Phase I study of MSB2311, a novel pH-dependent anti-PD-L1 monoclonal antibody, treating patients with advanced solid tumors and lymphoma.

MSB2311 is a novel pH-dependent humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody. This phase I study primarily aimed to determine the maximum tolerated dose (MTD)/recommended phase 2 dose level (RP2D) of MSB2311 in patients with advanced solid tumors or lymphoma. MSB2311 was intravenously administered at 3, 10, and 20 mg/kg every 3 weeks (Q3W) and 10 mg/kg every 2 weeks (Q2W) using 3 + 3 design. During expansion phase, eligible patients with either PD-L1 overexpression, Epstein-Barr Virus positive, microsatellite instability high/mismatch repair deficient, or high tumor mutation burden tumors were treated at RP2D. A total of 37 Chinese patients were treated, including 31 with solid tumors and 6 lymphoma. No dose limiting toxicity was reported and MTD was not reached. The trial was expanded at 20 mg/kg Q3W or 10 mg/kg Q2W, both of which were determined as RP2D. Most common drug-related treatment-emergent adverse events were anemia (43.2%), aspartate aminotransferase increase (27.0%), proteinuria (21.6%), alanine aminotransferase increase and hypothyroidism (18.9% each), thyroid stimulating hormone increased and hyperglycemia (16.2% each). Out of 20 efficacy evaluable patients with biomarker positive solid tumors, 6 achieved confirmed partial response with the median duration of response of 11.0 months (95% CI 7.0-11.4) and 4 had stable disease, resulting an objective response rate of 30.0% (95% CI 11.9, 54.3) and disease control rate of 50.0% (95% CI 27.2, 72.8). One partial response was also observed among 6 patients with lymphoma. MSB2311 demonstrated a manageable safety profile and promising antitumor activity in patients with advanced solid tumors and lymphomas.

Epidemic situation of the complex seasonality of imported influenza A and B virus transmission in Guangxi ports of China

Background/aim: Analysis of the characteristics of influenza virus in imported cases in Guangxi province of China. Materials and methods: Throat swabs of imported cases with influenza-like symptoms were detected by real-time PCR from July 2016 to December 2019. Results: 1292 laboratory detections of influenza were reported in 3974 influenza-like cases, of which 71.67% (926) were influenza A. The ratio of test positive was 32.82%. The proportion of detections of influenza B was 28.33% (366). A total of 70.51% of the cases mostly came from Vietnam (911). A total of 86.76% (1121) of the cases were imported from Dongxing Port, Nanning Airport, and Pingxiang Port. There was no statistical difference in all age groups. At the same time, 3 of the untyped A-type specimens were sequenced by next- generation sequencing. Among them, the sequences of 2 specimens from Vietnam had high homology with the influenza strain H3N2 in Hong Kong in 2017. The specimen sequence from Thailand is highly homologous to the influenza pandemic strain H1N1 in Brisbane, Australia in 2018. Conclusion: Imported influenza cases in Guangxi have occurred throughout the year, with higher numbers in winter and spring. The cases mostly came from Vietnam with influenza A. Relevant measures should be taken to control the further spread of the virus.

A naphthalimide-based fluorescent probe for rapid detection of nitrite and its application in food quality monitoring.

Nitrite (NO2-) is a widely used food additive and long-term aging of cooked leftovers may also contribute to the formation of NO2-, excessive consumption of NO2- is harmful to human health. Developing an effective sensing strategy for on-site monitoring of NO2- has attracted considerable attention. Herein, a novel colorimetric and fluorometric probe ND-1 based on photoinduced electron transfer effect (PET) was designed for highly selective and sensitive detection of nitrite (NO2-) in foods. The probe ND-1 was strategically constructed by employing naphthalimide as the fluorophore and o-phenylendiamine as the specific recognition site for NO2-. The triazole derivative ND-1-NO2- could be produced exclusively by reacting with NO2-, leading to a visible colorimetric change from yellow to colorless accompanied by a significantly enhanced fluorescence intensity at 440 nm. The probe ND-1 exhibited promising sensing performances towards NO2- including high selectivity, rapid response time (within 7 min), low detection limit (47.15 nM) and wide quantitative detection range (0-35 µM). In addition, probe ND-1 was capable of quantitative detecting of NO2- in real food samples (including pickled vegetables and cured meat products) with satisfactory recovery rates (97.61%-103.08%). Moreover, the paper device loaded by probe ND-1 could be utilized for visual monitoring of NO2- levels variation of stir-fried greens. This study provided a feasible method for the accurate, traceable and rapid on-site monitoring NO2- in foods.

Four-channel fluorescent sensor array based on various functionalized CdTe quantum dots for the discrimination of Chinese baijiu.

As a special carrier of traditional Chinese culture, baijiu is rich in terms of types and ingredients. Its quality analysis and control are always important and complex issues that urgently need reliable evaluation methods. In this study, four different modified CdTe quantum dots (QDs) were used to characterize their sensing performance to various baijiu. A sensor array was then constructed through the complementary properties of differential fluorescence signals. To achieve an accurate and rapid evaluation of different baijiu types, a linear discriminant analysis (LDA) was introduced to extract and process spectral information. And the array was able to distinguish commercial baijiu samples with different aroma-types, brands, qualities and storage years with a recognition rate of 100%. In addition, according to the heat map, the organic acids in baijiu were shown to be the main components causing the fluorescence change through electron transfer (hydrogen bond) and resonance energy transfer among QDs and acids. Furthermore, using the partial least squares regression (PLSR) model, five representative organic acids were accurately quantified with a quantitative range of 10 µmol/L-80 µmol/L with a high selectivity. This QDs fluorescence sensing strategy provides an accurate, simple, and fast baijiu sensing method, which provides a potential use for on-line baijiu monitoring.

Quantitative trait loci determining weight reduction of testes and pituitary by diethylstilbesterol in LEXF and FXLE recombinant inbred strain rats.

Increasing exposure to environmental endocrine disruptor, xeno-estrogen, is a serious hazard to male reproductive activity. To explore possible genetic control in susceptibility to xeno-estrogen, the weight reduction of testes induced by the continuous administration of a synthetic estrogen, diethylstilbesterol, were investigated by quantitative trait analysis in LEXF and FXLE recombinant inbred strain rats, consisting of 21 independent strains, 9 of their substrains, parental F344/Stm and LE/Stm strains, and (F344 x LE)F1. For the weight of testes, one highly significant quantitative trait locus (QTL) and one significant QTL were mapped on chromosomes 7 and 1, respectively. The QTL on chromosome 7 is closely associated with c-myc. Pituitary weight and serum prolactin were also variable among recombinant inbred strains, but no QTL was detected for them in this study.

Cigarette smoke impairs NK cell-dependent tumor immune surveillance.

In this study, we investigated the impact of cigarette smoke on tumor immune surveillance and its consequences to lung tumor burden in a murine lung metastasis model. Cigarette smoke exposure significantly increased the numbers of lung metastases following B16-MO5 melanoma challenge. This effect was reversible; we observed significantly fewer tumor nodules following smoking cessation. Using RAG2(-/-) and RAG2(-/-)gamma(c)(-/-) mice, we provide strong evidence that increased tumor incidence was NK cell dependent. Furthermore, we show that cigarette smoke suppressed NK activation and attenuated NK CTL activity, without apparent effect on activating or inhibitory receptor expression. Finally, activation of NK cells through bone marrow-derived dendritic cells conferred protection against lung metastases in smoke-exposed mice; however, protection was not as efficacious as in sham-exposed mice. To our knowledge, this is the first experimental evidence showing that cigarette smoke impairs NK cell-dependent tumor immune surveillance and that altered immunity is associated with increased tumor burden. Our findings suggest that altered innate immunity may contribute to the increased risk of cancer in smokers.

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice.

OBJECTIVE: To analyze the influence of the genetic background of an arthritis-prone strain of mice, MRL, on the spontaneous development of arthropathy in DBA/1 mice, which histopathologically resembles enthesopathy in humans, and to clarify the strain-specific gene loci and their interactions that confer susceptibility to arthropathy. METHODS: MRL, DBA/1, (MRL x DBA/1)F(1), and (MRL x DBA/1)F(2) intercross mice were prepared, and the severity and onset of arthropathy of the ankle joints in individual mice were quantified (0-3 and 0-5 scale, respectively). A genome-wide scan of 271 male F(2) intercross mice with polymorphic microsatellite markers was performed. RESULTS: Only male DBA/1, (MRL x DBA/1)F(1), and (MRL x DBA/1)F(2) mice developed arthropathy. The macroscopic and histopathologic findings of arthropathy in the F(2) mice were similar to those in the parental DBA/1 mice, but the onset was significantly earlier. In the quantitative trait locus analysis of male F(2) mice, 1 susceptibility locus for both the severity and early onset of the disease in the region of an MRL allele, Amd1, was located at marker D10Mit259 (map position 40.0 cM), which was common to 1 of the sialadenitis susceptibility loci in MRL mice, Asm1. Another susceptibility locus for the severity and early onset of arthropathy in the region of a DBA allele, Amd2, was located at D3Mit46 (29.5 cM). These loci manifested an additive effect on the development of arthropathy. CONCLUSION: Arthropathy in DBA/1 mice is under the control of an allelic combination of gene loci, one of which is common to the locus for sialadenitis in MRL/MpJ-lpr/lpr mice.

Genetic basis of tissue specificity of vasculitis in MRL/lpr mice.

OBJECTIVE: To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp-lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. METHODS: Vasculitis in individual MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr)F(1), and (MRL/lpr x C3H/lpr)F(2) intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F(2) intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. RESULTS: A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of medium-sized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. CONCLUSION: Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.