Highly porous nature of a primitive asteroid revealed by thermal imaging.

Carbonaceous (C-type) asteroids1 are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites2,3 and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth's atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)4 onboard the spacecraft Hayabusa25, indicating that the asteroid's boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m-2 s-0.5 K-1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites6 and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect7,8. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites6. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity9 of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies10.

Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists.

BACKGROUND: Although rituximab (RTX) is recommended by kidney disease improving global outcomes as one of the standard therapies for primary membranous nephropathy (pMN), given the constraint of insurance coverage, it is not clear how the drug is used in Japan. METHODS: This cross-sectional study was conducted via a web-based survey between November and December 2021. The participants were certified nephrologists and recruited through convenience sampling. Experience with RTX for pMN was compared to experience with RTX for minimal change nephrotic syndrome (MCNS). Reasons for withholding RTX for pMN, even when it is indicated, were also investigated. Furthermore, the proportion difference in RTX experience was analyzed. RESULTS: Responses from 380 nephrologists across 278 facilities were analyzed. RTX was used for pMN by 83 (21.8%), which was less than the 181 (47.6%) who had used RTX for MCNS (ratio of proportions: 0.46). RTX use for pMN was more frequent in facilities performing 41-80 and 81 or more kidney biopsies annually (vs. none) and by physicians with experience in anti-PLA2R antibody measurement. RTX administration for pMN was covered by insurance for 56 (67.5%), was facility-paid for 10 (12.0%), and was copaid by patients for 6 (7.2%). The most common reason for withholding RTX for pMN was difficulty in ensuring financing (146, 79.3%). CONCLUSIONS: RTX use for pMN is less common than for MCNS but not infrequent. Treatment with RTX was more frequent in biopsy-intensive facilities, and it was fully paid by the facility or patient in one-fifth of cases.

Preference for anti-phospholipase A2 receptor antibody assay in patients with suspected membranous nephropathy: a survey study on medical practice after publication of Japanese Guidelines for Nephrotic Syndrome 2020.

BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test. METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation. RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation. CONCLUSION: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.

Unique Crosslinking Properties of Psoralen-Conjugated Oligonucleotides Developed by Novel Psoralen N-Hydroxysuccinimide Esters.

Psoralens and their derivatives, such as trioxsalen, have unique crosslinking features to DNA. However, psoralen monomers do not have sequence-specific crosslinking ability with the target DNA. With the development of psoralen-conjugated oligonucleotides (Ps-Oligos), sequence-specific crosslinking with target DNA has become achievable, thereby expanding the application of psoralen-conjugated molecules in gene transcription inhibition, gene knockout, and targeted recombination by genome editing. In this study, we developed two novel psoralen N-hydroxysuccinimide (NHS) esters that allow the introduction of psoralens into any amino-modified oligonucleotides. Quantitative evaluation of the photo-crosslinking efficiencies of the Ps-Oligos to target single-stranded DNAs revealed that the crosslinking selectivity to 5-mC is the unique feature of trioxsalen. We found that the introduction of an oligonucleotide via a linker at the C-5 position of psoralen can promote favorable crosslinking to target double-stranded DNA. We believe our findings are essential information for the development of Ps-Oligos as novel gene regulation tools.

Terahertz bandpass filter with Babinet complementary metamaterial mirrors and silicon subwavelength structure.

We fabricated a rigid bandpass filter with a broad far-infrared wavelength range of high transmission using a silicon subwavelength structure with a Babinet complementary metamaterial half-mirror pair, despite its apparent light-blocking structure. The rigid one-piece filter was produced by a simple process involving photolithography, dry etching, and deposition, each performed only once. The transmission principle relies on the Fabry-Perot resonance with a metamaterial half-mirror pair that exhibits extraordinary optical transmission due to spoof surface plasmon polaritons. The transmission center wavelength was successfully predicted by the basic equation of Fabry-Perot resonance with an effective medium approximation. In contrast, a narrower bandwidth and a lower minimum transmittance than those predicted from the basic equation were provided by the subwavelength Si structure between the metamaterial mirrors, resulting in enhanced bandpass filter characteristics.

Water-Dispersible Carbon Nano-Test Tubes as a Container for Concentrated DNA Molecules.

Invited for the cover of this issue are Takashi Kyotani, Tetsuji Itoh and co-workers at Tohoku University, Gunma University and AIST. The image depicts the synthesis of water-dispersible carbon nano-test tubes by using a template technique and the selective adsorption of DNA into the inner space of these test tubes. Read the full text of the article at 10.1002/chem.202301422.

Water-Dispersible Carbon Nano-Test Tubes as a Container for Concentrated DNA Molecules.

Water-dispersible carbon nano-test tubes (CNTTs) with an inner and outer diameter of about 25 and 35 nm, respectively, were prepared by the template technique and then their inner carbon surface was selectively oxidized to introduce carboxy groups. The adsorption behavior of DNA molecules on the oxidized CNTTs (Ox-CNTTs) was examined in the presence of Ca2+ cations. Many DNA molecules are attracted to the inner space of Ox-CNTTs based on the Ca2+ -mediated electrostatic interaction between DNA phosphate groups and carboxylate anions on the inner carbon surface. Moreover, the total net charge of the DNA adsorbed was found to be equal to the total charge of the carboxylate anions. This selective adsorption into the interior of Ox-CNTTs can be explained from the fact that the electrostatic interaction onto the inner concave surface is much stronger than that on the outer convex surface. On the other hand, the desorption of DNA easily occurs whenever Ca2+ cations are removed by washing with deionized water. Thus, each of Ox-CNTTs works well as a nano-container for a large amount of DNA molecules, thereby resulting in the occurrence of DNA enrichment in the nanospace.

Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

BACKGROUND: With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). METHODS: This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. RESULTS: In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). CONCLUSION: Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

Serum Sclerostin Levels and Mortality in Hemodialysis Patients: An 8-Year Prospective Study.

INTRODUCTION: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure. Sclerostin might be involved in the pathogenesis of vascular calcification, but few studies have examined the association between sclerostin and mortality in hemodialysis patients. METHODS: We analyzed a prospective cohort of 654 patients undergoing maintenance hemodialysis. The primary exposure variable was the baseline serum sclerostin level measured at study enrollment. The primary outcome was 8-year all-cause mortality. Mortality risk was assessed using Cox regression models adjusted for potential confounders. RESULTS: During a median follow-up of 7.6 years (interquartile range, 4.1-8.0 years), 229 of the 654 participants died. In a univariate analysis, serum sclerostin levels were not associated with mortality (HR per doubling, 0.94; 95% CI, 0.76-1.17). This result was unchanged after adjustment for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, and body mass index (HR per doubling, 0.92; 95% CI, 0.72-1.17). Similar results were obtained for cardiovascular mortality. CONCLUSION: Serum sclerostin levels were not associated with mortality in maintenance hemodialysis patients. Further research is required to determine the role of sclerostin in vascular calcification and cardiovascular disease in kidney failure.

A novel method for successful induction of interdigitating process formation in conditionally immortalized podocytes from mice, rats, and humans.

Formation of processes in podocytes is regarded as the hallmark of maturity and normal physical condition for the cell. There are many accumulated findings about molecular mechanisms that cause retraction of podocyte processes; however, there is little knowledge of the positive mechanisms that promote process formation in vitro, and most previous reports about this topic have been limited to low-density cultures. Here, we found that process formation can be induced in 100% confluent cultures of conditionally immortalized podocytes in mouse, rat, and human species by combining serum depletion and Y-27632 ROCK inhibitor supplementation on the scaffold of laminin-521(L521). We noted the cytoskeletal reorganization of the radial extension pattern of vimentin filaments and downregulation of actin stress fiber formation under that condition. We also found that additional standard amount of serum, depletion of ROCK inhibitor, or slight mismatch of the scaffold as laminin-511(L511) hinder process formation. These findings suggest that the combination of reduced serum, podocyte-specific scaffold, and intracellular signaling to reduce the overexpression of ROCK are required factors for process formation.

Metacarpal bone mineral density by radiographic absorptiometry predicts fracture risk in patients undergoing maintenance hemodialysis.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guideline update suggests bone mineral density testing to assess fracture risk in patients with chronic kidney disease, but dual-energy X-ray absorptiometry is not available in most dialysis facilities. Radiographic absorptiometry is an inexpensive and quick method for evaluating bone mineral density. Therefore, we analyzed a historical cohort of 456 maintenance hemodialysis patients to determine whether metacarpal bone mineral density measured by digital image processing, a computer-assisted radiographic absorptiometry technique, predicts fracture risk. At baseline, the median metacarpal bone mineral density T-score was -2.05 (interquartile range, -3.35 to -0.99). During a mean follow-up of 5.3 years, there were 16 clinical fractures and 11 asymptomatic vertebral fractures as estimated by height loss. Metacarpal bone mineral density T-score was significantly lower in patients who sustained a clinical fracture than in those remaining event-free. Decreasing metacarpal bone mineral density T-score was significantly associated with increased risk of clinical fracture (hazard ratio, 1.41 per 1 standard deviation decrease in bone mineral density T-score [95% confidence interval, 1.09 to 1.83]; the hazard ratio for lowest versus highest tertile was 4.86 [1.03 to 22.92]. Similar associations were observed between metacarpal bone mineral density T-score and vertebral fracture or any fracture. The results were robust to different analysis strategies and were consistent across different subgroups. Thus, radiographic absorptiometry could be a useful tool for primary screening of hemodialysis patients at high risk for fracture. Additional studies are required to determine the predictive ability of radiographic absorptiometry techniques compared to dual-energy X-ray absorptiometry or other established methods.

Underwater Bubble and Oil Repellency of Biomimetic Pincushion and Plastron-Like Honeycomb Films.

Underwater highly bubble and oil-repellent surfaces were prepared based on honeycomb- and pincushion-structured films prepared by breath figure technique and post modifications including UV-ozone treatment and peeling the top layer. Furthermore, bubble generation from the plastron-like honeycomb gas chamber by attaching oil droplet onto the surface of honeycomb films was first observed. Both controlling gas bubbles and oil droplets underwater are important issues in the field of microfluidics since they are useful and may solve the maleficence to liquid transportation in narrow microchannels.

Skeletal and mineral metabolic effects of risedronate in a rat model of high-turnover renal osteodystrophy.

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.

Correction to: Preventive effect of early introduction of everolimus and reduced­exposure tacrolimus on renal interstitial fibrosis in de novo living­donor renal transplant recipients.

In the Original publication of the article, the co-author name has been misspelled as "Yousuke Nakagawa".

Preventive effect of early introduction of everolimus and reduced-exposure tacrolimus on renal interstitial fibrosis in de novo living-donor renal transplant recipients.

BACKGROUND: To improve the long-term outcomes following renal transplantation, prevention of renal-allograft interstitial fibrosis (IF), mainly due to calcineurin inhibitors, is an important therapeutic target. Everolimus (EVR) was reported to have antifibrotic effects. We aimed to investigate the safety, efficacy, and IF of our modified immunosuppressive regimen, which includes early introduction of EVR and reduced-exposure tacrolimus (Tac) (EVR group), and compare it with the standard-exposure tacrolimus-based regimen (Tac group) in de novo living-donor renal recipients. METHODS: In this retrospective, single-center cohort study, we compared the 2-year clinical courses between the two groups according to intention to treat. Additionally, in patients in whom biopsies were obtained at 1 h, 3 months, and 12 months post-transplant, we compared IF between the groups using imaging analysis. RESULTS: Overall, 47 patients were included (EVR group, n = 22; Tac group, n = 25). There were no significant differences in renal function and incidences of rejection and viral infections between the groups at the 2-year post-transplant follow-up. However, pathologic imaging analysis (n = 34) revealed chronological progression of IF in the Tac group during the first year post-transplant and no changes in the EVR group (fibrosis rate at 3 months: 20.8 vs. 13.6%, p < 0.001; at 12 months: 24.7 vs. 14.7%, p < 0.001, respectively). CONCLUSION: Our modified immunosuppressive regimen may have an antifibrotic effect on transplanted kidneys without loss of safety and efficacy.

Efficient Light-Harvesting Antennae Resulting from the Dense Organization of Dyes into DNA Junctions through d-Threoninol.

Herein we report the construction of efficient light-harvesting antennae by hybridization of DNA oligonucleotides containing high densities of fluorophores into DNA junctions through d-threoninol. Six pyrene donors could be incorporated into each arm without self-quenching. A perylene acceptor was located at the center of the junction. Antenna effects of a duplex and three- to eight-way junctions were systematically compared. Six- and eight-way junctions had the highest antenna effects, and their effective absorption coefficients were 8.5 times higher than that of perylene. Interestingly, even-numbered junctions had higher efficiencies than odd-numbered junctions. Nondenaturing gel analyses and fluorescence lifetime measurements demonstrated that the strong odd-even effects were derived from differences in the stability of junctions. The results presented will guide the design of efficient artificial photosynthetic systems.

Comprehensive three-dimensional analysis (CUBIC-kidney) visualizes abnormal renal sympathetic nerves after ischemia/reperfusion injury.

The sympathetic nervous system is critical in maintaining the homeostasis of renal functions. However, its three-dimensional (3D) structures in the kidney have not been elucidated due to limitation of conventional imaging methods. CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) is a newly developed tissue-clearing technique, which enables whole-organ 3D imaging without thin-sectioning. Comprehensive 3D imaging by CUBIC found that sympathetic nerves are primarily distributed around arteries in the mouse kidney. Notably, the sympathetic innervation density was significantly decreased 10 days after ischemia-reperfusion injury (voluminal ratio of innervation area to kidney) by about 70%. Moreover, norepinephrine levels in kidney tissue (output of sympathetic nerves) were significantly reduced in injured kidneys by 77%, confirming sympathetic denervation after ischemia-reperfusion injury. Time-course imaging indicated that innervation partially recovered although overall denervation persisted 28 days after injury, indicating a continuous sympathetic nervous abnormality during the progression of chronic kidney disease. Thus, CUBIC-kidney, the 3D imaging analysis, can be a strong imaging tool, providing comprehensive, macroscopic perspectives for kidney research.

Nutritional status and survival of maintenance hemodialysis patients receiving lanthanum carbonate.

Background: Hyperphosphatemia and poor nutritional status are associated with increased mortality. Lanthanum carbonate is an effective, calcium-free phosphate binder, but little is known about the long-term impact on mineral metabolism, nutritional status and survival. Methods: We extended the follow-up period of a historical cohort of 2292 maintenance hemodialysis patients that was formed in late 2008. We examined 7-year all-cause mortality according to the serum phosphate levels and nutritional indicators in the entire cohort and then compared the mortality rate of the 562 patients who initiated lanthanum with that of the 562 propensity score-matched patients who were not treated with lanthanum. Results: During a mean ± SD follow-up of 4.9 ± 2.3 years, 679 patients died in the entire cohort. Higher serum phosphorus levels and lower nutritional indicators (body mass index, albumin and creatinine) were each independently associated with an increased risk of death. In the propensity score-matched analysis, patients who initiated lanthanum had a 23% lower risk for mortality compared with the matched controls. During the follow-up period, the serum phosphorus levels tended to decrease comparably in both groups, but the lanthanum group maintained a better nutritional status than the control group. The survival benefit associated with lanthanum was unchanged after adjustment for time-varying phosphorus or other mineral metabolism parameters, but was attenuated by adjustments for time-varying indicators of nutritional status. Conclusions: Treatment with lanthanum is associated with improved survival in hemodialysis patients. This effect may be partially mediated by relaxation of dietary phosphate restriction and improved nutritional status.

Concentration-dependent photophysical switching in mixed self-assembled monolayers of pentacene and perylenediimide on gold nanoclusters.

Photophysical control and switching on organic-inorganic hybrid interfaces are of great interest in diverse fundamental and applicative research areas. 6,13-Bis(triisopropylsilylethynyl)pentacene (TP) is well-known to exhibit efficient singlet fission (SF) for generation of high-yield triplet excited states in aggregated forms, whereas perylenediimide (PDI) ensembles show the characteristic excimer formation. Additionally, a combination of pentacene (electron donor: D) and PDI (electron acceptor: A) is expected to undergo an efficient photoinduced electron transfer (PET), and absorption of two chromophores combined covers the entire visible region. Therefore, the concentration-dependent mixed self-assembled monolayers (SAMs) composed of two chromophores enable us to control and switch the photophysical processes on a surface. In this work, a series of mixed SAMs composed of TP and PDI units on gold nanoclusters (GNCs) were newly synthesized by changing the relative molecular concentration ratios. Structural control of mixed SAMs on a gold surface based on the concentration ratios was successfully achieved. Time-resolved femtosecond and nanosecond transient absorption measurements clearly demonstrate photophysical control and switching of the above competitive reactions such as SF, electron transfer (ET) and excimer formation. The maximum quantum yields of triplet states (ΦT = ∼170%) and electron transfer (ΦET = ∼95%) were quantitatively evaluated by changing the concentration ratios. The rate constants of SF and excimer processes are largely dependent on the concentration ratios, whereas the rate constants of ET processes approximately remain constant. These findings are also discussed based on the statistical framework of the assembly of chromophores on the gold surface.

Structural basis of a Ni acquisition cycle for [NiFe] hydrogenase by Ni-metallochaperone HypA and its enhancer.

The Ni atom at the catalytic center of [NiFe] hydrogenases is incorporated by a Ni-metallochaperone, HypA, and a GTPase/ATPase, HypB. We report the crystal structures of the transient complex formed between HypA and ATPase-type HypB (HypBAT) with Ni ions. Transient association between HypA and HypBAT is controlled by the ATP hydrolysis cycle of HypBAT, which is accelerated by HypA. Only the ATP-bound form of HypBAT can interact with HypA and induces drastic conformational changes of HypA. Consequently, upon complex formation, a conserved His residue of HypA comes close to the N-terminal conserved motif of HypA and forms a Ni-binding site, to which a Ni ion is bound with a nearly square-planar geometry. The Ni binding site in the HypABAT complex has a nanomolar affinity (Kd = 7 nM), which is in contrast to the micromolar affinity (Kd = 4 µM) observed with the isolated HypA. The ATP hydrolysis and Ni binding cause conformational changes of HypBAT, affecting its association with HypA. These findings indicate that HypA and HypBAT constitute an ATP-dependent Ni acquisition cycle for [NiFe]-hydrogenase maturation, wherein HypBAT functions as a metallochaperone enhancer and considerably increases the Ni-binding affinity of HypA.