Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae (Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-ß1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-ß1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.

A cell-free system for functional studies of small membrane proteins.

Numerous small proteins have been discovered across all domains of life, among which many are hydrophobic and predicted to localize to the cell membrane. Based on a few that are well-studied, small membrane proteins are regulators involved in various biological processes, such as cell signaling, nutrient transport, drug resistance, and stress response. However, the function of most identified small membrane proteins remains elusive. Their small size and hydrophobicity make protein production challenging, hindering function discovery. Here, we combined a cell-free system with lipid sponge droplets and synthesized small membrane proteins in vitro. Lipid sponge droplets contain a dense network of lipid bilayers, which accommodates and extracts newly synthesized small membrane proteins from the aqueous surroundings. Using small bacterial membrane proteins MgrB, SafA, and AcrZ as proof of principle, we showed that the in vitro produced membrane proteins were functionally active, for example, modulating the activity of their target kinase as expected. The cell-free system produced small membrane proteins, including one from human, up to micromolar concentrations, indicating its high level of versatility and productivity. Furthermore, AcrZ produced in this system was used successfully for in vitro co-immunoprecipitations to identify interaction partners. This work presents a robust alternative approach for producing small membrane proteins, which opens a door to their function discovery in different domains of life.

Relationships between gross motor skills, psychological resilience, executive function, and emotional regulation among Chinese rural preschoolers: A moderated mediation model.

Background: Emotional regulation is a critical component of emotional intelligence, particularly during the preschool stage, a key period for children's development. Previous studies have demonstrated that executive function mediates the effect of gross motor skills on emotional understanding. However, studies specifically focusing on children from rural areas and investigating the role of psychological resilience are limited. The present study fills this knowledge gap by examining the effect of gross motor skills on emotional regulation and the roles of executive function and psychological resilience among Chinese rural preschool children. Methods: This study included 430 children (aged 61.01 ± 6.98 months, 48.8 % boys) and their teachers from three rural preschools in China. Children's gross motor skills, including locomotor and object control skills, were assessed using the Test of Gross Motor Development-3. Executive function was measured using the Head-Toes-Knee-Shoulder task, and emotional regulation was assessed using the Emotional Regulation Checklist. Furthermore, psychological resilience was examined using the Devereux Early Childhood Assessment. Demographic information was collected, and the cross-sectional relationships between gross motor skills and emotional regulation were investigated through mediation and moderation analyses. Results: Gross motor skills, executive function, and psychological resilience were associated with emotional regulation (p < 0.05), after controlling for sex, age, and only-child status. Executive function was found to mediate the relationship between gross motor skills and emotional regulation, with a mediation effect of 0.045. Psychological resilience moderated the relationship between executive function and emotional regulation (ß = 0.078, p < 0.05). Simple slope analysis, based on categorizing psychological resilience into high, medium, and low groups, revealed that preschoolers with a higher level of psychological resilience exhibited a significantly stronger predictive effect of executive function on emotional regulation (ß = 0.202, p < 0.01). Conclusions: Gross motor skills significantly affect emotional regulation development in rural preschoolers, with executive function acting as a mediator in this relationship. Psychological resilience was found to moderate the effect of executive function on emotional regulation. The findings suggest that enhancing gross motor skills through physical activities can benefit children by promoting the development of executive function, which is crucial for emotional regulation. On the basis of our findings, we recommend focusing on cost-effective physical activity interventions for motor skills development among rural children while also addressing the development of executive function and psychological resilience. Future efforts should include workshops to improve physical literacy of parents and teachers regarding children's gross motor skills promotion.

Diagnostic value and clinical significance of serum miR-134-5p combined with uterine artery color Doppler ultrasound parameters in endometriosis.

OBJECTIVE: To exploit the combination diagnostic performance of serum microRNA-134-5p (miR-134-5p) and color Doppler ultrasound in patients with endometriosis patients. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) analysis was applied to measure relative abundance of miR-134-5p in serum of patients with endometriosis and gynecological benign diseases. Calculation of uterine artery blood flow parameters was conducted using Color Doppler ultrasound. Receiver operating characteristic (ROC) curve was established to evaluate the diagnostic capacity of miR-134-5p and Doppler parameters. Kaplan-Meier method was used for the analysis of recurrence-free survival rate. RESULTS: Compared with the control group, serum miR-134-5p expression was remarkably diminished in endometriosis patients (P < 0.001). End-diastolic velocity (EDV) and peak systolic velocity (PSV) were notably decreased in endometriosis patients compared with the control group (P < 0.001), while pulsatility index (PI) and resistance index (RI) were distinctly increased (P < 0.001). Serum miR-134-5p expression was positively correlated with EDV (r = 0.5777, P < 0.0001) and PSV (r = 0.6945, P < 0.0001), but negatively correlated with PI (r=-0.6382, P < 0.0001) and RI (r=-0.6247, P < 0.0001). The area under the ROC curve (AUC) of serum miR-134-5p combined with Doppler parameters was 0.905, with the sensitivity of 87.40%, and the specificity of 82.29%. The recurrence-free survival time was shorter in patients with low miR-134-5p expression than those with high miR-134-5p expression (P = 0.013). CONCLUSION: A better diagnostic value of endometriosis detection could be obtained when serum miR-134-5p was combined with Doppler parameters.

Optimal dose of vigorous physical activity on cardiorespiratory and perceptual response for sedentary youths using internal load monitoring.

Introduction: Vigorous physical activity (VPA) has been demonstrated to enhance cardiorespiratory fitness (CRF) in sedentary college students more effectively than other PA. However, differences in training volume may affect this outcome. This study examines the physiological, psychological, and internal training load (ITL) characteristics of VPA with varying volumes in a single session. Methods: Thirty sedentary college students were divided into three groups: high-intensity interval training (HIIT), sprint interval training (SIT), and threshold training (THR). PA process was monitored. The study measured various cardiorespiratory parameters, including heart rate (HR), respiratory waveform and amplitude, respiratory rate (RR), tidal volume (TV), minute ventilation volume (VE), fractional concentration of oxygen in end-tidal gas (O2%), fractional concentration of end-tidal carbon dioxide (CO2%), global oxygen consumption (VO2), carbon dioxide discharge (VCO2), and the amount of carbon dioxide in the air. The following physiological indicators were measured: carbon dioxide discharge (VCO2), Oxygen pulse (OP), and respiratory exchange ratio (RER). Additionally, subjective perception indicators were recorded, including the feeling scale (FS), rating of perceived exertion (RPE), and dual-mode model (DMM). The session-RPE (s-RPE) and Edward's TRIMP were used to measure ITL. Results: There were no significant differences in HR across the three conditions. THR had the highest level of TV (p = 0.043), but RR was significantly lower than that of HIIT and SIT (p < 0.01). HIIT had the highest levels of VO2, VCO2, O2%, and OP (p < 0.05). RPE was higher in HIIT and SIT compared to THR (p < 0.01), but the difference in FS was not significant. The DMM time-domain trajectories were similar in HIIT and THR. The correlation between exercise intensity, RPE, and FS was highest in THR group (r = 0.453, r = -0.58, r = -0.885). ITL did not show a significant difference between three conditions, but TRIMP and s-RPE readings were opposite in magnitude. Conclusion: This study proposes that using an appropriate amount of THR to foster interest and adaptive strength during the PA habit establishment period, incorporating HIIT to enhance exercise efficiency during the adaptation period, and implementing SIT to reduce the monotony may effectively enhance the cardiorespiratory fitness of sedentary college students and establish PA habit.

Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy.

BACKGROUND: Glioma is the most common primary malignant tumor in the brain, and even with standard treatments including surgical resection, radiotherapy, and chemotherapy, the long-term survival rate of patients remains unsatisfactory. Recurrence is one of the leading causes of death in glioma patients. The molecular mechanisms underlying glioma recurrence remain unclear. METHODS: Our study utilized single-cell sequencing, spatial transcriptomics, and RNA-seq data to identify a subtype of FN1 + tumor-associated macrophages (FN1 + TAMs) associated with glioma recurrence. RESULTS: This study revealed an increased abundance of FN1 + TAMs in recurrent gliomas, indicating their potential involvement as a critical factor in glioma recurrence. A negative correlation was observed between the abundance of FN1 + TAMs in primary gliomas and the interval time to recurrence, suggesting poor prognosis for glioma patients with high levels of FN1 + TAMs. Further investigation showed that FN1 + TAMs were enriched in hypoxic tumor regions, implying that metabolic changes in tumors drive the production and recruitment of FN1 + TAMs. Additionally, FN1 + TAMs were found to contribute to the regulation of an immunosuppressive microenvironment in gliomas, and their abundance might serve as an indicator of patients' sensitivity to immunotherapy. Finally, we developed a user-friendly website, PRIMEG ( http://www.szflab.site/PRIMEG/ ), for exploring the immune microenvironment of primary and recurrent gliomas. CONCLUSION: Our findings highlight a subtype of FN1 + TAMs associated with glioma recurrence, providing new insights into potential therapeutic targets. Moreover, the abundance of FN1 + TAMs hold promise for predicting immune therapy response and aiding in more precise risk stratification of recurrent glioma patients.

Smart paper-based materials incorporating nitrogen and boron co-doped MXene quantum dots for rapid adsorption and sensitive detection of Cr2O72.

Dichromate ion (Cr2O72-) is a highly toxic chromium-containing compound that poses significant hazards to the digestive, respiratory systems, skin, and mucous membranes. Currently, the detection and adsorption of Cr2O72- face significant challenges, including the time-consuming and low sensitivity nature of traditional analytical methods. The limited efficiency and capacity of existing adsorbents hinder their practical application in real-time water quality monitoring and environmental remediation. Herein, using polyethyleneimine-functionalized (PEI) pulp fiber paper as the substrate, we developed smart paper-based materials (designated as NB-MQDs@PP) incorporated with nitrogen and boron co-doped MXene quantum dots (NB-MQDs) for rapid adsorption and sensitive detection of Cr2O72-. Compared to undoped MQDs, NB-MQDs exhibited longer excitation wavelength and enhanced oxidation stability. As anticipated, NB-MQDs achieved rapid (response time of 10 s) and sensitive (detection limit of 1.2 µM) recognition of Cr2O72- within a wide pH range with a quenching efficiency of 99.9%. Simultaneously, two on-site detection methods, immersion and cyclic filtration, were constructed based on NB-MQDs@PP. The detection limit of the immersion method was 17.0 nM, while the cyclic filtration method had a detection limit as low as 3.8 nM, surpassing the majority of those reported literatures. Remarkably, NB-MQDs@PP exhibited outstanding enrichment capacity towards Cr2O72-, with an adsorption capacity of up to 162.4 mg/g. This work provides a novel strategy for creating unique paper-based materials with excellent capture and monitoring dual-function, which can be customized according to the requirements of various application scenarios.

CsPb2Br5 Plates/Quasi-2D Perovskite Heterojunction for Efficient Sky-Blue Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) have gained significant attention owing to their remarkable tunability and color stability, and substantial progress has been made with green and red PeLEDs. However, the advancement of blue PeLEDs still lags far behind their red and green counterparts. In this study, we report efficient sky-blue PeLEDs utilizing an in situ fabricated CsPb2Br5 plates/quasi-2D perovskite heterojunction using chelating molecules to modulate the crystallization process of perovskites. The wide bandgap of CsPb2Br5 facilitated the formation of a type-I band alignment at the heterojunction, allowing efficient carrier transfer from CsPb2Br5 to CsPbBr3. This heterojunction leads to a noteworthy enhancement of device efficiency. The PeLEDs exhibit a maximum brightness of 2311 cd m-2, accompanied by a maximum external quantum efficiency of 12.86% at 487 nm. Our tailored design of CsPb2Br5/perovskite heterojunction thin films offers a promising avenue for advancing PeLED performance. This work contributes valuable insights into the burgeoning field of perovskite electroluminescence, paving the way for further optimization of PeLED technologies.

Achieving optical transparency in live animals with absorbing molecules.

Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.

Flexible electronics for cardiovascular monitoring on complex physiological skins.

Cardiovascular diseases (CVDs) pose a significant global health threat, responsible for a considerable portion of worldwide mortality. Flexible electronics enable continuous, noninvasive, real-time, and portable monitoring, providing an ideal platform for personalized healthcare. Nevertheless, challenges persist in sustaining stable adherence across diverse and intricate skin environments, hindering further advancement toward clinical applications. Strategies such as structural design and chemical modification can significantly enhance the environmental adaptability and monitoring performance of flexible electronics. This review delineates processing techniques, including structural design and chemical modification, to mitigate signal interference from sebaceous skin, motion artifacts from the skin in motion, and infection risks from fragile skin, thereby enabling the accurate monitoring of key cardiovascular indicators in complex physiological environments. Moreover, it delves into the potential for the strategic development and improvement of flexible electronics to ensure their alignment with complex physiological environment requirements, facilitating their transition to clinical applications.

The gut microbiome modulate response to immunotherapy in cancer.

Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers. Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.

Association between fat-soluble vitamins and metabolic syndromes in US adults: a cross-section study from NHANES database.

BACKGROUND: Previous studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It's necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years. METHODS: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003-2006 and 2017-2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose-response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components. RESULTS: The presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose-response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels. CONCLUSION: Findings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds.

Two-Coordinate Gold(I) Complex with Rotational Freedom: A Platform Integrating Thermally Activated Delayed Fluorescence, Polymorphism, and Linearly Polarized Luminescence.

Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93% in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materialsfor advanced photonic applications.

FedETC: Encrypted traffic classification based on federated learning.

The current popular traffic classification methods based on feature engineering and machine learning are difficult to obtain suitable traffic feature sets for multiple traffic classification tasks. Besides, data privacy policies prohibit network operators from collecting and sharing traffic data that might compromise user privacy. To address these challenges, we propose FedETC, a federated learning framework that allows multiple participants to learn global traffic classifiers, while keeping locally encrypted traffic invisible to other participants. In addition, FedETC adopts one-dimensional convolutional neural network as the base model, which avoids manual traffic feature design. In the experiments, we evaluate the FedETC framework for the tasks of both application identification and traffic characterization in a publicly available real-world dataset. The results show that FedETC can achieve promising accuracy rates that are close to centralized learning schemes.

Genetic landscape of homologous recombination repair and practical outcomes of PARPi therapy in ovarian cancer management.

Background: Genetic studies of ovarian cancer (OC) have historically focused on BRCA1/2 mutations, lacking other studies of homologous recombination repair (HRR). Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit synthetic lethality to significantly improve OC treatment outcomes, especially in BRCA1/2 deficiency patients. Objectives: Our study aims to construct a mutation map of HRR genes in OC and identify factors influencing the efficacy of PARPi. Design: A retrospective observational analysis of HRR gene variation data from 695 OC patients from March 2019 to February 2022 was performed. Methods: The HRR gene variation data of 695 OC patients who underwent next-generation sequencing (NGS) in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Clinical data on the use of PARPi in these patients were also gathered to identify factors that may interfere with the efficacy of PARPi. Results: Out of 127 pathogenic variants in the BRCA1/2 genes, 104 (81.9%) were BRCA1 mutations, and 23 (18.1%) were BRCA2 mutations. Among the 59 variants of uncertain significance (VUS), 20 (33.9%) were BRCA1, while 39 (66.1%) were BRCA2 mutations. In addition to BRCA1/2, HRR gene results showed that 9 (69%) of 13 were HRR pathway pathogenic variants; and 16 (1.7%) of 116 VUS were Food and Drug Administration (FDA)-approved mutated HRR genes. Notably, the treatment regimen significantly influenced the effectiveness of PARPi, especially when using first-line maintenance therapy, leading to enhanced progression-free survival (PFS) compared to alternative protocols. Conclusion: Focusing on HRR gene mutations and supporting clinical research about PARPi in OC patients is crucial for developing precision treatment strategies and enhancing prognosis.

TIPE2 protein restrains invariant NKT activation and protects against immune-mediated hepatitis in mice.

BACKGROUND AND AIMS: Concanavalin A (ConA) administration induces a rapid and severe liver injury in mice, and invariant natural killer T (iNKT) cells are recognized to be the key effector cells in this process. However, the underlying regulatory mechanisms are not well defined. APPROACH AND RESULTS: We found that iNKT cells constitutively expressed TIPE2 (Tumor necrosis factor-α-induced protein 8-like 2, or TNFAIPL2). Genetic TIPE2 ablation strongly sensitized mice to ConA-induced hepatitis, accompanied with hyperactivation of iNKT cells. Moreover, Tipe2-/- mice were also more susceptible to α-galactosylceramide (αGalCer)-induced liver injury, with elevated serum ALT level and enhanced proinflammatory cytokine production. CD1d signaling blockade or iNKT cell elimination through antibodies reduced the effect of TIPE2 deficiency on liver injury. Mechanistic studies revealed that TIPE2 in iNKT cells functioned as a negative regulator, limiting iNKT cell activity and cytokine production through PIP3- AKT/mTOR pathway. TIPE2-mediated protection from liver injury was further validated by the administration of adeno-associated viruses expressing TIPE2, which effectively ameliorated ConA-induced hepatic injury. However, TIPE2 was dispensable in two other liver injury models, including D-GalN/LPS and APAP-induced hepatitis. CONCLUSION: Our findings reveal a new role of TIPE2 in the attenuation of iNKT cell-mediated hepatic injury. We propose that TIPE2 serves as an important regulator of immune homeostasis in the liver, and might be exploited for the therapeutic treatment of autoimmune liver diseases.

Perioperative and mid-term outcomes of robotic-assisted versus video-assisted minimally invasive esophagectomy for esophageal cancer: a retrospective propensity-matched analysis of 842 patients.

Aim: Comparing the safety, effectiveness, and mid-term survival rates of robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE). Methods: A total of 842 patients undergoing minimally invasive esophagectomy were analyzed, including 694 patients in VAMIE group and 148 in RAMIE group. PSM analysis was applied to generate matched pairs for further comparison. Operative outcomes, postoperative complications and Mid-term outcomes were compared between all patients in matched groups. Results: After 1:4 PSM, 148 patients in the RAMIE and 592 patients in the VAMIE. Compared to VAMIE, RAMIE exhibited earlier removal of chest and neck drainage tubes, shorter postoperative hospital stays, and a higher number of lymph node dissections. However, the surgical duration of RAMIE was longer than that of VAMIE. Postoperative complications were no statistically significant between the RAMIE and VAMIE groups. There was no statistically significant difference in the 3-year OS and DFS between the two groups. Conclusion: Compared to VAMIE, RAMIE emerges as a viable and safe surgical approach and suggests RAMIE as a potential alternative to minimally invasive esophagectomy.

Are Melanocortin Receptors Present in Extant Protochordates?

Functional melanocortin receptor (MCR) genes have been identified in the genomes of early chordates, e.g., the cyclostomata. Whether they appear in the most ancient chordates such as cephalochordate and urochordata, however, remains unclear due to missing genetic data. Herein, we studied five putative (from NCBI database), sequence-based predicted MCR-like receptors from urochordata and cephalochordate, including Styela clava, Ciona intestinalis, Branchiostoma floridae, and Branchiostoma belcheri. The BLAST and phylogenetic analyses suggested a relationship between these specific receptors and vertebrate MCRs. However, several essential residues for MCR functions in vertebrates were missing in these putative chordata MCRs. To test receptor functionality, several experimental studies were conducted. Binding assays and functional analyses showed no specific binding and no ligand-induced cAMP or ERK1/2 signaling (with either endogenous α-MSH or synthetic ligands for MC4R), despite successfully expressing four receptors in HEK 293T cells. These four receptors showed high basal cAMP signaling, likely mediated by ligand-independent Gs coupling. In summary, our results suggest that the five predicted MCR-like receptors are, indeed, class A G protein-coupled receptors (GPCRs), which in four cases show high constitutive activity in the Gs-cAMP signaling pathway but are not MCR-like receptors in terms of ligand recognition of known MCR ligands. These receptors might be ancient G protein-coupled receptors with so far unidentified ligands.

Benchmarking algorithms for single-cell multi-omics prediction and integration.

The development of single-cell multi-omics technology has greatly enhanced our understanding of biology, and in parallel, numerous algorithms have been proposed to predict the protein abundance and/or chromatin accessibility of cells from single-cell transcriptomic information and to integrate various types of single-cell multi-omics data. However, few studies have systematically compared and evaluated the performance of these algorithms. Here, we present a benchmark study of 14 protein abundance/chromatin accessibility prediction algorithms and 18 single-cell multi-omics integration algorithms using 47 single-cell multi-omics datasets. Our benchmark study showed overall totalVI and scArches outperformed the other algorithms for predicting protein abundance, and LS_Lab was the top-performing algorithm for the prediction of chromatin accessibility in most cases. Seurat, MOJITOO and scAI emerge as leading algorithms for vertical integration, whereas totalVI and UINMF excel beyond their counterparts in both horizontal and mosaic integration scenarios. Additionally, we provide a pipeline to assist researchers in selecting the optimal multi-omics prediction and integration algorithm.