Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial␣membrane.

Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high-resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both types of protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Biological functions of Circular RNA_LARP4/ Upstream frameshift 1 in development of gastric cancer.

Recently, the progression of gastric cancer (GC), as one of the most ordinary malignant tumors, has been reported to be associated with circular RNAs. This study aimed to identify the role of circular RNA_LARP4 in GC. We performed real-time quantitative polymerase chain reaction (RT-qPCR) in 46 paired GC patients and GC cell lines to detect the expression of circular RNA_LARP4. Moreover, the role of circular RNA_LARP4 in GC proliferation was identified through proliferation assay and colony formation assay, while the role of circular RNA_LARP4 in GC metastasis was measured through scratch wound assay and transwell assay. Furthermore, the potential targets of circular RNA_LARP4 were predicted through bioinformatics methods and further identified by western blot assay and RT-qPCR. Circular RNA_LARP4 expression was remarkably lower in GC tissues compared with that in adjacent samples. Besides, cell proliferation of GC was inhibited after overexpression of circular RNA_LARP4, while cell migration and invasion of GC was inhibited after overexpression of circular RNA_LARP4. Furthermore, Upstream frameshift 1 (UPF1) was predicted as the potential target of circular RNA_LARP4 and was upregulated via overexpression of circular RNA_LARP4 in GC. Circular RNA_LARP4 inhibits GC cell proliferation and metastasis via targeting UPF1 in vitro, which might provide a new tumor suppressor in GC development.

Cardiovascular health assessed by the new life's essential 8 and the prevalence of urinary incontinence in adults.

OBJECTIVE: To explore the association between cardiovascular health (CVH) measured by Life's Essential 8 (LE8) and the prevalence of urinary incontinence (UI). METHOD: A cross-section study was conducted using data from the National Health and Nutrition Examination Survey 2007-2012. 22,609 people aged ≥ 20 years with complete information on LE8 metrics and UI questionnaires were enrolled. Participants were divided into three groups (low: < 50, moderate: ≥ 50 and < 80, high: ≥ 80) based on the cut-off of LE8. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were performed to examine the association between LE8 and the prevalence of three types of UI separately (stress UI (SUI), urge UI (UUI), mixed UI (MUI)) by confounding factors adjusted. Spline smooth was conducted to find whether a linear relationship existed. In addition, sensitive analyses were also conducted to observe the stability. RESULT: A total of 22,609 adults were involved in the study, and participants were divided into three groups (low 42.2 ± 6.3, moderate 66.1 ± 8.1, high 86.8 ± 5.1) according to the cut-off points of LE8. The multivariable logistic regression suggested that LE8 is inversely associated with the prevalence of SUI (OR = 0.98, 95%CI 0.98 to 0.99), UUI (OR = 0.98, 95%CI 0.98 to 0.99), and MUI (OR = 0.98, 95%CI 0.97 to 0.98) in the fully-adjusted model. Compared with the low group, people with high scores of LE8 had a lower prevalence of SUI (OR = 0.45, 95%CI 0.37 to 0.55), UUI (OR = 0.49, 95%CI 0.40 to 0.60), and MUI (OR = 0.41, 95%CI 0.30 to 0.55). The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of UI (SUI, UUI, or MUI) is inversely associated with the LE8 score, which suggests that maintaining a good CVH with a higher LE8 score is accompanied by lower prevalence rates of UUI, SUI, and MUI.

Biaxial hyperelastic and anisotropic behaviors of the corneal anterior central stroma along the preferential fibril orientations. Part I: Measurement and calibration of personalized stress-strain curves.

Lacking specimens is the biggest limitation of studying the mechanical behaviors of human corneal. Extracting stress-strain curves is the crucial step in investigating hyperelastic and anisotropic properties of human cornea. 15 human corneal specimens extracted from the small incision lenticule extraction (SMILE) surgery were applied in this study. To accurately measure the personalized true stress-strain curve using corneal lenticules, the digital image correlation (DIC) method and finite element method were used to calibrate the stress and the strain of the biaxial extension test. The hyperelastic load-displacement curves obtained from the biaxial extension test were performed in preferential fibril orientations, which are arranged along the nasal-temporal (NT) and the superior-inferior (SI) directions within the anterior central stroma. The displacement and strain fields were accurately calibrated and calculated using the digital image correlation (DIC) method. A conversion equation was given to convert the effective engineering strain to the true strain. The stress field distribution, which was simulated using the finite element method, was verified. Based on this, the effective nominal stress with personalized characteristics was calibrated. The personalized stress-strain curves containing individual characteristic, like diopter and anterior surface curvature, was accurately measured in this study. These results provide an experimental method using biaxial tensile test with corneal lenticules. It is the foundation for investigating the hyperelasticity and anisotropy of the central anterior stroma of human cornea.

The photogalvanic effect induced by quantum spin Hall edge states from first-principles calculations.

Based on non-equilibrium Green's function combined with density functional theory (NEGF-DFT), we theoretically investigate the spin-related photogalvanic effect (PGE) in topological insulators BiBr and SbBr nanoribbons from atomic first-principles calculations. It is demonstrated that the PGE generated photocurrents by quantum spin Hall edge states (QSHES) are in general pure spin currents due to the presence of time reversal and mirror symmetries, which is independent of the photon energies, polarization, and incident angles. Although the QSHES are topologically protected and robust against defects and impurities during their transport, the spin photocurrent generated by these edge states via the PGE is particularly sensitive to defects. By tuning the defect position of the nanoribbons, the magnitude of spin related photocurrent generated by the PGE can be significantly increased compared with that in pristine nanoribbons. Our work not only reveals the defect effect of PGE but also demonstrates the great potential of defect engineered topological insulator nanoribbons for novel application in two-dimensional opto-spintronic devices.

Liquid Content Detection In Transparent Containers: A Benchmark.

Various substances that possess liquid states include drinking water, various types of fuel, pharmaceuticals, and chemicals, which are indispensable in our daily lives. There are numerous real-world applications for liquid content detection in transparent containers, for example, service robots, pouring robots, security checks, industrial observation systems, etc. However, the majority of the existing methods either concentrate on transparent container detection or liquid height estimation; the former provides very limited information for more advanced computer vision tasks, whereas the latter is too demanding to generalize to open-world applications. In this paper, we propose a dataset for detecting liquid content in transparent containers (LCDTC), which presents an innovative task involving transparent container detection and liquid content estimation. The primary objective of this task is to obtain more information beyond the location of the container by additionally providing certain liquid content information which is easy to achieve with computer vision methods in various open-world applications. This task has potential applications in service robots, waste classification, security checks, and so on. The presented LCDTC dataset comprises 5916 images that have been extensively annotated through axis-aligned bounding boxes. We develop two baseline detectors, termed LCD-YOLOF and LCD-YOLOX, for the proposed dataset, based on two identity-preserved human posture detectors, i.e., IPH-YOLOF and IPH-YOLOX. By releasing LCDTC, we intend to stimulate more future works into the detection of liquid content in transparent containers and bring more focus to this challenging task.

Lysosomal Adenosine Triphosphate-Activated Upconversion Nanoparticle/Carbon Dot Composite for Ratiometric Imaging of Hepatotoxicity.

Drug-induced hepatotoxicity (DIH) is a common cause of acute liver injury, endangering human health. Intracellular adenosine triphosphate (ATP) content in hepatocytes is related to hepatotoxicity. Thus, monitoring the dynamic changes in lysosomal ATP is promising to further understand the pathogenesis and accurate evaluation of DIH. Herein, we developed a lysosomal ATP-activated upconversion nanoprobe by decorating ATP-sensitive carbon dots (CDs) on the surface of upconversion nanoparticles (UCNPs) for ratiometric imaging of hepatotoxicity. Owing to the excellent optical characteristics of UCNPs as well as the high selectivity and biocompatibility of CDs, this nanoprobe showed robust reversibility and good sensitivity to ATP in an acidic environment. Noticeably, it was successfully applied in imaging the lysosomal ATP levels fluctuation in living cells and deep tissues and used for studying the production and remediation pathways of acetaminophen-induced hepatotoxicity. This nanoprobe is significant for further understanding the pathogenesis of DIH and may be a potentially effective tool for the clinical evaluation of DIH.

Sacubitril/valsartan attenuates myocardial ischemia/reperfusion injury via inhibition of the GSK3ß/NF-κB pathway in cardiomyocytes.

In ischemia/reperfusion (I/R) injury, both inflammation and apoptosis play a vital role, and the inhibition of excessive inflammation and apoptosis show substantial clinical potential in the treatment of I/R disease. The role of sacubitril/valsartan (SAC/VAL)-a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI)-in inflammation regulation and apoptosis in the context of I/R injury needs to be further explored. In this study, we investigate the short- and long-term effects of SAC/VAL administration in treating adult murine I/R injury both in vivo and in vitro. Our results verified that the application of SAC/VAL could reduce infarct size and suppress apoptosis and the inflammatory response in the acute phase post I/R. Long-term application of SAC/VAL for four weeks significantly improved ventricular function and reversed pathological ventricular remodeling. Mechanistically, SAC/VAL treatment induces the inhibition of the GSK3ß-mediated NF-κB pathway through synergistically blocking angiotensin 1 receptor (AT1R) and activating natriuretic peptide receptor (NPR). In summary, we reported the therapeutic role of SAC/VAL in regulating the GSK3ß/NF-κB signaling pathway to suppress the inflammatory response and apoptosis, thereby reducing cardiac dysfunction and remodeling post I/R.

Analyzing the impact of CFP1 mutational landscape on epigenetic signaling.

CXXC Zinc finger protein 1 (CFP1) is a multitasking protein playing essential roles during various developmental processes. Its ability to interact with several proteins contribute to several epigenetic events. Here, we review CFP1's functions and its impact on DNA methylation and the post-translational modification of histone proteins such as lysine acetylation and methylation. We will also discuss the potential role of CFP1 in carcinogenesis and the impact of the mutations identified in patients suffering from various cancers.

Self-Maintenance of Cardiac Resident Reparative Macrophages Attenuates Doxorubicin-Induced Cardiomyopathy Through the SR-A1-c-Myc Axis.

RATIONALE: Doxorubicin-induced cardiomyopathy (DiCM) is a primary cause of heart failure and mortality in cancer patients, in which macrophage-orchestrated inflammation serves as an essential pathological mechanism. However, the specific roles of tissue-resident and monocyte-derived macrophages in DiCM remain poorly understood. OBJECTIVE: Uncovering the origins, phenotypes, and functions of proliferative cardiac resident macrophages and mechanistic insights into the self-maintenance of cardiac macrophage during DiCM progression. METHODS AND RESULTS: Mice were administrated with doxorubicin to induce cardiomyopathy. Dynamic changes of resident and monocyte-derived macrophages were examined by lineage tracing, parabiosis, and bone marrow transplantation. We found that the monocyte-derived macrophages primarily exhibited a proinflammatory phenotype that dominated the whole DiCM pathological process and impaired cardiac function. In contrast, cardiac resident macrophages were vulnerable to doxorubicin insult. The survived resident macrophages exhibited enhanced proliferation and conferred a reparative role. Global or myeloid specifically ablation of SR-A1 (class A1 scavenger receptor) inhibited proliferation of cardiac resident reparative macrophages and, therefore, exacerbated cardiomyopathy in DiCM mice. Importantly, the detrimental effect of macrophage SR-A1 deficiency was confirmed by transplantation of bone marrow. At the mechanistic level, we show that c-Myc (Avian myelocytomatosis virus oncogene cellular homolog), a key transcriptional factor for the SR-A1-P38-SIRT1 (Sirtuin 1) pathway, mediated the effect of SR-A1 in reparative macrophage proliferation in DiCM. CONCLUSIONS: The SR-A1-c-Myc axis may represent a promising target to treat DiCM through augmentation of cardiac resident reparative macrophage proliferation.

Positive Charges in the Brace Region Facilitate the Membrane Disruption of MLKL-NTR in Necroptosis.

Necroptosis is a type of programmed cell death executed through the plasma membrane disruption by mixed lineage kinase domain-like protein (MLKL). Previous studies have revealed that an N-terminal four-helix bundle domain (NBD) of MLKL is the executioner domain for the membrane permeabilization, which is auto-inhibited by the first brace helix (H6). After necroptosis initiation, this inhibitory brace helix detaches and the NBD can integrate into the membrane, and hence leads to necroptotic cell death. However, how the NBD is released and induces membrane rupture is poorly understood. Here, we reconstituted MLKL2-154 into membrane mimetic bicelles and observed the structure disruption and membrane release of the first brace helix that is regulated by negatively charged phospholipids in a dose-dependent manner. Using molecular dynamics simulation we found that the brace region in an isolated, auto-inhibited MLKL2-154 becomes intrinsically disordered in solution after 7 ns dynamic motion. Further investigations demonstrated that a cluster of arginines in the C-terminus of MLKL2-154 is important for the molecular conformational switch. Functional mutagenesis showed that mutating these arginines to glutamates hindered the membrane disruption of full-length MLKL and thus inhibited the necroptotic cell death. These findings suggest that the brace helix also plays an active role in MLKL regulation, rather than an auto-inhibitory domain.

Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury.

BACKGROUND: A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism. METHODS: The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro. RESULTS: In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. CONCLUSIONS: Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.

Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening.

Adenylyl cyclases (ACs), which are responsible for catalyzing the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP), play a critical role in cell signal transduction. In this study, a combined approach involving docking-based virtual screening, with the combination of homology modeling followed by an in-vitro, and cell-based biological assay have been performed for discovering a class of novel potent and selective isoform adenylyl cyclase type 8 (AC8) agonist. The computer-aided virtual screening was used to identify fourteen virtual cluster compounds as potential hits which were further subjected to rigorous bioassays. A novel hit compound VHC-7 (ethyl 3-(2,4-dichlorobenzyl)-2-oxoindoline-3-carboxylate) was identified as a highly potent selective AC8 agonist with EC50 value of 0.1052 ± 0.038 µM. Remarkably, the molecule herein reported can be explored further to discover greater number of hit compounds with better pharmacokinetic properties as well as to serve as a promising novel hit agonist of AC8 for the treatment of various central nervous system disorders and its associated diseases.

Giant magnetoresistance and dual spin filtering effect in ferromagnetic 6,6,12/γ-graphyne zigzag nanoribbon lateral heterojunction.

Based on non-equilibrium Green's function combined with density functional theory (NEGF-DFT), we investigate the spin dependent transport in the ferromagnetic 6,6,12/γ-graphyne zigzag nanoribbon (GYZNR) heterojunction under different magnetic configurations. It is found that, at low bias ([-0.05, 0.1] V), the junction presents metallic transport with negligible spin polarization in parallel configuration (PC) while it behaves as an insulator in anti-parallel configuration (APC), which results in giant magnetoresistance. Interestingly, when we increase the bias voltage beyond [-0.05, 0.1] V, dual spin filtering characterized by electron transport of different spin channels under different polarity of bias is observed in APC but not in PC. All these findings are understood from the symmetry matching of wave functions in two nanoribbons at equilibrium or finite bias. Furthermore, dual spin filtering can also be achieved in PC by applying a gate voltage on the central interface region, which arises from the shift of different single spin channel of the central gate region into the bias window at a different polarity of the gate voltage. Thus, our work demonstrates the great potential of the 6,6,12/γ-GYZNR heterojunction as a multi-functional device and its great perspectives in carbon-based nanoelectronics and spintronics.

Pyrolysis of tyre powder using microwave thermogravimetric analysis: Effect of microwave power.

The pyrolytic characteristics of tyre powder treated under different microwave powers (300, 500, and 700 W) were studied via microwave thermogravimetric analysis. The product yields at different power levels were studied, along with comparative analysis of microwave pyrolysis and conventional pyrolysis. The feedstock underwent preheating, intense pyrolysis, and final pyrolysis in sequence. The main and secondary weight loss peaks observed during the intense pyrolysis stage were attributed to the decomposition of natural rubbers and synthetic rubbers, respectively. The total mass loss rates, bulk temperatures, and maximum temperatures were distinctively higher at higher powers. However, the maximum mass loss rate (0.005 s-1), the highest yields of liquid product (53%), and the minimum yields of residual solid samples (43.83%) were obtained at 500 W. Compared with conventional pyrolysis, microwave pyrolysis exhibited significantly different behaviour with faster reaction rates, which can decrease the decomposition temperatures of both natural and synthetic rubber by approximately 110 °C-140 °C.

Association between magnesium depletion score and the prevalence of kidney stones in the low primary income ratio: a cross-sectional study of NHANES 2007-2018.

INTRODUCTION: To explore the association between magnesium depletion score (MgDS) and the prevalence of kidney stones in the low primary income ratio (PIR). METHOD: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey 2007-2018. Within the low PIR, people aged ≥20 years with complete information on MgDS and kidney stones questionnaires were enrolled. Multivariable logistic regression and stratified logistic regression analyses were performed to examine the association between MgDS and the prevalence of kidney stones and recurrence of kidney stones by confounding factors adjusted. Stratified and interaction analysis was conducted to find whether some factors modified the association. In addition, sensitive analyses were also conducted to observe the stability. The work has been reported in line with the STROCSS criteria, Supplemental Digital Content 1, http://links.lww.com/JS9/C781. RESULT: A total of 7,600 adults were involved in the study, and the individuals were classified into four groups: 0 points for MgDS (n=3,814), 1 point for MgDS (n=2,229), 2 points for MgDS (n=1,020), and ≥3 points for MgDS (n=537). The multivariable logistic regression suggested that a positive association between MgDS and the prevalence of kidney stones (OR=1.123, 95%CI 1.019 to 1.238) in the fully-adjusted model. Compared with the lowest group, people with ≥3 points of MgDS had a had a significant relationship with kidney stones (OR=1.417, 95%CI 1.013 to 1.983). No significant association was observed between the recurrence of kidney stones and MgDS. The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of kidney stones is inversely associated with MgDS, which suggests that maintaining a higher MgDS is accompanied by higher prevalence rates of kidney stones in the low PIR.

MHCII-peptide presentation: an assessment of the state-of-the-art prediction methods.

Major histocompatibility complex Class II (MHCII) proteins initiate and regulate immune responses by presentation of antigenic peptides to CD4+ T-cells and self-restriction. The interactions between MHCII and peptides determine the specificity of the immune response and are crucial in immunotherapy and cancer vaccine design. With the ever-increasing amount of MHCII-peptide binding data available, many computational approaches have been developed for MHCII-peptide interaction prediction over the last decade. There is thus an urgent need to provide an up-to-date overview and assessment of these newly developed computational methods. To benchmark the prediction performance of these methods, we constructed an independent dataset containing binding and non-binding peptides to 20 human MHCII protein allotypes from the Immune Epitope Database, covering DP, DR and DQ alleles. After collecting 11 known predictors up to January 2022, we evaluated those available through a webserver or standalone packages on this independent dataset. The benchmarking results show that MixMHC2pred and NetMHCIIpan-4.1 achieve the best performance among all predictors. In general, newly developed methods perform better than older ones due to the rapid expansion of data on which they are trained and the development of deep learning algorithms. Our manuscript not only draws a full picture of the state-of-art of MHCII-peptide binding prediction, but also guides researchers in the choice among the different predictors. More importantly, it will inspire biomedical researchers in both academia and industry for the future developments in this field.

Investigation of the optimal cutting depth in small incision lenticule extraction based on a collagen fibril crimping constitutive model of the cornea.

To investigate the optimal cutting depth (Cap) in small incision lenticule extraction from the perspective of corneal biomechanics, a three-dimensional finite element model of the cornea was established using a stromal sub-regional material model to simulate small incision lenticule extraction. The displacement difference PΔ at the central point of the posterior corneal surface before and after lenticule extraction, as well as the von Mises stress at four points of different thicknesses in the center of the cornea, were analyzed using the finite element model considering the hyperelastic property and the difference in stiffness between the anterior and posterior of the cornea. The numerical curves of PΔ-Cap and von Mises Stress-Cap relations at different diopters show that the displacement difference PΔ has a smallest value at the same diopter. In this case, the von Mises stress at four points with different thicknesses in the center of the cornea was also minimal. Which means that the optimal cutting depth exsisting in the cornea. Moreover, PΔ-Cap curves for different depth of stromal stiffness boundaries show that the optimal cap thickness would change with the depth of the stromal stiffness boundary. These results are of guiding significance for accurately formulating small incision lenticule extraction surgery plans and contribute to the advancement of research on the biomechanical properties of the cornea.