Strategies for overcoming bottlenecks in allogeneic CAR-T cell therapy.

Patient-derived autologous chimeric antigen receptor (CAR)-T cell therapy is a revolutionary breakthrough in immunotherapy and has made impressive progress in both preclinical and clinical studies. However, autologous CAR-T cells still have notable drawbacks in clinical manufacture, such as long production time, variable cell potency and possible manufacturing failures. Allogeneic CAR-T cell therapy is significantly superior to autologous CAR-T cell therapy in these aspects. The use of allogeneic CAR-T cell therapy may provide simplified manufacturing process and allow the creation of 'off-the-shelf' products, facilitating the treatments of various types of tumors at less delivery time. Nevertheless, severe graft-versus-host disease (GvHD) or host-mediated allorejection may occur in the allogeneic setting, implying that addressing these two critical issues is urgent for the clinical application of allogeneic CAR-T cell therapy. In this review, we summarize the current approaches to overcome GvHD and host rejection, which empower allogeneic CAR-T cell therapy with a broader future.

Genetic and epidemic characteristics of porcine parvovirus 7 in the Fujian and Guangdong regions of southern China.

Porcine parvovirus (PPV) is the primary cause of reproductive disorders in pigs. The porcine parvovirus 7 (PPV7) subtype was first identified in the United States in 2016. In this study, PPV7 was detected in different porcine samples, including serum, feces, saliva, and milk, from 69 pig farms in the Fujian and Guangdong regions of South China, and its coinfection with porcine circovirus 2 (PCV2), porcine circovirus 3 (PCV3), and porcine reproductive and respiratory syndrome virus (PRRSV) was determined. Whole-genome sequencing, phylogenetic analysis, and recombination analysis were performed on seven isolates, with each selected isolate originating from a different farm. There was a high rate of PPV7 positivity in blood, stool, and saliva but PPV7 DNA was absent from breast milk. The findings also showed that PPV7-positive samples had a high rate of coinfection with PCV2, PCV3, and PRRSV. Real-time PCR was used to determine the viral copy numbers of PCV2, PCV3, PRRSV, and PPV7 in serum samples and to assess whether PPV7 affected PCV2, PCV3, and PRRSV viral loads. Phylogenetic analysis showed that PPV7e and PPV7f were the most prevalent and widespread subtypes in the Fujian and Guangdong regions, respectively. While the PPV7a, PPV7b, PPV7c, and PPV7f subtypes were most prevalent in Fujian Province, PPV7a-e subtypes were prevalent in Guangdong, indicating that PPV7 has rich genetic diversity in these regions. A putative recombinant strain, 21FJ09, was identified using SimPlot and the Recombination Detection Program 4 software.

Activity pattern study of Asiatic black bear (Ursus thibetanus) in the Qinling Mountains, China, by using infrared camera traps.

The study of activity patterns is important for understanding the capacity of animals for adapting their behavior based on their habitat conditions. Among bears, daily activity patterns are considered to be strongly influenced by regional climate conditions. We monitored the activity patterns (active vs. inactive) of the Asiatic black bear (Ursus thibetanus) using infrared camera traps (from May 2013 to November 2016) in the Qinling Mountains, China. We used 125 photos, with 19,132 camera days from 55 camera locations. Based on relative independent capture (RIC), bears were found to be intensively active during June (5.86 ± 1.05 SE), July (8.45 ± 2.74), September (14.83 ± 6.13), and October (8.70 ± 3.43), with activity levels gradually decreasing beyond October. After this decline, activities eventually come to a halt when the bears enter in hibernation. We found that their hibernation period was shorter in the Qinling bears, with only 3 months of denning from January to March. Based on their daily patterns, bears were predominantly active during the daytime both in spring (70.83 ± 35.41%) and summer (52.09 ± 28.89%), but more active at twilight during autumn (51.12 ± 42.88%). We assumed that food preferences and food availability (due to warmer regional climatic conditions) might be responsible for such deviations in daily and monthly activity patterns.

Novel "signal-on" electrochemiluminescence biosensor for the detection of PSA based on resonance energy transfer.

Here, we propose a simple and novel "signal-on" electrochemiluminescence (ECL) biosensor based on resonance energy transfer (RET) for detection of prostate specific antigen (PSA). The system is composed of Multi-walled carbon nanotubes (MWCNT), polyamidoamine (PAMAM) dendrimer and Au nanoparticles (NPs) film on glassy carbon electrode (GCE) to improve the electron transfer, provide abundant amine group for the immobilization of biomolecules, and amplify the ECL signal. After that, Au nanorods (Au NRs) labeled peptide is modified on electrode surface to serve as ECL-RET acceptor due to the excellent overlap between the ECL emission spectrum of Ru(bpy)32+ and the absorption spectrum of Au NRs, leading to the significant decrement of ECL signal. Upon the sensing cleavage of peptide with PSA, both Au NRs and peptide are released from electrode surface, resulting in the high recovery efficiency of ECL signal. The proposed approach exhibits a wide linear range from 0.1pg/mL to 10ng/mL with a detection limit of 0.03pg/mL. Results revealed that the recoveries were in a range from 95% to 108%, indicating good accuracy of the proposed method for PSA detection. In addition, the proposed biosensor exhibited well specificity for the detection of PSA.