Characterization of Ssc, an N-acetylgalactosamine-containing Staphylococcus aureus surface polysaccharide.

Whole genome sequencing has revealed that the genome of Staphylococcus aureus possesses an uncharacterized 5-gene operon (SAOUHSC_00088-00092 in strain 8325 genome) that encodes factors with functions related to polysaccharide biosynthesis and export, indicating the existence of a new extracellular polysaccharide species. We designate this locus as ssc for staphylococcal surface carbohydrate. We found that the ssc genes were weakly expressed and highly repressed by the global regulator MgrA. To characterize Ssc, Ssc was heterologously expressed in Escherichia coli and extracted by heat treatment. Ssc was also conjugated to AcrA from Campylobacter jejuni in E. coli using protein glycan coupling technology (PGCT). Analysis of the heat-extracted Ssc and the purified Ssc-AcrA glycoconjugate by tandem mass spectrometry revealed that Ssc is likely a polymer consisting of N-acetylgalactosamine. We further demonstrated that the expression of the ssc genes in S. aureus affected phage adsorption and susceptibility, suggesting that Ssc is surface-exposed. IMPORTANCE: Surface polysaccharides play crucial roles in the biology and virulence of bacterial pathogens. Staphylococcus aureus produces four major types of polysaccharides that have been well-characterized. In this study, we identified a new surface polysaccharide containing N-acetylgalactosamine (GalNAc). This marks the first report of GalNAc-containing polysaccharide in S. aureus. Our discovery lays the groundwork for further investigations into the chemical structure, surface location, and role in pathogenesis of this new polysaccharide.

Macrophages as determinants and regulators of systemic sclerosis-related interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD (SSc-ILD) occurs more frequently in females aged 30-55 years, whereas idiopathic pulmonary fibrosis (IPF) is more prevalent in males aged 60-75 years. SSc-ILD occurs earlier than IPF and progresses rapidly. FCN1, FABP4, and SPP1 macrophages are involved in the pathogenesis of lung fibrosis; SPP1 macrophages demonstrate upregulated expression in both SSc-ILD and IPF. To identify the differences between SSc-ILD and IPF using single-cell analysis, clarify their distinct pathogeneses, and propose directions for prevention and treatment. METHODS: We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE159354 and GSE212109, and analyzed lung tissue samples across healthy controls, IPF, and SSc-ILD. The primary measures were the filtered genes integrated with batch correction and annotated cell types for distinguishing patients with SSc-ILD from healthy controls. We proposed an SSc-ILD pathogenesis using cell-cell interaction inferences, and predicted transcription factors regulating target genes using SCENIC. Drug target prediction of the TF gene was performed using Drug Bank Online. RESULTS: A subset of macrophages activates the MAPK signaling pathway under oxidative stress. Owing to the lack of inhibitory feedback from ANNEXIN and the autoimmune characteristics, this leads to an earlier onset of lung fibrosis compared to IPF. During initial lung injury, fibroblasts begin to activate the IL6 pathway under the influence of SPP1 alveolar macrophages, but IL6 appears unrelated to other inflammatory and immune cells. This may explain why tocilizumab (an anti-IL6-receptor antibody) only preserves lung function in patients with early SSc-ILD. Finally, we identified BCLAF1 and NFE2L2 as influencers of MAPK activation in macrophages. Metformin downregulates NFE2L2 and could serve as a repurposed drug candidate. CONCLUSIONS: SPP1 alveolar macrophages play a role in the profibrotic activity of IPF and SSc-ILD. However, SSc-ILD is influenced by autoimmunity and oxidative stress, leading to the continuous activation of MAPK in macrophages. This may result in an earlier onset of lung fibrosis than in IPF. Such differences could serve as potential research directions for early prevention and treatment.

Successful long-term systemic sclerosis treatment by high-frequent low-dose B cell-depleting therapy.

OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc. METHODS: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed. RESULTS: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years. CONCLUSION: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.

Pyrrole ßC-B-N Fused Porphyrins: Molecular Structures and Opto-Electrochemical Studies.

Herein, we report the design, synthesis, structure, and electrochemical study of doubly ßC-B-N fused Ni(II) porphyrins (1-trans, 1-cis, 2-trans, and 2-cis). These compounds have been synthesized from A2B2 type dipyridyl Ni(II) porphyrins (Ar=Ph for 1 a; Ar=C6F5 for 2 a) via Lewis base-directed electrophilic aromatic borylation reactions. The solution state structures of these compounds have been established using 1H NMR, 11B NMR, 1H-1H COSY, 1H-13C HSQC, and 19F-13C HSQC NMR techniques. Single crystal X-ray analysis have revealed that 1-trans, 1-cis, and 2-trans adopt ruffled conformations, with alternate meso-carbons on the opposite sides of the mean porphyrin plane. The Soret bands in the absorption spectra of the B-N fused molecules are ~40 nm redshifted compared to unfused Ni(II) porphyrin precursors. The B-N fusion have diminished the redox potential of fused porphyrins. Although 1-trans and 1-cis, show four oxidation processes, 2-trans and 2-cis show only three oxidation processes. DFT studies have revealed that the tetrahedral geometry of the boron has induced a twist in the π-conjugation, which destabilizes the HOMO and stabilizes the LUMO in 1-trans, 1-cis, 2-trans, and 2-cis.

Exosomal ssc-miR-1343 targets FAM131C to regulate porcine epidemic diarrhea virus infection in pigs.

The porcine epidemic diarrhea virus (PEDV) causes diarrhea in piglets, thereby causing very significant economic losses for the global swine industry. In previous studies, it has been confirmed that microRNAs (miRNAs) play an important role in the infection caused by PEDV. However, the precise molecular mechanism of miRNAs in the regulation of PEDV infection is still not fully understood. In the present study, we utilized miRNA-seq analysis to identify ssc-miR-1343 with differential expression between PEDV-infected and normal piglets. The expression of ssc-miR-1343 was detected in isolated exosomes, and it was found to be significantly higher than that in the controls following PEDV infection. The ssc-miR-1343 mimic was found to decrease PEDV replication, whereas the ssc-miR-1343 inhibitor was observed to increase PEDV replication, and ssc-miR-1343 was delivered by exosomes during PEDV infection. Mechanistically, ssc-miR-1343 binds to the 3'UTR region of FAM131C, down-regulating its expression, and FAM131C has been shown to enhance PEDV replication through simultaneously suppressing pathways associated with innate immunity. The ssc-miR-1343/FAM131C axis was found to upregulate the host immune response against PEDV infection. In conclusion, our findings indicate that the transport of ssc-miR-1343 in exosomes is involved in PEDV infection. This discovery presents a new potential target for the development of drugs to treat PEDV.

Optimal isolation, culture, and in vitro propagation of spermatogonial stem cells in Huaixiang chicken.

Spermatogonial stem cells (SSCs) comprise the foundation of spermatogenesis and hence have great potential for fertility preservation of rare or endangered species and the development of transgenic animals and birds. Yet, developing optimal conditions for the isolation, culture, and maintenance of SSCs in vitro remains challenging, especially for chicken. The objectives of this study were to (1) find the optimal age for SSC isolation in Huaixiang chicken, (2) develop efficient protocols for the isolation, (3) enrichment, and (4) culture of isolated SSCs. In the present study, we first compared the efficiency of SSC isolation using 11 different age groups (8-79 days of age) of Huaixiang chicken. We found that the testes of 21-day-old chicken yielded the highest cell viability. Next, we compared two different enzymatic combinations for isolating SSCs and found that 0.125% trypsin and 0.02 g/L EDTA supported the highest number and viability of SSCs. This was followed by investigating optimal conditions for the enrichment of SSCs, where we observed that differential plating had the highest enrichment efficiency compared to the Percoll gradient and magnetic-activated cell sorting methods. Lastly, to find the optimal culture conditions of SSCs, we compared adding different concentrations of foetal bovine serum (FBS; 2%, 5%, 7%, and 10%) and different concentrations of GDNF, bFGF, or LIF (5, 10, 20, or 30 ng/mL). We found that a combination of 2% FBS and individual growth factors, including GDNF (20 ng/mL), bFGF (30 ng/mL), or LIF (5 ng/mL), best supported the proliferation and colony formation of SSCs. In conclusion, SSCs can be optimally isolated through enzymatic digestion from testes of 21-day-old chicken, followed by enrichment using differential plating. Furthermore, adding 2% FBS and optimized concentrations of GFNF, bFGF, or LIF in the culture promotes the proliferation of chicken SSCs.

Chemogenetics Modulation of Electroacupuncture Analgesia in Mice Spared Nerve Injury-Induced Neuropathic Pain through TRPV1 Signaling Pathway.

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.

IQGAP1 Regulates Actin Polymerization and Contributes to Bleomycin-Induced Lung Fibrosis.

We previously found IQ motif containing GTPase activating protein (IQGAP1) to be consistently elevated in lung fibroblasts (LF) isolated from patients with scleroderma (systemic sclerosis, SSc)-associated interstitial lung disease (ILD) and reported that IQGAP1 contributed to SSc by regulating expression and organization of α-smooth muscle actin (SMA) in LF. The aim of this study was to compare the development of ILD in the presence and absence of IQGAP1. Pulmonary fibrosis was induced in IQGAP1 knockout (KO) and wild-type (WT) mice by a single-intratracheal instillation of bleomycin. Two and three weeks later, mice were euthanized and investigated. We observed that the IQGAP1 KO mouse was characterized by a reduced rate of actin polymerization with reduced accumulation of actin in the lung compared to the WT mouse. After exposure to bleomycin, the IQGAP1 KO mouse demonstrated decreased contractile activity of LF, reduced expression of SMA, TGFß, and collagen, and lowered overall fibrosis scores compared to the WT mouse. The numbers of inflammatory cells and expression of pro-inflammatory cytokines in lung tissue were not significantly different between IQGAP1 KO and WT mice. We conclude that IQGAP1 plays an important role in the development of lung fibrosis induced by bleomycin, and the absence of IQGAP1 reduces the contractile activity of lung fibroblast and bleomycin-induced pulmonary fibrosis. Thus, IQGAP1 may be a potential target for novel anti-fibrotic therapies for lung fibrosis.

Safety of prolonged use of metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis.

Background: Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). Methods: A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25-80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. Results: Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. Conclusions: Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

Establishment and representativeness of the Stockholm Sodium Cohort: A laboratorial and pharmacoepidemiologic database covering 1.6 million individuals in the Stockholm County.

OBJECTIVE: Hyponatremia is associated with considerable morbidity and mortality, but causal links have been difficult to establish. Here, we describe the establishment and representativeness of the Stockholm Sodium Cohort (SSC), designed to study etiologies and outcomes of hyponatremia. STUDY DESIGN AND SETTING: All residents of Stockholm County undertaking at least one serum sodium test between 2005-2018 were included in the SSC. Individual-level test results from over 100 laboratory parameters relevant to hyponatremia were collected and linked to data on demographics, socioeconomic status, healthcare contacts, diagnoses and dispensed prescription medications using national registers. RESULTS: A total of 1,632,249 individuals, corresponding to 64% of the population of Stockholm County, were included in the SSC. Coverage increased with advancing age, ranging from 32% in children and adolescents (≤18 years) to 97% among the oldest (≥80 years). The coverage of SSC included the vast majority of patients in Stockholm County diagnosed with diabetes mellitus (93%), myocardial infarction (98%), ischemic stroke (97%), cancer (85%), pneumonias requiring inpatient care (95%) and deaths (88%). CONCLUSION: SSC is the first cohort specifically designed to investigate sodium levels in a large, population-based setting. It includes a wide range of administrative health data and laboratory analyses. The coverage is high, particularly among elderly and individuals with comorbidities. Consequently, the cohort has a large potential for exploration of various aspects of hyponatremia.

Porcine circovirus type 2 ORF5 induces an inflammatory response by up-regulating miR-21 levels through targeting nuclear ssc-miR-30d.

Porcine circovirus type 2 (PCV2) infection leads to multi-system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF-κB pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting pri-miR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it.

Expression profiles of miRNAs in the lung tissue of piglets infected with Glaesserella parasuis and the roles of ssc-miR-135 and ssc-miR-155-3p in the regulation of inflammation.

MicroRNAs (miRNAs) have been shown to play an important regulatory role in the process of pathogenic infection. However, the miRNAs that regulate the pathogenic process of G. parasuis and their functions are still unknown. Here, high-throughput sequencing was used to quantify the expression of miRNA in piglet lung tissue after G. parasuis XX0306 strain infection. A total of 25 differentially expressed microRNAs (DEmiRNAs) were identified. GO and KEGG pathway enrichment analysis showed that many of the functions of genes that may be regulated by DEmiRNA are related to inflammatory response and immune regulation. Further studies found that ssc-miR-135 may promote the expression of inflammatory factors through NF-κB signaling pathway. Whereas, ssc-miR-155-3p inhibited the inflammatory response induced by G. parasuis, and its regulatory mechanism remains to be further investigated. This study provides a valuable reference for revealing the regulatory effects of miRNAs on the pathogenesis of G. parasuis. DATA AVAILABILITY: The datasets generated during the current study are not publicly available due to this study is currently in the ongoing research stage, and some of the data cannot be made public sooner yet, but are available from the corresponding author on reasonable request.

Ssc-miR-429 expression proliles and functions on inducing Leydig cells apoptosis.

Leydig cells (LCs) play an indispensable role in testosterone synthesis, and their dysfunction can result in male reproductive disorders. Previous transcriptome sequencing revealed differential expression of MicroRNA-429 (miR-429) in both Leydig stem cells (SLCs) and LCs, indicating its potential regulatory function in LCs. In this study, we examined the expression of miR-429 in seven pig tissues (heart, liver, spleen, lung, kidney, testis, epididymis, brain) and investigated its impact on the proliferation and apoptosis of testicular interstitial cells using various techniques such as CCK-8, EdU, TUNEL, Western blot, among others. The results demonstrated that miR-429 exhibited lower expression levels in the testis, particularly in the LCs of testicular tissue. Upon upregulation of miR-429, TM3 cell density significantly increased, while downregulation led to a slight elevation in cell density. Further research indicated that the observed phenotype was due to miR-429-induced cell apoptosis, independent of cell proliferation. Additionally, a dual-luciferase reporter system revealed no targeting relationship between miR-429 and the predicted target genes (BMI1 and SOX5). Previous reports confirm Bcl2 as a known target of miR-429, leading us to hypothesize that miR-429 diminishes LCs' anti-apoptotic capability by inhibiting Bcl2. In summary, our findings suggest that miR-429 may induce LC apoptosis, supporting its potential as a biomarker for male reproductive disorders linked to Leydig cell dysfunction.

Fibroblast Subpopulations in Systemic Sclerosis: Functional Implications of Individual Subpopulations and Correlations with Clinical Features.

Fibroblasts constitute a heterogeneous population of cells. In this study, we integrated single-cell RNA-sequencing and bulk RNA-sequencing data as well as clinical information to study the role of individual fibroblast populations in systemic sclerosis (SSc). SSc skin demonstrated an increased abundance of COMP+, COL11A1+, MYOC+, CCL19+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblasts signatures and decreased proportions of CXCL12+ and PI16+ fibroblast signatures in the Prospective Registry of Early Systemic Sclerosis and Genetics versus Environment in Scleroderma Outcome Study cohorts. Numerical differences were confirmed by multicolor immunofluorescence for selected fibroblast populations. COMP+, COL11A1+, SFRP4/SFRP2+, PRSS23/SFRP2+, and PI16+ fibroblasts were similarly altered between normal wound healing and patients with SSc. The proportions of profibrotic COMP+, COL11A1+, SFRP4/SFRP2+, and PRSS23/SFRP2+ and proinflammatory CCL19+ fibroblast signatures were positively correlated with clinical and histopathological parameters of skin fibrosis, whereas signatures of CXCL12+ and PI16+ fibroblasts were inversely correlated. Incorporating the proportions of COMP+, COL11A1+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblast signatures into machine learning models improved the classification of patients with SSc into those with progressive versus stable skin fibrosis. In summary, the profound imbalance of fibroblast subpopulations in SSc may drive the progression of skin fibrosis. Specific targeting of disease-relevant fibroblast populations may offer opportunities for the treatment of SSc and other fibrotic diseases.

Isolation and In Vitro Propagation of Human Spermatogonial Stem Cells (SSCs).

Preservation of human spermatogonial stem cells (SSCs) may be suitable for young male patients at risk of male infertility due to various causes, such as gonadotoxic treatment or genetic diseases. With optimal cryopreservation, cell viability can be retained to reestablish spermatogenesis in the future through autologous transplantation or in vitro differentiation of SSCs. This protocol outlines techniques to optimize the SSCs isolation and in vitro culture. With particular emphasis on the microscopic characteristics encountered, this protocol outlines a broader approach to processing tissues with varying morphologies among patients.

Unveiling the potential of graphene and S-doped graphene nanostructures for toxic gas sensing and solar sensitizer cell devices: insights from DFT calculations.

CONTEXT: In this work, we explore the potential of 2D materials, particularly graphene and its derivatives, for eco-friendly electricity generation and air pollution reduction. Leveraging the significant surface area of graphene nanomaterials, the susceptibility of these graphene-based nanostructures to hazardous substances and their applicability in clean solar cell (SSC) devices were systematically investigated using density functional theory (DFT), as implemented within Gaussian 5.0 code. Time-dependent DFT (TD-DFT) was employed to characterize the UV-visible spectrum of unstrained nanostructures. Herein, we considered three potentially harmful gases-CO, NH3, and Br2. Adsorption calculations revealed a notable interaction between the pure graphene nanostructure and Br2 gas, while the S-doped counterpart exhibited reduced interaction. Saturated S-doped nanostructures demonstrated an enhanced affinity for NH3 and CO gases compared to their pure S-doped counterparts, attributed to the sulfur (S) atom facilitating gas molecule binding to the nanostructure's surface. Furthermore, simulations of the SSC device architecture indicated the superior performance of the pure graphene nanostructure in terms of light-harvesting efficiency, injection energy, and electron injection into the lower conduction band of CBM titanium dioxide (TiO2). These findings suggest a potential avenue for developing nanostructures tailored for SSC devices and gas sensors, offering a dual solution to address air pollution concerns. METHODS: Density function theory was used to compute the ground and excited state properties for pure and sulfur-doped graphene nanostructures. The hybrid function B3LYP with a 6-31G* basis set was utilized to describe the exchange correlation. Gauss Sum 2.2 software is used to estimate the density of state (DOS) for all structures under investigation.

Nanostructures and multi-scale aggregation of high ion exchange capacity short-side-chain perfluorosulfonic acid dispersion.

Short-side-chain perfluorosulfonic acid (SSC-PFSA) ionomers with high ion-exchange-capacity are promising candidates for high-temperature proton exchange membranes (PEMs) and catalyst layer (CL) binders. The solution-casting method determines the importance of SSC-PFSA dispersion characteristics in shaping the morphology of PEMs and CLs. Therefore, a thorough understanding of the chain behavior of SSC-PFSA in dispersions is essential for fabricating high-quality PEMs and CLs. In this study, we have employed multiple characterization techniques, including dynamic light scatting (DLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscope (Cryo-TEM), to fully study the chain aggregation behaviors of SSC-PFSA in water-ethanol solvents and elucidate the concentration-dependent self-assembly process. In dilute dispersions (2 mg/mL), SSC-PFSA assembles into mono-disperse rod-like aggregates, featuring a twisted fluorocarbon backbone that forms a hydrophobic stem, and the sulfonic acid side chains extending outward to suit the hydrophilic environment. As the concentration increases, the radius of rod particles increases from 1.47 to 1.81 nm, and the mono-disperse rod particles first form a "end-to-end" configuration that doubles length (10 mg/mL), and then transform into a swollen network structure in semi-dilute dispersion (20 mg/mL). This work provides a well-established structure model for SSC-PFSA dispersions, which is the key nanostructure to be inherited by PEMs.

Implications for miR-339-5p regulation of trophoblast proliferation and migration in placentas associated with porcine intrauterine growth retardation using integrated transcriptome sequencing analysis.

Placental dysfunction is considered as one of the main etiologies of fetal intrauterine growth retardation (IUGR). MicroRNAs (miRNAs) have been demonstrated to be a vital epigenetic modification involved in regulating the placental function and pregnancy outcomes in mammals. However, the mechanisms underlying placenta-specific miRNAs involved in the occurrence and development of pig IUGR remain unclear. In this work, we compared the placental morphologies of piglets with IUGR and normal birth weight (NBW) by using histomorphological analysis and performed a miRNA-mRNA integrative analysis of the gene expression profiles of IUGR and NBW placentas through RNA sequencing. We also investigated the role of differentially expressed ssc-miR-339-5p/GRIK3 through an in vitro experiment on porcine trophoblast cells (PTr2). IUGR piglets had significantly lower birth weight, placental weight, placental efficiency, and placental villus and capillary densities compared with the NBW piglets (P < 0.05). A total of 81 differentially expressed miRNAs and 726 differentially expressed genes in the placentas were screened out between the IUGR and NBW groups. The miRNA-mRNA interaction networks revealed the key core miRNA (ssc-miR-339-5p) and its corresponding target genes. Subsequently, we found that upregulation of ssc-miR-339-5p significantly inhibited the migration and proliferation of PTr2 cells (P < 0.05). The dual-luciferase reporter system showed that GRIK3 was the target gene of ssc-miR-339-5p, and the transcription level of GRIK3 may be negatively regulated by ssc-miR-339-5p. Additionally, overexpression of ssc-miR-339-5p significantly increased (P < 0.05) the mRNA expression levels of genes involved in the cytokine-cytokine receptor interaction pathway. These results indicate that ssc-miR-339-5p may affect the migration and proliferation of trophoblast cells by regulating the expression of GRIK3 and altering the placental inflammatory response, resulting in a suboptimal morphology and function of the placenta and the development of pig IUGR.

E Carwile LeRoy, MD.

E. Carwile LeRoy, M.D. was a pioneer in the study of systemic sclerosis (SSc, scleroderma). His early medical training was strongly influenced by notable clinical investigators including Dr Kenneth Brinkhous, Dr Charles Christian and Dr Albert Sjoerdsma. Dr LeRoy is remembered for his seminal observations on the over-production of collagen by scleroderma fibroblasts and for his vascular hypothesis on the pathogenesis of scleroderma. The Division of Rheumatology & Immunology at the Medical University of South Carolina, established by Dr LeRoy, is world renowned for its clinical and translational studies of scleroderma and has produced many of the leaders in the international scleroderma community.

Engineered Cementitious Composites with Super-Sulfated Cement: Mechanical, Physical, and Durability Performance.

This study aimed to bridge a research gap by exploring the utilization of super-sulphated cement (SSC) in engineered cementitious composites (ECCs) as a sustainable alternative to ordinary Portland cement (OPC)-based mixtures. The SSC was designed with slag, gypsum, and a small amount of OPC. The primary objective was to investigate the effects of incorporating SSC, both with and without fly ash (FA), at various FA/SSC ratios between 0 and 1.5. A comprehensive evaluation was conducted to assess the performance of the ECC-SSC mixtures, including the compressive and flexural strengths, ductility, ultrasonic pulse velocity, rapid chloride permeability, and drying shrinkage. Additionally, advanced microstructural evaluation techniques such as scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis as well as X-ray diffraction (XRD) analysis were employed to analyze the reaction products in selected mixtures. The results showed that the ECC mixture produced with SSC exhibited comparable strength to the ECC-OPC. In general, all the SSC-based ECCs fulfilled the criteria for various engineering applications, especially when the fly ash to SSC ratios were 0 and 0.8. In addition, ECCs with FA/SSC ratios of 1.2 and 1.5 showed ultra-ductile performance higher than the control ECC. Interestingly, all the FA-based ECC-SSC presented lower shrinkage characteristics than the control OPC-based ECC.