Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48-0.85), 0.94 (0.72-1.23), 0.68 (0.50-0.92) and 1.62 (1.24-2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.

Simultaneous sensing profiles of beam attenuation coefficient and volume scattering function at 180° using a single-photon underwater elastic-Raman lidar.

Lidar has emerged as a promising technique for vertically profiling optical parameters in water. The application of single-photon technology has enabled the development of compact oceanic lidar systems, facilitating their deployment underwater. This is crucial for conducting ocean observations that are free from interference at the air-sea interface. However, simultaneous inversion of the volume scattering function at 180° at 532 nm (ßm) and the lidar attenuation coefficient at 532 nm (K l i d a r m) from the elastic backscattered signals remains challenging, especially in the case of near-field signals affected by the geometric overlap factor (GOF). To address this challenge, this work proposes adding a Raman channel, obtaining Raman backscattered profiles using single-photon detection. By normalizing the elastic backscattered signals with the Raman signals, the sensitivity of the normalized signal to variations in the lidar attenuation coefficient is significantly reduced. This allows for the application of a perturbation method to invert ßm and subsequently obtain the K l i d a r m. Moreover, the influence of GOF and fluctuations in laser power on the inversion can be reduced. To further improve the accuracy of the inversion algorithm for stratified water bodies, an iterative algorithm is proposed. Additionally, since the optical telescope of the lidar adopts a small aperture and narrow field of view design, K l i d a r m tends to the beam attenuation coefficient at 532 nm (cm). Using Monte Carlo simulation, a relationship between cm and K l i d a r m is established, allowing cm derivation from K l i d a r m. Finally, the feasibility of the algorithm is verified through inversion error analysis. The robustness of the lidar system and the effectiveness of the algorithm are validated through a preliminary experiment conducted in a water tank. These results demonstrate that the lidar can accurately profile optical parameters of water, contributing to the study of particulate organic carbon (POC) in the ocean.

Shipborne single-photon fluorescence oceanic lidar: instrumentation and inversion.

Laser-induced fluorescence (LIF) technology has been widely applied in remote sensing of aquatic phytoplankton. However, due to the weak fluorescence signal induced by laser excitation and the significant attenuation of laser in water, profiling detection becomes challenging. Moreover, it remains difficult to simultaneously retrieve the attenuation coefficient (K l i d a r m f) and the fluorescence volume scattering function at 180° (ßf) through a single fluorescence lidar. To address these issues, a novel all-fiber fluorescence oceanic lidar is proposed, characterized by: 1) obtaining subsurface fluorescence profiles using single-photon detection technology, and 2) introducing the Klett inversion method for fluorescence lidar to simultaneously retrieve K l i d a r m f and ßf. According to theoretical analysis, the maximum relative error of ßf for the chlorophyll concentration ranging from 0.01 mg/m3 to 10 mg/m3 within a water depth of 10 m is less than 20%, while the maximum relative error of K l i d a r m f is less than 10%. Finally, the shipborne single-photon fluorescence lidar was deployed on the experimental vessel for continuous experiments of over 9 hours at fixed stations in the offshore area, validating its profiling detection capability. These results demonstrate the potential of lidar in profiling detection of aquatic phytoplankton, providing support for studying the dynamic changes and environmental responses of subsurface phytoplankton.

Structural architecture of TolQ-TolR inner membrane protein complex from opportunistic pathogen Acinetobacter baumannii.

Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for both division and survival. The IM TolQ-TolR complex is the essential part of the Tol-Pal system, serving as a conduit for PMF energy transfer to the outer membrane. Here we present cryo-EM reconstructions of Acinetobacter baumannii TolQ in apo and TolR- bound forms at atomic resolution. The apo TolQ configuration manifests as a symmetric pentameric pore, featuring a trans-membrane funnel leading towards a cytoplasmic chamber. In contrast, the TolQ-TolR complex assumes a proton non-permeable stance, characterized by the TolQ pentamer's flexure to accommodate the TolR dimer, where two protomers undergo a translation-based relationship. Our structure-guided analysis and simulations support the rotor-stator mechanism of action, wherein the rotation of the TolQ pentamer harmonizes with the TolR protomers' interplay. These findings broaden our mechanistic comprehension of molecular stator units empowering critical functions within the Gram-negative bacterial cell envelope. Teaser: Apo TolQ and TolQ-TolR structures depict structural rearrangements required for cell envelope organization in bacterial cell division.

S-Sulfenylation Driven Antigen Capture Boosted by Radiation for Enhanced Cancer Immunotherapy.

Radiotherapy (RT)-induced in situ vaccination greatly promotes the development of personalized cancer vaccines owing to the massive release of antigens initiated by tumor-localized RT eliciting the tumor-specific immune response. However, its broad application in cancer treatment is seriously impeded by poor antigen cross-presentation, low response rate, and short duration of efficacy. Herein, the tumor-antigen-capturing nanosystem dAuNPs@CpG consisting of gold nanoparticles, 3,5-cyclohexanedione (CHD), and immunoadjuvant CpG were fabricated to enhance RT-induced vaccination. Taking advantage of the specific covalent binding between CHD and sulfenic acids of antigen proteins, we show that this nanoplatform has an unexpected potential to capture the sulfenylated tumor-derived protein antigens (TDPAs) induced by RT to in situ generate a vaccination effect, achieving significant growth suppression of both primary and distant tumors in combination with PD-1 blockade. We thus believe that our work presents a powerful and effective means to improve the synergistic tumor radioimmunotherapy.