A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma.

Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody-cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma. ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab conjugation. The in vivo xenograft study demonstrated that ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed toxicity. Mass spectrometry analysis indicated that cell activation receptors including the TCR complex, integrins and cytokine receptors were conjugated with rituximab. Intriguingly, the antigen recognition of the ACC-linked antibody/receptor complex stimulated NFAT activation and contributed to ACE1831-mediated cytotoxicity against CD20-expressing cancer cells. This study elucidates the role of the ACC-linked antibody/receptor complex in cytotoxicity and supports the potential of ACE1831 as an off-the-shelf γδ2 cell therapy against relapsed/refractory B-cell lymphoma.

Local temperature responses to actual land cover changes present significant latitudinal variability and asymmetry.

Land cover changes (LCCs) affect surface temperatures at local scale through biophysical processes. However, previous observation-based studies mainly focused on the potential effects of virtual afforestation/deforestation using the space-for-time assumption, while the actual effects of all types of realistic LCCs are underexplored. Here, we adopted the space-and-time scheme and utilized extensive high-resolution (1-km) satellite observations to perform the first such assessment. We showed that, from 2006 to 2015, the average temperature in the areas with LCCs increased by 0.08 K globally, but varied significantly across latitudes, ranging from -0.05 to 0.18 K. Cropland expansions dominated summertime cooling effects in the northern mid-latitudes, whereas forest-related LCCs caused warming effects elsewhere. These effects accounted for up to 44.6% of overall concurrent warming, suggesting that LCC influences cannot be ignored. In addition, we revealed obvious asymmetries in the actual effects, i.e., LCCs with warming effects occurred more frequently, with stronger intensities, than LCCs with cooling effects. Even for the mutual changes between two covers in the same region, warming LCCs generally had larger magnitudes than their cooling counterparts due to asymmetric changes in transition fractions and driving variables. These novel findings, derived from the assessment of actual LCCs, provide more realistic implications for land management and climate adaptation policies.

Biophysical impacts of earth greening can substantially mitigate regional land surface temperature warming.

Vegetation change can alter surface energy balance and subsequently affect the local climate. This biophysical impact has been well studied for forestation cases, but the sign and magnitude for persistent earth greening remain controversial. Based on long-term remote sensing observations, we quantify the unidirectional impact of vegetation greening on radiometric surface temperature over 2001-2018. Here, we show a global negative temperature response with large spatial and seasonal variability. Snow cover, vegetation greenness, and shortwave radiation are the major driving factors of the temperature sensitivity by regulating the relative dominance of radiative and non-radiative processes. Combined with the observed greening trend, we find a global cooling of -0.018 K/decade, which slows down 4.6 ± 3.2% of the global warming. Regionally, this cooling effect can offset 39.4 ± 13.9% and 19.0 ± 8.2% of the corresponding warming in India and China. These results highlight the necessity of considering this vegetation-related biophysical climate effect when informing local climate adaptation strategies.

The dose-effect relationships of cigarette and alcohol consumption with depressive symptoms: a multiple-center, cross-sectional study in 5965 Chinese middle-aged and elderly men.

BACKGROUND: Although association of depressive symptoms with cigarette or alcohol is well documented, the dose-response relationship between them is rarely studied. This study aims to evaluate dose-response relationships of cigarette and alcohol consumption with depressive symptoms in Chinese middle-aged and elderly men, providing evidence to guide cigarette and alcohol control. METHODS: This multiple-center, cross-sectional study including 5965 Chinese men aged 40-79 years was conducted in 2013-2016 in China. Depressive symptoms were evaluated by Beck Depression Inventory-Short Form. History of cigarette smoking and alcohol drinking were collected with a structured questionnaire. Prevalence of depressive symptoms was compared depending on cigarette and alcohol consumption. Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated by binary logistic regression. Interpolation analysis was applied to test dose-effect relationships. RESULTS: A parabolic-shaped relationship was observed between cigarette consumption and depressive symptoms. Compared to never smokers, 59.0% (OR = 1.59, 95% CI 1.30-1.94) and 29.0% (OR = 1.29, 95% CI 1.08-1.54) higher odds of depressive symptoms were observed in men smoking < 10 cigarettes/day and 10-20 cigarettes/day, whereas, similar odds of depressive symptoms among men smoking > 20 cigarettes/day (P = 0.092). An inverted J-shaped relationship was observed between alcohol consumption and depressive symptoms. Compared to never drinkers, a tendency of higher prevalence of depressive symptoms (OR = 1.16, 95% CI 0.99-1.36) was observed in men drinking < 140 g/week, and similar prevalence was observed in those drinking 140-280 g/week (P = 0.920), whereas, 29.4% (OR = 0.71, 95% CI 0.57-0.88) lower odds in men drinking > 280 g/week. CONCLUSIONS: Associations of cigarette smoking and alcohol drinking with depressive symptoms differ with consumption in middle-aged and elderly men. Health-care providers should exercise great caution on depressive symptoms in conducting cigarette and alcohol control.

Associations of benzotriazoles and benzothiazoles with estrogens and androgens among pregnant women: A cohort study with repeated measurements.

People are extensively exposed to benzotriazoles (BTRs) and benzothiazoles (BTHs) derivatives, which are environmental pollutants that may possess endocrine-disrupting potential; however, no epidemiological evidence is available on the associations of BTRs and BTHs with estrogens and androgens. This study aimed at investigating the associations of BTRs and BTHs with estrogens and androgens among pregnant women. Based on a prospective cohort study, we included 459 pregnant women who donated a complete serial of urine samples at each trimester and had repeated measurements of four BTRs, four BTHs, three estrogens (estrone, 17ß-estradiol, and estrio), and two androgens (dehydroepiandrosterone and testosterone) in the urine samples. Associations of repeatedly measured BTRs and BTHs with maternal urinary estrogens and androgens were analyzed, and the cross-sectional associations were also analyzed. Tolyltriazole (TTR) (≥59.3%) and benzothiazole (BTH) (≥93.5%) had the highest detection rate among the BTRs and BTHs, respectively. Repeated measurement analysis and cross-sectional analysis consistently found the target BTRs and BTHs were positively associated with 17ß-estradiol, estriol, and testosterone, while the trend of the associations with estrone and dehydroepiandrosterone was inconsistent. Among the positive associations with 17ß-estradiol, estriol, and testosterone, the percent of change in estriol associated with TTR was the most prominent [28.5% (95% confidential interval: 24.2%, 32.9%) for each doubling in TTR]. The significant associations with estrone, estriol, testosterone, and dehydroepiandrosterone were stronger among pregnant women who gave birth to a boy than those who gave birth to a girl. These findings add epidemiological evidence on the endocrine-disrupting potential of BTRs and BTHs and highlight the importance of focusing on the health outcomes of BTRs and BTHs related to disturbed estrogens and androgens. Future studies are needed to validate these findings and explore the underlying mechanisms.

Prediction of vegetation phenology with atmospheric reanalysis over semiarid grasslands in Inner Mongolia.

Vegetation phenology is a sensitive indicator of climate change and vegetation growth. In the present study, two phenological phases with respect to vegetation growth at the initial and mature stages, namely, the start of the season (SOS) and the peak of the season (POS), were estimated from a satellite-derived normalized difference vegetation index (NDVI) dataset over a long-term period of 32 years (1983 to 2014) and used to explore their responses to atmospheric variables, including air temperature, precipitation, solar radiation, wind speed and soil moisture. First, the forward feature selection method was used to determine whether each independent variable was linear or nonlinear to the SOS and POS. In addition, a generalized additive model (GAM) was used to analyze the correlation between the phenological phases and each independent variable at different temporal scales. The results show that soil moisture and precipitation are linearly correlated with the SOS, whereas the other variables are nonlinearly correlated. Meanwhile, soil moisture, wind speed and solar radiation are found to be nonlinearly correlated with the POS. However, air temperature and precipitation reveal a significant negative correlation with the POS. Furthermore, it was concluded that the aforementioned independent variables from the previous year could contribute to approximately 63%-85% of the SOS variations in the present year, whereas the atmospheric variables from April to June could contribute to approximately 70%-85% of the POS variations in the same year. Finally, the SOS and POS predicted by the GAM exhibit significant agreement with those derived from the satellite NDVI dataset, with the root mean square error of approximately 3 to 5 days.

Comparison of the effectiveness of BG-trap mosquito traps using carbon dioxide versus BG-lure attractants / 中国热带医学

@#Abstract: Objective　To compare the mosquito trapping effect of BG-trap mosquito trap using carbon dioxide versus BG-lure attractant under filed conditions. Methods　In August and September 2020, two areas were set with a distance of 100 m. Two sites were set at each area, and one mosquito trap BG trap was set with a distance of 5 m. Each site was set with different flow of CO2 and different amount of BG-lure attractants. The BG-trap mosquito traps on the same area would exchange positions every other day. The mosquitoes captured by each mosquito trap was collected and classified. and the species, sex and number of mosquitoes captured were recorded and counted. Results　The densities of Aedes albopictus captured by BG+/CO2-and BG-/CO2+were 14 and 31, and that of Culex pipiens pallens were 2 and 16, respectively. The differences were statistically significant (Aedes albopictus, t=-2.675, P<0.05; Culex pipiens pallens, t=-4.873, P<0.05). With BG-lure attractant, the females of Aedes albopictus and Culex pipiens pallens in the CO2+group were 2.6 (25/9.5) and 12.0 (12 /1) times higher than those in the CO2-group, and the differences were statistically significant (female Aedes albopictus, t=-4.119, P<0.01; female Culex pipiens pallens, t=-4.592, P<0.01), suggesting that the most important attractant to female mosquitoes is CO2. With BG-lure attractant, the male Aedes albopictus in the CO2+ group was 3.0 (12/4) times higher than that in the CO2-group, and the difference was statistically significant (male Aedes albopictus, t=-3.284, P<0.01). Without BG-lure attractant, female Aedes albopictus and female Culex pipiens pallens in the CO2 + group were 1.8 (18 / 10) and 15.5 (15.5/1.0) times higher than those in the CO2-group, and the difference was statistically significant (female Aedes albopictus, t=-2.868, P<0.05; female Culex pipiens pallens, t=-5.259, P<0.05). Without BG-lure attractant, the male Aedes albopictus in the CO2+group was 2.0 (9.0/4.5) times higher than that in the CO2-group, with a statistically significant difference (t=-2.508, P<0.05). With CO2, Aedes albopictus and Culex pipiens pallens in the BG + attractant group were 1.4 (43.5/31) and 0.78 (12.5/16.0) times higher than those in the BG-attractant group, and the differences were not statistically significant (Aedes albopictus, t=-0.943, P>0.05 ; Culex pipiens pallens, t=0.709, P>0.05). Without CO2, Aedes albopictus and Culex pipiens pallens in the BG + attractant group were 1.0 (14/14) and 2.0 (2.0/1.0) times higher than those in the BG + attractant group, and the differences were not statistically significant (Aedes albopictus, t=-0.500, P>0.05; Culex pipiens pallens, t=-1.000, P>0.05). Without BG-lure attractant, the densities of female Aedes albopictus captured by adding 0, 1 and 2 parts of dry ice were 10, 17.5 and 18 respectively, and the difference was statistically significant among the three groups (F=3.942, P<0.05). The densities of female Culex pipiens pallens captured were 1, 13 and 18 respectively, and the difference was statistically significant among the three groups (F=13.881, P<0.05). However, there was no significant difference between the capture of female Aedes albopictus and female Culex pipiens pallens by adding 1 part of dry ice and 2 parts of dry ice (female Aedes albopictus, t=0.112, P>0.05; female Culex pipiens pallens, t=-0.540, P>0.05). Without CO2, 10, 10, 9.5 and 1, 1 and 1.5 female Aedes albopictus and Culex pipiens pallens were captured by adding 0, 1 and 2 portions of BG-lure attractants, respectively. There were no significant differences between the three groups (female Aedes albopictus, F=0.120, P>0.05; female Culex pipiens pallens, F=0.477, P>0.05). Conclusions　In the monitoring of BG-trap mosquito trap, the mosquito trapping effect of CO2 is better than that of BG-lure attractant. When the same monitoring effect is obtained, the use of CO2 (100 mL/min) can save the use cost.

Simulation of the Urban Space Thermal Environment Based on Computational Fluid Dynamics: A Comprehensive Review.

Rapid urbanization has made urban space thermal environment (USTE) problems increasingly prominent. USTE research is important for improving urban ecological environment and building energy consumption. Most studies on USTE research progress have focused on meteorological observations and remote sensing methods, and few studies on USTE are based on computational fluid dynamics (CFD). During the past two decades, with the increasing applications of CFD in USTE research, comprehensively summarizing the phased results have become necessary tasks. This paper analyzes the current research status of CFD-based USTE simulation from six perspectives. First, we summarize the current research status of USTE simulation with CFD models that integrate ground observations and remote sensing technology. Second, we define and classify the spatial scope of CFD-based USTE simulations at different scales. Third, we systematically analyze the quantitative relationships among urban land type, the underlying surface structure, water bodies, green space and the corresponding changes in CFD-based USTE simulations. Fourth, we quantitatively analyze the impact of anthropogenic heat in CFD-based USTE simulations. Fifth, we summarize the corresponding USTE mitigation measures and methods based on the CFD simulation results. Finally, the outlooks and the existing problems in current research on CFD simulations of the USTE are analyzed.

Coagulation-flocculation: a potential application for mosquito Larval Source Management (LSM).

Larval mosquitoes have a more limited home range and lower resistance to adverse environment than adults, thus can be ideal targets for vector control in some cases. Coagulation-flocculation technology, which could be used for water treatment in breeding sites of several vector mosquito species, can significantly change both the distribution of organic particles and surface sediment characteristics in water environment. The aim of this study was to explore the effect, principle and possibility of using coagulation-flocculation technology in immature mosquitoes killing. In this study, dechlorinated water was treated with Poly Aluminum Chloride (PACl, sewage treatment using), and we observed the impacts of PACl treatment on the development and survival of immature Culex pipiens pallens mosquitoes. When exposed to PACl treatment, physical effect is believed to be a main reason of coagulation-flocculation caused high larvae mortality: Ⅰ) alum floc layer increases the difficulty of larvae foraging, leads larvae starving to death; (Ⅱ) the little floc particles could attach to the lateral hair of larvae, which impede floatation process and then surface respiration by larval mosquitoes. The alum floc layer had a good killing effect on the mosquito larvae, presented the half lethal time (LT50) of 2d, the 90% lethal time (LT90) of 8.7±7.3 ∼ 14±4.5 d, and the pupation rate of 0 ∼ (6.5±0.5)%, respectively. Our results indicates alum floc, produced by PACl coagulation-flocculation, was shown to be highly active against 1st∼2nd instar larvae, the high mortality rate of immature mosquitoes as a result of physical effect. The observations suggest that coagulation-flocculation technology offers a novel potential approach to a sustainable and low-impact mosquito control method.

Autogeny, Fecundity, and Other Life History Traits of Culex pipiens molestus (Diptera: Culicidae) in Shanghai, China.

Culex pipiens molestus Forskål is common in subterranean and aboveground environments in Shanghai, China. However, little is known about its autogeny, fecundity, and other life history traits. In this study, Cx. p. molestus larvae were collected from four different types of underground parking lots and artificially maintained, without blood feeding, in a laboratory. Life history traits parameters were recorded from the F0 to F9 generation. Culex pipiens molestus from Shanghai can autogenously persist for at least 10 generations, and some females can develop more than one egg batch without blood feeding (oviposition rate in Lot C was >100% in some generations). The average number of eggs per raft produced autogenously ranged from 36.94 to 42.19. The average generation time (GT) ranged from 20.06 to 21.30 d, and the pre-oviposition time (POT) ranged from 2.17 to 12.68 d among the generations. Culex pipiens molestus from the four groups had different autogeny, fecundity, and longevity patterns. This variability may result from genetic polymorphism caused by co-occurrence with other Culex pipiens subspecies (Diptera: Culicidae).

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric identification and antifungal susceptibility analysis of Candida species isolated from patients with invasive yeast infections in five university hospitals.

In this multicenter study, we compared the performance of the Bruker Biotyper MS system and VITEK 2 YST systems for invasive yeast identification, investigated the distribution of isolated species, and evaluated the antifungal susceptibility profiles of Candida albicans, Candida parapsilosis, and Candida tropicalis. In cases of discrepant results lack of identification with either method, molecular identification techniques were employed. We tested 216 clinical isolates, and concordance between the two methods was observed for 192/216 isolates (88.9%). For five unidentified strains (2.3%), an internal transcribed spacer (ITS) sequencing approach was used. In brief, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) provided short turnaround times and more reliable results than those of Vitek 2 YST. In Wuhan, C. albicans, C. parapsilosis, Candida glabrata, and C. tropicalis were the most common pathogens (93.0%) in patients with candidemia. Cryptococcus neoformans was mainly detected in cerebrospinal fluid samples (88.9%). Trichosporon asahii were all isolated from drainage fluids in the Surgery. Candida albicans was clearly susceptible to azoles, while C. parapsilosis and C. tropicalis displayed differences in susceptibility to azoles. Our findings provide a basis for the practical application of MALDI-ToF MS for identification and for the use of ATB FUNGUS 3 to characterize the susceptibility of Candida spp., thereby providing significant data for therapeutic decisions.

Fucoidan induces Toll-like receptor 4-regulated reactive oxygen species and promotes endoplasmic reticulum stress-mediated apoptosis in lung cancer.

Fucoidan, a sulfated polysaccharide extracted from brown algae, exhibits anti-cancer activity. However, the effects and mechanism of fucoidan-induced apoptosis via endoplasmic reticulum (ER) stress is unclear. In this study, we demonstrated that fucoidan prevents tumorigenesis and reduces tumor size in LLC1-xenograft male C57BL/6 mice. Fucoidan induces an ER stress response by activating the PERK-ATF4-CHOP pathway, resulting in apoptotic cell death in vitro and in vivo. Furthermore, ATF4 knockdown abolishes fucoidan-induced CHOP expression and rescues cell viability. Specifically, fucoidan increases intracellular reactive oxygen species (ROS), which increase ATF4 and CHOP in lung cancer cells. Using the ROS scavenger N-acetyl-l-cysteine (NAC), we found that ROS generation is involved in fucoidan-induced ER stress-mediated apoptosis. Moreover, via Toll-like receptor 4 (TLR4) knockdown, we demonstrated that fucoidan-induced ROS and CHOP expression were attenuated. Our study is the first to identify a novel mechanism for the antitumor activity of fucoidan. We showed that fucoidan inhibits tumor viability by activating the TLR4/ROS/ER stress axis and the downstream PERK-ATF4-CHOP pathway, leading to apoptosis and suppression of lung cancer cell progression. Together, these results indicate that fucoidan is a potential preventive and therapeutic agent for lung cancer that acts via activation of ROS-dependent ER stress pathways.

A novel, colorimetric method for biogenic amine detection based on arylalkylamine N-acetyltransferase.

We developed a novel colorimetric method for rapid detection of biogenic amines based on arylalkylamine N-acetyltransferase (aaNAT). The proposed method offers distinct advantages including simple handling, high speed, low cost, good sensitivity and selectivity.

Allosteric regulation of a protein acetyltransferase in Micromonospora aurantiaca by the amino acids cysteine and arginine.

ACT domains (amino acid-binding domains) are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Seventy proteins with ACT-GCN5-related N-acetyltransferase (GNAT) domain organization were found in actinomycetales. In this study, we investigate the ACT-containing GNAT acetyltransferase, Micau_1670 (MaKat), from Micromonospora aurantiaca ATCC 27029. Arginine and cysteine were identified as ligands by monitoring the conformational changes that occur upon amino acids binding to the ACT domain in the MaKat protein using FRET assay. It was found that MaKat is an amino acid-regulated protein acetyltransferase, whereas arginine and cysteine stimulated the activity of MaKat with regard to acetylation of acetyl-CoA synthetase (Micau_0428). Our research reveals the biochemical characterization of a protein acetyltransferase that contains a fusion of a GNAT domain with an ACT domain and provides a novel signaling pathway for regulating cellular protein acetylation. These findings indicate that acetylation of proteins and acetyltransferase activity may be tightly linked to cellular concentrations of some amino acids in actinomycetales.

[SRY gene-testing in the diagnosis of disorders of sex development among children].

OBJECTIVE: To investigate the value of direct sequencing of sex-determining region Y (SRY) gene, as well as peripheral blood karyotype analysis, in the diagnosis of disorders of sex development (DSD) among children and adolescents with ambiguous genitalia. METHODS: The karyotypes of 20 children and adolescents with ambiguous genitalia were determined by conventional G-banding analysis. PCR amplification was used to detect SRY gene in these patients, and direct sequencing was used to judge whether there was SRY gene mutation. RESULTS: Of the 20 cases, 17 were positive for SRY gene, and 3 were negative for SRY gene. Direct sequencing revealed no SRY gene mutation in the positive cases, however karyotype analysis found 4 special karyotypes in these patients: 46, XY, del(Y) (q12)/45, X; 46, XY, add(Y) (p11); 46, XY, r(9); 46, XY, 9qh+. CONCLUSIONS: SRY gene detection can help determine the type of DSD among children and has the advantage of quick detection. Used together with G-banding analysis, it is helpful for primary diagnosis of DSD among children.

[Estimation of vegetation canopy water content using Hyperion hyperspectral data].

Vegetation canopy water content (VCWC) has widespread utility in agriculture, ecology and hydrology. Based on the PROSAIL model, a novel model for quantitative inversion of vegetation canopy water content using Hyperion hyperspectral data was explored. Firstly, characteristics of vegetation canopy reflection were investigated with the PROSAIL radiative transfer model, and it was showed that the first derivative at the right slope (980 - 1 070 nm) of the 970 nm water absorption feature (D98-1 070) was closely related to VCWC, and determination coefficient reached to 0.96. Then, bands 983, 993, 1 003, 1 013, 1 023, 1 033, 1 043, 1 053 and 1 063 nm of Hyperion data were selected to calculate D980-1 070, and VCWC was estimated using the proposed method. Finally, the retrieval result was verified using field measured data in Yingke oasis of the Heihe basin. It indicated that the mean relative error was 12.5%, RMSE was within 0.1 kg x m(-2) and the proposed model was practical and reliable. This study provides a more efficient way for obtaining VCWC of large area.