Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells ...in patients with progressive relapsed or refractory Hodgkin lymphoma.
Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).
Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 10
CAR-positive T cell per kg (SD, 0.25; range, 1.1-2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.
CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment.
.
Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants ...including patients with stage 1-5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD.
The halophyte Suaeda salsa displayed strong resistance to salinity. Up to date, molecular mechanisms underlying tolerance of S. salsa to salinity have not been well understood. In the present study, ...S. salsa seedlings were treated with 30‰ salinity and then leaves and roots were subjected to Illumina sequencing. Compared with the control, 68,599 and 77,250 unigenes were significantly differentially expressed in leaves and roots in saline treatment, respectively. KEGG enrichment analyses indicated that photosynthesis process, carbohydrate, lipid and amino acid metabolisms were all downregulated in saline treatment, which should inhibit growth of S. salsa. Expression levels of Na+/H+ exchanger, V-H+ ATPase, choline monooxygenase, potassium and chloride channels were upregulated in saline treatment, which could relieve reduce over-accumulation of Na+ and Cl-. Fe-SOD, glutathione, L-ascorbate and flavonoids function as antioxidants in plants. Genes in relation to them were all upregulated, suggesting that S. salsa initiated various antioxidant mechanisms to tolerate high salinity. Besides, plant hormones, especially auxin, ethylene and jasmonic acid signaling transduction pathways were all upregulated in response to saline treatment, which were important to gene regulations of ion transportation and antioxidation. These changes might comprehensively contribute to tolerance of S. salsa to salinity. Overall, the present study provided new insights to understand the mechanisms underlying tolerance to salinity in halophytes.
Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial ...omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G
or G
trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.
The undoped and Mo-doped TiO2 nanoparticles were synthesized by sol-gel method. The as-prepared samples were characterized by X-ray diffraction (XRD), diffuse reflectance UV-visible absorption ...spectra (UV-vis DRS), X-ray photoelectron spectra (XPS), and transmission electron microscopy (TEM). The photocatalytic activity was evaluated by photocatalytic degradation of methylene blue under irradiation of a 500 W xenon lamp and natural solar light outdoor. Effects of calcination temperatures and Mo doping amounts on crystal phase, crystallite size, lattice distortion, and optical properties were investigated. The results showed that most of Mo6+ took the place of Ti4+ in the crystal lattice of TiO2, which inhibited the growth of crystallite size, suppressed the transformation from anatase to rutile, and led to lattice distortion of TiO2. Mo doping narrowed the band gap (from 3.05 eV of TiO2 to 2.73 eV of TiMo0.02O) and efficiently increased the optical absorption in visible region. Mo doping was shown to be an efficient method for degradation of methylene blue under visible light, especially under solar light. When the calcination temperature was 550°C and the Mo doping amount was 2.0%, the Mo-doped TiO2 sample exhibited the highest photocatalytic activity.
Graphene/cotton composite fabrics were successfully synthesized
via
a facile "dipping and drying" process followed by a NaBH
4
reduction method. The flexible 3D conductive network constructed by ...graphene sheets greatly enhances the conductivity of cotton fabrics. The morphology, structure and conductivity of the graphene/cotton composite fabrics were detailed characterized using scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR) and a standard four-point probe method. Electrochemical measurements demonstrated that the graphene/cotton composite fabrics were used as flexible electrodes for electrochemical capacitors showing good capacitance, excellent mechanical flexibility, and good stability, which may lead to their future potential application in flexible and wearable electronic devices.
Graphene/cotton composite fabrics were successfully synthesized
via
a facile "dipping and drying" process followed by a NaBH
4
reduction method.
γ‐Aromatic butenolides (γ‐AB) are an important type of structures found in many bioactive microbial secondary metabolites (SMs). γ‐AB refer to a group of natural products (NPs) containing ...five‐membered (unsaturated) lactones with 3‐phenyl and 4‐benzyl substituents. Their wide‐range biological activities have inspired pharmaceutical chemists to explore its biosynthesis mechanisms and design strategies to construct the γ‐AB skeleton. Recently, there are a great deal of interesting research progress on the structures, biological activities and biosynthesis of γ‐AB. This review will focus on these aspects and summarize the important achievements of γ‐AB from 1975 to 2021.
Textile-based electrode materials have attracted intensive attention for flexible supercapacitors. However, the low electrochemical capacitance hinders their further application. In this study, MnO2 ...with high theoretical capacitance was successfully deposited on the conductive graphene/polyester composite fabric using a hydrothermal method. The MnO2 morphology can be controlled by adjusting the reaction time. The effects of MnO2 morphology, electrode structure, mechanical bending and stretching on the electrochemical performance of MnO2/graphene/polyester composite electrode materials were studied in detail. When a MnO2 sheet layer deposited on the graphene/polyester composite fabric, the resulted composite electrode material exhibited a specific capacitance of 332Fg−1 at a scan rate of 2mVs−1 and excellent cycling stability. The electrochemical performances of MnO2/graphene/polyester composite electrode material and its corresponding solid-state supercapacitor device were stable under mechanical bending and stretching conditions.
Abstract
The aroma of peach fruit is predominantly determined by the accumulation of γ-decalactone and ester compounds. A previous study showed that the biosynthesis of these aroma compounds in peach ...fruit is catalyzed by PpAAT1, an alcohol acyltransferase. In this work, we investigated the key active site residues responsible for γ-decalactone and ester biosynthesis. A total of 14 candidate amino acid residues possibly involved in internal esterification and 9 candidate amino acid residues possibly involved in esterification of PpAAT1 were assessed via site-directed mutagenesis. Analyses of the in vitro enzyme activities of PpAAT1 and its site-directed mutant proteins (PpAAT1-SMs) with different amino acid residue mutations as well as the contents of γ-decalactone in transgenic tobacco leaves and peach fruits transiently expressing PpAAT1 and PpAAT1-SMs revealed that site-directed mutation of H165 in the conserved HxxxD motif led to lost enzymatic activity of PpAAT1 in both internal esterification and its reactions, whereas mutation of the key amino acid residue D376 led to the total loss of γ-decalactone biosynthesis activity of PpAAT1. Mutations of 9 and 7 other amino acid residues also dramatically affected the enzymatic activity of PpAAT1 in the internal esterification and esterification reactions, respectively. Our findings provide a biochemical foundation for the mechanical biosynthesis of γ-decalactone and ester compounds catalyzed by PpAAT1 in peach fruits, which could be used to guide the molecular breeding of new peach species with more favorable aromas for consumers.
Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their ...structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1–9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD50 values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).
PDF
