CRISPR-array-mediated imaging of non-repetitive and multiplex genomic loci in living cells.

Dynamic imaging of genomic loci is key for understanding gene regulation, but methods for imaging genomes, in particular non-repetitive DNAs, are limited. We developed CRISPRdelight, a DNA-labeling system based on endonuclease-deficient CRISPR-Cas12a (dCas12a), with an engineered CRISPR array to track DNA location and motion. CRISPRdelight enables robust imaging of all examined 12 non-repetitive genomic loci in different cell lines. We revealed the confined movement of the CCAT1 locus (chr8q24) at the nuclear periphery for repressed expression and active motion in the interior nucleus for transcription. We uncovered the selective repositioning of HSP gene loci to nuclear speckles, including a remarkable relocation of HSPH1 (chr13q12) for elevated transcription during stresses. Combining CRISPR-dCas12a and RNA aptamers allowed multiplex imaging of four types of satellite DNA loci with a single array, revealing their spatial proximity to the nucleolus-associated domain. CRISPRdelight is a user-friendly and robust system for imaging and tracking genomic dynamics and regulation.

Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC1 contributes to neuronal function.

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

Different effects of 24 dietary intakes on gastroesophageal reflux disease: A mendelian randomization.

BACKGROUND: In observational studies, dietary intakes are associated with gastroesophageal reflux disease (GERD). AIM: To conduct a two-sample mendelian randomization (MR) analysis to determine whether those associations are causal. METHODS: To explore the relationship between dietary intake and the risk of GERD, we extracted appropriate single nucleotide polymorphisms from genome-wide association study data on 24 dietary intakes. Three methods were adopted for data analysis: Inverse variance weighting, weighted median methods, and MR-Egger's method. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the causal association between dietary intake and GERD. RESULTS: Our univariate Mendelian randomization (UVMR) results showed significant evidence that pork intake (OR, 2.83; 95%CI: 1.76-4.55; P = 1.84 × 10-5), beer intake (OR, 2.70, 95%CI: 2.00-3.64; P = 6.54 × 10-11), non-oily fish intake (OR, 2.41; 95%CI: 1.49-3.91; P = 3.59 × 10-4) have a protective effect on GERD. In addition, dried fruit intake (OR, 0.37; 95%CI: 0.27-0.50; 6.27 × 10-11), red wine intake (OR, 0.34; 95%CI: 0.25-0.47; P = 1.90 × 10-11), cheese intake (OR, 0.46; 95%CI: 0.39-0.55; P =3.73 × 10-19), bread intake (OR, 0.72; 95%CI: 0.56-0.92; P = 0.0009) and cereal intake (OR, 0.45; 95%CI: 0.36-0.57; P = 2.07 × 10-11) were negatively associated with the risk of GERD. There was a suggestive association for genetically predicted coffee intake (OR per one SD increase, 1.22, 95%CI: 1.03-1.44; P = 0.019). Multivariate Mendelian randomization further confirmed that dried fruit intake, red wine intake, cheese intake, and cereal intake directly affected GERD. In contrast, the impact of pork intake, beer intake, non-oily fish intake, and bread intake on GERD was partly driven by the common risk factors for GERD. However, after adjusting for all four elements, there was no longer a suggestive association between coffee intake and GERD. CONCLUSION: This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD, providing new insights for the treatment and prevention of GERD.

Salvianolic acid B protects against UVB-induced skin aging via activation of NRF2.

BACKGROUND: Prolonged exposure to sun radiation may result in harmful skin photoaging. Therefore, discovering novel anti-photoaging treatment modalities is critical. An active component isolated from Salvia miltiorrhiza (SM), Salvianolic acid B (Sal-B), is a robust antioxidant and anti-inflammatory agent. This investigation aimed to discover the therapeutic impact and pathways of salvianolic acid B for UVB-induced skin photoaging, an area that remains unexplored. METHODS: We conducted in vitro experiments on human dermal fibroblasts (HDFs) exposed to UVB radiation, assessing cellular senescence, superoxide dismutase (SOD) activity, cell viability, proliferation, migration, levels of reactive oxygen species (ROS), and mitochondrial health. The potential mechanism of Sal-B was analyzed using RNA sequencing, with further validation through Western blotting, PCR, and nuclear factor erythroid 2-related factor 2 (NRF2) silencing methods. In vivo, a model of skin photoaging induced by UVB in nude mice was employed. The collagen fiber levels were assessed utilizing hematoxylin and eosin (H&E), Masson, and Sirus red staining. Additionally, NRF2 and related gene and protein expression levels were identified utilizing PCR and Western blotting. RESULTS: Sal-B was found to significantly counteract photoaging in UVB-exposed skin fibroblasts, reducing aging-related decline in fibroblast proliferation and an increase in apoptosis. It was observed that Sal-B aids in protecting mitochondria from excessive ROS production by promoting NRF2 nuclear translocation. NRF2 knockdown experiments established its necessity for Sal-B's anti-photoaging effects. The in vivo studies also verified Sal-B's anti-photoaging efficacy, surpassing that of tretinoin (Retino-A). These outcomes offer novel insights into the contribution of Sal-B in developing clinical treatment modalities for UVB-induced photodamage in skin fibroblasts. CONCLUSION: In this investigation, we identified the Sal-B protective impact on the senescence of dermal fibroblasts and skin photoaging induced by radiation of UVB. The outcomes suggest Sal-B as a potential modulator of the NRF2 signaling pathway.

Single Droplet Tweezer Revealing the Reaction Mechanism of Mn(II)-Catalyzed SO2 Oxidation.

Sulfate aerosol is one of the major components of secondary fine particulate matter in urban haze that has crucial impacts on the social economy and public health. Among the atmospheric sulfate sources, Mn(II)-catalyzed SO2 oxidation on aerosol surfaces has been regarded as a dominating one. In this work, we measured the reaction kinetics of Mn(II)-catalyzed SO2 oxidation in single droplets using an aerosol optical tweezer. We show that the SO2 oxidation occurs at the Mn(II)-active sites on the aerosol surface, per a piecewise kinetic formulation, one that is characterized by a threshold surface Mn(II) concentration and gaseous SO2 concentration. When the surface Mn(II) concentration is lower than the threshold value, the reaction rate is first order with respect to both Mn(II) and SO2, agreeing with our traditional knowledge. But when surface Mn(II) concentration is above the threshold, the reaction rate becomes independent of Mn(II) concentration, and the reaction order with respect to SO2 becomes greater than unity. The measured reaction rate can serve as a tool to estimate sulfate formation based on field observation, and our established parametrization corrects these calculations. This framework for reaction kinetics and parametrization holds promising potential for generalization to various heterogeneous reaction pathways.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

An injectable PC10ARGD/Cu2+/DOX hydrogel for combined chemodynamic and chemotherapy of tumors.

Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC10ARGD/Cu2+/DOX based on Cu2+, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC10ARGD was prepared. First, Cu2+ was attached to the histidines in the PC10ARGD polypeptide by the coordination reaction to form PC10ARGD/Cu2+ hydrogel, then the PC10ARGD/Cu2+/DOX hydrogel was prepared by encapsulating the DOX into the PC10ARGD/Cu2+ hydrogel. The results of scanning electron microscopy showed that the PC10ARGD/Cu2+/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC10ARGD/Cu2+/DOX hydrogel could continuously produce ·OH in the presence of H2O2. In vitro MTT results showed that the PC10ARGD/Cu2+/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC10ARGD/Cu2+/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC10ARGD/Cu2+/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC10ARGD/Cu2+/DOX hydrogel possessed good biocompatibility.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

Sugar status in preexisting leaves determines systemic stomatal development within newly developing leaves.

Stomata are pores found in the epidermis of stems or leaves that modulate both plant gas exchange and water/nutrient uptake. The development and function of plant stomata are regulated by a diverse range of environmental cues. However, how carbohydrate status in preexisting leaves might determine systemic stomatal formation within newly developing leaves has remained obscure. The glucose (Glc) sensor HEXOKINASE1 (HXK1) has been reported to decrease the stability of an ethylene/Glc signaling transcriptional regulator, EIN3 (ETHYLENE INSENSITIVE3). EIN3 in turn directly represses the expression of SUC2 (sucrose transporter 2), encoding a master transporter of sucrose (Suc). Further, KIN10, a nuclear regulator involved in energy homeostasis, has been reported to repress the transcription factor SPCH (SPEECHLESS), a master regulator of stomatal development. Here, we demonstrate that the Glc status of preexisting leaves determines systemic stomatal development within newly developing leaves by the HXK1-¦EIN3-¦SUC2 module. Further, increasing Glc levels in preexisting leaves results in a HXK1-dependent decrease of EIN3 and increase of SUC2, triggering the perception, amplification and relay of HXK1-dependent Glc signaling and thereby triggering Suc transport from mature to newly developing leaves. The HXK1-¦EIN3-¦SUC2 molecular module thereby drives systemic Suc transport from preexisting leaves to newly developing leaves. Subsequently, increasing Suc levels within newly developing leaves promotes stomatal formation through the established KIN10⟶ SPCH module. Our findings thus show how a carbohydrate signal in preexisting leaves is sensed, amplified and relayed to determine the extent of systemic stomatal development within newly developing leaves.

Advancements in adipose-derived stem cell therapy for skin fibrosis.

Pathological scarring and scleroderma, which are the most common conditions of skin fibrosis, pathologically manifest as fibroblast proliferation and extracellular matrix (ECM) hyperplasia. Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling, causing an exaggerated and prolonged wound-healing response. The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects. Currently, a promising and relatively low-cost treatment has emerged-adipose-derived stem cell (ASC) therapy as a branch of stem cell therapy, including ASCs and their derivatives-purified ASC, stromal vascular fraction, ASC-conditioned medium, ASC exosomes, etc., which are rich in sources and easy to obtain. ASCs have been widely used in therapeutic settings for patients, primarily for the defection of soft tissues, such as breast enhancement and facial contouring. In the field of skin regeneration, ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis. The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review, as well as their new applications in the treatment of skin fibrosis. Although the long-term effect of ASC therapy is still unclear, ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.

Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway.

More and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-α) in LPS-treated BV-2 cells. 1H-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway.

Tracking of Mutational Signature of SARS-CoV-2 Omicron on Distinct Continents and Little Difference was Found.

The Omicron variant is currently ravaging the world, raising serious concern globally. Monitoring genomic variations and determining their influence on biological features are critical for tracing its ongoing transmission and facilitating effective measures. Based on large-scale sequences from different continents, this study found that: (i) The genetic diversity of Omicron is much lower than that of the Delta variant. Still, eight deletions (Del 1-8) and 1 insertion, as well as 130 SNPs, were detected on the Omicron genomes, with two deletions (Del 3 and 4) and 38 SNPs commonly detected on all continents and exhibiting high-occurring frequencies. (ii) Four groups of tightly linked SNPs (linkage I-IV) were detected, among which linkage I, containing 38 SNPs, with 6 located in the RBD, increased its occurring frequency remarkably over time. (iii) The third codons of the Omicron shouldered the most mutation pressures, while the second codons presented the least flexibility. (iv) Four major mutants with amino acid substitutions in the RBD were detected, and further structural analysis suggested that the substitutions did not alter the viral receptor binding ability greatly. It was inferred that though the Omicron genome harbored great changes in antigenicity and remarkable ability to evade immunity, it was immune-pressure selected. This study tracked mutational signatures of Omicron variant and the potential biological significance of the SNPs, and the linkages await further functional verification.

Salvianolic Acid B Attenuates Hypertrophic Scar Formation In Vivo and In Vitro.

BACKGROUND: Hypertrophic scars (HTSs) are a fibroproliferative disorder that occur following skin injuries. Salvianolic acid B (Sal-B) is an extractant from Salvia miltiorrhiza that has been reported to ameliorate fibrosis in multiple organs. However, the antifibrotic effect on HTSs remains unclear. This study aimed to determine the antifibrotic effect of Sal-B in vitro and in vivo. METHODS: In vitro, hypertrophic scar-derived fibroblasts (HSFs) were isolated from human HTSs and cultured. HSFs were treated with (0, 10, 50, 100 µmol/L) Sal-B. Cell proliferation and migration were evaluated by EdU, wound healing, and transwell assays. The protein and mRNA levels of TGFßI, Smad2, Smad3, α-SMA, COL1, and COL3 were detected by Western blots and real-time PCR. In vivo, tension stretching devices were fixed on incisions for HTS formation. The induced scars were treated with 100 µL of Sal-B/PBS per day according to the concentration of the group and followed up for 7 or 14 days. The scar condition, collagen deposition, and α-SMA expression were analyzed by gross visual examination, H&E, Masson, picrosirius red staining, and immunofluorescence. RESULTS: In vitro, Sal-B inhibited HSF proliferation, migration, and downregulated the expression of TGFßI, Smad2, Smad3, α-SMA, COL1, and COL3 in HSFs. In vivo, 50 and 100 µmol/L Sal-B significantly reduced scar size in gross and cross-sectional observations, with decreased α-SMA expression and collagen deposition in the tension-induced HTS model. CONCLUSIONS: Our study demonstrated that Sal-B inhibits HSFs proliferation, migration, fibrotic marker expression and attenuates HTS formation in a tension-induced HTS model in vivo. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of boiling on texture of scallop adductor muscles and its mechanism based on label-free quantitative proteomic technique.

The mechanism behind textural changes in scallop adductor muscle during boiling was investigated through proteomic analysis, determination of water holding capacity (WHC) and oxidative indices, as well as observation with scanning electron microscopy and multiphoton nonlinear optical microscopy. The hardness and shear force showed the trend of first rising and then falling in 45 min-boiling time. The results suggested that short-time boiling caused the oxidation, denaturation and aggregation of proteins, resulting in the transverse contraction of myofibers and lateral cross-linked aggregation of muscle fibers and a rise in WHC, which led to the increase in hardness and shear force. While long-time boiling caused the progressive degradation of structural proteins such as fibrillin-1, collagen alpha-2(I) chain, myosin heavy chain, basement membrane-specific heparan sulfate proteoglycan core protein, and paramyosin, resulting in a loose myofibril network and the decrease in WHC, which led to the decrease in hardness and shear force.

Analysis of texture properties and water-soluble fraction proteome of sea cucumber body wall with different boiling heating treatment.

Label-free quantitative proteomic analysis was utilized to determine the key proteins that affect texture properties of sea cucumber body wall (SCBW) with different boiling heating treatment. 862, 363, 315, and 258 proteins were confirmed in water-soluble fractions from fresh group, 0.5 h-, 2 h- and 4 h-heat treatment group, respectively. During boiling heating treatment, proteins with an increased abundance in water-soluble fraction primarily belong to structural proteins, such as collagens, microfibril-associated proteins, glycoproteins, and muscle proteins. It was speculated that the degradation of these structural proteins caused the progressive disintegration of network skeleton of collagen fibres and FMs as well as the gelatinization, thus resulted in the decrease of hardness and shear force. Besides, the degradation of FMs was occurred layer by layer during boiling heating treatment, and the fibrilin-1 outer layer degraded first, followed by the fibrilin-2 core component.

Salvianolic Acid B Reduces the Inflammation of Fat Grafts by Inhibiting the NF-Kb Signalling Pathway in Macrophages.

BACKGROUND: Autologous fat grafting is a common method for soft tissue defect repair. However, the high absorption rate of transplanted fat is currently a bottleneck in the process. Excessive inflammation is one of the main reasons for poor fat transplantation. Salvianolic acid B (Sal-B) is a herbal medicine that shows promise for improving the effectiveness of fat transplantation. OBJECTIVE: The aim of this study was to improve fat graft survival by injecting Sal-B into fat grafts locally. METHODS: In vivo, 0.2 mL of Coleman fat was transplanted into nude mice along with Sal-B. The grafts were evaluated by histologic analysis at 2, 4, and 12 weeks posttransplantation and by microcomputed tomography at 4 weeks posttransplantation. In vitro ribonucleic acid sequencing, cell proliferation assays, anti-inflammatory activity assays, molecular docking studies, and kinase activity assays were performed in RAW264.7 cells to detect the potential mechanism. RESULTS: Sal-B significantly improved fat graft survival and attenuated adipose tissue fibrosis and inflammation. Sal-B also inhibited the polarization of M1 macrophages in fat grafts. In vitro, Sal-B inhibited the proliferation and activation of inflammatory pathways in RAW264.7 cells. In addition, Sal-B had an inhibitory effect on NF-κB (nuclear factor κ light polypeptide gene enhancer in B cells) signaling. This bioactivity of Sal-B may result from its selective binding to the kinase domain of the inhibitor of NF-κB kinase subunit ß. CONCLUSIONS: Sal-B could serve as a promising agent for improving the effect of fat transplantation by inhibiting the polarization of M1 macrophages through NF-κB signaling.

Differences in texture and digestive properties of different parts in boiled abalone muscles.

Differences in texture and digestive properties of different parts in 80 °C-boiled abalone muscle (adductor and transition part) after different processing time were investigated. With the extension of boiling time, the shear force and hardness of adductor increased first (6 min) and then decreased (30 min and 240 min), while the two indexes of transition part dramatically decreased after boiling for 6 min and then maintained until 240 min. Meanwhile, for adductor, the degree of protein hydrolysis, protein digestibility, and peptide transport levels declined with the extension of boiling time; While for transition part, those protein digestion and transport indexes significantly decreased first (6 min and 30 min) and then increased (240 min). By contrast, the adductor contained higher myofibrillar proteins content but lower collagen content than the transition part, which contributed to the differences in texture and digestive properties of the boiled samples.

Studying on effects of boiling on texture, microstructure and physiochemical properties of sea cucumber body wall and its mechanism using second harmonic generation (SHG) microscopy.

The structural foundation of texture changes in sea cucumber body wall (SCBW) during boiling was investigated using second harmonic generation (SHG) microscopy for the first time. The results from SHG signal imaging, light microscopy, scanning electron microscopy and transmission electron microscopy indicated the hierarchical structures of collagen in SCBW underwent progressive destruction with the prolongation of boiling time, including the depolymerization of collagen fibres, the uncoiling and disaggregation of collagen fibrils, the destruction of collagen microfibrils, the loosing of triple helix structure of collagen, and the degradation and gelatinization of collagen, which contributed to the progressive decline in texture indicators including shear force and hardness. SHG analysis also indicated that although collagen macromolecules such as collagen fibres, collagen fibrils and collagen microfibrils could be observed in 0.5 h-boiled and 2 h-boiled SCBW, monomeric collagen, the basic structural components of those macromolecules, has been already damaged.

Demand and influencing factors of non-occupational post-exposure prophylaxis for AIDS among men who have sex with men in Wuhan / 中国热带医学

@#Abstract: Objective　To investigate the drug demand and related influencing factors of AIDS non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM) in Wuhan, and to provide a scientific basis for the development of subsequent intervention policies for MSM. Methods　With the assistance of social organizations in Wuhan, MSM was recruited by the snowball method to carry out an online questionnaire survey to collect information on demographics, AIDS-related knowledge, high-risk behaviors, and the need for nPEP medication. The χ2 test and unconditional Logistic regression were used to analyze the related factors of the demand for nPEP medication. Results　A total of 308 valid subjects were included in this study, with predominantly 18-29 years old (78.57%, 242/308). The self-reported sexual orientation was mainly homosexuality (82.47%, 254/308), and the awareness rate of AIDS knowledge was high (89.29%, 275/308). Among the survey respondents, 35.06% (108/308) did not know the situation of HIV infection among MSM population in Wuhan; 55.19% (170/308) had two or more same-sex sexual partners in the last six months; 90.91% (280/308) had heard of nPEP before participating in this survey. After passing nPEP and informing the protective effect of nPEP, 59.42% (183/308) of them needed nPEP. After HIV exposure, 73.38% (226/308) were willing to spend money to buy nPEP drugs, and 88.64% (273/308) were willing to take nPEP drugs because of the known side effects. Logistic regression analysis showed that in the last six months, the needs for taking nPEP medication in those who had 2 or more same-sex sexual partners (OR=2.121, 95%CI: 1.329-3.386) and who had received peer education (OR=1.740, 95%CI: 1.088-2.781) were higher than those of those who had a same-sex sexual partner in the last six months and who had not received peer education. Conclusions　The MSM population in Wuhan has a great demand for nPEP drugs, and peer education is an important way to carry out nPEP publicity and promotion. At the same time, we should continue to strengthen warning publicity and education and behavioral intervention to reduce MSM risky sexual behaviors and reduce new HIV infections.