Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vγ9Vδ2 T cells.

In both cancer and infections, diseased cells are presented to human Vγ9Vδ2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A11-4. Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vγ9Vδ2 T cell activation. Analyses using structure-based molecular-dynamics simulations, 19F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated γδ T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human γδ T cell function.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

A structure-dependent ratiometric fluorescence sensor based on metal-organic framework for detection of 2,6-pyridinedicarboxylic acid.

In the present work, a structure-dependent ratiometric fluorescence (RF) sensor constructed with boric acid-modified carbon quantum dots (B-CQDs) and Tb-MOF(MOF-76) was developed for sensing 2,6-pyridinedicarboxylic acid (DPA). Based on the distinct fluorescent responses of B-CQDs and MOF-76 to DPA, MOF-76/B-CQDs can be developed as a RF sensor for DPA detection. In this RF sensor, the reticulated cross-linked structure of MOF-76/B-CQDs can be destroyed by DPA due to a strong coordination effect between DPA and the Tb of MOF-76, resulting in the quenching of the fluorescence of B-CQD and the restoration of the fluorescence of MOF-76 after the addition of DPA. Benefiting from the confinement effect of the special structure change, the presented sensor showed high sensitivity toward DPA with a detection limit of 3.05 µM and excellent selectivity over the monochromatic fluorescence sensor.

Preparation and Application of Nanozymes with Uricase-Like Activity Based on Molecularly Imprinted Polymers.

Nanozymes have advantages over natural enzymes in terms of efficiency, stability, and economy. MVSM (Mixed Valence State MOF) is a nano-oxidase with uricase-like activity that may catalyze uric acid (UA) in the body into allantoin and H2 O2 to treat gout and hyperuricemia by substituting natural uricase. However, it cannot specifically identify and choose UA. To increase the selectivity and affinity of MVSM for UA, the composite material MVSM@MIP is innovatively synthesized using a new synthetic approach termed the "two-step synthesis method," which may prevent UA from being oxidized by MVSM during manufacture in this study. At the same time, this study also provides experimental proof of the effective creation of the material, the advantages of the "two-step synthesis approach," and the high selectivity and affinity of MVSM@MIP for UA. Based on these findings, the suggested technique may be used to effectively catalyze uric acid in human urine with high activity.

COVID-19 vaccination status and associated factors among lactating women during the COVID-19 outbreak: a cross-sectional study in southern China.

OBJECTIVES: Different countries and institutions around the world have debated whether lactating women should receive the COVID-19 vaccine during the COVID-19 pandemic. In China, lactating is not a contraindication to vaccination, but many women are still hesitant to get vaccinated. The purpose of this study was to investigate the current status of COVID-19 vaccination among lactating women and the related factors affecting vaccination. METHODS: An online cross-sectional survey involving 506 lactating women was conducted in southern China. We explored the related factors affecting COVID-19 vaccination of lactating women from three aspects: general information, knowledge-attitude-behaviour towards COVID-19 and its vaccine, and postpartum psychological state. RESULTS: A total of 432 lactating women completed the questionnaire, 198 of whom had received the COVID-19 vaccine. On the knowledge-attitude-behaviour questionnaire on COVID-19 and its vaccines, the vaccinated group scored higher than the unvaccinated group on both the three subdimensions of the questionnaire and the total score (p<0.01). The results of binary logistics regression analysis showed that mixed feeding (OR=2.68, 95% CI: 1.82 to 3.96), longer breastfeeding duration (OR=1.31, 95% CI: 1.16 to 1.49), better physical condition (OR=5.28, 95% CI: 1.82 to 15.32), higher attitude score of COVID-19 and its vaccine (OR=1.18, 95% CI: 1.10 to 1.27), and having a travel history in medium high-risk areas (OR=3.49, 95% CI: 1.46 to 8.37) were significantly associated with COVID-19 vaccination in lactating women. Having a master's degree or above (OR=0.03, 95% CI: 0.01 to 0.30), and having higher anxiety score (OR=0.66, 95% CI: 0.54 to 0.81) and depression score (OR=0.84, 95% CI: 0.75 to 0.93) were inversely associated with COVID-19 vaccination in lactating women. CONCLUSION: 45.8% of lactating women were vaccinated against COVID-19. Education level, feeding methods, duration of breast feeding, travel history in medium high-risk areas, physical condition, attitude score of COVID-19 and its vaccine, anxiety symptom and depressive symptom score were associated with vaccination of lactating women. More interventions based on these factors were needed to reduce concerns for lactating women and increase their vaccination rates.

Sulfonic acid-functionalized PCP(Cr) catalysts with Cr3+ and -SO3H sites for 5-ethoxymethylfurfural production from glucose.

5-Ethoxymethylfurfural (EMF) has been identified as a potential biofuel and fuel additive, for which the production from glucose (the most abundant and inexpensive monosaccharide) in a one-step process would be highly desirable. Here, the synthesis of sulfonic acid-functionalized porous coordination polymers (PCPs) and their application as catalysts for EMF synthesis are reported. PCP(Cr)-BA (PCP material with Cr3+ ions and H2BDC-SO3H linkers) and PCP(Cr)-NA (PCP material with Cr3+ ions and H2NDC(SO3H)2 linkers) materials containing both Cr3+ sites and Brønsted-acidic -SO3H sites were prepared. The morphology, pore structure, acidity, chemical composition, and thermal stability of the two functionalized PCP(Cr) catalysts were analyzed by systematic characterization. The catalysts featured a porous morphology and dual Cr3+ and -SO3H sites, which enabled the cascade conversion of glucose to EMF. PCP(Cr)-BA exhibited higher performance than PCP(Cr)-NA with an EMF yield of 23.1% in the conversion of glucose at 140 °C after 22 h in an ethanol/water system. In addition, the as-prepared catalyst exhibited a high stability in the current catalytic system for EMF production from glucose with a constant catalytic activity in a four-run recycling test without an intermediate regeneration step.