Interface-regulated S-type core-shell PCN-224@TiO2 heterojunction for visible-light-driven generation of singlet oxygen for selective photooxidation of 2-chloroethyl ethyl sulfide.

Selective oxidation of sulfur mustard gas (HD) to non-toxic sulfoxide by the visible-light-catalyzed generation of singlet oxygen (1O2) is a promising degradation strategy. Although PCN-224 can absorb visible light, it suffers from rapid electron-hole recombination and low redox capacity, which limits the performance of HD degradation. Titanium dioxide (TiO2) is an excellent photocatalyst but it lacks visible-light-activity in degrading HD. In this study, PCN-224@TiO2 heterojunction with S-type core-shell structure was synthesized by in-situ growth method to prolong the visible light absorption capacity of TiO2 and inhibit the rapid recombination of PCN-224. The interface formation and internal electric field were optimized by adjusting the Zr/Ti ratio to enhance the charge transfer, redox capacity, electron-hole separation, and visible light absorption. In this study, the formation of heterojunction composites based on Zr-O-Ti linkages is demonstrated by a series of characterization methods. It is demonstrated by experiments and theoretical calculations that PCN-224@TiO2 can generate nearly 100 % 1O2 under visible light conditions without a sacrificial agent, resulting in efficient and selective oxidation of 2-chloroethyl ethyl sulfide (CEES), a simulant of HD, to non-toxic sulfoxide form.

Construction of logic gate computation for the assay of the nerve agent sarin based on an AChE-based dual-channel sensing system.

Nerve agents have posed a huge threat to national and human security, and their sensitive detection is crucial. Herein, based on the oxidation of Ce4+ and the aggregation-induced emission (AIE) of glutathione-protected gold nanoclusters (GSH-Au NCs), a cascade reaction was designed to prepare oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) and GSH-Au NCs crosslinked by Ce3+ (Ce3+-GSH-Au NCs). oxTMB had a broad UV-visible absorption range (500-700 nm) and was capable of quenching the fluorescence of Ce3+-GSH-Au NCs at 590 nm through the internal filtration effect (IFE). Thiocholine (TCh), the hydrolysis product of acetylthiocholine chloride (ATCl) catalyzed by acetylcholinesterase (AChE), reduced oxTMB completely, resulting in a decrease in the absorption of oxTMB and the recovery of IFE-quenched fluorescence of Ce3+-GSH-Au NCs. Nerve agent sarin (GB) hindered the production of TCh and the reduction of oxTMB by inhibiting the AChE activity, leading to the fluorescence of Ce3+-GSH-Au NCs being quenched again. The dual-output sensing system (AChE + ATCl + oxTMB + Ce3+-GSH-Au NCs) exhibited a low limit of detection to GB (2.46 nM for colorimetry and 1.18 nM for fluorimetry) and excellent selectivity toward common interferences being unable to inhibit AChE. Moreover, the intelligent logic gate constructed based on the sensing system showed promising applications in the field of smart sensing of nerve agents.

A predictive model for premature atherosclerosis in systemic lupus erythematosus based on clinical characteristics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE. METHOD: The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81%) met the definition of premature atherosclerosis. Hypertension, antiphospholipid syndrome, azathioprine use, duration of glucocorticoid, and age of patients were included in the multivariable regression. The nomogram, based on the non-overfitting multivariable model, was internally validated and demonstrated sufficient clinical utility for assessing the risk of premature atherosclerosis (area under curve: 0.867). CONCLUSIONS: The comprehensive nomogram constructed in this study serves as a useful and convenient tool for evaluating the risk of premature atherosclerosis in SLE patients. It is helpful for clinicians to early identify SLE patients with premature atherosclerosis and facilitates the implementation of more effective preventive measures. Key Points • SLE patients are at a significantly higher risk of developing premature atherosclerosis compared to the general population, and this risk persists even in cases with low disease activity. Traditional models used to evaluate and predict premature atherosclerosis in SLE patients often underestimate the risk. • This study establishes a comprehensive and visually orientated predictive model of premature atherosclerosis in SLE patients, based on clinical characteristics. • The scoring system allows for convenient and effective prediction of individual incidence of premature atherosclerosis, and could provide valuable information for identification and making further intervention decision.

Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder.

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).

Designing diverse coordination modes for the covalent attachment of Wells-Dawson type polyoxometalate onto porphyrins.

Five covalently bonded polyoxometalate (POM)-porphyrin hybrids were synthesized by reacting the Wells-Dawson type polyoxometalate [N(C4H9)4]5H4P2W15V3O62 with five tris-functionalized porphyrins containing different numbers of tris groups at different peripheral positions. These hybrids were thoroughly characterized using elemental analysis, NMR (1H, 31P, and 51V), mass spectrometry (ESI-MS, MALID-TOF-MS), FT-IR, UV-Vis, and fluorescence spectroscopies. The results proved that different quantities (one, two, and three) of the vanadium-capped Wells-Dawson type metal-oxide cluster P2W15V3O629- can be grafted onto a porphyrin moiety via covalent bonding with different orientations, depending on the number and position of peripheral functional groups on the porphyrin. Interestingly, remarkable fluorescence quenching (60% in 3Py-P@1POM, 75% in trans-2PyP@2POM, 80% in cis-2PyP@2POM, 85% in cis-2PhP@2POM, and 55% in 1Py-P@3POM, as compared to the fluorescence intensity of their corresponding porphyrin precursor) was observed under excitation (λexc = 328 nm), indicating electron transfer from the porphyrin moiety to the POM moiety through covalent linkage.

Rapid diffusion of H2 and strong adsorption of D2 in Ni-4PyC realized the efficient separation of H2/D2 by gas chromatography.

In this work, Ni-4PyC was selected as the material for the separation of hydrogen isotopes H2/D2, and the mechanism of hydrogen isotope H2/D2 separation was investigated by molecular simulation. The results showed that the adsorption selectivity of Ni-4PyC for D2/H2 increased from 1.26 to 1.46 when the temperature was decreased from 77 K to 20 K, indicating that Ni-4PyC effected chemical affinity quantum sieving on D2/H2. Also, the diffusion rates of H2/D2 were different at different temperatures. At 20 K, the kinetic selectivity of D2/H2 reached 1.30, indicating that Ni-4PyC had a kinetic quantum sieving effect on D2/H2 at low temperatures. However, when the temperature was higher than 30 K, the diffusion rate of H2 was faster than that of D2, and when the temperature was 77 K, Ni-4PyC exhibited the kinetic sieving effect with a kinetic selectivity of 1.59 for H2/D2. Due to the chemical affinity quantum sieving and kinetic sieving effects of Ni-4PyC on H2/D2, the adsorption capacity of Ni-4PyC for D2 was better than that for H2 and the diffusion rate of H2 was faster than that of D2 at 77 K. Therefore, Ni-4PyC was expected to achieve the separation of H2/D2. In order to verify the accuracy of the theoretical calculation results, an Ni-4PyC@γ-Al2O3 composite material was synthesized by a liquid phase epitaxy method and was used to separate H2/D2 at 77 K in a 0.6 m × 2 mm chromatographic column. Under optimal separation conditions, the resolution R reached 1.84 with a separation time t = 7.47 min. In addition, Ni-4PyC@γ-Al2O3 showed excellent separation performances for different ratios of H2/D2 mixtures. The stationary phase was repeatable and reproducible.

Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe).

It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.

H2/D2 Separation Using UTSA-16@CAU-10-H@γ-AlOOH Composites as the Stationary Phase in Gas Chromatography via the Additive Effects of Kinetic Sieving and Chemical Affinity Quantum Sieving.

In this work, CAU-10-H@γ-AlOOH is prepared, and then UTSA-16 is loaded on CAU-10-H@γ-AlOOH to obtain UTSA-16@CAU-10-H@γ-AlOOH. Using the as-prepared composites as stationary materials by cryogenic gas chromatography at 77 K, while CAU-10-H@γ-AlOOH achieves the complete separation of ortho-H2 (o-H2) and D2 with a resolution R of 1.66 and a separation time t of 9.52 min, UTSA-16@CAU-10-H@γ-AlOOH achieves higher efficiency separation of hydrogen isotopes in a shorter separation time (4.56 min) with R = 1.7. Molecular simulation results show that CAU-10-H has both chemical affinity quantum sieving and kinetic sieving effects for H2/D2 at 77 K, and UTSA-16 can only exert the kinetic sieving effect. UTSA-16's load on CAU-10-H@γ-AlOOH weakens the adsorption of hydrogen isotopes, and the presence of Co2+ in UTSA-16 promotes the conversion of para-H2 to ortho-H2. In gas chromatography, H2 was preferentially desorbed from the system due to strong D2 adsorption caused by the chemical affinity quantum sieving effect and faster H2 diffusion caused by the kinetic sieving effect. These additive effects achieved efficient hydrogen isotope separation at 77 K.

H2/D2 separation in gas chromatography through a MOF-on-MOF strategy using γ-AlOOH@Al(OH)(1,4-NDC)@ZIF-67 as the stationary phase via additive effects of chemical affinity quantum sieving and kinetic sieving.

The reaction of porous γ-Al2O3 particles acting as both a sacrificial template and an aluminum source with 1,4-naphthalene diacid (H2NDC) resulted in the formation of γ-AlOOH@Al(OH)(1,4-NDC) composites, in which ZIF-67 was then loaded by the in situ crystallization method, leading to the formation of γ-AlOOH@Al(OH)(1,4-NDC)@ZIF-67 composites. The deliberately designed composite was used to separate H2/D2 at 77 K in a 1 m chromatographic column. The results demonstrated that the optimized composite can achieve the effective separation of H2/D2 in gas chromatography due to the additive effects of kinetic sieving and chemical affinity quantum sieving of Al(OH)(1,4-NDC) and ZIF-67. By optimizing chromatographic separation conditions, the resolution R reached 2.02 with the separation time t = 7.72 min. The composite also showed satisfactory repeatability and reproducibility.

Differentiation of lower limb vasculitis from physiological uptake on FDG PET/CT imaging.

PURPOSES: To analyze the difference of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) uptake between vasculitis and non-vasculitic patients in PET/CT imaging and the factors related to vascular uptake in non-vasculitic patients. To investigate the feasibility of identifying vasculitis of the lower limb and physiological uptake with delayed imaging. PROCEDURES: Among 244 patients who underwent PET/CT examination, imaging features of patients with or without vasculitis were retrospectively analyzed. The factors related to FDG uptake in the lower limb vessels of non-vasculitic patients were analyzed. Another 44 patients with suspected systemic vasculitis in PET/CT were prospectively studied to analyze the efficacy of delayed imaging on differentiating vascular uptake in lower limbs. RESULTS: In PET/CT imaging of patients with vasculitis, involvement of trunk vessels showed segmental or diffuse FDG distribution. Lower limb vascular involvement showed reticular uptake accompanied by nodular or patchy changes. In non-vasculitic patients, vascular uptake mainly showed linear uptake in lower limb vessels and there was no significant difference in uptake degree compared with vasculitis patients. Body weight and interval time were the independent influence factors of vascular uptake in lower limbs of non-vasculitic patients. In delayed imaging, lower limb vasculitis all showed reticular uptake and physiological uptake all showed a linear pattern. ROC analysis showed the change rate of SUVmax (≥ 20%) between early and delayed imaging could delineate physiological vascular uptake with a sensitivity of 100% and specificity of 81.0%. CONCLUSIONS: When PET/CT is used for the diagnosis and classification of vasculitis, the physiological uptake of lower limb vessels may mislead the diagnosis. PET/CT imaging features or delayed imaging improved diagnostic efficacy.

Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals.

A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs.

Tonsillar Microbiome-Derived Lantibiotics Induce Structural Changes of IL-6 and IL-21 Receptors and Modulate Host Immunity.

Emerging evidence emphasizes the functional impacts of host microbiome on the etiopathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). However, there are limited mechanistic insights into the contribution of microbial biomolecules especially microbial peptides toward modulating immune homeostasis. Here, by mining the metagenomics data of tonsillar microbiome, a deficiency of the encoding genes of lantibiotic peptides salivaricins in RA patients is identified, which shows strong correlation with circulating immune cells. Evidence is provided that the salivaricins exert immunomodulatory effects in inhibiting T follicular helper (Tfh) cell differentiation and interleukin-21 (IL-21) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL-6 and IL-21 receptors, thereby inhibiting the bindings of IL-6 and IL-21 to their receptors and suppressing the downstream signaling pathway. Finally, salivaricin administration exerts both prophylactic and therapeutic effects against experimental arthritis in a murine model of RA. Together, these results provide a mechanism link of microbial peptides-mediated immunomodulation.

Enhancing the quantum yield of singlet oxygen: photocatalytic degradation of mustard gas simulant 2-chloroethyl ethyl sulfide catalyzed by a hybrid of polyhydroxyl aluminum cations and porphyrin anions.

By combining the anionic salt meso-tetra(4-carboxyphenyl)porphyrin (TCPP4-) and the Keggin polyoxometalate cation cluster [Al13O4(OH)24(H2O)12]7+ via a simple ion-exchange method, a hybrid (C48H26N4O8)[Al13O4(OH)24(H2O)12]2(OH)10·18H2O (Al13-TCPP) was prepared and thoroughly characterized as a prototype of polyoxometalate-porphyrin hybrids for the photocatalytic degradation of the mustard gas simulant 2-chloroethyl ethyl sulfide (CEES). The experimental results showed that the catalytic degradation rate of CEES in the presence of Al13-TCPP reached 96.16 and 99.01% in 180 and 90 min in methanol and methanol-water solvent mixture (v/v = 1 : 1), respectively. The reaction followed first-order reaction kinetics, and the half-life and kinetic constant in methanol and solvent mixture were 39.8 min, -0.017 min-1 and 14.7 min, -0.047 min-1. Mechanism analysis indicated that under visible light irradiation in air, CEES was degraded through a combination of oxidation and alcoholysis/hydrolysis in methanol and the methanol-water solvent mixture. The superoxide radical (O2˙-) and singlet molecular oxygen (1O2) generated by Al13-TCPP selectively oxidized CEES into a non-toxic sulfoxide. The singlet oxygen capture experiments showed that Al13-TCPP (Φ = 0.236) had a higher quantum yield of singlet oxygen generation than H4TCPP (Φ = 0.135) under visible light irradiation in air. The material Al13-TCPP has good reusability, and the degradation rate of CEES can still reach 98.37% after being recycled five times.

Risk Factors and Outcomes of Acute Myocardial Infarction in a Cohort of Antiphospholipid Syndrome.

Background: Antiphospholipid syndrome (APS) is a disorder associated with thromboembolic diseases, including acute myocardial infarction (AMI). Given that AMI is a relatively common condition with poor prognostic features, identification of risk factors for AMI in APS is important. Methods: A retrospective cohort study was performed consisting of 332 patients with APS, and 239 patients with thrombotic APS were finally included. Patients were followed up in the outpatient department for 5 years. Clinical data and laboratory parameters were analyzed to identify the risk factors for AMI in APS. The primary and secondary clinical outcomes were all-cause mortality and recurrence of thrombosis, respectively. Results: AMI was observed in 12.1% (29/239) of patients with APS. Compared to patients without AMI, patients with AMI had multiple organ thrombosis (55.1 vs. 34.3%, p = 0.029), recurrent thrombosis (58.6 vs. 34.3%, p = 0.011), a higher incidence of atherosclerosis (62.1 vs. 23.8%, p < 0.001), higher neutrophil count (×109/L) [4.68 (3.25, 8.17) vs. 3.71 (2.64, 5.80), p = 0.036], longer QT interval (ms) [438 ms (423, 454) vs. 425 ms (410, 446), p = 0.016], and fewer venous thrombosis events (27.6 vs. 63.3%, p < 0.001). Multivariate logistic regression analysis (adjusted for age and gender) identified several factors that were positively associated with AMI, including multiple organ thrombosis [odds ratio (OR) 8.862, 95% confidence interval (CI): 1.817-43.212, p = 0.007), atherosclerosis (OR 5.397, 95%CI: 1.943-14.994, p = 0.001), and elevated neutrophil count (>6.3 ×109/L) (OR 3.271, 95%CI: 1.268-8.440, p = 0.014). The venous thrombosis was negatively associated with AMI (OR 0.106, 95%CI: 0.036-0.314, p < 0.001). Kaplan-Meier analysis revealed that the recurrence rates of arterial thrombosis differed significantly between patients with AMI and those without AMI [hazard ratio (HR) = 3.307, p = 0.038]. Conclusion: Atherosclerosis, multiple organ thrombosis, an increased number of neutrophils are variables positively associated with AMI in APS, and venous thrombosis had a negative association with AMI. AMI only predicts the subsequent recurrence of arterial thrombosis. These findings suggest that distinct pathophysiological mechanisms may exist and contribute to the development of venous or arterial thrombotic APS.

The COVID-19 vaccine: Attitudes and vaccination in patients with autoimmune inflammatory rheumatic diseases.

Background: We examined attitudes toward the COVID-19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods: A multicenter, web-based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results: Of the unvaccinated patients, 32.9% were willing to receive the COVID-19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine-related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID-19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow-up of 88 (38, 131) days, patients' disease activities were stable. Conclusions: The findings show that AIIRD patients were unwilling to receive the COVID-19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID-19 disease and vaccines had a significant effect on vaccination willingness.

Third-order optical nonlinearities of zinc porphyrins accommodated in the cavity of a doughnut-like molybdenum crown cluster.

In this paper, three zinc porphyrins bearing carboxyl, amino or hydroxyl groups on the porphyrin ring, namely, 5,10,15,20-tetra(4-carboxyphenyl) zinc porphyrin (ZnTCPP), 5,10,15,20-tetra(4-hydroxyphenyl) zinc porphyrin (ZnTHPP) and 5,10,15,20-tetra(4-aminophenyl) zinc porphyrin (ZnTAPP), reacted with the doughnut-like molybdenum crown cluster [(MoO3)176(H2O)63(CH3OH)17H16]16- (denoted as {Mo176}), resulting in the formation of three porphyrin-polyoxometalate hybrids (denoted as hybrids 1-3), respectively, with the ratio of {Mo176} to the porphyrin molecules in each compound being 1 : 3. Compared with the corresponding parent porphyrins, the fluorescence quenching efficiency of hybrid 1, hybrid 2 and hybrid 3 was found to be 51%, 58% and 66%, respectively, indicating electron/energy transfer occurring from the porphyrin moiety to the POM moiety. Z-Scan experimental results showed that the three porphyrins and hybrids 1-3 exhibited nonlinear reverse saturated absorption and self-defocusing properties. The molecular second hyperpolarizability (γ) values of hybrids 1-3 (7.38 × 10-27, 7.26 × 10-27 and 4.26 × 10-27 (esu)) are higher than those of the corresponding porphyrins (1.18 × 10-27, 1.34 × 10-27 and 1.36 × 10-27 (esu)), indicating that the doughnut-like molybdenum crown cluster in the hybrids 1-3 improved the third-order optical nonlinearities of the accommodated H-aggregate of the zinc porphyrin molecules, wherein the optical nonlinearities of the porphyrin with the electron-withdrawing functional group of -COOH (γ = 7.38 × 10-27 for hybrid 1vs. γ = 1.18 × 10-27 for ZnTCPP) were enhanced the most. In addition, studies on the optical limiting properties of hybrid 1 and hybrid 2 showed that the nonlinear attenuation factor (NAF) of both hybrid 1 and hybrid 2 was larger than that of their corresponding porphyrins (NAF = 5.65 for hybrid 1vs. 1.82 for ZnTCPP) and the limiting threshold of hybrid 1 and hybrid 2 can reach 0.3 J cm-2 and 0.32 J cm-2, which proved that hybrids 1 and 2 are potential optical limiting materials.

Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial.

Rheumatoid arthritis (RA) is an aggressive autoimmune arthritis, and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects. Low-dose interleukin-2 (Ld-IL2) is potentially a therapeutic approach to further improve the disease. This randomized, double-blind, placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA. Patients were randomly assigned (1:1) to receive Ld-IL2, defined as a dose of 1 million IU, or placebo in a 12-week trial with a 12-week follow-up. Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks (a total of 7 doses), followed by a 2-week break. All patients received a stable dose of methotrexate (MTX). The primary outcomes were the proportion of patients achieving the ACR20, DAS28-ESR <2.6, and the change from baseline in CDAI or SDAI at week 24. Secondary endpoints included other clinical responses and safety. The primary outcomes were achieved in the per-protocol population. The improvements from baseline in CDAI and SDAI were significantly greater across time points for the Ld-IL2 + MTX group (n = 17) than for the placebo+MTX group (n = 23) (P = 0.018 and P = 0.015, respectively). More patients achieved ACR20 response in the Ld-IL2 + MTX group than those in the placebo+MTX group at week 12 (70.6% vs 43.5%) and at week 24 (76.5% vs 56.5%) (P = 0.014). In addition, low Treg and high IL-21 were associated with good responses to Ld-IL2. Ld-IL-2 treatment was well-tolerated in this study. These results suggested that Ld-IL2 was effective and safe in RA. ClinicalTrials.gov number: NCT02467504.

Current situation and cost-effectiveness of 18F-FDG PET/CT for the diagnosis of fever of unknown origin and inflammation of unknown origin: A single-center, large-sample study from China.

PURPOSE: 18F-FDG PET/CT has an important role in the evaluation of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Our study was to investigate the current status of the inclusion of 18F-FDG PET/CT within FUO/ IUO diagnostic work-up and evaluate the cost-effectiveness of it in China. METHODS: A total of 741 FUO/IUO patients admitted to our hospital from January 2012 to December 2019 were retrospectively reviewed. The clinical characteristic, medical expenses to reach diagnosis and the proportion of definite etiological diagnosis achieved upon hospital discharge were compared between patients examined by 18F-FDG PET/CT (18F-FDG PET/CT group) and patients not examined by 18F-FDG PET/CT (non-18F-FDG PET/CT group). RESULTS: The mean age, proportion of critically-ill patients, proportion of rheumatologic diseases, the number of examinations and hospitalisation days to reach diagnosis in the 18F-FDG PET/CT group were significantly higher than those in the non-18F-FDG PET/CT group. The mean medical costs of 18F-FDG PET/CT group were significantly higher than those of non-18F-FDG PET/CT group, whereas the proportion of definite etiological diagnosis achieved upon hospital discharge of 18F-FDG PET/CT group was significantly higher than that of non-18F-FDG PET/CT group. The mean hospitalisation days and mean medical costs before diagnosis were significantly lower in patients who undertook 18F-FDG PET/CT ≤ 7 days after hospital admission than those in patients who undertook 18F-FDG PET/CT > 7 days after hospital admission. CONCLUSIONS: 18F-FDG PET/CT is mostly used in critically-ill and hard-to-diagnose FUO/IUO patients currently in China, which may conceal its cost-effective advantage. While the early use of 18F-FDG PET/CT according to patient characteristics and etiological clues could help to reduce hospitalization stay, limit medical costs, thus producing its diagnostic effect to the great extent.

Imaging features of 18F-FDG PET/CT in different types of systemic vasculitis.

OBJECTIVE: To analyze 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) image features in different types of systemic vasculitis and explore its classification and diagnostic significance for systemic vasculitis. METHODS: Clinical and 18F-FDG PET/CT imaging data of 71 consecutive patients (34 males, 37 females, mean age 53.4 ± 20.5 years) who were examined at Peking University People's Hospital and diagnosed with active systemic vasculitis were analyzed retrospectively, and 18F-FDG PET/CT imaging features of different types of systemic vasculitis were analyzed in patients with positive 18F-FDG PET/CT findings. RESULTS: The proportions of large-, medium-, small-, and variable-vessel vasculitis were 36.6%, 15.5%, 29.6%, and 18.3%, respectively, and 93.0% of patients had positive findings on PET/CT, of which 63.6% had vascular involvement and 53.0% had extravascular involvement. Different types of vasculitis had different lesion sites, distribution patterns, and morphological changes. Large-vessel vasculitis mainly affected the aorta and its branches to the head and neck. Takayasu arteritis showed segmental involvement of the vascular and morphological changes of the vessel wall. Giant cell arteritis manifested as diffuse vascular involvement, which usually involved the temporal artery and the abdominal aorta and its branches. Medium-vessel vasculitis polyarteritis nodosa manifested as diffuse vascular involvement of both lower extremities. Small-vessel vasculitis anti-neutrophil cytoplasmic antibody-associated vasculitis manifested as granulomatous inflammation of extravascular regions. Variable-vessel vasculitis Behcet's disease involved both blood vessels and extravascular regions. CONCLUSION: Different types of systemic vasculitis show characteristic manifestations in 18F-FDG PET/CT images, which may be useful for the diagnosis and classification of systemic vasculitis. KEY POINTS: • Determining an early diagnosis of systemic vasculitis may be challenging. • Different types of systemic vasculitis show characteristic manifestations in 18F-FDG PET/CT images. • 18F-FDG PET/CT may be useful for the diagnosis and classification of systemic vasculitis.

Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents.

Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), ζ-potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.