Case report: BTK inhibitors is effective in type II mixed cryoglobulinemia with wild-type MyD88.

This study presents two cases of type II mixed cryoglobulinemia. One case is essential, while the other is presumably associated with hepatitis B virus (HBV) infection. Both patients tested positive for monoclonal IgMκ, but negative for MyD88 mutation. They showed resistance to rituximab combined with a glucosteroid regimen, but responded positively to BTK inhibitors. These cases highlight the remarkable effectiveness of BTK inhibitors in treating refractory type II cryoglobulinemia without MyD88 mutation. The first patient achieved rapid complete remission of nephrotic syndrome within one month of starting ibrutinib, along with a significant reduction in cryoglobulin levels and abnormal clonal cells. The second patient had a rapid disappearance of rash within three days and accelerated wound healing within one week of initiating orelabrutinib, accompanied by a reduction in C-reactive protein. However, there was no reduction in cryoglobulin levels during the 12-month follow-up. These findings suggest varied mechanisms of action of BTK inhibitors in type II cryoglobulinemia through different mechanisms.

Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Angular-resolved Rabi oscillations of orthorhombic spins in a Co(II) molecular qubit.

Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.

Symmetry-breaking of Dibenzo[b,d]thiophene Sulfone Enhancing Polaron Generation for Boosted Photocatalytic Hydrogen Evolution.

The current bottleneck in the development of efficient photocatalysts for hydrogen evolution is the limited availability of high-performance acceptor units. Over the past nine years, dibenzo[b,d]thiophene sulfone (DBS) has been the preferred choice for the acceptor unit. Despite extensive exploration of alternative structures as potential replacements for DBS, a superior substitute remains elusive. In this study, a symmetry-breaking strategy was employed on DBS to develop a novel acceptor unit, BBTT-1SO. The asymmetric structure of BBTT-1SO proved beneficial for increasing multiple moment and polarizability. BBTT-1SO-containing polymers showed higher efficiencies for hydrogen evolution than their DBS-containing counterparts by up to 166%. PBBTT-1SO exhibited an excellent hydrogen evolution rate (HER) of 222.03 mmol g-1 h-1 and an apparent quantum yield of 27.5% at 500 nm. Transient spectroscopic studies indicated that the BBTT-1SO-based polymers facilitated electron polaron formation, which explains their superior HERs. PBBTT-1SO also showed 14% higher HER in natural seawater splitting than that in deionized water splitting. Molecular dynamics simulations highlighted the enhanced water-PBBTT-1SO polymer interactions in salt-containing solutions. This study presents a pioneering example of a substitute acceptor unit for DBS in the construction of high-performance photocatalysts for hydrogen evolution.

Overcrowded 14,14'-Bidibenzo[a,j]anthracenes: Challenges in Syntheses and Atypical Property of Lacking Symmetry-Breaking Charge Transfer (SBCT).

14,14'-Bidibenzo[a,j]anthracenes (BDBAs) were prepared by iridium-catalyzed annulation of 5,5'-biterphenylene with alkynes. Overcrowded BDBAs with highly distorted molecular halves and a small interplanar angle between two anthryl moieties (down to approximately 31º, currently the lowest reported value) were verified by X-ray crystallography. The strong intramolecular interactions and electronic couplingsbetween two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO-LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry-breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C-C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time.

Radical-Induced Photochromic Silver(I) Metal-Organic Frameworks: Alternative Topology, Dynamic Photoluminescence and Efficient Photothermal Conversion Modulated by Anionic Guests.

Photogenerated radicals are an indispensable member of the state-of-the-art photochromic material family, as they can effectively modulate the photoluminescence and photothermal conversion performance of radical-induced photochromic complexes. Herein, two novel radical-induced photochromic metal‒organic frameworks (MOFs), [Ag(TEPE)](AC)⋅7/4H2O⋅5/4EtOH (1) and [Ag(TEPE)](NC)⋅3H2O⋅EtOH (2), are reported. Distinctly different topological networks can be obtained by judiciously introducing alternative π-conjugated anionic guests, including a new topological structure (named as sfm) first reported in this work, describing as 4,4,4,4-c net. EPR data and UV-Vis spectra prove the radical-induced photochromic mechanism. Dynamic photochromism exhibits tunability in a wide CIE color space, with a linear segment from yellow to red for 1, while a curved coordinate line for 2, resulting in colorful emission from blue to orange. Moreover, photogenerated TEPE* radicals effectively activate the near-infrared (NIR) photothermal conversion effect of MOFs. Under 1 W cm-2 808 nm laser irradiation, the surface temperatures of photoproducts 1* and 2* can reach ~160 ℃ and ~120 ℃, respectively, with competitive NIR photothermal conversion efficiencies η = 51.8% (1*) and 36.2% (2*). This work develops a feasible electrostatic compensation strategy to accurately introduce photoactive anionic guests into MOFs to construct multifunctional radical-induced photothermal conversion materials with tunable photoluminescence behavior.

Singlet Fission in a New Series of Systematically Designed Through-space Coupled Tetracene Oligomers.

Singlet fission (SF) holds great promise for current photovoltaic technologies, where tetracenes, with their relatively high triplet energies, play a major role for application in silicon-based solar cells. However, the SF efficiencies in tetracene dimers are low due to the unfavorable energetics of their singlet and triplet energy levels. In the solid state, tetracene exhibits high yields of triplet formation through SF, raising great interest about the underlying mechanisms. To address this discrepancy, we designed and prepared a novel molecular system based on a hexaphenylbenzene core decorated with 2 to 6 tetracene chromophores. The spatial arrangement of tetracene units, induced by steric hindrance in the central part, dictates through-space coupling, making it a relevant model for solid-state chromophore organization. We then revealed a remarkable increase in SF quantum yield with the number of tetracenes, reaching quantitative (196 %) triplet pair formation in hexamer. We observed a short-lived correlated triplet pair and limited magnetic effects, indicating ineffective triplet dissociation in these through-space coupled systems. These findings emphasize the crucial role of the number of chromophores involved and the interchromophore arrangement for the SF efficiency. The insights gained from this study will aid designing more efficient and technology-compatible SF systems for applications in photovoltaics.

Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor.

INTRODUCTION: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. OBJECTIVE: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. METHODS AND RESULTS: Collecting duct NCOR1 knockout (KO) mice manifested increased BP and aggravated vascular and renal injury in an angiotensin II (Ang II)-induced hypertensive model. KO mice also showed significantly higher BP than littermate control (LC) mice in deoxycorticosterone acetate (DOCA)-salt model. Further study showed that collecting duct NCOR1 deficiency aggravated volume and sodium retention after saline challenge. Among the sodium transporter in the collecting duct, the expression of the three epithelial sodium channel (ENaC) subunits was markedly increased in the renal medulla of KO mice. Consistently, BP in Ang II-infused KO mice decreased significantly to the similar level as those in LC mice after amiloride treatment. ChIP analysis revealed that NCOR1 deficiency increased the enrichment of mineralocorticoid receptor (MR) on the promoters of the three ENaC genes in primary inner medulla collecting duct (IMCD) cells. Co-IP results showed interaction between NCOR1 and MR, and luciferase reporter results demonstrated that NCOR1 inhibited the transcriptional activity of MR. Knockdown of MR eliminated the increased ENaC expression in primary IMCD cells isolated from KO mice. Finally, BP was significantly decreased in Ang II-infused KO mice after treatment of MR antagonist spironolactone and the difference between LC and KO mice was abolished. CONCLUSIONS: NCOR1 interacts with MR to control ENaC activity in the collecting duct and to regulate sodium reabsorption and ultimately BP. Targeting NCOR1 might be a promising tactic to interrupt the volume and sodium retention of the collecting duct in hypertension.

Overcoming small-bandgap charge recombination in visible and NIR-light-driven hydrogen evolution by engineering the polymer photocatalyst structure.

Designing an organic polymer photocatalyst for efficient hydrogen evolution with visible and near-infrared (NIR) light activity is still a major challenge. Unlike the common behavior of gradually increasing the charge recombination while shrinking the bandgap, we present here a series of polymer nanoparticles (Pdots) based on ITIC and BTIC units with different π-linkers between the acceptor-donor-acceptor (A-D-A) repeated moieties of the polymer. These polymers act as an efficient single polymer photocatalyst for H2 evolution under both visible and NIR light, without combining or hybridizing with other materials. Importantly, the difluorothiophene (ThF) π-linker facilitates the charge transfer between acceptors of different repeated moieties (A-D-A-(π-Linker)-A-D-A), leading to the enhancement of charge separation between D and A. As a result, the PITIC-ThF Pdots exhibit superior hydrogen evolution rates of 279 µmol/h and 20.5 µmol/h with visible (>420 nm) and NIR (>780 nm) light irradiation, respectively. Furthermore, PITIC-ThF Pdots exhibit a promising apparent quantum yield (AQY) at 700 nm (4.76%).

Performance and Solution Structures of Side-Chain-Bridged Oligo (Ethylene Glycol) Polymer Photocatalysts for Enhanced Hydrogen Evolution under Natural Light Illumination.

Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h-1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination.

Renal outcomes in IgA nephropathy following inactivated SARS-CoV-2 vaccination.

INTRODUCTION: There are increasing case reports on de novo or relapsing IgA nephropathy (IgAN) following SARS-CoV-2 vaccines, although the follow-up information on renal outcomes in IgAN patients post-SARS-CoV-2 vaccination is limited. In this study, we evaluated the renal outcomes of IgAN patients following inactivated vaccines. METHODS: We investigated the change in eGFR, proteinuria and hematuria in 113 primary IgAN patients post-vaccination. Worsening proteinuria was defined as an increase in proteinuria by more than 0.5 times and proteinuria > 1 g/d. Univariate and multivariable logistic regression analysis were used to evaluate possible predictors of worsening proteinuria. We then compared the renal outcomes of vaccinated patients after 6 months with 101 unvaccinated patients who were followed during the same period. RESULTS: A 2.54% (0.64, 8.61) decrease in renal function was observed in post-vaccination patients. Subgroup analysis revealed a significant decrease in eGFR in patients with 30 ≤ eGFR < 60 (mL/min/1.73 m2) post second SARS-CoV-2 dose (n = 18, p = 0.01). In addition, 10 individuals displayed worsening proteinuria post-vaccination, with the proteinuria subsequently ameliorating significantly after 6-month. Multivariate analysis showed that higher eGFR levels was an independent protective factor for worsening proteinuria. The renal outcome tended towards a decrease in eGFR in vaccinated patients after 6 months follow-up, although the difference was not significant (p = 0.06). CONCLUSION: Kidney function in IgAN patients tended to worsen after SARS-CoV-2 vaccination, particularly those with initial poor kidney function. This pattern of disease flare appears to be clinically mild, and further research is needed to determine whether the impact on kidney function is long-term.

A New Series of Sandwich-Type 5,5'-Biterphenylenes: Synthetic Challenge, Structural Uniqueness and Photodynamics.

A new series of biaryls, bi-linear-terphenylenes (BLTPs), were prepared using the tert-butyllithium-mediated cyclization as the key synthetic step. The three-dimensional structures of the studied compounds were verified using X-ray crystallography and DFT calculations. Tetraaryl(ethynyl)-substituted BLTPs are highly crowded molecules, and the internal rotation around the central C-C bond is restricted due to a high barrier (>50 kcal/mol). These structures contain several aryl/terphenylenyl/aryl sandwiches, where the through-space π-π (TSPP) interactions are strongly reflected in the shielding of 1 H NMR chemical shifts, reduction of oxidation potentials, increasing aromaticity of the central six-membered ring and decreasing antiaromaticity of the four-membered rings in a terphenylenyl moiety based on NICS(0) and iso-chemical shielding surfaces. Despite the restricted C-C bond associated intramolecular TSPP interactions for BLTPs in the ground state, to our surprise, the electronic coupling between two linear terphenylenes (LTPs) in BLTPs in the excited state is weak, so that the excited-state behavior is dominated by the corresponding monomeric LTPs. In other words, all BLTPs undergo ultrafast relaxation dynamics via strong exciton-vibration coupling, acting as a blue-light absorber with essentially no emission.

Highly Efficient MAPbI3 -Based Quantum Dots Exhibiting Unusual Nonblinking Single Photon Emission at Room Temperature.

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

Rational Design of an Air-Stable, High-Spin Diradical with Diazapyrene.

Stable carbon-based polyradicals exhibiting strong spin-spin coupling and slow depolarization processes are particularly attractive functional materials. A new molecular motif synthesized by a convenient method that allows the integration of stable, high-spin radicals to (hetero)aromatic polycycles has been developed, as illustrated by a non-Kekulé diradical showing a triplet ground state with long persistency (τ1/2 ≈31 h) in air. Compared to the widely used 1,3-phenylene, the newly designed (diaza)pyrene-4,10-diyl moiety is for the first time demonstrated to confer ferromagnetic (FM) spin coupling, allowing delocalized non-disjoint SOMOs. With the X-ray crystallography unambiguously proving the diradical structure, the triplet ground state was thoroughly characterized. A large ΔES-T of 1.1 kcal/mol, proving the strong FM coupling effect, was revealed consistently by superconducting quantum interference device (SQUID) measurements and variable-temperature electron paramagnetic resonance (EPR) spectroscopy, while the zero-field splitting and triplet nutation characters were examined by continuous-wave and pulsed EPR spectroscopy. A millisecond spin-lattice relaxation time was also detected. The current study not only offers a new molecular motif enabling FM coupling between carbon-based spins, but more importantly presents a general method for installing stable polyradicals into functional π-systems.

Semi-Transparent, Pixel-Free Upconversion Goggles with Dual Audio-Visual Communication.

The intractable brittleness and opacity of the crystalline semiconductor restrict the prospect of developing low-cost imaging systems. Here, infrared visualization technologies are established with large-area, semi-transparent organic upconversion devices that bring high-resolution invisible images into sight without photolithography. To exploit all photoinduced charge carriers, a monolithic device structure is proposed built on the infrared-selective, single-component charge generation layer of chloroaluminum phthalocyanine (ClAlPc) coupled to two visible light-emitting layers manipulated with unipolar charges. Transient pump-probe spectroscopy reveals that the ClAlPc-based device exhibits an efficient charge dissociation process under forward bias. This process is indicated by the prompt and strong features of electroabsorption screening. Furthermore, by imposing the electric field, the ultrafast excited state dynamic suggests a prolonged charge carrier lifetime from the ClAlPc, which facilitates the charge utilization for upconversion luminance. For the first time, >30% of the infrared photons are utilized without photomultiplication strategies owing to the trivial spectrum overlap between ClAlPc and the emitter. In addition, the device can broadcast the acoustic signal by synchronizing the device frequency with the light source, which enables to operate it in dual audio-visual mode. The work demonstrates the potential of upconversion devices for affordable infrared imaging in wearable electronics.

Self-Assembled Monolayers of Bi-Functionalized Porphyrins: A Novel Class of Hole-Layer-Coordinating Perovskites and Indium Tin Oxide in Inverted Solar Cells.

Self-assembled monolayers (SAMs) offer the advantage of facile interfacial modification, leading to significant improvements in device performance. In this study, we report the design and synthesis of a new series of carboxylic acid-functionalized porphyrin derivatives, namely AC-1, AC-3, and AC-5, and present, for the first time, a strategy to exploit the large π-moiety of porphyrins as a backbone for interfacing the indium tin oxide (ITO) electrode and perovskite active layer in an inverted perovskite solar cell (PSC) configuration. The electron-rich nature of porphyrins facilitates hole transfer and the formation of SAMs, resulting in a dense surface that minimizes defects. Comprehensive spectroscopic and dynamic studies demonstrate that the double-anchored AC-3 and AC-5 enhance SAMs on ITO, passivate the perovskite layer, and function as conduits to facilitate hole transfer, thus significantly boosting the performance of PSCs. The champion inverted PSC employing AC-5 SAM achieves an impressive solar efficiency of 23.19 % with a high fill factor of 84.05 %. This work presents a novel molecular engineering strategy for functionalizing SAMs to tune the energy levels, molecular dipoles, packing orientations to achieve stable and efficient solar performance. Importantly, our comprehensive investigation has unraveled the associated mechanisms, offering valuable insights for future advancements in PSCs.

Synthesis, structural analysis, and properties of highly twisted alkenes 13,13'-bis(dibenzo[a,i]fluorenylidene) and its derivatives.

The rotation of a C = C bond in an alkene can be efficiently accelerated by creating the high-strain ground state and stabilizing the transition state of the process. Herein, the synthesis, structures, and properties of several highly twisted alkenes are comprehensively explored. A facile and practical synthetic approach to target molecules is developed. The twist angles and lengths of the central C = C bonds in these molecules are 36-58° and 1.40-1.43 Å, respectively, and confirmed by X-ray crystallography and DFT calculations. A quasi-planar molecular half with the π-extended substituents delivers a shallow rotational barrier (down to 2.35 kcal/mol), indicating that the rotation of the C = C bond is as facile as that of the aryl-aryl bond in 2-flourobiphenyl. Other versatile and unique properties of the studied compounds include a broad photoabsorption range (from 250 up to 1100 nm), a reduced HOMO-LUMO gap (1.26-1.68 eV), and a small singlet-triplet energy gap (3.65-5.68 kcal/mol).

Electronic Preresonance Stimulated Raman Scattering Spectromicroscopy Using Multiple-Plate Continuum.

Stimulated Raman scattering (SRS) spectromicroscopy is a powerful technique that enables label-free detection of chemical bonds with high specificity. However, the low Raman cross section due to typical far-electronic resonance excitation seriously restricts the sensitivity and undermines its application to bio-imaging. To address this bottleneck, the electronic preresonance (EPR) SRS technique has been developed to enhance the Raman signals by shifting the excitation frequency toward the molecular absorption. A fundamental weakness of the previous demonstration is the lack of dual-wavelength tunability, making EPR-SRS only applicable to a limited number of species in the proof-of-concept experiment. Here, we demonstrate the EPR-SRS spectromicroscopy using a multiple-plate continuum (MPC) light source able to examine a single vibration mode with independently adjustable pump and Stokes wavelengths. In our experiments, the C═C vibration mode of Alexa 635 is interrogated by continuously scanning the pump-to-absorption frequency detuning throughout the entire EPR region enabled by MPC. The results exhibit 150-fold SRS signal enhancement and good agreement with the Albrecht A-term preresonance model. Signal enhancement is also observed in EPR-SRS images of the whole Drosophila brain stained with Alexa 635. With the improved sensitivity and potential to implement hyperspectral measurement, we envision that MPC-EPR-SRS spectromicroscopy can bring the Raman techniques closer to a routine in bio-imaging.

Risk nomogram for assessing renal recovery in patients with newly diagnosed multiple myeloma-related renal impairment.

To determine risk factors affecting renal recovery in newly diagnosed multiple myeloma (NDMM) patients with renal impairment (RI) and establish a risk nomogram. This multi-center, retrospective cohort study included 187 NDMM patients with RI, 127 of whom were admitted to Huashan Hospital and assigned to the training cohort and 60 were admitted to Changzheng Hospital and assigned to the external validation cohort. The baseline data of the 2 cohorts were compared, and survival and renal recovery rates were analyzed. Independent risk factors affecting renal recovery were determined by binary logistic regression analysis, and a risk nomogram was established and subsequently tested in the external validation cohort. Results: The median overall survival (OS) improved in patients who achieved renal recovery etc within 6 courses of MM directed treatment compared with patients without renal recovery. Median time to renal recovery was 2.65 courses, and the cumulative renal recovery rate during the first 3 courses was 75.05%. Involved serum free light chain (sFLC) ratio of >120 at diagnosis, time from renal impairment to treatment > 60 days, and a hematologic response without a very good partial remission (VGPR) or better resulted as independent risk factors for renal recovery during the first 3 courses. The established risk nomogram had good discriminative ability and accuracy. Involved sFLC was a key factor affecting renal recovery. Starting treatment as soon as possible after detecting RI and achieving deep hematologic remission during the first 3 courses of treatment helped achieve renal recovery and improve prognosis.