly form a weak plugging effect on the pores of 10-20 µm. The overall profile control effect of 10 wt% submicro particles is the best, and changes in concentration parameters have a more significant effect on the profile control effect. In the macroscopic core profile control, enhanced oil recovery (EOR) can reach 16%, and the gel particles show plugging, deformation migration, and re-plugging. The research results provide theoretical guidance for tapping the potential of the remaining oil in strong heterogeneous reservoirs. To date, the gel particles have been applied in the Tahe oilfield and have produced an obvious profile control effect; the oil production has risen to the highest value of 26.4 t/d, and the comprehensive water content has fallen to the lowest percentage of 32.1%.

Dual-coupling effect enables a high-performance self-powered UV photodetector.

Self-powered ultraviolet photodetectors generally operate by utilizing the built-in electric field within heterojunctions or Schottky junctions. However, the effectiveness of self-powered detection is severely limited by the weak built-in electric field. Hence, advances in modulating the built-in electric field within heterojunctions are crucial for performance breakthroughs. Here, we suggest a method to enhance the built-in electric field by taking advantage of the dual-coupling effect between heterojunction and the self-polarization field of ferroelectrics. Under zero bias, the fabricated AgNWs/TiO2/PZT/GaN device achieves a responsivity of 184.31 mA/W and a specific detectivity of 1.7 × 1013 Jones, with an on/off ratio of 8.2 × 106 and rise/decay times reaching 0.16 ms/0.98 ms, respectively. The outstanding properties are primarily attributed to the substantial self-polarization of PZT induced by the p-GaN and the subsequent enhancement of the built-in electric field of the TiO2/PZT heterojunction. Under UV illumination, the dual coupling of the enhanced heterojunction and the self-polarizing field synergistically boost the photo-generated carrier separation and transport, leading to breakthroughs in ferroelectric-based self-powered photodetectors.

Effects of Dietary Fish Meal Replaced by Fish Steak Meal on Growth Performance, Antioxidant Capacity, Intestinal Health and Microflora, Inflammatory Response, and Protein Metabolism of Large Yellow Croaker Larimichthys crocea.

Although fish steak meal (FSM) is a potentially available protein source, its efficiency as a fish meal (FM) substitute remains unclear to date. To this end, this study was carried out to determine the effects of dietary FM replaced by FSM on growth performance, antioxidant capacity, intestinal health and microflora, inflammatory response, and protein metabolism of large yellow croaker. Five isolipidic and isonitrogenous diets were formulated by substituting FM with FSM at levels of 0% (FSM0, control diet), 25% (FSM25), 50% (FSM50), 75% (FSM75), and 100% (FSM100), and were fed to juvenile large yellow croaker for 8 weeks. Compared with the control diet, the replacement of 25% dietary FM with FSM did not markedly alter the weight gain (WG) and specific growth rate (SGR). When the FM substitution level was over 25%, WG and SGR markedly reduced. The intestinal structure observation found that the FSM75 and FSM100 diets markedly decreased villus height, villus width, and muscle thickness of the anterior intestine. The FSM75 and FSM100 diets significantly decreased enzyme activities of amylase (AMS), lipase (LPS), trypsin, catalase (CAT), and total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), and increased the malondialdehyde (MDA) content in the liver of large yellow croaker. The mRNA expression levels of intestinal barrier and inflammatory response-related genes suggested that the FSM50, FSM75, and FSM100 diets significantly decreased the mRNA abundances of intestinal barrier-related genes and anti-inflammatory response-related genes, and increased the mRNA abundances of proinflammatory gene il-6 in the anterior intestine. The compositions of intestinal microflora displayed that the FSM50, FSM75, and FSM100 diets decreased relative abundances of Firmicutes phylum and increased relative abundances of Proteobacteria phylum. In addition, the results of protein expression levels showed that the phosphorylation level of mammalian target of rapamycin (mTOR) and 4E-binding protein 1 (4E-BP1) in FSM75 and FSM100 groups were markedly reduced. In conclusion, FSM can replace up to 25% dietary FM without compromising the growth performance, intestinal health, and protein metabolism of the large yellow croaker.

Partial Substitution of Fish Meal with Soy Protein Concentrate on Growth, Liver Health, Intestinal Morphology, and Microbiota in Juvenile Large Yellow Croaker (Larimichthys crocea).

The present study investigated the growth performance, feed utilization, intestinal morphology, and microbiota communities of juvenile large yellow croaker (Larimichthys crocea) fed diets containing different proportions of soy protein concentrate (SPC) (0, 15%, 30%, and 45%, namely FM, SPC15, SPC30, and SPC45) as a substitute for fish meal (FM) for 8 weeks. The weight gain (WG) and specific growth rate (SGR) in fish fed SPC45 were significantly lower than those fed FM and SPC15 but not differ with these fed SPC30. The feed efficiency (FE) and protein efficiency ratio (PER) decreased sharply when the dietary SPC inclusion level was higher than 15%. The activity of alanine aminotransferase (ALT) and expression of alt and aspartate aminotransferase (ast) were significantly higher in fish fed SPC45 than those fed FM. The activity and mRNA expression of acid phosphatase were opposite. The villi height (VH) in distal intestine (DI) showed a significant quadratic response to increasing dietary SPC inclusion levels and was highest in SPC15. The VH in proximal intestine, middle intestine decreased significantly with increasing dietary SPC levels. The 16S rRNA sequences in intestine revealed that fish fed SPC15 had higher bacterial diversity and abundance of Phylum Firmicutes such as order Lactobacillales and order Rhizobiaceae than those fed other diets. Genus vibrio, family Vibrionaceae and order Vibrionales within phylum Proteobacteria were enriched in fish fed FM and SPC30 diets. Tyzzerella and Shewanella that belongs to phylum Firmicutes and Proteobacteria, respectively, were enriched in fish fed SPC45 diet. Our results indicated that SPC replacing more than 30% FM could lead to lower quality diet, retard growth performance, ill health, disordered intestine structure, and microbiota communities. Tyzzerella could be the bacteria indicator of intestinal in large yellow croaker fed low quality diet due to high SPC content. Based on the quadratic regression analysis of WG, the best growth performance could be observed when the replacement of FM with SPC was 9.75%.

Effects of Compound Feed Attractants on Growth Performance, Feed Utilization, Intestinal Histology, Protein Synthesis, and Immune Response of White Shrimp (Litopenaeus Vannamei).

To investigate the effects of compound attractants on the growth performance, feed utilization, intestinal morphology, protein synthesis, and immune response of Litopenaeus vannamei, the following seven diets were formulated: a positive control (P), a negative control (N), and five diets with compound attractants which were labeled as A, B, C, D, and E, each with four of five tested attractants (yeast extract, squid visceral powder, fish soluble, and squid paste, shrimp paste), respectively. Shrimp (0.71 ± 0.00 g) were distributed to seven groups of four replicates and fed for 7 weeks. Results showed that the final body weight, feed intake, specific growth rate, and weight gain of shrimp in the B and D groups were the greatest. Hemolymph total antioxidant capacity of shrimp in the B, D, and E groups reached the highest level. In the hepatopancreas, the activity of total nitric oxide synthase, malondialdehyde content, the expression levels of sod, myd88, eif4e2, and raptor in shrimp fed the B diet were the highest, and the highest levels of dorsal and relish were observed in the C group. In the intestine, intestinal muscle thickness and expression levels of toll and eif2α in the C group were the highest, while the highest expression level of sod and relish occurred in the B group. In summary, the B and E diets promoted the feed intake, growth performance and the antioxidant enzyme activity of L. vannamei. The C diet enhanced the protein synthesis of shrimp. Regression analysis indicated that the WG and FI of shrimp were increased as the dietary inclusion levels of squid paste and shrimp paste increased, while they were decreased as the dietary inclusion levels of yeast extract and fish soluble increased.

An efficient synthesis of deuterium-labeled degarelix acetate, a third-generation gonadotropin-releasing hormone receptor antagonist.

Degarelix acetate, a third-generation gonadotropin-releasing hormone receptor antagonist, shows great potential in the treatment of many androgen-related diseases. To support clinical studies of degarelix acetate, deuterium-labeled degarelix is highly desired for use as an internal standard. Using D2 O/D3 PO4 as a deuterium source, 2-amino-3-(naphthalen-2-yl)propanoic acid was converted to deuterated degarelix acetate in 13 steps and in 14% overall yield.

2-[(5-Methyl-thio-phen-2-yl)methyl-idene]malono-nitrile.

There are two independent molecules in the asymmetric unit of the title compound, C9H6N2S, which is an inter-mediate compound of a cardiovascular drug. The two molecules are nearly planar, displaying dihedral angles of 3.5 (2) and 5.7 (2)° between the thiophene ring and the malononitrile moiety. In the crystal, C-H⋯N inter-actions lead to the formation of a sheet structure that packs in a parallel fashion.