Assisted reproductive technologies and postpartum depressive symptoms: A meta-analysis.

BACKGROUND: Assisted reproductive technologies (ARTs) have become the main treatment for infertility. ART treatment can be a stressful life event for infertile females. Whether there is an association between ARTs and postpartum depressive symptoms (PDS) has not been established. METHODS: PubMed, MEDLINE, EMBASE, PsycINFO, and CNKI were searched. The pooled outcome was the difference in incidence of PDS within 1 year postpartum between ARTs and the spontaneous pregnancy group. RESULTS: A total of 12 cohort studies, which were conducted in eight developed countries and two developing countries, were involved. In total, 106,338 pregnant women, including 4990 infertile females with ARTs treatment and 101,348 women with spontaneous pregnancy, were enrolled in our final analysis. ARTs women had a lower incidence of PDS compared to the spontaneous pregnancy group according to a random effect model (OR = 0.83, 95 % CI: 0.71-0.97, p = 0.022, I2 = 62.0 %). Subgroup analyses indicated that studies on late PDS (follow-up: 3-12 months postpartum) were more heterogeneous than those on early PDS (follow-up: <3 months postpartum) (I2 = 24.3 % vs. I2 = 0 %, interaction p-value < 0.001). There was a strong relationship between ARTs and late PDS (OR = 0.65, 95 % CI: 0.55-0.77, p < 0.001). Therefore, the possible source of heterogeneity was the postpartum evaluation time, which was confirmed by post-hoc meta-regression. LIMITATIONS: Some underlying confounders, such as previous psychiatric illness, the limited availability of ARTs, and ethnic disparities, cannot be ignored and may have biased interpretation of the results. CONCLUSION: The available data suggested that ARTs were associated with lower incidence of PDS, especially when follow-up lasted over 3 months. However, these findings should be interpreted with caution. Better-designed trials are needed to confirm this association.

Outpatient cervical ripening with balloon catheters: A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: One in four labors are induced. The process of cervical ripening can be lengthy and pre-labor hospitalization is required. Outpatient cervical ripening can be an attractive alternative. OBJECTIVES: To evaluate the efficacy and safety of outpatient cervical ripening with a balloon catheter compared with inpatient balloon catheter or prostaglandin E2 (PGE2 ). SEARCH STRATEGY: The PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases were searched from their inception to October 15, 2022. SELECTION CRITERIA: Randomized controlled trials comparing the outpatient balloon catheter with inpatient balloon catheter or inpatient PGE2 for term cervical ripening. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis was performed. The primary outcome was the cesarean delivery rate. The secondary outcomes included instrumental delivery, the time from intervention-to-birth, oxytocin augmentation, total hospital duration, and maternal/neonatal adverse events. MAIN RESULTS: Twenty-nine randomized controlled trials with a total of 6004 participants were identified. No difference in the cesarean delivery rate was revealed among the three interventions. Compared with inpatient balloon catheter, outpatient balloon catheter had shorter total hospital duration (mean difference -8.58, 95% confidence interval -17.02 to -1.10). No differences were revealed in the time from intervention-to-birth, instrumental delivery, postpartum hemorrhage, 5-min Apgar score less than 7, umbilical cord arterial pH less than 7.1, and neonatal intensive care unit admission among the three interventions. CONCLUSIONS: Outpatient balloon catheter in low-risk term pregnancies is an available option that could be considered for cervical ripening. The safety and effectiveness are comparable to inpatient cervical ripening methods.

Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral.

BACKGROUND: Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. MATERIAL AND METHODS: Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (µCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1ß, IL-4). RESULTS: Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1ß levels, and less active MMP-9 in cell culture. CONCLUSION: This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

Discovery and characterization of cross-reactive intrahepatic antibodies in severe alcoholic hepatitis.

The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.

Reduced CPU Workload for Human Pose Detection with the Aid of a Low-Resolution Infrared Array Sensor on Embedded Systems.

Modern embedded systems have achieved relatively high processing power. They can be used for edge computing and computer vision, where data are collected and processed locally, without the need for network communication for decision-making and data analysis purposes. Face detection, face recognition, and pose detection algorithms can be executed with acceptable performance on embedded systems and are used for home security and monitoring. However, popular machine learning frameworks, such as MediaPipe, require relatively high usage of CPU while running, even when idle with no subject in the scene. Combined with the still present false detections, this wastes CPU time, elevates the power consumption and overall system temperature, and generates unnecessary data. In this study, a low-cost low-resolution infrared thermal sensor array was used to control the execution of MediaPipe's pose detection algorithm using single-board computers, which only runs when the thermal camera detects a possible subject in its field of view. A lightweight algorithm with several filtering layers was developed, which allowed the effective detection and isolation of a person in the thermal image. The resulting hybrid computer vision proved effective in reducing the average CPU workload, especially in environments with low activity, almost eliminating MediaPipe's false detections, and reaching up to 30% power saving in the best-case scenario.

A single amino acid substitution in the capsid protein of Zika virus contributes to a neurovirulent phenotype.

Increasing evidence shows the African lineage Zika virus (ZIKV) displays a more severe neurovirulence compared to the Asian ZIKV. However, viral determinants and the underlying mechanisms of enhanced virulence phenotype remain largely unknown. Herein, we identify a panel of amino acid substitutions that are unique to the African lineage of ZIKVs compared to the Asian lineage by phylogenetic analysis and sequence alignment. We then utilize reverse genetic technology to generate recombinant ZIKVs incorporating these lineage-specific substitutions based on an infectious cDNA clone of Asian ZIKV. Through in vitro characterization, we discover a mutant virus with a lysine to arginine substitution at position 101 of capsid (C) protein (termed K101R) displays a larger plaque phenotype, and replicates more efficiently in various cell lines. Moreover, K101R replicates more efficiently in mouse brains and induces stronger inflammatory responses than the wild type (WT) virus in neonatal mice. Finally, a combined analysis reveals the K101R substitution promotes the production of mature C protein without affecting its binding to viral RNA. Our study identifies the role of K101R substitution in the C protein in contributing to the enhanced virulent phenotype of the African lineage ZIKV, which expands our understanding of the complexity of ZIKV proteins.

Microplastic transport during desertification in drylands: Abundance and characterization of soil microplastics in the Amu Darya-Aral Sea basin, Central Asia.

Desertification and microplastic pollution are major environmental issues that impact the function of the ecosystem and human well-being of drylands. Land desertification may influence soil microplastics' abundance, transport, and distribution, but their distribution in the dryland deserts of Central Asia's Amu Darya-Aral Sea basin is unknown. Here, we investigated the abundance and distribution of microplastics in dryland desert soils from the Amu Darya River to the Aral Sea basin in Central Asia at a spatial scale of 1000 km and soil depths ranging from 0 to 50 cm. Microplastics were found in soils from all sample locations, with abundances ranging from 182 to 17841 items kg-1 and a median of 3369. Twenty-four polymers were identified, with polyurethane (PU, 37.3%), silicone resin (SR, 17.0%), and chlorinated polyethylene (CPE, 9.8%) accounting for 64.1% of all polymer types. The abundance of microplastics was significantly higher in deep (20-50 cm) soils than in surface (0-5, 5-20 cm) soils. The main morphological characteristics of the observed microplastics were small size (20-50 µm) and irregular particles with no round edges (mean eccentricity 0.65). The abundance was significantly and positively related to soil EC and TP. According to the findings, desertification processes increase the abundance of microplastic particles in soils and promote migration to deeper soil layers. Human activities, mainly grazing, may be the region's primary cause of desertification and microplastic pollution. Our findings provide new information on the diffusion of microplastics in drylands during desertification; these findings are critical for understanding and promoting dryland plastic pollution prevention and control.

Coarse-Graining Waters: Unveiling The Effective Hydrophilicity/Hydrophobicity of Individual Protein Atoms and The Roles of Waters' Hydrogens.

There have been many coarse-graining methods developed that aim to reduce the sizes of simulated systems and their computational costs. In this work, we develop a new coarse-graining method, called coarse-graining-delta (or δ-CG in short), that reduces the degrees of freedom of the potential energy surface by coarse-graining relative locations of atoms from their unit centers. Our method extends and generalizes the methods used in the coarse-grained normal mode analysis and enables us to study the roles of the individual removed atoms in a system, which have been difficult to study in molecular dynamics simulations. By applying δ-CG to coarse-grain three-point water molecules into single-point solvent particles, we successfully identify the effective hydrophilicity and hydrophobicity of all the individual protein atom types, which collectively correlate well with the known hydrophilic, hydrophobic, and amphipathic characteristics of amino acids. Moreover, our investigation shows that water's hydrogens have two roles in interacting with protein atoms. First, water molecules adjust their poses around different amino acids and their atoms, and the statistical preferences of the hydrogen poses near the atoms determine the effective hydrophilicity and hydrophobicity of the atoms, which have not been successfully addressed before. Second, the collective dynamics of the hydrogens assist the water molecules in escaping from the potential energy wells of the hydrophilic atoms. Our method also shows that coarse-graining a system mathematically leads to breaking antisymmetry of the nonbonded interactions; as a result, two interacting coarse-grained units exert different forces on each other. Our study indicates that the accuracy of coarse-grained force fields, such as the MARTINI force field and the UNRES force field, can be improved in two ways: (i) refining their potential energy functions and coefficients by analyzing the coarse-grained potential energy surface using δ-CG, and (ii) introducing non-antisymmetric interactions.

Intrinsic half-metallicity in two-dimensional Cr2TeX2 (X = I, Br, Cl) monolayers.

Two-dimensional (2D) materials with intrinsic half-metallicity at or above room temperature are important in spin nanodevices. Nevertheless, such 2D materials in experiment are still rarely realized. In this work, a new family of 2D Cr2TeX2 (X = I, Br, Cl) monolayers has been predicted using first-principles calculations. The monolayer is made of five atomic sublayers with ABCAB-type stacking along the perpendicular direction. It is found that the energies for all the ferromagnetic (FM) half-metallic states are the lowest. The phonon spectrum calculations and molecular dynamics simulations both demonstrate that the FM states are stable, indicating the possibility of experimentally obtaining the 2D Cr2TeX2 monolayers with half-metallicity. The Curie temperatures from Monte Carlo simulations are 486, 445, and 451 K for Cr2TeI2, Cr2TeBr2, and Cr2TeCl2 monolayers, respectively, and their half-metallic bandgaps are 1.72, 1.86 and 1.90 eV. The corresponding magnetocrystalline anisotropy energies (MAEs) are about 1185, 502, 899 µeV per Cr atom for Cr2TeX2 monolayers, in which the easy axes are along the plane for the Cr2TeBr2 and Cr2TeCl2 monolayers, but being out of the plane in the Cr2TeI2. Our study implies the potential application of the 2D Cr2TeX2 (X = I, Br, Cl) monolayers in spin nanodevices.

Non-volatile control of topological phase transition in an asymmetric ferroelectric In2Te2S monolayer.

The coupling of topological electronic states and ferroelectricity is highly desired due to their abundant physical phenomenon and potential applications in multifunctional devices. However, it is difficult to achieve such a phenomenon in a single ferroelectric (FE) monolayer because the two polarized states are topologically equivalent. Here, we demonstrate that the symmetry of polarized states can be broken by constructing a Janus structure in a FE monolayer. We illustrate such a general idea by replacing a layer of Te atoms in the In2Te3 monolayer with S atoms. Using first-principles calculations, we show that the In2Te2S monolayer has two asymmetric polarized states, which are characterized by a metal and semiconductor, respectively. Importantly, as the spin-orbit coupling is included, a band gap (50.4 meV) is created in the metallic state, resulting in a non-trivial topological phase. Thus, it proves to be a feasible method to engineer non-volatile FE control of topological order in a single-phase system. We also demonstrate the underlying physical mechanism of topological phase transition, which is unveiled to be related to the weakened intrinsic electric field resulting from charge transfer. These interesting results provide a general way to design asymmetric FE materials and shed light on their potential application in non-volatile multifunctional devices.

Exploring the Interplay Between Vitamin B12-related Biomarkers, DNA Methylation, and Gene-Nutrition Interaction in Esophageal Precancerous Lesions.

BACKGROUND: Vitamin B12 depletion has been suggested to be associated with esophageal precancerous lesions (EPL). However, the potential mechanisms remain unclear. AIMS: This study aims to evaluate the role of vitamin B12 and its regulated epigenetic modification in EPL and provide preliminary information on the identification of potential molecular biomarkers for the early prediction of EPL. METHODS: We collected information and samples from the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 200 EPL cases and 200 matched controls. Vitamin B12, one-carbon metabolism biomarkers, genetic polymorphism of TCN2 C776G, and DNA methylation were compared. Preliminarily identified candidate promoters of differentially methylated CpG positions were further verified by targeted bisulfite sequencing. RESULTS: EPL cases had significantly lower serum levels of vitamin B12 and transcobalamin II, and higher serum levels of homocysteine and 5-methyltetrahydrofolate than controls. The TCN2 C776G polymorphism was found to be associated with susceptibility to EPL and may interact with vitamin B12 nutritional status to influence the risk of EPL in male subjects. In addition, global hypomethylation related to vitamin B12 depletion was observed in EPL cases, along with region-specific hypermethylation of UGT2B15 and FGFR2 promoters. CONCLUSIONS: This study suggests that vitamin B12 depletion may be associated with aberrant DNA methylation and increased risk of EPL through the one-carbon metabolism pathway, presents that the TCN2 C776G polymorphism may interact with vitamin B12 nutritional status to affect EPL risk in males, and also identifies specific locations in the UGT2B15 and FGFR2 promoters with potential as promising molecular biomarkers.

Metabolome and Microbiome Analysis to Study the Flavor of Summer Black Tea Improved by Stuck Fermentation.

Tea is the most popular and widely consumed beverage worldwide, especially black tea. Summer tea has a bitter and astringent taste and low aroma compared to spring tea due to the higher content of polyphenols and lower content of amino acids. Microbial fermentation is routinely used to improve the flavor of various foods. This study analyzed the relationship between the quality of black tea, metabolic characteristics, and microbial communities after microbial stuck fermentation in summer black tea. Stuck fermentation decreased the bitterness, astringency sourness, and freshness, and increased the sweetness, mellowness, and smoothness of summer black tea. The aroma also changed from sweet and floral to fungal, with a significant improvement in overall quality. Metabolomics analysis revealed significant changes in 551 non-volatile and 345 volatile metabolites after fermentation. The contents of compounds with bitter and astringent taste were decreased. Sweet flavor saccharides and aromatic lipids, and acetophenone and isophorone that impart fungal aroma showed a marked increase. These changes are the result of microbial activities, especially the secretion of extracellular enzymes. Aspergillus, Pullululanibacillus, and Bacillus contribute to the reduction of bitterness and astringency in summer black teas after stuck fermentation, and Paenibacillus and Basidiomycota_gen_Incertae_sedis contribute positively to sweetness. In addition, Aspergillus was associated with the formation of fungal aroma. In summary, our research will provide a suitable method for the improvement of tea quality and utilization of summer tea, as well as provide a reference for innovation and improvement in the food industry.

Secretome of senescent hepatic stellate cells favors malignant transformation from nonalcoholic steatohepatitis-fibrotic progression to hepatocellular carcinoma.

Background: Hepatic fibrosis is a premalignant lesion, and how injured hepatocytes transform into malignancy in a fibrotic microenvironment is poorly understood. Senescence is one of major fates of activated hepatic stellate cells (HSCs). Paucity of literature is available regarding the influence of senescent HSCs on behavior of steatotic hepatocytes. Methods: Senescent HSCs were identified in a murine model of nonalcoholic steatohepatitis (NASH)-fibrosis-hepatocellular carcinoma (HCC) and human NASH-HCC specimens. Secretome of senescent HSCs was analyzed by label-free mass-spectrum (NanoRPLC-MS/MS) and verified quantitatively. Results: Senescent HSCs were increased along with the progression from nonalcoholic fatty liver (NAFL), NASH to NASH-fibrosis, and reached a peak at the stage of advanced fibrosis and then decreased when hepatocellular dysplasia or HCC was developed. Critical components affecting proliferation, epithelial-mesenchymal transition (EMT) or migration were identified from secretome of senescent HSCs, and may activate morphogenic hedgehog or oncogenic Wnt signaling pathways to accelerate malignant transformation of steatotic or dysplastic hepatocytes. Primary hepatocytes stimulated with conditioned medium from senescent HSCs, in co-culture or co-cultured in 3D spheroids with senescent HSCs exhibited an enhanced proliferating or EMT profile. Conclusion: Senescent HSCs secreted a characterized protein profile favoring malignant transformation of steatotic or dysplastic hepatocytes through activating morphogenic hedgehog or oncogenic Wnt signaling pathways in the progression from NASH to malignancy.

Identification of Anti-SNRPA as a Novel Serological Biomarker for Systemic Sclerosis Diagnosis.

Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.

Comparison of regional anesthetic techniques for postoperative analgesia after adult cardiac surgery: bayesian network meta-analysis.

Background: Patients usually suffer acute pain after cardiac surgery. Numerous regional anesthetic techniques have been used for those patients under general anesthesia. The most effective regional anesthetic technique was still unclear. Methods: Five databases were searched, including PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library. The efficiency outcomes were pain scores, cumulative morphine consumption, and the need for rescue analgesia in this Bayesian analysis. Postoperative nausea, vomiting and pruritus were safety outcomes. Functional outcomes included the time to tracheal extubation, ICU stay, hospital stay, and mortality. Results: This meta-analysis included 65 randomized controlled trials involving 5,013 patients. Eight regional anesthetic techniques were involved, including thoracic epidural analgesia (TEA), erector spinae plane block, and transversus thoracic muscle plane block. Compared to controls (who have not received regional anesthetic techniques), TEA reduced the pain scores at 6, 12, 24 and 48 h both at rest and cough, decreased the rate of need for rescue analgesia (OR = 0.10, 95% CI: 0.016-0.55), shortened the time to tracheal extubation (MD = -181.55, 95% CI: -243.05 to -121.33) and the duration of hospital stay (MD = -0.73, 95% CI: -1.22 to -0.24). Erector spinae plane block reduced the pain score 6 h at rest and the risk of pruritus, shortened the duration of ICU stay compared to controls. Transversus thoracic muscle plane block reduced the pain scores 6 and 12 h at rest compared to controls. The cumulative morphine consumption of each technique was similar at 24, 48 h. Other outcomes were also similar among these regional anesthetic techniques. Conclusions: TEA seems the most effective regional postoperative anesthesia for patients after cardiac surgery by reducing the pain scores and decreasing the rate of need for rescue analgesia. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, ID: CRD42021276645.

Evaluating the characteristics of myocardial work by two-dimensional echocardiography during pre-eclampsia pregnancy.

This study aimed to analyze the changes in myocardial work (MyW) properties and the correlation of MyW with cardiovascular and clinical indices during the pre-eclampsia (PE) pregnancy. Standard two-dimensional and speckle-tracking echocardiography were sequentially performed on 77 women with PE and 89 with normal pregnancy. Four components of MyW: global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were measured. The significant increased GWI, GCW and GWW were observed, while GWW elevated more than GCW with consequently resulting the decline in GWE among PE cases. Although there was a diverse relationship between MyW components and LV morphological as well as functional indices, MyW parameters were significantly correlated with the grades of arterial hypertension and the incidence of adverse outcome of PE. With the hypertension stages, GWI, GCW and GWW gradually increased but GWE decreased. Meanwhile, the higher GWI and GCW and the lower GWE, the more adverse events occurred in PE group. In conclusion, during the PE pregnancy, GWI, GCW and GWW increase, while GWW elevates more than GCW, which leads to the decrease in GWE. Moreover, the changes in MyW are associated with the hypertension grades and the poor prognosis in PE. The non-invasive manner for MyW assessment provides a new perspective on the myocardial biomechanics, cardio-metabolic conditions and pathophysiological changes in the condition of PE.

Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

Differential expression profiles and functional analysis of long non-coding RNAs in calcific aortic valve disease.

AIM: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action. METHODS: The gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potential cis- or trans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hub cis- or trans-regulatory genes were verified in GSE148219 and GSE199718 respectively. RESULTS: There were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj ≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hub cis- or trans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found that MIR4435-2HG was the top hub trans-acting lncRNA which also plays a crucial role by ceRNA pattern. CONCLUSION: LncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.

Towards a free energy-based elastic network model and its application to the SARS-COV2 binding to ACE2.

Classical normal mode analysis (cNMA) is a standard method for studying the equilibrium vibrations of macromolecules. A major limitation of cNMA is that it requires a cumbersome step of energy minimization that also alters the input structure significantly. Variants of normal mode analysis (NMA) exist that perform NMA directly on PDB structures without energy minimization, while maintaining most of the accuracy of cNMA. Spring-based NMA (sbNMA) is such a model. sbNMA uses an all-atom force field as cNMA does, which includes bonded terms such as bond stretching, bond angle bending, torsional, improper, and non-bonded terms such as van der Waals interactions. Electrostatics was not included in sbNMA because it introduced negative spring constants. In this work, we present a way to incorporate most of the electrostatic contributions in normal mode computations, which marks another significant step toward a free-energy-based elastic network model (ENM) for NMA. The vast majority of ENMs are entropy models. One significance of having a free energy-based model for NMA is that it allows one to study the contributions of both entropy and enthalpy. As an application, we apply this model to study the binding stability between SARS-COV2 and angiotensin converting enzyme 2 (or ACE2). Our results show that the stability at the binding interface is contributed nearly equally by hydrophobic interactions and hydrogen bonds.