Direct Synthesis of Mixed-Metal Paddle-Wheel Metal-Organic Frameworks with Controlled Metal Ratios under Ambient Conditions.

Currently, synthesizing mixed-metal metal-organic frameworks (MM-MOFs) in a single step remains a challenge due to the varying reactivities of different metal cations. This often results in the formation of mixtures of monometallic MOFs or MM-MOFs with nonstoichiometric metal ratios. A promising approach to overcoming this issue is the controlled precursor method, which uses prebuilt polynuclear complexes with structures similar to the secondary building units (SBUs) of the desired MOFs. In this study, we report that metal acetates can serve as natural prebuilt SBUs, enabling the controlled synthesis of MBDs ([M2(BDC)2DABCO]n, M = metal, BDC = 1,4-benzenedicarboxylic acid, DABCO = 1,4-diazabicyclo[2,2,2]octane) under ambient conditions. By exploiting the fact that metal acetates readily form soluble paddle-wheel dimers similar to the SBUs of MBDs, we achieve the direct synthesis of mixed-metal MBDs at room temperature. The metal ratios (Zn, Co, and Ni) in the resulting MBDs are controllable, and the production yields exceed 90%. The use of metal acetates facilitates the fast and uniform nucleation of MBDs, regardless of the metal cations involved. This similarity in nucleation rates leads to the formation of bimetallic and trimetallic MBDs with predefined metal ratios and homogeneous metal distribution while maintaining the quality of the MOFs. Importantly, this strategy offers an efficient pathway for synthesizing mixed metal MBDs using stoichiometric amounts of metal salts without toxic additives, high energy consumption, and complex synthesis steps.

Development of recombinant secondary antibody mimics (rSAMs) for immunoassays through genetic fusion of monomeric alkaline phosphatase with antibody binders.

In conventional immunoassays, a secondary antibody is used to amplify the signal generated by the binding of the primary antibody to the target analyte. Due to concerns regarding animal use and cost-inefficiency of secondary antibody productions, there is a significant demand for the development of recombinant secondary antibody mimics (rSAMs). Here, we developed rSAMs using a signal-generating enzyme, monomeric alkaline phosphatase (mALP), and antibody-binders, including monomeric streptavidin (mSA2) and mouse IgG1- or rabbit IgG-binding nanobodies (MG1Nb or RNb). The mALP-MG1Nb, mALP-RNb, and mALP-mSA2 were genetically constructed and produced in large quantities using bacterial overexpression systems, which reduced manufacturing costs and time without the use of animals. Each rSAM exhibited high and selective binding to its respective primary antibody, generating linear band signals corresponding to the amounts of target analytes in western blots. The rSAMs also successfully generated sigmoidal signal curves that increased as the sample concentration increased. Moreover, they generated stronger signals than conventional ALP-conjugated secondary antibodies and SA, particularly in the medium to high sample concentration range, in both indirect and sandwich-type indirect ELISAs at the same sample concentration. The rSAMs we developed here may provide new insights to develop novel immunoassay-based analytical and diagnostic tools.

Therapeutic Effect of Dupilumab on Systemic and Vascular Inflammation in Adults with Severe Atopic Dermatitis: Feasibility Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Atopic dermatitis (AD) is an inflammatory skin disease associated with increased systemic and vascular inflammation. Although dupilumab has been proven to be effective against severe AD, imaging studies analysing its inflammation-reducing effect have rarely been reported. The aim of this study was to evaluate the effect of dupilumab on systemic and vascular inflammation in adult patients with severe AD, using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). A total of 33 adult patients with severe AD and 25 healthy controls underwent 18F-FDG PET/CT at baseline. Patients on dupilumab treatment underwent 18F-FDG PET/CT again after achieving a 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75). Patients with AD exhibited increased 18F-FDG uptake values in the liver, spleen, pancreas, and carotid artery compared with healthy controls. However, compared with baseline, there was no statistically significant difference in 18F-FDG uptake in major organs and arteries after achieving EASI-75 with dupilumab treatment. In conclusion, while dupilumab treatment resulted in a significant clinical improvement and reduced serum inflammatory markers in adult patients with severe AD, no changes in systemic and vascular inflammation were observed on 18F-FDG PET/CT imaging.

Venous Insufficiency is a Clear Provoker of Pigmented Purpuric Dermatosis.

BACKGROUND: Pigmented purpuric dermatosis (PPD) is a chronic disorder characterized by distinct petechial hemorrhage and brownish pigmentation. The cause of PPD is unclear, but several underlying conditions are associated with it. Previous reports suggest that venous insufficiency (VI) might be related to PPD; however, a clear correlation remains unelucidated. OBJECTIVE: To elucidate the causal relationship between PPD and VI. METHODS: A total 118 patients diagnosed with PPD in the Department of Dermatology, Pusan National University Hospital from November 2006 to July 2019 were retrospectively reviewed. Doppler ultrasonography of the lower extremities was performed in 56 PPD patients, who were then divided into two groups: PPD with and without VI. We compared the clinical features between the two groups. In the PPD with VI group, we assessed the correspondence ratios between PPD and VI lateralities, and between the PPD distribution and the veins involved. RESULTS: VI was detected in 35 of the 56 patients (62.5%). The PPD with VI group was significantly associated with wider distribution, darker coloration and longer disease duration. There was a positive correlation of laterality between PPD and VI, and between PPD distribution and the vein involved. CONCLUSION: This findings suggest that VI is a clear provoker of PPD.

Characteristic Clinical and Dermoscopic Features of Nonvolar Poroma.

BACKGROUND: A poroma typically presents as a solitary, pink-to-red papule or nodule in acral volar areas. However, in nonvolar areas, this typical clinical feature (TCF) can be difficult to identify. OBJECTIVE: We aimed to compare clinical and dermoscopic characteristics between nonvolar poroma (NVP) and volar (ie, typical) poroma (VP). METHODS: We assessed the clinical and dermoscopic characteristics of 40 patients with poromas who were divided into the NVP and VP groups. RESULTS: Of the 40 patients, 20 (50.0%) were allocated to the NVP group and 20 (50.0%) to the VP group. Pigmented variants were more common in the NVP group than in the VP group (60.0% vs 5.0%). The TCF of poroma was observed less frequently in the NVP than the VP group (45.0% vs 85.0%). Approximately one-third (30.0%) of patients with NVP received an initial clinical diagnosis of skin cancer. Dermoscopic patterns associated with melanoma or basal cell carcinoma were more common in the NVP group than in the VP group (65% vs 30%). CONCLUSIONS: Skin cancer-associated clinicodermoscopic features were more frequently observed in patients with NVP, who simultaneously lost dermoscopic patterns associated to poromas and acquired those associated with skin cancer, than those with VP.

LSM12-EPAC1 defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient.

Nucleocytoplasmic transport (NCT) defects have been implicated in neurodegenerative diseases such as C9ORF72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we identify a neuroprotective pathway of like-Sm protein 12 (LSM12) and exchange protein directly activated by cyclic AMP 1 (EPAC1) that sustains the nucleocytoplasmic RAN gradient and thereby suppresses NCT dysfunction by the C9ORF72-derived poly(glycine-arginine) protein. LSM12 depletion in human neuroblastoma cells aggravated poly(GR)-induced impairment of NCT and nuclear integrity while promoting the nuclear accumulation of poly(GR) granules. In fact, LSM12 posttranscriptionally up-regulated EPAC1 expression, whereas EPAC1 overexpression rescued the RAN gradient and NCT defects in LSM12-deleted cells. C9-ALS patient-derived neurons differentiated from induced pluripotent stem cells (C9-ALS iPSNs) displayed low expression of LSM12 and EPAC1. Lentiviral overexpression of LSM12 or EPAC1 indeed restored the RAN gradient, mitigated the pathogenic mislocalization of TDP-43, and suppressed caspase-3 activation for apoptosis in C9-ALS iPSNs. EPAC1 depletion biochemically dissociated RAN-importin ß1 from the cytoplasmic nuclear pore complex, thereby dissipating the nucleocytoplasmic RAN gradient essential for NCT. These findings define the LSM12-EPAC1 pathway as an important suppressor of the NCT-related pathologies in C9-ALS/FTD.

Unilateral facial erythematous patch as the presenting sign of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can have many cutaneous manifestations including malar rash, discoid rash or oral ulcer. Isolated unilateral involvement of face is uncommon in SLE. It lacks typical clinical features of LE, and may impose a diagnostic challenge for clinicians. Herein we report a case of 62-year-old woman presenting with a 2-year history of erythematous patches on left cheek and eyelid. Initially, she was diagnosed as having recurrent blepharitis or cellulitis that did not respond to conventional treatment with ophthalmic medicaments. As time went by, the patches spread to her left cheek, and she was referred to our dermatologic department. Histopathologic examination was consistent with LE. Further physical and laboratory tests have found that she had oral ulcers, proteinuria, thrombocytopenia and abnormal titer of anti-nuclear antibody satisfying the diagnosis of SLE. From this case, we think unilateral erythematous patches on face could be a rare manifestation of SLE and more intention should be paid to this type of patients, because unilateral facial symptom may mimic other dermatoses.