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Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188 Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188 Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188 Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188 Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.

A long-lived metastable minor fraction has been detected and characterized in myeloma protein IgG4 MAM by hydro- and thermodynamic methods. The sedimentation constants of the minor and the major protein fractions are different. The stability of the two C H 2 domains in the minor fraction varies. The unique characteristics of these IgG4 MAM conformers arise from the fact that on exchange of the heavy chains between IgG4 molecules, in some of them only one non-canonical bond Cys226-Cys229 is formed in the central part of the “hinge region” instead of two canonical interchain disulfide bonds Cys226-Cys226 and Cys229-Cys229. This leads to asymmetric structure of the IgG4 MAM molecules.

A long-range forecast system based on the improved version of the SLAV072L96 global atmosphere model has been verified at the Hydrometcenter of Russia. The model has the horizontal resolution of 0.9°   0.72° in longitude and latitude and 96 vertical levels and includes modern parametrizations for the subgrid-scale processes in the atmosphere and active soil layer. Main features and particularities of this model version are presented along with a brief description of ensemble long-range meteorological forecast technology using this model. Some verification scores for long-range forecasts based on the archive data from ERA5 reanalysis for 1991–2015 and on the data for 2023 are presented.

AbstractProstate cancer is a serious social and medical problem all over the world. It ranks fifth in the total structure of cancer morbidity and second in the structure of morbidity and mortality of men with neoplasms and takes the lead in growth rates. Androgen-deprivation therapy is insufficiently effective for the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC). This makes it relevant to develop novel methods for treating patients with this disease. Radioligand therapy (RLT) for metastatic castrate-resistant prostate cancer using low molecular ligands with high affinity to prostate specific membrane antigen (PSMA) labeled with β- and α-emitting isotopes is currently under rapid development. One of the most promising radionuclide medicines is the 177Lu-PSMA-617 radiopharmaceutical based on the PSMA-617 ligand. The decay of 177Lu results in the emission of both β particles and γ-rays. Therefore, it may also be used for therapy and SPECT diagnostics of malignancies. 177Lu-PSMA-617 is currently at different phases of clinical trials in many countries; however, it has not yet been registered. Most medical centers use the standard activity of 6 or 7.5 GBq per cycle (six or eight weeks between cycles), which causes less than 10% of serious adverse events (mainly hematological ones). Grade 3 anemia and thrombocytopenia develop in about 10% of patients, grade 1–2 dry mouth in 66%, and transient nausea of the 1st or 2nd degree in 48% of patients. The positive effect of RLT has been recorded: pain relief in 33–70% of patients, improvement of life quality in 60%, and an increase in Karnofsky’s status in 74%. A biochemical response after RLT has been detected in more than half of the patients; among them, the PSA decreased by more than 50% in 45% of cases; in addition, this was observed after the first course in most cases; according to the data based on imaging methods, a partial response was recorded in more than a third of patients.

For the territory of Northern Eurasia, a scheme for the statistical correction of surface air temperature forecasts has been developed for periods of 1–4 months on the basis of the SL-AV model using the MOS concept. For statistical correction of operational temperature forecasts, the regression parameters and EOF expansion coefficients obtained by cross-validation on historical forecasts were used. Due to the internal relationships of the model output data, the proposed scheme allows improving the skill of surface characteristic forecasts. A significant improvement in the skill of deterministic air temperature forecasts by using statistical correction is manifested in transition seasons. The scheme of statistical correction is constantly evolving. Further development of the statistical correction technology involves the use of neural networks and forecast indices of atmospheric circulation.

AbstractThe limiting mode of the generation of low-frequency torsional whistlers is obtained for the first time. Laser plasma clouds create only weak whistlers in a weakly magnetized laboratory plasma (argon), allowing the whistler magnetic field to reach record values of ~25% of the background magnetic field.

Fc fragments (hFc) of human myeloma IgG2 proteins LOM and SIN having core hinge (Cys-Cys-Val-Glu-Cys-Pro-Pro-Cys) were first obtained by a modified proteolytic procedure. The thermostability of C H 2 domains inside of standard Fc, hFc fragments, and intact IgG2 LOM and SIN was studied by fluorescence spectroscopy. It was found that C H 2 domains of intact IgG2 are destabilized. The destabilization is accompanied by reduced ability of IgG2 to inhibit the activation of complement system by classical pathway. This could be due to the decrease in the affinity of C H 2 domains to factor C1q.

Isolated constant domains of two Bence Jones proteins, VAD and BIR, are able to form amyloid fibrils, but only the first one retains this feature within the intact protein. The conformation and stability of these proteins were studied using scanning microcalorimetry, circular dichroism, fluorescence spectroscopy, and analytical centrifugation at physiological conditions (10 mM phosphate buffer, pH 7.0, 100 mM NaCl), and it was shown that isolated pairs of constant domains (C L -C L ) of VAD and BIR had reduced stability in comparison to ordinary (nonamyloidogenic) Bence Jones proteins. However, in the intact BIR protein, the stability of the constant domain block increased dramatically, in agreement with the loss of ability to form amyloid fibrils.

A long-lived metastable minor fraction has been detected and characterized in myeloma protein IgG4 MAM by hydro- and thermodynamic methods. The sedimentation constants of the minor and the major protein fractions are different. The stability of the two C sub(H)2 domains in the minor fraction varies. The unique characteristics of these IgG4 MAM conformers arise from the fact that on exchange of the heavy chains between IgG4 molecules, in some of them only one non-canonical bond Cys226-Cys229 is formed in the central part of the \"hinge region\" instead of two canonical interchain disulfide bonds Cys226-Cys226 and Cys229-Cys229. This leads to asymmetric structure of the IgG4 MAM molecules.

A long-lived metastable minor fraction has been detected and characterized in myeloma protein IgG4 MAM by hydro- and thermodynamic methods. The sedimentation constants of the minor and the major protein fractions are different. The stability of the two C^sub H^2 domains in the minor fraction varies. The unique characteristics of these IgG4 MAM conformers arise from the fact that on exchange of the heavy chains between IgG4 molecules, in some of them only one non-canonical bond Cys226-Cys229 is formed in the central part of the \"hinge region\" instead of two canonical interchain disulfide bonds Cys226-Cys226 and Cys229-Cys229. This leads to asymmetric structure of the IgG4 MAM molecules.