Engineering Stimuli-Responsive Materials for Precision Medicine.

Over the past decade, precision medicine has garnered increasing attention, making significant strides in discovering new therapeutic drugs and mechanisms, resulting in notable achievements in symptom alleviation, pain reduction, and extended survival rates. However, the limited target specificity of primary drugs and inter-individual differences have often necessitated high-dosage strategies, leading to challenges such as restricted deep tissue penetration rates and systemic side effects. Material science advancements present a promising avenue for these issues. By leveraging the distinct internal features of diseased regions and the application of specific external stimuli, responsive materials can be tailored to achieve targeted delivery, controllable release, and specific biochemical reactions. This review aims to highlight the latest advancements in stimuli-responsive materials and their potential in precision medicine. Initially, we introduce disease-related internal stimuli and capable external stimuli, elucidating the reaction principles of responsive functional groups. Subsequently, we provide a detailed analysis of representative pre-clinical achievements of stimuli responsive materials across various clinical applications, including enhancements in the treatment of cancers, injury diseases, inflammatory diseases, infection diseases, and high-throughput microfluidic biosensors. Finally, we discuss some clinical challenges, such as off-target effects, long-term impacts of nano-materials, potential ethical concerns, and offer insights into future perspectives of stimuli-responsive materials.

Topological Network Modes in a Twisted Moiré Phononic Crystal.

Twisted moiré materials, a new class of layered structures with different twist angles for neighboring layers, are attracting great attention because of the rich intriguing physical phenomena associated with them. Of particular interest are the topological network modes, first proposed in the small angle twisted bilayer graphene under interlayer bias. Here we report the observations of such topological network modes in twisted moiré phononic crystals without requiring the external bias fields. Acoustic topological network modes that can be constructed in a wide range of twist angles are both observed in the domain walls with and without reconstructions, which serve as the analogy of the lattice relaxations in electronic moiré materials. Topological robustness of the topological network modes is observed by introducing valley-preserved defects to the network channel. Furthermore, the network can be reconfigured into two-dimensional patterns with any desired connectivity, offering a unique prototype platform for acoustic applications.

Recyclable V2O5/g-C3N4 Heterojunction-Catalyzed Visible-Light-Promoted C3-H Trifluoromethylation of Quinoxalin-2-(1H)-ones.

A visible-light-initiated C-H trifluoromethylation of quinoxalin-2(1H)-ones was established using a Z-scheme V2O5/g-C3N4 heterojunction as a recyclable photocatalyst in an inert atmosphere at room temperature under additive-free and mild conditions. A variety of trifluoromethylated quinoxalin-2-(1H)-one derivatives were heterogeneously generated in moderate to high yields, exhibiting good functional group tolerance. Remarkably, the recyclable V2O5/g-C3N4 catalyst could be reused five times with a slight loss of catalytic activity.

HIV infection increases the risk of inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVE: In order to synthesize available results regarding human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD), we conducted a systematic review and meta-analysis to provide quantitative estimates of associated risk. METHODS: A systematic search of four scientific databases, PubMed, the Cochrane Library, EMBASE, and Scopus, was performed. The overall odds ratio (OR) with the corresponding 95% CI was calculated via a random effects model. Sensitivity analyses and tests for publication bias were then performed. RESULTS: Of the 3046 articles retrieved, seven studies with a cumulative sample size greater than 57,000,000 were included in our analysis. A subsequent meta-analysis based on a random effects model (heterogeneity test, I2 = 99.9) revealed an association between HIV infection and IBD: OR = 2.68 (95% CI: 1.17, 6.13). The funnel plot of this meta-analysis was asymmetric (Egger's test: P = 0.01), and significant publication bias was found. Sensitivity analysis of the 3 dimensions revealed that the results of this meta-analysis were relatively stable. CONCLUSIONS: A significant correlation may exist between HIV infection and intestinal disease, and more large-scale studies are needed to draw firm conclusions. It is recommended that HIV patients be screened for intestinal diseases.

Comparative analysis for the impacts of VOC subgroups and atmospheric oxidation capacity on O3 based on different observation-based methods at a suburban site in the North China Plain.

The persistent O3 pollution in the Beijing-Tianjin-Hebei (BTH) region remains unresolved, largely due to limited comprehension of O3-precursor relationship and photochemistry drivers. In this work, intraday O3 sensitivity evolution from VOC-limited (volatile organic compound) regime in the forenoon to transition regime in the late afternoon was inferred by relative incremental reactivity (RIR) in summer 2019 at Xianghe, a suburban site in BTH region, suggesting that VOC-focused control policy could combine with stringent afternoon NOx control. Then detailed impacts of VOC subgroups on O3 formation were further comprehensively quantified by parametric OH reactivity (KOH), O3 formation potential (OFP), as well as RIR weighted value and O3 formation path tracing (OFPT) approach based on photochemical box model. O3 episode days corresponded to stronger O3 formation, depicted by higher KOH (10.4 s-1), OFP (331.7 µg m-3), RIR weighted value (1.2), and F(O3)-OFPT (15.5 ppbv h-1). High proportions of isoprene and OVOCs (oxygenated VOCs) to the total KOH and the OFPT method were demonstrated whereas results of OFP and RIR-weighted presented extra great impacts of aromatics on O3 formation. The OFPT approach captured the process that has already happened and included final O3 response to the original VOC, thus reliable for replicating VOC impacts. The comparison results of the four methods showed similarities when utilizing KOH and OFPT methods, which reveals that the potential applicability of simple KOH for contingency VOC control and more complex OFPT method for detailed VOC- and source-oriented control during policy-making. To investigate propulsion of VOC-involved O3 photochemistry, atmospheric oxidation capacity (AOC) was quantified by two atmospheric oxidation indexes (AOI). Both AOIp_G (7.0 × 107 molec cm-3 s-1, potential AOC calculated by oxidation reaction rates) and AOIe_G (8.5 µmol m-3, estimated AOC given redox electron transfer for oxidation products) were stronger on O3 episode days, indicating that AOC promoted the radical cycling initiated from VOC oxidation and subsequent O3 production. Result-oriented AOIe_G reasonably characterized actual AOC inferred by good linear correlation between AOIe_G and O3 concentrations compared to process-oriented AOIp_G. Therefore, with continuous NOx abatement, AOIe_G should be considered to represent actual AOC, also O3-inducing ability.

Clinical efficacy and safety of ultrasound-guided high-intensity focused ultrasound for breast fibroadenoma: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis was to assess the clinical efficacy and safety of ultrasound (US)-guided high intensity focused ultrasound (HIFU) in the treatment of breast fibroadenoma in different studies. METHODS: Studies evaluating the efficacy and safety of US-guided HIFU in the treatment of histologically-proven FA with follow-up outcomes of more than 3 months were searched through MEDLINE/PubMed databases. Volume reduction rate (VRR) and side effects were extracted and compared for further analysis. RESULTS: Of 29 identified articles, 10 studies involving 385 women and more than 545 FAs met the inclusion criteria. The mean VRR at 6 months and 12 months after HIFU was 52.00% and 72.00%. In terms of intraoperative safety, nine studies reported mild to moderate pain, with an average visual analogue scale (VAS) score ranging from 1.60 to 7.10. The most common postoperative side effect associated with HIFU was subcutaneous ecchymosis and less frequent were pain, erythema, and skin pigmentation, most of which disappeared within weeks. No serious side effects were observed. CONCLUSION: S-guided HIFU is an effective and safe noninvasive treatment for breast FA that does not cause serious side effects. Further studies are needed to explore crucial influencing factors of VRR.

PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.

INTRODUCTION: To investigate the role of a novel type of protein kinase C delta (PKCδ) in the neuroinflammation of Alzheimer's disease (AD). METHODS: We analyzed PKCδ and inflammatory cytokines levels in cerebrospinal fluid (CSF) of AD and normal controls, as well as their correlations. The cellular expression pattern of PKCδ and the effects of PKCδ modulation on microglia-mediated neuroinflammation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, RNA sequencing (RNA-seq), and immunofluorescence staining. RESULTS: PKCδ levels were increased dramatically in the CSF of AD patients and positively correlated with cytokines. PKCδ is expressed mainly in microglia in the brain. Amyloid beta (Aß) stimulation increased PKCδ expression and secretion, which led to upregulation of the nuclear factor kappa B (NF-κB) pathway and overproduction of proinflammatory cytokines. Downregulation or inhibition of PKCδ attenuated Aß-induced microglial responses and improved cognitive function in an AD mouse model. DISCUSSION: Our study identifies PKCδ as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD. HIGHLIGHTS: Protein kinase C delta (PKCδ) levels increase in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), and positively correlate with elevated inflammatory cytokines in human subjects. PKCδ is expressed mainly in microglia in vivo, whereas amyloid beta (Aß) stimulation increases PKCδ expression and secretion, causing upregulation of the nuclear factor kappa B (NF-κB) pathway and production of inflammatory cytokines. Downregulation or inhibition of PKCδ attenuates Aß-enhanced NF-κB signaling and cytokine production in microglia and improves cognitive function in AD mice. PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in AD.

Heme Oxygenase-1 Regulates Zearalenone-Induced Oxidative Stress and Apoptosis in Sheep Follicular Granulosa Cells.

Zearalenone (ZEA) is a common non-steroidal estrogenic mycotoxin found in a range of animal feeds and poses a serious threat to the reproductive health of farm animals and humans. However, the mechanism underlying ZEA-induced reproductive toxicity in sheep remains unknown. Granulosa cells are crucial for egg maturation and the fertility of female sheep. In this study, we aimed to examine the impact of different ZEA concentrations on sheep follicular granulosa cells and to elucidate the potential molecular mechanism underlying ZEA-induced toxicity using transcriptome sequencing and molecular biological approaches. Treating primary sheep follicular granulosa cells with different concentrations of ZEA promoted the overproduction of reactive oxygen species (ROS), increased lipid peroxidation products, led to cellular oxidative stress, decreased antioxidant enzyme activities, and induced cell apoptosis. Using transcriptome approaches, 1395 differentially expressed genes were obtained from sheep follicular granulosa cells cultured in vitro after ZEA treatment. Among them, heme oxygenase-1 (HMOX1) was involved in 11 biological processes. The protein interaction network indicated interactions between HMOX1 and oxidative and apoptotic proteins. In addition, N-acetylcysteine pretreatment effectively reduced the ZEA-induced increase in the expression of HMOX1 and Caspase3 by eliminating ROS. Hence, we suggest that HMOX1 is a key differential gene involved in the regulation of ZEA-induced oxidative stress and apoptosis in follicular granulosa cells. These findings provide novel insights into the prevention and control of mycotoxins in livestock.

[Characteristics of early cognitive development in children with Williams syndrome: a prospective cohort study]. / Williamsç»¼åˆå¾å„¿ç«¥æ—©æœŸè®¤çŸ¥å‘è‚²ç‰¹å¾ï¼šä¸€é¡¹å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the early cognitive development characteristics of children with Williams syndrome (WS) at different age stages. METHODS: From September 2018 to June 2023, 106 children diagnosed with WS at the Department of Pediatric Health Care, Children's Hospital, Zhejiang University School of Medicine, aged 1 to <5 years, were prospectively enrolled. All children underwent Gesell developmental diagnostic assessments to analyze the cognitive development characteristics of WS children across different age groups. RESULTS: The average age of the 106 WS children was (3.1±1.2) years; 58 were male, and 48 were female. There were no significant differences in developmental levels between males and females in the five domains of gross motor skills, fine motor skills, language, personal-social skills, and adaptive behavior (P>0.05). The incidence rates of mild, moderate, severe, and profound developmental disabilities among children of different age groups showed no significant differences (P>0.05). Comparisons of developmental levels in gross motor skills, language, personal-social skills, and adaptive behavior among different age groups were also not statistically significant (P>0.05). With the increase of age, the developmental level of fine motor skills showed a decreasing trend (P<0.05). There were no significant differences in verbal IQ and non-verbal IQ within each age group of WS children (P>0.05). CONCLUSIONS: The overall developmental level of WS children stabilizes with age, and their early language abilities do not significantly exceed their non-verbal abilities.

Anti-inflammatory and analgesic effect of Forsythiaside B on complete Freund's adjuvant-induced inflammatory pain in mice.

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

A visual defect detection for optics lens based on the YOLOv5 -C3CA-SPPF network model.

Defects in the optical lens directly affect the scattering properties of the optical lens and decrease the performance of the optical element. Although machine vision instead of manual detection has been widely valued, the feature fusion technique of series operation and edge detection cannot recognize low-contrast and multi-scale targets in the lens. To address these challenges, in this study, an improved YOLOv5-C3CA-SPPF network model is proposed to detect defects on the surface and inside of the lens. The hybrid module combining the coordinate attention and CSPNet (C3) is incorporated into YOLOv5-C3CA for improving the extraction of target feature information and detection accuracy. Furthermore, an SPPF features fusion module is inserted into the neck of the network model to improve the detection accuracy of the network. To enhance the performance of supervised learning algorithms, a dataset containing a total of 3800 images is created, more than 600 images for each type of defect samples. The outcome of the experiment manifests that the mean average precision (mAP) of the YOLOv5-C3CA-SPPF algorithm is 97.1%, and the detection speed FPS is 41 f/s. Contrast to the traditional lens surface defects detection algorithms, YOLOv5-C3CA-SPPF can detect the types of optical lens surface and inside defects more accurately and quickly, the experimental results show that the YOLOv5-C3CA-SPPF model for identifying optical lens defects has good generalizability and robustness, which is favorable for on-line quality automatic detection of optical lens defects and provide an important guarantee for the quality consistency of finished products.

Rapid single-photon color imaging of moving objects.

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

Circ-Ntrk2 acts as a miR-296-5p sponge to activate the TGF-ß1/p38 MAPK pathway and promote pulmonary hypertension and vascular remodelling.

BACKGROUND: Circular RNAs (circRNAs), a novel class of non-coding RNAs, play an important regulatory role in pulmonary arterial hypertension (PAH); however, the specific mechanism is rarely studied. In this study, we aimed to discover functional circRNAs and investigate their effects and mechanisms in hypoxia-induced pulmonary vascular remodelling, a core pathological change in PAH. METHODS: RNA sequencing was used to illustrate the expression profile of circRNAs in hypoxic PAH. Bioinformatics, Sanger sequencing, and quantitative real-time PCR were used to identify the ring-forming characteristics of RNA and analyse its expression. Then, we established a hypoxia-induced PAH mouse model to evaluate circRNA function in PAH by echocardiography and hemodynamic measurements. Moreover, microRNA target gene database screening, fluorescence in situ hybridisation, luciferase reporter gene detection, and western blotting were used to explore the mechanism of circRNAs. RESULTS: RNA sequencing identified 432 differentially expressed circRNAs in mouse hypoxic lung tissues. Our results indicated that circ-Ntrk2 is a stable cytoplasmic circRNA derived from Ntrk2 mRNA and frequently upregulated in hypoxic lung tissue. We further found that circ-Ntrk2 sponges miR-296-5p and miR-296-5p can bind to the 3'-untranslated region of transforming growth factor-ß1 (TGF-ß1) mRNA, thereby attenuating TGF-ß1 translation. Through gene knockout or exogenous expression, we demonstrated that circ-Ntrk2 could promote PAH and vascular remodelling. Moreover, we verified that miR-296-5p overexpression alleviated pulmonary vascular remodelling and improved PAH through the TGF-ß1/p38 MAPK pathway. CONCLUSIONS: We identified a new circRNA (circ-Ntrk2) and explored its function and mechanism in PAH, thereby establishing potential targets for the diagnosis and treatment of PAH. Furthermore, our study contributes to the understanding of circRNA in relation to PAH.

Extracellular Vesicles Derived from Human Umbilical Cord MSC Improve Vascular Endothelial Function in In Vitro and In Vivo Models of Preeclampsia through Activating Arginine Metabolism.

Endothelial cell damage is an important feature of preeclampsia (PE). Human umbilical mesenchymal stem-cell-derived extracellular vesicles (HUMSCs-derived EVs) have been shown to have therapeutic effects on a variety of diseases and tissue damage. However, the therapeutic effect of HUMSCs-derived EVs on endothelial injury in PE remains unclear. This study explored the possible mechanism of HUMSCs-derived EVs in the treatment of endothelial cell injury. Tumor necrosis factor α- and lipopolysaccharide-induced endothelial dysfunction models were used to evaluate the therapeutic effect of HUMSCs-derived EVs on endothelial injury. We further constructed PE mouse models to explore the function of HUMSCs-derived EVs in vivo. The changes of metabolites in endothelial cells after HUMSCs-derived EVs treatment were analyzed by metabolomics analysis and further validated by cell experiments. HUMSCs-derived EVs treatment can alleviate endothelial cell injury in PE, involving cell proliferation, migration, angiogenesis, and anti-inflammatory. Importantly, administration of HUMSCs-derived EVs improves hypertension and proteinuria in PE mice, alleviates kidney damage, and promotes vascularization in the placenta. Furthermore, metabolomics analysis found that the arginine metabolic pathway is activated after HUMSCs-derived EVs treatment. We also observed increased arginine level, nitric oxide content, and nitric oxide synthase activity, and further experiments proved that activating the arginine metabolic pathway could alleviate endothelial dysfunction. Our results reveal that HUMSCs-derived EVs could ameliorate PE endothelial dysfunction by activating the arginine metabolic pathway and may serve as a therapeutic method for treating PE.

Milk fat globule membrane: composition, production and its potential as encapsulant for bioactives and probiotics.

Milk fat globule membrane (MFGM) is a complex trilayer structure present in mammalian milk and is mainly composed of phospholipids and proteins (>90%). Many studies revealed MFGM has positive effects on the immune system, brain development, and cognitive function of infants. Probiotics are live microorganisms that have been found to improve mental health and insulin sensitivity, regulate immunity, and prevent allergies. Probiotics are unstable and prone to degradation by environmental, processing, and storage conditions. In this review, the processes used for encapsulation of probiotics particularly the potential of MFGM and its constituents as encapsulating materials for probiotics are described. This study analyzes the importance of MFGM in encapsulating bioactive substances and emphasizes the interaction with probiotics and the gut as well as its resistance to adverse environmental factors in the digestive system when used as a probiotic embedding material. MFGM can enhance the gastric acid resistance and bile resistance of probiotics, mainly manifested in the survival rate of probiotics. Due to the role of digestion, MFGM-coated probiotics can be released in the intestine, and due to the biocompatibility of the membrane, it can promote the binding of probiotics to intestinal epithelial cells, and promote the colonization of some probiotics in the intestine.

A spectral learning path for simultaneous multi-parameter detection of water quality.

Water quality parameters (WQP) are the most intuitive indicators of the environmental quality of water body. Due to the complexity and variability of the chemical environment of water body, simple and rapid detection of multiple parameters of water quality becomes a difficult task. In this paper, spectral images (named SPIs) and deep learning (DL) techniques were combined to construct an intelligent method for WQP detection. A novel spectroscopic instrument was used to obtain SPIs, which were converted into feature images of water chemistry and then combined with deep convolutional neural networks (CNNs) to train models and predict WQP. The results showed that the method of combining SPIs and DL has high accuracy and stability, and good prediction results with average relative error of each parameter (anions and cations, TOC, TP, TN, NO3--N, NH3-N) at 1.3%, coefficient of determination (R2) of 0.996, root mean square error (RMSE) of 0.1, residual prediction deviation (RPD) of 16.2, and mean absolute error (MAE) of 0.067. The method can achieve rapid and accurate detection of high-dimensional water quality multi-parameters, and has the advantages of simple pre-processing and low cost. It can be applied not only to the intelligent detection of environmental waters, but also has the potential to be applied in chemical, biological and medical fields.

Improved STMask R-CNN-based defect detection model for automatic visual inspection of an optics lens.

A lens defect is a common quality issue that has seriously harmed the scattering characteristics and performance of optical elements, reducing the quality consistency of the finished products. Furthermore, the energy hotspots coming from the high-energy laser through diffraction of optical component defects are amplified step by step in multi-level laser conduction, causing serious damage to the optical system. Traditional manual detection mainly relies on experienced workers under a special light source environment with high labor intensity, low efficiency, and accuracy. The common machine vision techniques are incapable of detecting low contrast and complex morphological defects. To address these challenges, a deep learning-based method, named STMask R-CNN, is proposed to detect defects on the surface and inside of a lens in complex environments. A Swin Transformer, which focuses on improving the modeling and representation capability of the features in order to improve the detection performance, is incorporated into the Mask R-CNN in this case. A challenge dataset containing more than 3800 images (18000 defect sample targets) with five different types of optical lens defects was created to verify the proposed approach. According to our experiments, the presented STMask R-CNN reached a precision value of 98.2%, recall value of 97.7%, F1 score of 97.9%, mAP@0.5 value of 98.1%, and FPS value of 24 f/s, which outperformed the SSD, Faster R-CNN, and YOLOv5. The experimental results demonstrated that the proposed STMask R-CNN outperformed other popular methods for multiscale targets, low contrast target detection and nesting, stacking, and intersecting defects sample detection, exhibiting good generalizability and robustness, as well as detection speed to meet mechanical equipment production efficiency requirements. In general, this research offers a favorable deep learning-based method for real-time automatic detection of optical lens defects.

Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review.

INTRODUCTION: Despite intensive research, preterm birth (PTB) rates have not decreased significantly in recent years due to a lack of understanding of the underlying causes and insufficient treatment options for PTB. We are committed to finding promising biomarkers for the treatment of PTB. METHODS: An extensive search of the literature was conducted with MEDLINE/PubMed, and in total, 151 studies were included and summarized in the present review. RESULTS: Substantial evidence supports that the infection and/or inflammatory cascade associated with infection is an early event in PTB. Toll-like receptor (TLR) is a prominent pattern recognition receptor (PRR) found on both immune and non-immune cells, including fetal membrane cells. The activation of TLR downstream molecules, followed by TLR binding to its ligand, is critical for infection and inflammation, leading to the involvement of the TLR signaling pathway in PTB. TLR ligands are derived from microbial components and molecules released by damaged and dead cells. Particularly, TLR4 is an essential TLR because of its ability to recognize lipopolysaccharide (LPS). In this comprehensive overview, we discuss the role of TLR signaling in PTB, focus on numerous host-derived genetic and epigenetic regulators of the TLR signaling pathway, and cover ongoing research and prospective therapeutic options for treating PTB by inhibiting TLR signaling. CONCLUSION: This is a critical topic because TLR-related molecules and mechanisms may enable obstetricians to better understand the physiological changes in PTB and develop new treatment and prevention strategies.

Immobilization of Actinobacillus succinogenes on nano- and micro-fiber membranes for efficient and robust production of succinic acid.

This work aimed to study the efficiency of nano- and micro- fiber membranes in immobilizing Actinobacillus succinogenes CCTCC M2012036 for succinic acid production. Among the four kinds of electrospun nanofiber membranes of cellulose acetate, chitosan, poly(vinyl alcohol) (PVA) and chitosan-PVA, the cellulose acetate nanofiber membrane-immobilized cells performed the best with a succinic acid concentration and yield to be 27.3 ± 3.5 g/L and 70.9 ± 5.8%. The cell-immobilized viscose microfiber membrane presented good reuse stability, and 17 batches of fermentation without activity loss were realized with the highest succinic acid yield of 83.20%. A microfiber membrane bioreactor was further constructed with the cell-immobilized viscose microfiber membrane to perform fermentation on a larger scale, and the concentration, yield and productivity of succinic acid were 73.20 g/L, 86.50% and 1.49 g/(L⋅h) using a fed-batch strategy, which were 124.30%, 127.60% and 124.2% of those obtained in the traditional fermenter. This study provided an approach for improving the practicality of biological succinic acid production.

Characterization of Molecular Diversity and Organization of Phycobilisomes in Thermophilic Cyanobacteria.

Thermophilic cyanobacteria are cosmopolitan and abundant in the thermal environment. Their light-harvesting complexes, phycobilisomes (PBS), are highly important in photosynthesis. To date, there is limited information on the PBS composition of thermophilic cyanobacteria whose habitats are challenging for survival. Herein, genome-based methods were used to investigate the molecular components of PBS in 19 well-described thermophilic cyanobacteria. These cyanobacteria are from the genera Leptolyngbya, Leptothermofonsia, Ocullathermofonsia, Thermoleptolyngbya, Trichothermofonsia, Synechococcus, Thermostichus, and Thermosynechococcus. According to the phycobiliprotein (PBP) composition of the rods, two pigment types are observed in these thermophiles. The amino acid sequence analysis of different PBP subunits suggests several highly conserved cysteine residues in these thermophiles. Certain amino acid contents in the PBP of thermophiles are significantly higher than their mesophilic counterparts, highlighting the potential roles of specific substitutions of amino acid in the adaptive thermostability of light-harvesting complexes in thermophilic cyanobacteria. Genes encoding PBS linker polypeptides vary among the thermophiles. Intriguingly, motifs in linker apcE indicate a photoacclimation of a far-red light by Leptolyngbya JSC-1, Leptothermofonsia E412, and Ocullathermofonsia A174. The composition pattern of phycobilin lyases is consistent among the thermophiles, except for Thermostichus strains that have extra homologs of cpcE, cpcF, and cpcT. In addition, phylogenetic analyses of genes coding for PBPs, linkers, and lyases suggest extensive genetic diversity among these thermophiles, which is further discussed with the domain analyses. Moreover, comparative genomic analysis suggests different genomic distributions of PBS-related genes among the thermophiles, indicating probably various regulations of expression. In summary, the comparative analysis elucidates distinct molecular components and organization of PBS in thermophilic cyanobacteria. These results provide insights into the PBS components of thermophilic cyanobacteria and fundamental knowledge for future research regarding structures, functions, and photosynthetic improvement.