Compression Eliminates Charge Traps by Stabilizing Perovskite Grain Boundary Structures: An Ab Initio Analysis with Machine Learning Force Field.

Grain boundaries (GBs) play an important role in determining the optoelectronic properties of perovskites, requiring an atomistic understanding of the underlying mechanisms. Strain engineering has recently been employed in perovskite solar cells, providing a novel perspective on the role of perovskite GBs. Here, we theoretically investigate the impact of axial strain on the geometric and electronic properties of a common CsPbBr3 GB. We develop a machine learning force field and perform ab initio calculations to analyze the behavior of GB models with different axial strains on a nanosecond time scale. Our results demonstrate that compressing the GB efficiently suppresses structural fluctuations and eliminates trap states originating from large-scale distortions. The GB becomes more amorphous under compressive strain, which makes the relationship between the electronic structure and axial strain nonmonotonic. These results can help clarify the conflicts in perovskite GB experiments.

STARDUST: a pipeline for the unbiased analysis of astrocyte regional calcium dynamics.

Calcium imaging has become an increasingly popular way to probe the activity of astrocytes. However, the governing principles of astrocyte calcium dynamics are still elusive and their relationship to cellular events ill-defined. Useful assumptions and 'shortcuts' commonly applied to neuronal recordings therefore do not hold true for astrocytes. The imaging of astrocyte calcium activity per se can be relatively straightforward, subsequent analysis methods that adequately capture the richness and complexity of calcium dynamics remain scant. Here, we introduce STARDUST, a pipeline and python-based data processing for the Spatio-Temporal Analysis of Regional Dynamics & Unbiased Sorting of Transients from astrocyte calcium recordings. STARDUST builds upon AQuA to identify patches of active signals, from which it builds a data-driven map of regions of activity (ROAs) that can be combined with cell-segmentation and/or correlated to cellular morphology. For each ROA, STARDUST extracts fluorescence time-series, and performs signal identification and features extraction. STARDUST is agnostic to cell morphology (or cells altogether) and putative calcium propagation across ROAs. Instead, it focuses on decomposing calcium dynamics in a regionalized fashion by treating ROAs as independent units, for instance allowing investigations by signal feature-based ROA rank. STARDUST also identifies ROAs as "stable" (active throughout), "ON" (turned on during drug application) and "OFF" (turned off during drug application) in pharmacology experiments, permitting studies of astrocyte calcium "micro-domains" based on their functional responses. With a systematic set of instructions and troubleshooting tips, and minimal computational/coding background required, STARDUST is a user-friendly addition to the growing toolbox for the exploration of astrocyte calcium dynamics.

Precise Distance Control and Functionality Adjustment of Frustrated Lewis Pairs in Metal-Organic Frameworks.

We report the construction of frustrated Lewis pairs (FLPs) in a metal-organic framework (MOF), where both Lewis acid (LA) and Lewis base (LB) are fixed to the backbone. The anchoring of a tritopic organoboron linker as LA and a monotopic linker as LB to separate metal oxide clusters in a tetrahedron geometry allows for the precise control of distance between them. As the type of monotopic LB linker varies, pyridine, phenol, aniline, and benzyl alcohol, a series of 11 FLPs were constructed to give fixed distances of 7.1, 5.5, 5.4, and 4.8 Å, respectively, revealed by 11B-1H solid-state nuclear magnetic resonance spectroscopy. Keeping LA and LB apart by a fixed distance makes it possible to investigate the electrostatic effect by changing the functional groups in the monotopic LB linker, while the LA counterpart remains unaffected. This approach offers new chemical environments of the active site for FLP-induced catalysis.

Photocatalytic activity of dual defect modified graphitic carbon nitride is robust to tautomerism: machine learning assisted ab initio quantum dynamics.

Two-dimensional graphitic carbon nitride (GCN) is a popular metal-free polymer for sustainable energy applications due to its unique structure and semiconductor properties. Dopants and defects are used to tune GCN, and dual defect modified GCN exhibits superior properties and enhanced photocatalytic efficiency in comparison to pristine or single defect GCN. We employ a multistep approach combining time-dependent density functional theory and nonadiabatic molecular dynamics (NAMD) with machine learning (ML) to investigate coupled structural and electronic dynamics in GCN over a nanosecond timescale, comparable to and exceeding the lifetimes of photo-generated charge carriers and photocatalytic events. Although frequent hydrogen hopping transitions occur among four tautomeric structures, the electron-hole separation and recombination processes are only weakly sensitive to the tautomerism. The charge separated state survives for about 10 ps, sufficiently long to enable photocatalysis. The employed ML-NAMD methodology provides insights into rare events that can influence excited state dynamics in the condensed phase and nanoscale materials and extends NAMD simulations from pico- to nanoseconds. The ab initio quantum dynamics simulation provides a detailed atomistic mechanism of photoinduced evolution of charge carriers in GCN and rationalizes how GCN remains photo-catalytically active despite its multiple isomeric and tautomeric forms.

Pan-Cancer Single-Cell and Spatial-Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy.

The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single-cell RNA sequencing (scRNA-seq) and machine learning methods. The scRNA-seq and bulk RNA-seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single-cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan-cancer patients. The proportion of APOE+ macrophages is higher in ICI non-responders of triple-negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor-bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real-world immunotherapy data accurately predicts the ICI response of pan-cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells.

The vulnerability assessment and obstacle factor analysis of urban agglomeration along the Yellow River in China from the perspective of production-living-ecological space.

Urban agglomerations are sophisticated territorial systems at the mature stage of city development that are concentrated areas of production and economic activity. Therefore, the study of vulnerability from the perspective of production-living-ecological space is crucial for the sustainable development of the Yellow River Basin and global urban agglomerations. The relationship between productivity, living conditions, and ecological spatial quality is fully considered in this research. By constructing a vulnerability evaluation index system based on the perspectives of production, ecology, and living space, and adopting the entropy value method, comprehensive vulnerability index model, and obstacle factor diagnostic model, the study comprehensively assesses the vulnerability of the urban agglomerations along the Yellow River from 2001 to 2020. The results reveal that the spatial differentiation characteristics of urban agglomeration vulnerability are significant. A clear three-level gradient distribution of high, medium, and low degrees is seen in the overall vulnerability; these correspond to the lower, middle, and upper reaches of the Yellow River Basin, respectively. The percentage of cities with higher and moderate levels of vulnerability did not vary from 2001 to 2020, while the percentage of cities with high levels of vulnerability did. The four dimensions of economic development, leisure and tourism, resource availability, and ecological pressure are the primary determinants of the urban agglomeration's vulnerability along the Yellow River. And the vulnerability factors of various urban agglomerations showed a significant evolutionary trend; the obstacle degree values have declined, and the importance of tourism and leisure functions has gradually increased. Based on the above conclusions, we propose several suggestions to enhance the quality of urban development along the Yellow River urban agglomeration. Including formulating a three-level development strategy, paying attention to ecological and environmental protection, developing domestic and foreign trade, and properly planning and managing the tourism industry.

Preparation of Ti3C2Tx modified rare earth doped PbO2 electrodes for efficient removal of sulfamethoxazole.

In this study, we deposited Ti3C2Tx-modified, rare-earth-doped PbO2 on the surface of a carbon fabric via electrodeposition. The surface morphology and electronic structure of the electrode were characterized with SEM, XRD and XPS. The layered Ti3C2Tx did not change the structure of ß-PbO2, and at the same time, it improved the crystallinity of the material and reduced the grains of PbO2. Electrochemical experiments showed that the addition of Ti3C2Tx increased the electrochemical activity of the electrode and produced more H2O2, which contributed to the degradation of pollutants. The efficiency of sulfamethoxazole (SMX) degradation reached 95% after 120 min at pH 3 with a current density of 50 mA/cm2. Moreover, the electrode has good cycling performance, and the degradation efficiency was still 80% after 120 min after 10 cycles of recycling. Based on the intermediates identified by HPLC‒MS, a mechanism for SMX degradation was proposed. Our results will provide a new idea for the development of efficient electrocatalytic degradation of antibiotics.

[Characteristics of resting energy expenditure and evaluation of prediction formulas in young men with different body mass indexes].

OBJECTIVE: To compare the resting energy expenditure (REE) characteristics among young men with different body mass indexes (BMI). METHODS: Thirty young men [average age was (26.93±4.16) years] were enrolled in this study. They underwent resting metabolism tests in the Department of Sports Medicine of Peking University Third Hospital from December 2017 to June 2021. The resting metabolic rate (RMR) was measured by indirect calorimetry, the body composition was measured by bioresistance antibody component analyzer. The REE characteristics were analyzed, and 11 predictive equations were used to estimate RMR and compared with the measured value. The differences were analyzed by paired t-test and intra-class correlation coefficient (ICC). RESULTS: The RMR of the overall 30 young men was (1 960.17±463.11) kcal/d (1 kcal=4.186 8 kJ). Including (1 744.33±249.62) kcal/d in those with normal BMI, which was significantly lower than that in those who were overweight or obese [(2 104.06± 520.32) kcal/d, P < 0.01], but the weight-corrected RMR in those with normal BMI was significantly higher than that in those who were overweight or obese [(24.02±2.61) kcal/(kg·d) vs. (19.98±4.38) kcal/(kg·d), P < 0.01]. The RMR was significantly and positively correlated with body weight, adiposity, lean body mass, body surface area, and extracellular fluid in the subjects with diffe-rent BMI (all P < 0.05). The predicted values of the 11 prediction equations were not in good agreement with the measured values (all ICC < 0.75), with relatively high agreement between the predicted and measured values of the World Health Organization (WHO) equation in overweight obese young men (ICC=0.547, P < 0.01). CONCLUSION: There were significant differences in RMR among young men with different BMI, and the RMR after weight correction should be considered for those who were overweight or obese. The consistency between the predicted values of different prediction equations and the actual measured values of RMR was relatively poor, and it is recommended to accurately measure RMR by indirect calorimetry. For overweight or obese young men, the WHO prediction equation can be considered to calculate RMR, but it is necessary to establish an RMR prediction equation applicable to different BMI populations.

Cannabinoids regulate an insula circuit controlling water intake.

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the regulation of water intake. However, our understanding of the topographical, circuit, and molecular mechanisms for controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid (CB1) receptors in the insular cortex cells participate in the regulation of water intake and deconstructed the circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both the anterior insula (aIC) and posterior insula (pIC) increases in response to water intake, yet only the specific removal of CB1 receptors in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we recorded the neurons of the aIC or pIC targeting the BLA (aIC-BLA and pIC-BLA) and found that they decreased their activity upon water drinking. Additionally, chemogenetic activation of pIC-BLA projection neurons decreased water intake. Finally, we uncovered CB1-dependent short-term synaptic plasticity (depolarization-induced suppression of excitation [DSE]) selectively in pIC-BLA, compared with aIC-BLA synapses. Altogether, our results support a model where CB1 receptor signaling promotes water intake by inhibiting the pIC-BLA pathway, thereby contributing to the fine top-down control of thirst responses.

ASSIST-U: A system for segmentation and image style transfer for ureteroscopy.

Kidney stones require surgical removal when they grow too large to be broken up externally or to pass on their own. Upper tract urothelial carcinoma is also sometimes treated endoscopically in a similar procedure. These surgeries are difficult, particularly for trainees who often miss tumours, stones or stone fragments, requiring re-operation. Furthermore, there are no patient-specific simulators to facilitate training or standardized visualization tools for ureteroscopy despite its high prevalence. Here a system ASSIST-U is proposed to create realistic ureteroscopy images and videos solely using preoperative computerized tomography (CT) images to address these unmet needs. A 3D UNet model is trained to automatically segment CT images and construct 3D surfaces. These surfaces are then skeletonized for rendering. Finally, a style transfer model is trained using contrastive unpaired translation (CUT) to synthesize realistic ureteroscopy images. Cross validation on the CT segmentation model achieved a Dice score of 0.853 ± 0.084. CUT style transfer produced visually plausible images; the kernel inception distance to real ureteroscopy images was reduced from 0.198 (rendered) to 0.089 (synthesized). The entire pipeline from CT to synthesized ureteroscopy is also qualitatively demonstrated. The proposed ASSIST-U system shows promise for aiding surgeons in the visualization of kidney ureteroscopy.

Towards navigation in endoscopic kidney surgery based on preoperative imaging.

Endoscopic renal surgeries have high re-operation rates, particularly for lower volume surgeons. Due to the limited field and depth of view of current endoscopes, mentally mapping preoperative computed tomography (CT) images of patient anatomy to the surgical field is challenging. The inability to completely navigate the intrarenal collecting system leads to missed kidney stones and tumors, subsequently raising recurrence rates. A guidance system is proposed to estimate the endoscope positions within the CT to reduce re-operation rates. A Structure from Motion algorithm is used to reconstruct the kidney collecting system from the endoscope videos. In addition, the kidney collecting system is segmented from CT scans using 3D U-Net to create a 3D model. The two collecting system representations can then be registered to provide information on the relative endoscope position. Correct reconstruction and localization of intrarenal anatomy and endoscope position is demonstrated. Furthermore, a 3D map is created supported by the RGB endoscope images to reduce the burden of mental mapping during surgery. The proposed reconstruction pipeline has been validated for guidance. It can reduce the mental burden for surgeons and is a step towards the long-term goal of reducing re-operation rates in kidney stone surgery.

Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity.

Living tissue and extracellular matrices possess viscoelastic properties, but understanding how viscoelastic matrix regulates chromatin and the epigenome is limited. Here, we find that the regulation of the epigenetic state by the viscoelastic matrix is more pronounced on softer matrices. Cells on viscoelastic matrices exhibit larger nuclei, increased nuclear lamina ruffling, loosely organized chromatin, and faster chromatin dynamics, compared to those on elastic matrices. These changes are accompanied by a global increase in euchromatic marks and a local increase in chromatin accessibility at the cis -regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic matrices enhanced the efficiency of reprogramming fibroblasts into neurons and induced pluripotent stem cells, respectively. Together, our findings demonstrate the key roles of matrix viscoelasticity in the regulation of epigenetic state, and uncover a new mechanism of biophysical regulation of chromatin and cell reprogramming, with implications for the design of smart materials to engineer cell fate.

3D-bioprinted alginate-based bioink scaffolds with ß-tricalcium phosphate for bone regeneration applications.

Background/purpose: 3D-printed bone tissue engineering is becoming recognized as a key approach in dentistry for creating customized bone regeneration treatments fitting patients bone defects requirements. 3D bioprinting offers an innovative method to fabricate detailed 3D structures, closely emulating the native bone micro-environment and better bone regeneration. This study aimed to develop an 3D-bioprintable scaffold using a combination of alginate and ß-tricalcium phosphate (ß-TCP) with the Cellink® BioX printer, aiming to advance the field of tissue engineering. Materials and methods: The physical and biological properties of the resulting 3D-printed scaffolds were evaluated at 10 %, 12 %, and 15 % alginate combined with 10 % ß-TCP. The scaffolds were characterized through printability, swelling behavior, degradability, and element analysis. The biological assessment included cell viability, alkaline phosphatase (ALP) activity. Results: 10 % alginate/ß-TCP 3D printed at 25 °C scaffold demonstrated the optimal condition for printability, swelling capability, and degradability of cell growth and nutrient diffusion. Addition of ß-TCP particles significantly improved the 3D printed material viscosity over only alginate (P < 0.05). 10 % alginate/ß-TCP enhanced MG-63 cell's proliferation (P < 0.05) and alkaline phosphatase activity (P < 0.001). Conclusion: This study demonstrated in vitro that 10 % alginate/ß-TCP bioink characteristic for fabricating 3D acellular bioprinted scaffolds was the best approach. 10 % alginate/ß-TCP bioink 3D-printed scaffold exhibited superior physical properties and promoted enhanced cell viability and alkaline phosphatase activity, showing great potential for personalized bone regeneration treatments.

Association between oral health status and occlusal bite force in young adults.

Background/purpose: Oral health is related to general health and a person's overall well-being. The aim of the present study was to explore the association between oral health status and bite force among young adults. Materials and methods: Maximum bite force (MBF) was measured using Dental Prescale II in conjunction with a pressure-sensitive film and bite force analyzer in 40 young adults aged 20 to 40. Supragingival dental plaque was collected and cultured. Plaque weight, pH, and colony counts were assessed. The decayed, missing, and filled teeth index (DMFT) and body mass index (BMI) were recorded. Results: Bite force was negatively correlated with the number of missing teeth and the sum of missing and filled teeth. When the filled-to-remaining-teeth ratio (F/R ratio) was less than 8%, the bite force was significantly higher compared to an F/R ratio of 8-25%. Additionally, the amount of total bacteria was positively correlated with total bite force, and the quantity of Streptococcus mutans (S. mutans) along with total bacteria was positively correlated with bite force in the molar region (∗P < 0.05). The molar region predominantly contributed to bite force. Conclusion: Elevated levels of cariogenic bacteria may increase the risk of tooth loss, subsequently leading to reduced bite force. This reduction in bite force can further impact the efficiency of chewing function and, consequently, the quality of life. An F/R ratio above 8% could be easily calculated clinically and could serve as a guide to identify patients, particularly young adults, at risk of reduced bite force.

Does adjunctive fixation in conjunction with miniplate affect condylar position and morphology after mandibular advancement through bilateral sagittal split ramus osteotomy? A retrospective 3-dimensional CT comparative study.

To minimize condylar positional and morphological changes after mandibular advancement through bilateral sagittal split ramus osteotomy (BSSRO), surgeons add either a bicortical screw or a two-hole plate distal to the conventional single miniplate. Since there have been no previous studies investigating the effect of this combination, our study aimed to evaluate the short- and long-term effects of these adjunctive fixation methods (AFM) on condylar positional and morphological changes after mandibular advancement through BSSRO. This retrospective cohort study included consecutive patients with retruded mandibles who were treated in the Department of Orthognathic and TMJ Surgery at West China Hospital of Stomatology, Sichuan University. The patients were divided into two groups based on the primary predictor variable, which was the addition of AFM - either a single bicortical screw or a two-hole plate in addition to the single miniplate. The primary outcome variable was the condylar positional and morphological changes after mandibular advancement through BSSRO. Three-dimensional facial CT scans were obtained at three different time points (preoperatively - T0, 1 week postoperatively - T1, and 1 year postoperatively - T2) and analyzed using ITK-SNAP, 3D Slicer, and SlicerSALT software. Intergroup comparisons were conducted with an independent t-test, with a p-value of <0.05 considered significant. Correlations between the variables were estimated by Pearson correlation. The study comprised 51 patients (32 females, 19 males; mean age 25.13 ± 4.24 years), involving a total of 81 condyles (21 unilateral and 60 bilateral). There was a significant difference in long-term condylar displacement in favor of AFM along with a single miniplate (p < 0.001). The bicortical screw group recorded less condylar displacement than the two-hole plate group horizontally (0.11 mm vs 0.22 mm) and sagittally (0.03 mm vs 0.17 mm), but more vertically (0.85 mm vs 0.03 mm). Bone formation associated with AFM occurred on all condylar surfaces, compared with only three surfaces in the single miniplate group. The adjunctive method in addition to the single miniplate fixation method showed less condylar displacement and more bone apposition after mandibular advancement through BSSRO. The follow-up duration variable was the only significant determinant for volumetric changes in the condyle.

Effects of a novel Bacillus subtilis GXYX crude lipopeptide against Salmonella enterica serovar Typhimurium infection in mice.

The increased rate of antibiotic resistance strongly limits the resolution of Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. Therefore, new strategies to control bacterial infections are urgently needed. Bacillus subtilis (B. subtilis) and its metabolites are desirable antibacterial agents. Here, we aimed to evaluate the antibacterial activity of the novel B. subtilis strain GXYX (No: PRJNA940956) crude lipopeptide against S. Typhimurium. In vitro, GXYX crude lipopeptides affected S. Typhimurium biofilm formation and swimming and attenuated the adhesion and invasion abilities of S. Typhimurium toward BHK-21 cells; in addition, it inhibited the mRNA expression of the filA, filC, csgA, and csgB genes, which are related to the adhesion and invasion ability of S. Typhimurium. In vivo, pretreatment with GXYX crude lipopeptide via intragastric administration improved the survival rate by 30%, which was related to reductions in organ bacterial loads and clinical signs in mice. Intragastric administration of GXYX crude lipopeptide significantly downregulated the mRNA levels of TNF-α, IL-1ß, IL-12 and IL-6 in response to S. Typhimurium-induced inflammation compared with intraperitoneal injection. Moreover, it significantly improved the intestinal barrier-related gene (ZO-1, claudin-1, occludin-1) mRNA levels in intestinal tissue damaged by S. Typhimurium infection. In conclusion, GXYX crude lipopeptides were effective at reducing S. Typhimurium colonization, laying a foundation for the further development of novel antibacterial agents.

Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR-II Fluorescence Imaging.

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

Th2-skewed peripheral T helper cells drives B cells in allergic bronchopulmonary aspergillosis.

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. However, the involvement of T cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. Th1, Th2, Th17, Treg and IL-21+CD4+T cells in total or sorted subsets of peripheral blood mononuclear cells (PBMCs) and ABPA Bronchoalveolar Lavage fluid (BALF) were analyzed by flow cytometry. RNA sequencing of subsets of CD4+T cells were done in exacerbated ABPA patients and healthy controls. Antibodies of T-B cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T cells was rarely detected in healthy controls but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T cells were mainly peripheral T helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T helper (Tfh) cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.

An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.

Globotriaosylsphingosine improves risk stratification of kidney progression in Fabry disease patients.

BACKGROUND: Kidney damage is common in patients with Fabry disease (FD), but more accurate information about the risk of progression to kidney failure is needed for clinical decision-making. In particular, FD patients with mild renal involvement often lack timely intervention and treatment. We aimed to utilize a model to predict the risk of renal progression in FD patients. METHODS: Between November 2011 and November 2019, ERT-naive patients with FD were recruited from three medical centers in China. To assess the risk of a 50% decline in the estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD), Cox proportional hazards models were utilized. The performance of these models was assessed using discrimination, calibration, and reclassification. RESULTS: A total of 117 individuals were enrolled. The mean follow-up time was 4.8 years, during which 35 patients (29.9 %) progressed to the composite renal outcomes. Male sex, baseline proteinuria, eGFR and globotriaosylsphingosine (Lyso-Gb3) were found to be independent risk factors for kidney progression by the Cox model, based on which a combined model containing those clinical variables and Lyso-Gb3 and clinical models including only clinical indicators were constructed. The two prediction models had relatively good performance, with similar model fit measured by R2 (59.8 % vs. 61.1 %) and AIC (51.54 vs. 50.08) and a slight increase in the C statistic (0.949 vs. 0.951). Calibration curves indicated closer alignment between predicted and actual renal outcomes in the combined model. Furthermore, subgroup analysis revealed that Lyso-Gb3 significantly improved the predictive performance of the combined model for kidney prognosis in low-risk patients with a baseline eGFR over 60 ml/min/1.73 m2 or proteinuria levels less than 1 g/d when compared to the clinical model. CONCLUSIONS: Lyso-Gb3 improves the prediction of kidney outcomes in FD patients with a low risk of progression, suggesting that these patients may benefit from early intervention to assist in clinical management. These findings need to be externally validated.