Large-scale 2D heterostructures from hydrogen-bonded organic frameworks and graphene with distinct Dirac and flat bands.

The current strategies for building 2D organic-inorganic heterojunctions involve mostly wet-chemistry processes or exfoliation and transfer, leading to interface contaminations, poor crystallizing, or limited size. Here we show a bottom-up procedure to fabricate 2D large-scale heterostructure with clean interface and highly-crystalline sheets. As a prototypical example, a well-ordered hydrogen-bonded organic framework is self-assembled on the highly-oriented-pyrolytic-graphite substrate. The organic framework adopts a honeycomb lattice with faulted/unfaulted halves in a unit cell, resemble to molecular "graphene". Interestingly, the topmost layer of substrate is self-lifted by organic framework via strong interlayer coupling, to form effectively a floating organic framework/graphene heterostructure. The individual layer of heterostructure inherits its intrinsic property, exhibiting distinct Dirac bands of graphene and narrow bands of organic framework. Our results demonstrate a promising approach to fabricate 2D organic-inorganic heterostructure with large-scale uniformity and highly-crystalline via the self-lifting effect, which is generally applicable to most of van der Waals materials.

Deep analysis of total serum N-glycome suggests glyco-signatures for phospholipase A2 receptor 1-related idiopathic membranous nephropathy diagnosis.

Idiopathic membranous nephropathy (IMN) is an antibody-mediated and kidney-specific autoimmune disease, with the antigen phospholipase A2 receptor 1 (PLA2R1) accounting for approximately 70% of IMN cases. Although a variety of new podocyte target antigens and their autoantibodies have been identified, they are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. N-glycans play vital roles in renal system and their pathobiological relevance has become increasingly recognized in many kidney diseases, but not fully explored in IMN. To find possible glyco-signatures for PLA2R1-related IMN diagnosis, we herein established a comprehensive workflow for total serum N-glycome analysis based on our recently developed mass spectrometry (MS)-based N-glycan purification method, named Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG). A total of 191 N-glycans were identified from IMN patients, representing the largest N-glycome dataset in IMN. Compared to healthy controls, up-regulation of sialylation and core-fucosylation as well as down-regulation of galactosylation were observed in PLA2R1-positive IMN patients, and up-regulation of hyper-galactosylation was specific for PLA2R1-negative IMN patients. A six-glycan marker panel consisting of H4N3S1, H4N3F1, H6N4S2, H6H5F1S2, H6N5 and H6N6F1S1, was proposed to aid in the accurate diagnosis of PLA2R1-related IMN, which provided new insights into IMN biomarker study. SIGNIFICANCE: PLA2R1-related IMN is a kidney-specific autoimmune disease with a high risk of developing end-stage renal disease (ESRD) and even kidney failure. Current biomarkers are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. An in-depth MS analysis of total serum N-glycome of PLA2R1-related IMN patients was conducted for the first time. We generated the largest dataset of serum N-glycome for IMN to date, and proposed a novel six-glycan marker panel that may help the accurate diagnosis of PLA2R1-related IMN.

Optimized optical system with a 1.65 m wide-field corrector for the 6.5 m high-performance MUltiplexed Survey Telescope.

The development of modern large-scale spectroscopic survey telescopes responds to the urgent demand for spectral information in astronomical research. Tsinghua University has previously proposed a 6.5 m MUltiplexed Survey Telescope consisting of a Ritchey-Chretien configuration and a 1.8 m multi-element wide-field corrector, achieving excellent performance and world-leading survey efficiency. However, an optimized 1.65 m multi-element corrector with five lenses is proposed to overcome the constraints on glass uniformity and verification in fabrication of the previous corrector design. It maintains outstanding image quality, with the 80% enclosed energy diameter not more than 0.559 arcsec within 3° FoV over up to a 55° zenith angle. The optimized optical system does not revise the working mode of the ADC or the curvature of the primary mirror while ensuring the reasonability and accuracy of manufacturing of large corrector elements. It provides a more feasible reference optical design for the MUltiplexed Survey Telescope in subsequent iterations and communications with manufacturers.

Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy.

BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy accounts for the majority of membranous nephropathy; however, few studies have determined the prognostic impact and clinical application of renal pathologic change on this disease. METHODS: A retrospective cohort study of 262 patients with PLA2R-associated membranous nephropathy was conducted. The total renal chronicity score calculated according to the degree of glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis was applied to evaluate renal chronicity. Baseline bias was adjusted by inverse probability weight when assessing the prognostic impact of chronicity, and multiple parameters were used to evaluate the application value of renal chronicity. RESULTS: During a median follow-up of 24.5 months, renal outcome (kidney function deterioration and/or end-stage kidney disease) was observed in 22 (8.40%) patients. Not only did a higher total renal chronicity score independently predict renal outcome [odds ratio (OR): 1.562, 95% confidence interval (CI) 1.073-2.273, P = 0.020], but non-minimal chronicity was also an independent risk factor for renal outcome (OR: 3.170, 95% CI 1.040-9.659, P = 0.042). Moreover, the membranous nephropathy risk classification in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline integrated with non-minimal chronicity showed improvements in categorical net reclassification (0.174, 95% CI 0.012-0.335, P = 0.035), continuous net reclassification (0.462, 95% CI 0.087-0.838, P = 0.016), and integrated discrimination (0.019, 95% CI 0.003-0.035, P = 0.020) compared to the original classification. CONCLUSIONS: Renal chronicity is closely associated with renal outcomes in PLA2R-associated membranous nephropathy, and combining the KDIGO risk classification with chronicity scores may provide a more accurate prognostic prediction.

An online-predictive model of acute kidney injury after pancreatic surgery.

OBJECTIVE: Acute kidney injury(AKI) after pancreatic surgery is associated with increased mortality, longer hospital stays and poor prognosis. This study aims to identify the risk factors and establish an easy-to-use prediction calculator by the nomogram to predict the risk of AKI after pancreatic surgery. METHODS: From January 2016 to June 2018, 1504 patients who underwent pancreatic surgery in our center were included in this retrospective analysis and randomly assigned to primary (1054 patients) and validation (450 patients) cohorts. The independent risk factors of AKI were identified using univariate and multivariate analyses. A risk-predicted nomogram for AKI was developed through multivariate logistic regression analysis in the primary cohort while the nomogram was evaluated in the validation cohort. Nomogram discrimination and calibration were assessed using C-index and calibration curves in the primary and validation cohorts. The clinical utility of the final nomogram was evaluated using decision curve analysis. RESULTS: The overall incidence of AKI after pancreatic surgery was 5.3% (79/1504). Independent risk factors including smoking history, cardiovascular disease, ASA score, baseline eGFR, bilirubin＞2 â€‹mg/dL, undergoing pancreaticoduodenectomy, and intraoperative blood loss＞400 â€‹mL were identified by multivariate analysis. Nomogram revealed moderate discrimination and calibration in estimating the risk of AKI, with an unadjusted C-index of 0.79 (95 %CI, 0.73-0.85). Application of the nomogram in the validation cohort provided moderate discrimination (C-index,0.80 [95% CI, 0.72-0.88]) and good calibration. Besides, the decision curve analysis (DCA) confirmed the clinical usefulness of the nomogram. CONCLUSIONS: An easy-to-use online prediction calculator comprised of preoperative and intraoperative factors was able to individually predict the occurrence risk of AKI among patients with pancreatic surgery, which may help identify reasonable risk judgments and develop proper treatment strategies to a certain extent.

Median arcuate ligament syndrome complicated with gallbladder stones: A case report.

BACKGROUND: Median arcuate ligament syndrome (MALS) is a rare disease caused by compression of the celiac trunk artery by the median arcuate ligament (MAL). It can cause symptoms of postprandial abdominal pain, weight loss, and nausea and vomiting. CASE SUMMARY: A 55-year-old woman was admitted due to abdominal pain, nausea and vomiting. On admission, the patient presented with epigastric pain that worsened after eating, without signs of peritoneal irritation. Computed tomography angiography of the upper abdomen showed compression of the proximal segment of the abdominal trunk, local luminal stenosis with angular "fishhook" changes, which changed significantly during forceful inspiration and expiration; gallbladder stones; and multiple cysts in the liver. Abdominal duplex ultrasonography showed that peak systolic velocity was 352 cm/s. After diagnosis of MALS was confirmed, an arch ligament release procedure was performed. MALS has no specific symptoms and can be misdiagnosed as other abdominal diseases. Awareness of MALS should be improved to avoid misdiagnosis. The commonly used treatment option is MAL release and resection of the peripheral ganglion of the celiac trunk artery. CONCLUSION: The diagnosis and treatment of MALS must be individualized, and MAL release is effective and provides immediate symptomatic relief.

Quantitative evaluation on thermal seeing induced 2m ring solar telescope.

Thermal seeing is one of the factors that affect solar telescope observations. A comprehensive analysis method is developed to quantify the thermal seeing effects. A three-dimensional Large Eddy Simulation (LES) turbulence model is used to obtain the transient flow fields around the primary mirror, the secondary mirror and the heat-stop. The thermal seeing is calculated based on the stochastic dynamic influence of turbulence on the light rays. The key parameters of the simulation were calibrated by experiments, and the simulation results were validated by empirical formulas. This method has been applied to evaluate the thermal seeing of the 2m Ring Solar Telescope (2m-RST). Error allocation is performed based on the research results to ensure the Observation effect of 2m-RST.

High power single-frequency 1112†nm laser by an insertable Nd:YAG/YAG bonded monolithic planar ring oscillator.

A high power single-frequency operation at 1112 nm with novel insertable monolithic planar ring oscillator based on a Nd:YAG/YAG bonded crystal is proposed. In a proof-of-principle experiment, a finely designed coating on the output surface is carried out to ensure single-wavelength oscillation at 1112 nm, together with a half-wave plate and a Tb3Ga5O12 crystal inserted in the open space of the bonded block to realize the unidirectional operation with power scalability. Consequently, the single-frequency laser delivers an output power of 3.9 W at 1112.3 nm with a slope efficiency of 58.6% and an optical-to-optical efficiency of 17.7%. The power fluctuation is measured to be within ± 0.26% over 20 min, and the laser linewidth is estimated to be 4.15 MHz (Δλ = 0.017 pm).

ANA-negative severe lupus-like presentation: Is it lupus or not?

Key Clinical Message: Systemic lupus erythematosus is difficult to diagnose in patients who are antinuclear antibody (ANA) negative and lack typical clinical manifestations. For such patient who presented ANA-negative severe lupus-like manifestations, the diagnosis and treatment are a huge challenge. Histological findings may provide clues to diagnosis. Abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by formation of autoantibodies to nuclear and cytoplasmic antigens. It was reported that a small subset of patients had typical clinical features of SLE with consistently negative antinuclear antibody (ANA), but such disease is usually mild and rarely involves multisystem. At present, there are no reports about severe lupus with ANA continued negative. Our report describes a 34-year-old Chinese woman who presented renal failure, multiple serous cavity effusion, and epilepsy, without malar rash, photosensitivity, lymphopenia, and arthritis. Further renal biopsy pathology revealed lupus-like nephritis. Autoantibodies, including ANA, antibodies against Smith and against double stranded DNA, were negative. Such a ANA negative and lack of typical clinical symptoms of SLE patient, but with severe lupus-like manifestations, whether it was lupus or not is worth discussing.

Intrinsic surface p-wave superconductivity in layered AuSn4.

The search for topological superconductivity (TSC) is currently an exciting pursuit, since non-trivial topological superconducting phases could host exotic Majorana modes. However, the difficulty in fabricating proximity-induced TSC heterostructures, the sensitivity to disorder and stringent topological restrictions of intrinsic TSC place serious limitations and formidable challenges on the materials and related applications. Here, we report a new type of intrinsic TSC, namely intrinsic surface topological superconductivity (IS-TSC) and demonstrate it in layered AuSn4 with Tc of 2.4 K. Different in-plane and out-of-plane upper critical fields reflect a two-dimensional (2D) character of superconductivity. The two-fold symmetric angular dependences of both magneto-transport and the zero-bias conductance peak (ZBCP) in point-contact spectroscopy (PCS) in the superconducting regime indicate an unconventional pairing symmetry of AuSn4. The superconducting gap and surface multi-bands with Rashba splitting at the Fermi level (EF), in conjunction with first-principle calculations, strongly suggest that 2D unconventional SC in AuSn4 originates from the mixture of p-wave surface and s-wave bulk contributions, which leads to a two-fold symmetric superconductivity. Our results provide an exciting paradigm to realize TSC via Rashba effect on surface superconducting bands in layered materials.

Efficient Secretory Production of δ-Tocotrienol by Combining Pathway Modularization and Transportation Engineering.

The vitamin E component δ-tocotrienol has shown impressive activities in radioprotection, neuroprotection, and cholesterol reduction. Its production is limited by the low content in plants and difficulty in separation from other tocotrienols. Fermentative production using a microbial cell factory that exclusively produces and secretes δ-tocotrienol is a promising alternative approach. Assembly of the δ-tocotrienol synthetic pathway in Saccharomyces cerevisiae followed by comprehensive pathway engineering led to the production of 73.45 mg/L δ-tocotrienol. Subsequent addition of 2-hydroxypropyl-ß-cyclodextrin (CD) and overexpression of the transcription factor PDR1 significantly elevated δ-tocotrienol titer to 241.7 mg/L (63.65 mg/g dry cell weight) in shake flasks, with 30.4% secreted. By properly adding CD and the in situ extractant olive oil, 181.12 mg/L of δ-tocotrienol was collected as an extracellular product, accounting for 85.6% of the total δ-tocotrienol production. This process provides not only a promising δ-tocotrienol cell factory but also insights into yeast engineering toward secretory production of other terpenoids.

A bifunctional fusion protein protected against diabetic nephropathy by suppressing NLRP3 activation.

Diabetic nephropathy (DN), the principal pathogeny of end-stage renal disease (ESRD), is related to metabolic disorders, chronic inflammation, and oxidative stress. It was reported that high expression of interleukin-17A (IL-17A) was intimately related to the progression of DN, and targeting IL-17A exhibited regulating effects on inflammation and autoimmunity but had only limited impact on the oxidative stress damage in DN. Recent studies showed that interleukin-22 (IL-22) could inhibit mitochondrial damage and inflammatory response. Thus, the cytokine IL-22 was first fused to anti-IL-17A antibody for endowing the antibody with the anti-hyperglycemia and anti-inflammation activity. Our study demonstrated that the fusion molecule, anti-IL17A/IL22 fusion protein, could not only lead to the increase of M1 macrophages and the decrease of M2 macrophages, further improving the immune microenvironment, but also prevent the loss of mitochondrial membrane potential by reducing the production of ROS in murine DN model. In addition, the fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways, further synergistically restraining the production of NLRP3, thus suppressing the inflammatory response and playing beneficial effect on slowing down the progression of DN. In conclusion, our findings demonstrated that the bifunctional IL-17A antibody and IL-22 fusion protein were of great benefit to DN, which highlighted a potential therapeutic strategy. KEY POINTS: • Anti-IL17A/IL22 fusion protein could improve the immune microenvironment and reduce the production of ROS. • Anti-IL17A/IL22 fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways and then restrain the activation of NLRP3.

Growth of Mesoscale Ordered Two-Dimensional Hydrogen-Bond Organic Framework with the Observation of Flat Band.

Flat bands (FBs), presenting a strongly interacting quantum system, have drawn increasing interest recently. However, experimental growth and synthesis of FB materials have been challenging and have remained elusive for the ideal form of monolayer materials where the FB arises from destructive quantum interference as predicted in 2D lattice models. Here, we report surface growth of a self-assembled monolayer of 2D hydrogen-bond (H-bond) organic frameworks (HOFs) of 1,3,5-tris(4-hydroxyphenyl)benzene (THPB) on Au(111) substrate and the observation of FB. High-resolution scanning tunneling microscopy or spectroscopy shows mesoscale, highly ordered, and uniform THPB HOF domains, while angle-resolved photoemission spectroscopy highlights a FB over the whole Brillouin zone. Density-functional-theory calculations and analyses reveal that the observed topological FB arises from a hidden electronic breathing-kagome lattice without atomically breathing bonds. Our findings demonstrate that self-assembly of HOFs provides a viable approach for synthesis of 2D organic topological materials, paving the way to explore many-body quantum states of topological FBs.

Simultaneous blockade of VEGF-B and IL-17A ameliorated diabetic kidney disease by reducing ectopic lipid deposition and alleviating inflammation response.

The pathogenesis of diabetic kidney disease (DKD) is complicated. Current clinical treatments fail to achieve satisfactory efficacy in the prevention of DKD progression, it urgently needs novel and effective treatment for DKD. In this study, we firstly demonstrated that renal lipid metabolism abnormality and inflammation significantly changed in DKD conditions by mining public transcriptomic data of DKD patient samples. KEGG analysis further exhibited the critical role of vascular endothelial growth factor B (VEGF-B) and interleukin 17A (IL-17A) signal pathways in DKD progression, indicating that VEGF-B and IL-17A might be the promising targets for DKD treatment. Then the potential of a novel combination therapy, anti-VEGF-B plus anti-IL-17A antibody, was evaluated for DKD treatment. Our results demonstrated that simultaneous blockade of VEGF-B and IL-17A signaling with their neutralizing antibodies alleviated renal damage and ameliorated renal function. The therapeutic effectiveness was not only related to the reduced lipid deposition especially the neutral lipids in kidney but also associated with the decreased inflammation response. Moreover, the therapy alleviated renal fibrosis by reducing collagen deposition and the expression of fibronectin and α-SMA in kidney tissues. RNA-seq analysis indicated that differential expression genes (DEGs) in db/db mice were significantly clustered into lipid metabolism, inflammation, fibrosis and DKD pathology-related pathways, and 181 of those DEGs were significantly reversed by the combinatory treatment, suggesting the underlying mechanism of administration of anti-VEGF-B and anti-IL-17A antibodies in DKD treatment. Taken together, this study identified that renal lipid metabolism abnormality and inflammation were critically involved in the progression of DKD, and simultaneous blockade of VEGF-B and IL-17A signaling represents a potential DKD therapeutic strategy.

Hierarchical dynamic regulation of Saccharomyces cerevisiae for enhanced lutein biosynthesis.

Lutein, as a carotenoid with strong antioxidant capacity and an important component of macular pigment in the retina, has wide applications in pharmaceutical, food, feed, and cosmetics industries. Besides extraction from plant and algae, microbial fermentation using engineered cell factories to produce lutein has emerged as a promising route. However, intra-pathway competition between the lycopene cyclases and the conflict between cell growth and production are two major challenges. In our previous study, de novo synthesis of lutein had been achieved in Saccharomyces cerevisiae by dividing the pathway into two stages (δ-carotene formation and conversion) using temperature as the input signal to realize sequential cyclation of lycopene. However, lutein production was limited to microgram level, which is still too low to meet industrial demand. In this study, a dual-signal hierarchical dynamic regulation system was developed and applied to divide lutein biosynthesis into three stages in response to glucose concentration and culture temperature. By placing the genes involved in δ-carotene formation under the glucose-responsive ADH2 promoter and genes involved in the conversion of δ-carotene to lutein under temperature-responsive GAL promoters, the growth-production conflict and intra-pathway competition were simultaneously resolved. Meanwhile, the rate-limiting lycopene ε-cyclation and carotene hydroxylation reactions were improved by screening for lycopene ε-cyclase with higher activity and fine tuning of the P450 enzymes and their redox partners. Finally, a lutein titer of 19.92 mg/L (4.53 mg/g DCW) was obtained in shake-flask cultures using the engineered yeast strain YLutein-3S-6, which is the highest lutein titer ever reported in heterologous production systems.

Assessing the contribution of mild high-altitude exposure to obstructive sleep apnea-hypopnea syndrome comorbidities.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder. The lower atmospheric pressure and decreased oxygen levels of high-altitude areas can exacerbate the severity of OSAHS, but research into OSAHS in high-altitude areas remains limited. This study, from June 2015 to January 2020, involved 4,667 patients with suspected OSAHS and 38 healthy volunteers. The non-OSAHS group (AHI <5/h) had 395 patients, while the larger OSAHS group (AHI ≥5/h) comprised 4,272 patients. The significant size difference between the groups emphasized the study's focus on OSAHS, using the non-OSAHS mainly for comparison. Methods: Sleep technicians monitored the OSAHS patient group overnight by polysomnography (PSG), the apnea-hypopnea index (AHI), the mean oxygen saturation (MSpO2), lowest oxygen saturation (LSpO2), the oxygen desaturation index (ODI) and the total sleep time with oxygen saturation less than 90% (TST-SpO2 <90%). Healthy volunteers self-monitored sleep patterns at home, using the CONTEC RS01 respiration sleep monitor with a wristwatch sleep apnea screen meter. The RSO1 wristwatch-style device has already been studied for consistency and sensitivity with the Alice-6 standard multi-lead sleep monitor and can be used for OSAHS screening in this region. Results: LSpO2 recordings from healthy volunteers (86.36 ± 3.57%) and non-OSAHS (AHI <5/h) cohort (78.59 ± 11.99%) were much lower than previously reported normal values. Regression analysis identified no correlations between AHI levels and MSpO2 or TST-SpO2 <90%, weak correlations between AHI levels and LSpO2 or MSpO2, and a strongly significant correlation between AHI levels and the ODI (r = 0.76, p < 0.05). The data also indicated that the appropriate clinical thresholds for OSAHS patients living at mild high altitude are classified as mild, moderate, or severe based on LSpO2 saturation criteria of 0.85-0.90, 0.65-0.84, or <0.65, respectively. Conclusion: The study findings suggest that individuals with an AHI score below 5 in OSAHS, who reside in high-altitude areas, also require closer monitoring due to the elevated risk of nocturnal hypoxia. Furthermore, the significant correlation between ODI values and the severity of OSAHS emphasizes the importance of considering treatment options. Additionally, the assessment of hypoxemia severity thresholds in OSAHS patients living in high-altitude regions provides valuable insights for refining diagnostic guidelines.

Compact 200 W level linearly polarized microsecond-pulse Nd:YAG oscillator with nearly diffraction-limited beam quality.

A compact 200 W level diode-side-pumped microsecond (µs) pulse linearly polarized rod Nd:YAG laser oscillator was demonstrated with nearly diffraction-limited beam quality. The oscillator was based on a thermally near-unstable cavity design with two concave lenses in the cavity to enlarge the volume of the fundamental mode, leading to improvement of the laser efficiency and beam quality. Consequently, a record-high average power of 222 W was obtained at a repetition rate of 400 Hz with a 180 µs pulse width, corresponding to an optical-to-optical (o-o) conversion efficiency of 37%. The average beam quality factor was measured to be M2=1.32, resulting in a brightness value as high as of 11.25GW/sr⋅cm2. To the best of our knowledge, this represented the highest average power, the highest o-o efficiency, and the highest brightness for a µs pulse 1064 nm rod Nd:YAG laser oscillator.

Discrete scale invariance of the quasi-bound states at atomic vacancies in a topological material.

Recently, log-periodic quantum oscillations have been detected in the topological materials zirconium pentatelluride (ZrTe5) and hafnium pentatelluride (HfTe5), displaying an intriguing discrete scale invariance (DSI) characteristic. In condensed materials, the DSI is considered to be related to the quasi-bound states formed by massless Dirac fermions with strong Coulomb attraction, offering a feasible platform to study the long-pursued atomic-collapse phenomenon. Here, we demonstrate that a variety of atomic vacancies in the topological material HfTe5 can host the geometric quasi-bound states with a DSI feature, resembling an artificial supercritical atom collapse. The density of states of these quasi-bound states is enhanced, and the quasi-bound states are spatially distributed in the "orbitals" surrounding the vacancy sites, which are detected and visualized by low-temperature scanning tunneling microscope/spectroscopy. By applying the perpendicular magnetic fields, the quasi-bound states at lower energies become wider and eventually invisible; meanwhile, the energies of quasi-bound states move gradually toward the Fermi energy (EF). These features are consistent with the theoretical prediction of a magnetic field-induced transition from supercritical to subcritical states. The direct observation of geometric quasi-bound states sheds light on the deep understanding of the DSI in quantum materials.

Mass spectrometry-based N-glycosylation analysis in kidney disease.

Kidney disease is a global health concern with an enormous expense. It is estimated that more than 10% of the population worldwide is affected by kidney disease and millions of patients would progress to death prematurely and unnecessarily. Although creatinine detection and renal biopsy are well-established tools for kidney disease diagnosis, they are limited by several inevitable defects. Therefore, diagnostic tools need to be upgraded, especially for the early stage of the disease and possible progression. As one of the most common post-translational modifications of proteins, N-glycosylation plays a vital role in renal structure and function. Deepening research on N-glycosylation in kidney disease provides new insights into the pathophysiology and paves the way for clinical application. In this study, we reviewed recent N-glycosylation studies on several kidney diseases. We also summarized the development of mass spectrometric methods in the field of N-glycoproteomics and N-glycomics.

In-depth profiling of urinary N-glycome in diabetic kidney disease by ultrafast glycoprotein immobilization for glycan extraction (UltraGIG).

Diabetic kidney disease (DKD) is a common and serious kidney-related complication of diabetic mellitus. Although albuminuria and estimated glomerular filtration rate (eGFR) are commonly used diagnostic biomarkers, they have limitations in the diagnosis of DKD due to the lack of specificity and sensitivity. Urinary N-glycans are emerging as novel biomarkers for predicting renal prognosis in DKD. However, most of the current N-glycan profiling methods for DKD were based on lectin affinity enrichment or hydrophilic interaction chromatography (HILIC) with optical detection, which provided limited N-glycome coverage in low throughput. Herein, we developed a novel N-glycan purification method, termed Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG), for in-depth profiling of urinary N-glycome in DKD using mass spectrometry (MS). In UltraGIG, proteins were rapidly (within 40 min) immobilized to resin with high efficiency (over 98%) through NHS-reactive chemistry, and then N-glycans were enzymatically released from the resin by PNGase F. Owing to good efficiency of immobilization of proteins to resin, the subsequent washing steps to remove proteins and other impurities could be easily performed. The UltraGIG showed good selectivity towards glycans (extracting N-glycans from the mixture of IgG and BSA at a 1:100 M ratio) and samples loss was minimized (detection sensitivity at fmol level). A total of 237 N-glycan compositions were identified from urine samples with DKD and healthy controls, which representing the largest data set of N-glycome from DKD. Compared to healthy controls, 3 N-glycans were up-regulated and 14 N-glycans were down-regulated in DKD patients. Collectively, UltraGIG offers a competitive sample purification method for in-depth analysis of urinary N-glycome by MS and provide new insights into biomarker study for the diagnosis of DKD.