A statistical analysis method for probability distributions in Erdös-Rényi random networks with preferential cutting-rewiring operation.

The study of specific physiological processes from the perspective of network physiology has gained recent attention. Modeling the global information integration among the separated functionalized modules in structural and functional brain networks is a central problem. In this article, the preferentially cutting-rewiring operation (PCRO) is introduced to approximatively describe the above physiological process, which consists of the cutting procedure and the rewiring procedure with specific preferential constraints. By applying the PCRO on the classical Erdös-Rényi random network (ERRN), three types of isolated nodes are generated, based on which the common leaves (CLs) are formed between the two hubs. This makes the initially homogeneous ERRN experience drastic changes and become heterogeneous. Importantly, a statistical analysis method is proposed to theoretically analyze the statistical properties of an ERRN with a PCRO. Specifically, the probability distributions of these three types of isolated nodes are derived, based on which the probability distribution of the CLs can be obtained easily. Furthermore, the validity and universality of our statistical analysis method have been confirmed in numerical experiments. Our contributions may shed light on a new perspective in the interdisciplinary field of complexity science and biological science and would be of great and general interest to network physiology.

Snapshotting quantum dynamics at multiple time points.

Measurement-induced state disturbance is a major challenge in obtaining quantum statistics at multiple time points. We propose a method to extract dynamic information from a quantum system at intermediate time points, namely snapshotting quantum dynamics. To this end, we apply classical post-processing after performing the ancilla-assisted measurements to cancel out the impact of the measurements at each time point. Based on this, we reconstruct a multi-time quasi-probability distribution (QPD) that correctly recovers the probability distributions at the respective time points. Our approach can also be applied to simultaneously extract exponentially many correlation functions with various time-orderings. We provide a proof-of-principle experimental demonstration of the proposed protocol using a dual-species trapped-ion system by employing 171Yb+ and 138Ba+ ions as the system and the ancilla, respectively. Multi-time measurements are performed by repeated initialization and detection of the ancilla state without directly measuring the system state. The two- and three-time QPDs and correlation functions are reconstructed reliably from the experiment, negativity and complex values in the QPDs clearly indicate a contribution of the quantum coherence throughout dynamics.

Crystallization ripening and erosion of calcium oxalate under the effect of bacteria and a polymer materials surface.

As typical examples of pathological biomineralization, urinary stones and stent encrustation have been associated with bacteria, yet the underlying mechanisms remain unclear. In this study, the effect of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus on the nucleation and growth of calcium oxalate crystals both in solution and on material surfaces in vitro was investigated. Both bacteria can promote calcium oxalate crystallization, and E. coli shows a prominent ability to boost the nucleation and growth rate. Interestingly, we discovered an Ostwald ripening phenomenon after the initial nucleation on the material surfaces, where larger particles emerge upon the disappearance of small nuclei particles, evident in the case of S. aureas. Over an extended period of time, erosion and disintegration of the crystals was observed when bacteria were involved. Based on these understandings, we developed a new functional surface by synthesizing an antibacterial polypeptoid in-house and utilizing polyurethane as the substrate material. This surface exhibits a synergistic effect that inhibits the formation of calcium oxalate crystals. This study helps to elucidate the role of bacteria in calcium oxalate biomineralization and supports further development of treatment approaches such as anti-encrustation polymer materials.

Liquid Biopsy in Lung Cancer: Nano-Flow Cytometry Detection of Non-Small Cell Lung Cancer in Blood.

Non-small cell lung cancer (NSCLC) remains a leading cause of global mortality, with current screening and diagnostic methods often lacking in sensitivity and specificity. In our endeavor to develop precise, objective, and easily accessible diagnostic biomarkers for NSCLC, this study aimed to leverage rapidly evolving liquid biopsy techniques in the field of pathology to differentiate NSCLC patients from healthy controls by isolating peripheral blood samples and enriching extracellular vesicles (EVs) containing lung-derived proteins (TTF-1 and SFTPB), along with the cancer-associated protein CD151+ EVs. Additionally, for practical applications, we established a nano-flow cytometry assay to detect plasma EVs readily. NSCLC patients demonstrated significantly reduced counts of TTF-1+ EVs and CD151+ EVs in plasma compared to healthy controls (P<0.0001), while SFTPB+ EVs showed no significant difference (P>0.05). Integrated analysis of TTF-1+, CD151+ and SFTPB+ EVs yielded area under the curve (AUC) values of 0.913 and 0.854 in the discovery and validation cohorts, respectively. Thus, while further validation is essential, the newly developed technologies are of great significance for the robust detection of NSCLC biomarkers.

Sleep disturbances and psychomotor retardation in the prediction of cognitive impairments in patients with major depressive disorder.

BACKGROUND: Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder (MDD). Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients. We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments. We also hypothesize that anxiety symptoms, especially psychic anxiety, is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors. AIM: To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode. METHODS: A comprehensive neurocognitive test battery assessed executive function, attention, processing speed, and memory in 162 medication-free MDD patients and 142 matched healthy controls. The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms, and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms. Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms, as well as their interactions, on cognitive impairments. RESULTS: Among the depressive symptoms, sleep disturbances were associated with poorer executive function (P = 0.004), lower processing speed (P = 0.047), and memory impairments (P < 0.001), and psychomotor retardation (PR) was associated with lower processing speed in patients with MDD (P = 0.019). Notably, PR was found to mediate the impact of sleep disturbances on the processing speed. Regarding anxiety symptoms, psychic anxiety, rather than somatic anxiety, was associated with cognitive impairments in all aspects. Sleep disturbances mediated the effect of psychic anxiety on executive function [ß = -0.013, BC CI (-0.027, -0.001)] and memory [ß = -0.149, BC CI (-0.237, -0.063)], while PR mediated its effect on processing speed (ß = -0.023, BC CI (-0.045, -0.004)]. CONCLUSION: Sleep disturbances may be a key predictor of poorer executive function, lower processing speed, and memory loss, while PR is crucial for lower processing speed during a depressive episode. Psychic anxiety contributes to all aspects of cognitive impairments, mediated by sleep disturbances and PR.

Dietary "Beigeing" Fat Contains More Phosphatidylserine and Enhances Mitochondrial Function while Counteracting Obesity.

Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity. However, as an important source of lipids for ketogenic and daily diets, the function of fats extracted from different adipose tissue sites was largely unknown. In this study, we illustrated the function of fats extracted from adipose tissues with different "beigeing" properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure. We found that the anti-obesity effect of ketogenic diets was potentiated by using "beigeing" fat [porcine subcutaneous adipose tissue (SAT)] as a major energy-providing ingredient. Through lipidomic analyses, phosphatidylserine (PS) was identified as a functional lipid activating thermogenesis in adipose tissue. Moreover, in vivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice. In vitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes. Mechanistically, PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGC1α pathway. In addition, PS-PGC1a binding may affect the stability of the PGC1α protein, which further augments PS-induced thermogenesis. These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function. Thus, our findings suggest that as dietary fat, "beigeing" fat provides more beneficial lipids that contribute to the improvement of mitochondrial function, including PS, which may become a novel, nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases.

Risk Assessment of Roundabout Scenarios in Virtual Testing Based on an Improved Driving Safety Field.

With the advancement of autonomous driving technology, scenario-based testing has become the mainstream testing method for intelligent vehicles. However, traditional risk indicators often fail in roundabout scenarios and cannot accurately define dangerous situations. To accurately quantify driving risks in roundabout scenarios, an improved driving safety field model is proposed in this paper. First, considering the unique traffic flow characteristics of roundabouts, the dynamic characteristics of vehicles during diverging or merging were taken into account, and the driving safety field model was improved to accurately quantify the driving risks in roundabout scenarios. Second, based on data from the rounD dataset, the model parameters were calibrated using the social force model. Finally, a DENCLUE-like method was used to extract collision systems, calculate vehicle risk degree, and analyze these risks for both the temporal and the spatial dimensions, providing guidance for virtual testing. The proposed method significantly improves detection efficiency, increasing the number of identified dangerous scenarios by 175% compared to the Time to Collision (TTC) method. Moreover, this method can more accurately quantify driving risks in roundabout scenarios and enhance the efficiency of generating dangerous scenarios, contributing to promoting the safety of autonomous vehicles.

Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study.

BACKGROUND: The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. METHODS: In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. FINDINGS: We screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. INTERPRETATION: Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. FUNDING: US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.

Binuclear Enamino-Oxazolinate Rare-Earth Metal Complexes: Synthesis and Their Catalytic Performance in Isoprene Polymerization.

We have synthesized a series of binuclear rare-earth metal complexes bearing the newly designed enamino-oxazolinate ligands that feature bridging para-phenyl, meta-phenyl, 1,5-naphthalenyl, and 1,5-anthracenyl moieties. NMR and X-ray diffraction analyses confirmed the binuclear structures of the obtained complexes with two enamino-oxazolinate-metal units located at a trans position against the bridged aryl plane. After activation by [Ph3C][B(C6F5)4], all the rare-earth metal complexes served as efficient catalysts for isoprene polymerization, producing polymers with high cis-1,4 regularity (up to 96.1%) and high molecular weight. The steric and electronic effects exerted on the active metal centers, as well as the radius of metal centers, were the major contributing factors for determining both the catalytic activity and cis-1,4-selectivity of the binuclear catalytic systems. Compared to its mononuclear analogue, the binuclear yttrium catalytic system with a para-phenyl bridge exhibited a higher thermostability and catalytic efficiency during polymerization, revealing a special binuclear effect in this binuclear catalytic system.

Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

Emergence of chimeralike oscillation modes in excitable complex networks with preferentially cutting-rewiring operation.

In this paper, the preferentially cutting-rewiring operation (PCRO) consisting of the cutting procedure and the rewiring procedure is proposed and is applied on an excitable Erdös-Rényi random network (EERRN), by which the structure of the initially homogeneous network changes dramatically, and lots of common leaves (CLs) are formed between the two hubs. Subsequently, besides the single-mode oscillations that can be usually observed in homogeneous excitable systems, a new kind of multi-mode oscillations composed of synchronous and asynchronous parts can self-organize to emerge, which are similar to the coherent and incoherent clusters in traditional chimera states and are consequently named as the chimeralike oscillation modes (CLOMs). Importantly, by utilizing the dominant phase-advanced driving method, both the mechanisms for the formation and the emergence of CLOMs in EERRNs with PCRO are well explained, among which the CL is exposed to play a key role in forming the CLOMs. Furthermore, the PCRO-induced CLOM phenomena can also be observed in other paradigmatic network models or with other paradigmatic excitable dynamics, which definitely confirms that the PCRO is an universal method in inducing the CLOMs in excitable complex networks. Our contributions may shed lights on a new perspective of the emergence of CLOMs in complex systems and would have great impacts in related fields.

Lipidomics and single-cell RNA sequencing reveal lipid and cell dynamics of porcine glycerol-injured skeletal muscle regeneration model.

AIMS: Intramuscular fat (IMF) infiltration and extracellular matrix (ECM) deposition are characteristic features of muscle dysfunction, such as muscular dystrophy and severe muscle injuries. However, the underlying mechanisms of cellular origin, adipocyte formation and fibrosis in skeletal muscle are still unclear. MAIN METHODS: Pigs were injected with 50 % glycerol (GLY) to induce skeletal muscle injury and regeneration. The acyl chain composition was analyzed by lipidomics, and the cell atlas and molecular signatures were revealed via single-cell RNA sequencing (scRNA-seq). Adipogenesis analysis was performed on fibroblast/fibro-adipogenic progenitors (FAPs) isolated from pigs. KEY FINDINGS: The porcine GLY-injured skeletal muscle regeneration model was characterized by IMF infiltration and ECM deposition. Skeletal muscle stem cells (MuSCs) and FAP clusters were analyzed to explore the potential mechanisms of adipogenesis and fibrosis, and it was found that the TGF-ß signaling pathway might be a key switch that regulates differentiation. Consistently, activation of the TGF-ß signaling pathway increased SMAD2/3 phosphorylation and inhibited adipogenesis in FAPs, while inhibition of the TGF-ß signaling pathway increased the expression of PPARγ and promoted adipogenesis. SIGNIFICANCE: GLY-induced muscle injury and regeneration provides comprehensive insights for the development of therapies for human skeletal muscle dysfunction and fatty infiltration-related diseases in which the TGF-ß/SMAD signaling pathway might play a primary regulatory role.

[Identification of HSP70 gene family members in Fritillaria cirrhosa and expression analysis in different tissues under high temperature stress].

The heat shock protein 70 family contains the stress proteins ubiquitous in plants. These proteins are involved in the responses to different abiotic stress conditions and have highly conserved gene sequences. However, little is known about the molecular mechanisms of Fritillaria cirrhosa in response to high-temperature stress. Here, 26 HSP70s, FcHSP70-1 to FcHSP70-26, were identified from the transcriptome data of root, bulb, stem, leaf, and fruit samples of F. cirrhosa. The proteins encoded by FcHSP70s had the lengths ranging from 560 aa to 944 aa, with the molecular weight of 61.64-100.01 kDa and the theoretical isoelectric point between 5.00 and 6.59. The secondary structural elements of HSP70s were mainly random coils and α-helixes. Subcellular localization prediction revealed that FcHSP70s were distributed in mitochondria, chloroplasts, nuclei, endoplasmic reticulum, and cytoplasm. The phylogenetic tree showed that 7 members of the HSP70 family belonged to the Dnak subfamily and 19 members belonged to the HSP110/SSE subfamily. In addition, the qRT-PCR results showed that the expression of FcHSP70-5, FcHSP70-8, FcHSP70-17, FcHSP70-18, and FcHSP70-23 in F. cirrhosa was significantly up-regulated at 35 ℃, which indicated that these genes might play a role in the response to high temperature stress. In addition, compared with other tissues, stems and leaves were sensitive to high temperature stress, with the expression of 18 genes up-regulated by 18.18 and 8.03 folds on average, respectively. These findings provide valuable information about the molecular mechanism of HSP70s of F. cirrhosa in response to high temperature stress.

High-Resolution Crossed-Beam Dynamics Studies of the D + Para-H2 → HD + H Reaction at 1.21 eV.

Understanding kinetic isotope effects is important in the study of the reaction dynamics of elementary chemical reactions, particularly those involving hydrogen atoms and molecules. As one of the isotopic variants of the hydrogen exchange reaction, the D + para-H2 reaction has attracted much attention. However, experimental studies of this reaction have been limited primarily due to its strong experimental background noise. In this study, by using the velocity map ion imaging method and the near-threshold ionization technique, together with improvements on the vacuum condition in the vicinity of the collision zone, background noise was reduced significantly, and quantum state-resolved differential cross sections (DCSs) for the D + para-H2 reaction at a collision energy of 1.21 eV were acquired in a crossed molecular beams experiment. Interestingly, clear rotational state-dependent angular distributions were noticed in the quantum state-resolved DCSs. The most intense peak's positions for HD (v', j') products shift to different scattering directions as the product's ro-vibrational quantum number increases. Two different microscopic reaction mechanisms are found to be involved in this reaction for HD products in different vibrational states. The results show a direct correlation between the scattering angle and the product's rotational quantum number, revealing that the contributions of impact parameters are strongly influenced by the corresponding centrifugal barrier.

Constructing an Al3+/Zn2+-Based Solid Electrolyte Interphase to Enable Extraordinarily Stable Al3+-Based Electrochromic Devices.

The interface between the electrochromic (EC) electrode and ionic conductor is crucial for high-performance and extraordinarily stable EC devices (ECDs). Herein, the effect of the ALD-AZO interfacial layer on the performance of the WO3 thin film was examined, revealing that an introduction of the ALD-AZO interfacial layer to the Al3+-based complementary ECDs can lead to improved EC performance and stability, such as an extraordinary cyclability of more than 20,000 cycles, an outstanding coloration efficiency of 109.69 cm2 C-1, and a maximum transmittance modulation of 63.44%@633 nm. The probable explanation is that the introduced ALD-AZO interfacial layer can effectively regulate the band gap of WO3, promote the electron transport process, and induce the formation of a robust solid electrolyte interphase to protect the electrode during cycling. These findings offer valuable insights for enhancing the EC performance of the EC thin films and new space for the construction of advanced multivalent Al3+-based ECDs.

The fate of pharmaceuticals and personal care products (PPCPs) in sewer sediments:Adsorption triggering resistance gene proliferation.

In recent years, large quantities of pharmaceuticals and personal care products (PPCPs) have been discharged into sewers, while the mechanisms of PPCPs enrichment in sewer sediments have rarely been revealed. In this study, three PPCPs (tetracycline, sulfamethoxazole, and triclocarban) were added consecutively over a 90-day experimental period to reveal the mechanisms of PPCPs enrichment and the transmission of resistance genes in sewer sediments. The results showed that tetracycline (TC) and triclocarban (TCC) have higher adsorption concentration in sediments compared to sulfamethoxazole (SMX). The absolute abundance of Tets and suls genes increased in sediments under PPCPs pressure. The increase in secretion of extracellular polymeric substances (EPS) and the loosening of the structure exposed a large number of hydrophobic functional groups, which promoted the adsorption of PPCPs. The absolute abundance of antibiotic resistance genes (ARGs), EPS and the content of PPCPs in sediments exhibited significant correlations. The enrichment of PPCPs in sediments was attributed to the accumulation of EPS, which led to the proliferation of ARGs. These findings contributed to further understanding of the fate of PPCPs in sewer sediments and opened a new perspective for consideration of controlling the proliferation of resistance genes.

The influence of the molecular chain length of PVA on the toughening mechanism of calcium silicate hydrates.

In recent years, polymers have been demonstrated to effectively toughen cementitious materials. However, the mechanism of interaction between the polymers and C-S-H at the nanoscale remains unclear, and the quantitative impact of the polymer chain length on toughening effectiveness is lacking in research. This study employs molecular dynamics techniques to examine the impact of the polyvinyl alcohol (PVA) chain length on the tensile performance and toughening mechanism of C-S-H. The toughening effect in both the X and Z directions exhibits an initial enhancement followed by a decline with increasing chain length. The optimal degrees of polymerization are determined to be 8 and 12 in the X and Z directions, respectively, resulting in an improvement of fracture energy by 146.7% and 29.5%, respectively. During the stretching process along the X and Z axes, the chain length of PVA molecules significantly influences the variation in the number of Ca⋯O bonds in the system, leading to different stress responses. Additionally, PVA molecules form C-O-Si bonds with the silicate layers of C-S-H, bridging the adjacent layers in a left-right or up-down manner. The toughening effect of PVA on C-S-H depends on the behavior of PVA molecules with different chain lengths, and there exists an optimal range of chain length for PVA, enabling it to enhance structural uniformity and adjust its own conformation to absorb strain energy. When the length of PVA molecular chains is too short, it can easily cause stress concentration in the system and its connection with silicates is not significant. Conversely, when the length of PVA molecular chains is too long, the large molecular structure restricts its extension in the defects of C-S-H, and as the stretching progresses, PVA molecules break and form numerous small segments, thereby losing the advantage of the chain length. This study provides a theoretical basis for the ability of polymers to toughen cementitious materials.

Revealing the Genetic Diversity of Chinese Chlamydia trachomatis Strains Directly From Clinical Samples Through Selective Whole Genome Amplification.

BACKGROUND: Chlamydia trachomatis is the causative agent of the most prevalent bacterial sexually transmitted infections globally. Whole genome sequencing is essential for molecular Chlamydia surveillance; however, its application is hampered by the pathogen's low abundance in clinical specimens and the expensive labor-intensive nature of existing enrichment methodologies for Chlamydia. METHODS: We developed a targeted whole genome amplification tool termed SWITCH by integrating phi29 DNA polymerase-mediated amplification with meticulously designed primer sets to enrich the C trachomatis genome, followed by whole genome sequencing. This method underwent evaluation through testing synthetic and clinical specimens. RESULTS: SWITCH demonstrated robust ability to achieve up to 98.3% genomic coverage of C trachomatis from as few as 26.4 genomic copies present in synthetic specimens, and it exhibited excellent performance across diverse C trachomatis serovars. Utilizing SWITCH, we directly generated 21 Chlamydia genomes from 26 clinical samples, enabling us to gain insights into the genetic relationships and phylogeny of current Chlamydia strains circulating in the country. Remarkably, this study marked the first instance of generating Chinese Chlamydia genomes directly from clinical samples. CONCLUSIONS: SWITCH represents a practical cost-efficient approach to enrich the Chlamydia genome directly from clinical specimens, offering an efficient avenue for molecular surveillance of Chlamydia.

IL-5 antagonism reverses priming and activation of eosinophils in severe eosinophilic asthma.

Eosinophils are key effector cells mediating airway inflammation and exacerbation in patients with severe eosinophilic asthma. They are present in increased numbers and activation states in the airway mucosa and lumen. Interleukin-5 (IL-5) is the key eosinophil growth factor that is thought to play a role in eosinophil priming and activation. However, the mechanism of these effects is still not fully understood. The anti-IL-5 antibody mepolizumab reduces eosinophil counts in the airway modestly but has a large beneficial effect on the frequency of exacerbations of severe eosinophilic asthma, suggesting that reduction in eosinophil priming and activation is of central mechanistic importance. In this study, we used the therapeutic effect of mepolizumab and single-cell ribonucleic acid sequencing to investigate the mechanism of eosinophil priming and activation by IL-5. We demonstrated that IL-5 is a dominant driver of eosinophil priming and plays multifaceted roles in eosinophil function. It enhances eosinophil responses to other stimulators of migration, survival, and activation by activating phosphatidylinositol-3-kinases, extracellular signal-regulated kinases, and p38 mitogen-activated protein kinases signaling pathways. It also enhances the pro-fibrotic roles of eosinophils in airway remodeling via transforming growth factor-ß pathway. These findings provide a mechanistic understanding of eosinophil priming in severe eosinophilic asthma and the therapeutic effect of anti-IL-5 approaches in the disease.

Coarse-resolution burned area datasets severely underestimate fire-related forest loss.

Global coarse-resolution (≥250 m) burned area (BA) products have been used to estimate fire related forest loss, but we hypothesised that a significant part of fire impacts might be undetected because of the underestimation of small fires (<100 ha), especially in the tropics. In this paper, we analysed fire-related forest cover loss in sub-Saharan Africa (SSA) for 2016 and 2019 based on a BA product generated from Sentinel-2 data (20 m), which was observed to have significantly lower omission errors than the coarse-resolution BA products. Using these higher resolution BA datasets, we found that fires contribute to >46 % of total forest losses over SSA, more than twice the estimates from coarse-resolution BA products. In addition, burned forest areas showed more than twofold likelihood of subsequent loss compared to unburned ones. In moist tropical forests, the most fire-vulnerable biome, burning had even six times more chance to precede forest loss than unburned areas. We also found that fire-related characteristics, such as fire size and season, and forest fragmentation play a major role in the determination of tree cover fate. Our results reveal that medium-resolution BA detects more fires in late fire season, which tend to have higher impact on forests than early season ones. On the other hand, small fires represented the major driver of forest loss after fires and the vast majority of these losses occur in fragmented landscapes near forest edge (<260 m). Therefore medium-resolution BA products are required to obtain a more accurate evaluation of fire impacts in tropical ecosystems.