BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction.

BACKGROUND: Cholestatic liver fibrosis (CLF) is caused by inflammatory destruction of the intrahepatic bile duct and abnormal proliferation of the small bile duct after cholestasis. Activation of the Notch signaling pathway is required for hepatic stem cells to differentiate into cholangiocytes during the pathogenesis of CLF. Our previous research found that the expression of the Numb protein, a negative regulator of Notch signaling, was significantly reduced in the livers of patients with primary biliary cholangitis and CLF rats. However, the relationship between the Numb gene and CLF is largely unclear. In this study, we investigated the role of the Numb gene in the treatment of bile duct ligation (BDL)-induced CLF. METHODS: In vivo, bone marrow-derived mesenchymal stem cells (BM-MSCs) with Numb gene overexpression or knockdown obtained using lentivirus transfection were transplanted into the livers of rats with BDL-induced CLF. The effects of the Numb gene on stem cell differentiation and CLF were evaluated by performing histology, tests of liver function, and measurements of liver hydroxyproline, cytokine gene and protein levels. In vitro, the Numb gene was overexpressed or knocked down in the WB-F344 cell line by lentivirus transfection, Then, cells were subjected immunofluorescence staining and the detection of mRNA levels of related factors, which provided further evidence supporting the results from in vivo experiments. RESULTS: BM-MSCs overexpressing the Numb gene differentiated into hepatocytes, thereby inhibiting CLF progression. Conversely, BM-MSCs with Numb knockdown differentiated into biliary epithelial cells (BECs), thereby promoting the ductular reaction (DR) and the progression of CLF. In addition, we confirmed that knockdown of Numb in sodium butyrate-treated WB-F344 cells aggravated WB-F344 cell differentiation into BECs, while overexpression of Numb inhibited this process. CONCLUSIONS: The transplantation of BM-MSCs overexpressing Numb may be a useful new treatment strategy for CLF.

Eugenol eliminates carbapenem-resistant Klebsiella pneumoniae via reactive oxygen species mechanism.

Multidrug-resistant (MDR) bacterial infections have gained increasing attention due to the high incidence rates and high mortality, especially for the carbapenem-resistant Klebsiella pneumoniae (CRKP) infection that can cause severe complications (e.g., pneumonia and sepsis) in multiple organs. Therefore, the development of new antibacterial agents against CRKP is imperative. Inspired by natural plant antibacterial agents with broad-spectrum antibacterial properties, the antibacterial/biofilm activity of eugenol (EG) on CRKP and their underlying mechanisms are investigated in our work. It is found that EG exhibits remarkable inhibitory effects on planktonic CRKP in a dose-dependent fashion. Meanwhile, the destruction of membrane integrity induced by the formation of reactive oxygen species (ROS) and glutathione reduction results in the leakage of bacterial cytoplasmic components, including DNA, ß-galactosidase, and protein. Moreover, when EG contacts with bacterial biofilm, the whole thickness of the dense biofilm matrix decreases, and the integrity is destroyed. Overall, this work verified that EG could eliminate CRKP via ROS-induced membrane rupture, which offers vital evidence to explain the antibacterial ability of EG against CRKP.

Root-shaped antibacterial alginate sponges with enhanced hemostasis and osteogenesis for the prevention of dry socket.

Tooth extraction commonly causes uncontrolled bleeding, loss of blood clots, and bacterial infection, leading to the dry socket and bone resorption. Thus, it is highly attractive to design a bio-multifunctional scaffold with outstanding antimicrobial, hemostatic, and osteogenic performances for avoiding dry sockets in clinical applications. Herein, alginate (AG)/quaternized chitosan (Qch)/diatomite (Di) sponges were fabricated via electrostatic interaction, Ca2+ cross-linking, as well as lyophilization methods. The composite sponges are facilely made into the shape of the tooth root, which could be well integrated into the alveolar fossa. The sponge shows a highly interconnected and hierarchical porous structure at the macro/micro/nano levels. The prepared sponges also possess enhanced hemostatic and antibacterial abilities. Moreover, in vitro cellular assessment indicates that the developed sponges have favorable cytocompatibility and significantly facilitate osteogenesis by upregulating the formation of alkaline phosphatase and calcium nodules. The designed bio-multifunctional sponges display great potential for trauma treatment after tooth extraction.

Isorhynchophylline inhibits inflammatory responses in endothelial cells and macrophages through the NF-κB/NLRP3 signaling pathway.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease of arterial wall, which is closely related to inflammatory reaction. In this study, the anti-inflammatory effect of isorhynchophylline was studied by NF- κB / NLRP3 pathway. METHODS: (1) ApoE-/- mice were fed with high-fat diet to establish atherosclerotic model, while C57 with the same genetic background was fed with common diet as control group. Body weight was recorded and blood lipids were detected. The expression of NLRP3, NF-κB, IL-18 and Caspase-1 in aorta was detected by Western-Blot and PCR, and plaque formation was detected by HE and oil red O staining. (2) Lipopolysaccharide interfered with Human Umbilical Vein Endothelial Cells (HUVECs) and RAW264.7 to form inflammatory model, and was treated with isorhynchophylline. The expression of NLRP3, NF-κB, IL-18 and Caspase-1 in aorta was detected by Western-Blot and PCR, and the ability of cell migration was detected by Transwell and scratch test. RESULTS: (1) the expression of NLRP3, NF- κB, IL-18 and Caspase-1 in aorta of model group was higher than that of control group, and plaque formation was obvious. (2) the expressions of NLRP3, NF- κB, IL-18 and Caspase-1 in HUVECs and RAW264.7 model groups were higher than those in control group, while isorhynchophylline decreased their expression and enhanced cell migration ability. CONCLUSION: Isorhynchophylline can reduce the inflammatory reaction induced by lipopolysaccharide and promote the ability of cell migration.

[Preparation of chitosan hydrochloride stabilized emulsion and its immunostimulatory effect].

In order to increase the ability of oil-emulsion adjuvant to stimulate cellular immunity, chitosan hydrochloride with positive charge was selected to stabilize oil-in-water emulsion (CHE). In this paper, model antigen ovalbumin was selected to prepare vaccines with emulsion adjuvant, commercial adjuvant or no adjuvant. The emulsion was characterized by measuring the particle size, electric potential and antigen adsorption rate. BALB/c mice were immunized by intramuscular injection. Serum antibody levels, the numbers of IL-4-secreting cells in splenocytes, cytotoxic T lymphocyte (CTL) response, and the expression of central memory T cells were measured to evaluate the immunostimulatory effect. The results showed that chitosan hydrochloride can effectively stabilize the emulsion. The emulsion size is about 600 nm, and the antigen adsorption rate is more than 90%. After immunization, CHE could increase serum antibodies levels and increase IL-4 secretion. Expression of CTL surface activation molecules was also increased to stimulate CTL response further and to increase the CD44+CD62L+ in T cells proportion. CHE as adjuvant can stimulate humoral and cellular immunity more efficiently, and is expected to extend the duration of protection.

Distributed receiving system with local digitization and combination for SNR enhancement.

We demonstrate an X-band distributed receiving system with 4 remote ends for signal-to-noise ratio (SNR) enhancement. The X-band analog signal received by 4 remote ends is first transmitted to the local end through optical fiber links and is then down-converted with a photonic method for digitization and further coherent combination. Finally, a combined signal with a higher SNR can be obtained. In the proposed system, a frequency-tunable single-tone signal is stably transmitted to the remote end for both down-converting the received signal and for generating a dithered sample clock to eliminate the transmission delay jitter with an unlimited compensation range. Experimentally, X-band binary phase shift keying signals are used for system performance evaluation. After 20 to 25 km transmission, the relative timing drifts between different links are at the order of picoseconds, and a near-theoretical SNR enhancement is achieved. The proposed scheme has a simple remote structure with no need for time synchronization, increasing its signal combining precision, flexibility, and scalability, making it an ideal candidate for long-distance weak signal detection.

Organosulfur Materials for Rechargeable Batteries: Structure, Mechanism, and Application.

Lithium-ion batteries have received significant attention over the last decades due to the wide application of portable electronics and increasing deployment of electric vehicles. In order to further enhance the performance of the batteries and overcome the capacity limitations of inorganic electrode materials, it is imperative to explore new cathode and functional materials for rechargeable lithium batteries. Organosulfur materials containing sulfur-sulfur bonds as a kind of promising organic electrode materials have the advantages of high capacities, abundant resources, tunable structures, and environmental benignity. In addition, organosulfur materials have been widely used in almost every aspect of rechargeable batteries because of their multiple functionalities. This review aims to provide a comprehensive overview on the development of organosulfur materials including the synthesis and application as cathode materials, electrolyte additives, electrolytes, binders, active materials in lithium redox flow batteries, and other metal battery systems. We also give an in-depth analysis of structure-property-performance relationship of organosulfur materials, and guidance for the future development of organosulfur materials for next generation rechargeable lithium batteries and beyond.

Elderly people's preferences for healthcare facilities in Shanghai: gender features and influencing factor analysis.

BACKGROUND: China has one of the fastest paces of the growing aging population, High-level policymakers have recently recognized the aging population presents significant challenges to the Chinese healthcare system. In this context, the healthcare-seeking behaviors of the elderly population have become an essential field of study. It is necessary to understand their access to health services and to improve their quality of life, as well as to help policymakers to formulate healthcare policy. The study empirically investigates the factors influencing the elderly population's healthcare-seeking behaviors in Shanghai, China, especially in choosing the quality of healthcare facilities to visit. METHODS: We designed a cross-sectional study. The data of this study were derived from the "Shanghai elderly medical demand characteristics questionnaire" in the middle of November to early December 2017. A total of 625 individuals were included in the final sample. Logistic regression was adopted to investigate the differences in healthcare-seeking behaviors between elderly people when suffer from mild illness, severe illness and follow-up treatment. Next, the differences in gender were also discussed. RESULTS: Factors affecting the healthcare-seeking behaviors of the elderly differ in mild illness and severe illness situations. For mild illness, demographic factors (gender and age) and socioeconomic factors (income and employment) play an important role in elderly healthcare choices. Female and older elderlies are more likely to choose local, lower-quality facilities, whereas those with high income and private employment are more likely to choose higher-quality facilities. For severe illness, socioeconomic factors (income and employment) are important. Furthermore, individuals with basic medical insurance are more likely to choose lower-quality facilities. CONCLUSION: This study has shown that the affordability of public health services should be addressed. Medical policy support may be an important way to reduce the gap in access to medical services. We should pay attention to the gender differences in the elderly's choice of medical treatment behavior, consider the differences in the needs of male and female elderly. our findings are only for elderly Chinese participants in the greater Shanghai area.

Reservoir flood regulation affects nutrient transport through altering water and sediment conditions.

The effect of reservoir construction on nutrient dynamics is well recognized, at flood event-scale influence of reservoir flood regulation on nutrient transport however has received less attention. Taking the Three Gorges Reservoir (TGR) in the Changjiang River as an example, during the TGR's regulation on a flood in Sep., 2021, this study collected water samples along the mainstream of the reservoir as well as pre/post-dam, with the aim to identify the impact of flood regulation on nutrient (nitrogen and phosphorus) distribution and transportation. Results show that nitrate nitrogen (NO3N) and particulate phosphorus (PP) were the main fraction of the total nitrogen (TN) and total phosphorus (TP) with the proportion of 46.5%-95.6% and 57.4%-81.6%, respectively. N and P responded different to flood regulation: (i) along the stream P concentration significantly decreased due to PP deposited with sediment while N concentration barely changed during flood regulation; (ii) P concentration was significantly higher at post-dam section than at pre-dam section, while N concentration maintained the same. The diffed response to flood regulation caused TN/TP ratio increased from 4 to 8 in the reservoir tail to over 20 near the dam, which probably arise eutrophication in the reservoir head area. This study reveals the influence of flood regulation on nutrient transport in flood event and provides scientific basis for reservoir management.

Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity.

Sex is known to be an important factor in the incidence, progression, and outcome of cancer. A better understanding of the underlying mechanisms could help improve cancer prevention and treatment. Here, we demonstrated a crucial role of antitumor immunity in the sex differences in cancer. Consistent with observations in human cancers, male mice showed accelerated tumor progression compared with females, but these differences were not observed in immunodeficient mice. Androgen signaling suppressed T-cell immunity against cancer in males. Mechanistically, androgen-activated androgen receptor upregulated expression of USP18, which inhibited TAK1 phosphorylation and the subsequent activation of NF-κB in antitumor T cells. Reduction of testosterone synthesis by surgical castration or using the small-molecular inhibitor abiraterone significantly enhanced the antitumor activity of T cells in male mice and improved the efficacy of anti-PD-1 immunotherapy. Together, this study revealed a novel mechanism contributing to sex differences in cancer. These results indicate that inhibition of androgen signaling is a promising approach to improve the efficacy of immunotherapy in males. SIGNIFICANCE: Androgen signaling induces immunosuppression in cancer by blocking T-cell activity through upregulation of USP18 and subsequent inhibition of NF-κB activity, providing a targetable axis to improve antitumor immunity in males.

Application of a Dual-Probe Coloading Nanodetection System in the Process Monitoring and Efficacy Assessment of Photodynamic Therapy: An In Vitro Study.

The oxygen-consuming property of photodynamic therapy (PDT) affects its effects and aggravates tumor hypoxia, thus upregulating the vascular endothelial growth factor (VEGF) to exacerbate tumor metastasis and lead to treatment failure. Therefore, it is necessary to monitor the dynamic changes in the factors related to PDT and tumor development trends in real time, thus helping to improve PDT efficiency. This study fabricated a fluorescent probe, TPE-2HPro, and a fluorescein-labeled aptamer probe, FAM-AptamerVEGF, to detect hydrogen peroxide (H2O2) and VEGF through the photoinduced electron-transfer effect and the specific affinity of the aptamer to VEGF, respectively. The two probes were loaded into the inner pores and absorbed on the surface of polydopamine coating-wrapped mesoporous silica nanoparticles (MSN@PDA) to construct the dual-probe-loaded system, MSNTH@PDAApt, which was kept stable in fetal bovine serum (FBS) solution and achieved pH-responsive release behavior, thus helping to increase the accumulation of the two probes in tumor cells. The dichloroacetic acid-mediated in vitro antitumor tests showed that the changing trends of H2O2 and VEGF levels were consistent with the results of related mechanism studies and could be monitored by MSNTH@PDAApt. The in vitro chlorin e6 (Ce6)-mediated PDT treatment demonstrated that when the illumination condition was 650 nm, 50 mW/cm2 for 10 min, cells were more inclined to metastasis and invasion rather than death due to a substantial increase in VEGF expression at the low Ce6 concentrations. With the increase of the Ce6 concentration, the growth of the H2O2 level gradually exceeded that of VEGF, and the reactive oxygen species (ROS)-mediated cell death dominated when the Ce6 concentration was about 2 times its IC50 values. Besides, hypoxia also affected the H2O2 and VEGF changes. These results demonstrated that MSNTH@PDAApt could precisely monitor and assess the tumor development trends during PDT treatment, thus helping improve the treatment effect.

Mucoadhesive Nanoparticles Enhance the Therapeutic Effect of Dexamethasone on Experimental Ulcerative Colitis by the Local Administration as an Enema.

Background: As the first-line drug to treat ulcerative colitis (UC), long-term use of glucocorticoids (GCs) produces severe toxic and side effects. Local administration as enema can increase the local GCs concentrations and reduce systemic exposure to high oral doses by directly delivering GCs to the inflammation site in the distal colorectum. However, UC patients are often accompanied by diarrhea, leading to the short colonic residence time of GCs and failure to exert their function fully. Purpose: A kind of mucoadhesive nanoparticles (NPs) loading different dexamethasone derivatives (DDs) were developed, which could attach to the positively charged inflammatory colonic mucosa through electrostatic adsorption after administered by enema, thereby improving the local concentration and achieving effective targeted therapy for UC. Methods: Two DDs, dexamethasone hemisuccinate and dexamethasone phosphate, were synthesized. In NPs preparation, The core PEI-DDs NPs were built by the electrostatic adsorption of DDs and the cationic polymer polyethyleneimine (PEI). Then, the natural polyanionic polysaccharide sodium alginate (SA) was electronically coated around NPs to construct the final SA-PEI-DDs NPs, followed by the in vitro stability and release tests, in vitro and in vivo colonic mucosal adhesion tests. In the in vivo anti-UC test, the experimental colitis mice were induced by 2,4,6-trinitrobenzenesulfonic acid. The body weight and disease activity index changes were measured, and the myeloperoxidase activity, pro-inflammatory cytokines concentration, and hematoxylin and eosin staining were also investigated to evaluate the therapeutic effect of NPs. Results: The structures of two DDs were demonstrated by 1H-NMR and MS. Both NPs were negatively charged and achieved high loading efficiency of DDs, while their particle sizes were significantly different. NPs showed good stability and sustained release properties in the simulated colonic environment. Moreover, the negative charge on the of NPs surface made them easier to adhere to the positively charged inflammatory colonic mucosa, thereby enhancing the enrichment and retention of DDS in the colitis site. Furthermore, the NPs exhibited better therapeutic effects than free Dex on the experimental colitis mice induced by TNBS through the enema rectal. Conclusion: These results indicated the mucoadhesive NPs as a kind of novel nano-enema showed great potential to achieve efficient treatment on UC.

In vitro study on nonthermal argon atmospheric plasma improving the bonding interface between dentin and self-etch adhesive / 口腔疾病防治

Objective@#To study the effect of nonthermal argon atmospheric pressure plasma (NTAPP) treatment on the bonding strength between dentine and self-etch adhesive and the wettability of dentine surfaces under different treatment times.@*Methods@#The plasma jet was operated at an input power of 9 W. Argon was used as the operating gas at a flow rate of 5 L/min. The dentin surface was exposed to the plasma jet (n=6) for various times (0, 5, 10, 15, 20 s). After a one-step self-etch adhesive (S3 Bond) was applied to the treated dentine surface, microtensile bonding specimens were made, and the microtensile bonding strength was tested. Then, the dentine surface contact angles were measured after NTAPP treatment for 5, 10, 15, and 20 s with the same gas flow rate and input power described above. @*Results@#Along with the NTAPP treatment time, the dentin immediate bonding strength was significantly increased. The 15 s group showed significantly elevated bonding strength (31.82±2.80 MPa) in contrast to the other groups. The contact angles of each experimental group significantly decreased compared with the contact angles of the negative control group (75.57°±1.45°). The contact angles decreased the most to 33.56°±2.14° with NTAPP treatment for 15 s, and its wettability was the highest.@*Conclusion @#NTAPP treatment can significantly increase the wettability of the dentin surface and improve the adhesive strength of the adhesive interface with self-etching adhesive, which is also related to the treatment time.

Inclusion Complexation of S-Nitrosoglutathione for Sustained Nitric Oxide Release from Catheter Surfaces: A Strategy to Prevent and Treat Device-Associated Infections.

S-Nitrosoglutathione (GSNO) is a nontoxic nitric oxide (NO)-donating compound that occurs naturally in the human body. The use of GSNO to deliver exogenous NO for therapeutic and protective applications is limited by the high lability of dissolved GSNO in aqueous formulations. In this paper, we report a host-guest chemistry-based strategy to modulate the GSNO reactivity and NO release kinetics for the design of anti-infective catheters and hydrogels. Cyclodextrins (CDs) are host molecules that are typically used to encapsulate hydrophobic guest molecules into their hydrophobic cavities. However, we found that CDs form inclusion complexes with GSNO, an extremely hydrophilic molecule with a solubility of over 1 M at physiological pH. More interestingly, the host-guest complexation reduces the decomposition reactivity of GSNO in the order of αCD > γCD > hydroxypropyl ßCD. The lifetime of 0.1 M GSNO is increased to up to 15 days in the presence of CDs at 37 °C, which is more than twice the lifetime of free GSNO. Quantum chemistry calculations indicate that GSNO in αCD undergoes a conformational change that significantly reduces the S-NO bond distance and increases its stability. The calculated S-NO bond dissociation enthalpies of free and complexed GSNO well agree with the experimentally observed GSNO decomposition kinetics. The NO release from GSNO-CD solutions, compared to GSNO solutions, has suppressed initial bursts and extended durations, enhancing the safety and efficacy of NO-based therapies and device protections. In an example application as an anti-infective lock solution for intravascular catheters, the GSNO-αCD solution exhibits potent antibacterial activities for both planktonic and biofilm bacteria, both intraluminal and extraluminal environments, both prevention and treatment of infections, and against multiple bacterial strains, including a multidrug-resistant strain. In addition to solutions, the inclusion complexation also enables the preparation of GSNO hydrogels with enhanced stability and improved antibacterial efficacy. Since methods to suppress and control the GSNO decomposition rate are rare, this supramolecular strategy provides new opportunities for the formulation and application of this natural NO donor.

Isorhynchophylline Regulates the Circadian Rhythm of the Hypothalamus in Spontaneously Hypertensive Rats to Treat Hypertension.

BACKGROUND: The neurotransmitter metabolism in spontaneously hypertensive rats (SHR) is disordered, and these disturbances in neurotransmitter levels can further exacerbate the development of hypertension. Neurotransmitters can affect the expression of circadian clock genes. OBJECTIVE: To clarify the time-dependent internal mechanism of the imbalance of the target neurotransmitter metabolic rhythm of spontaneously hypertensive rats, the circadian research was carried out by the method of targeted metabolomics and molecular biology technology. METHODS: We have explored the mechanism of isorhynchophylline regulating the circadian rhythm through the ERK signaling pathway and thus treating hypertension by detecting the changes of central hypothalamic biological clock rhythm genes after isorhynchophylline intervention, from hypothalamic neurotransmitter rhythmicity. RESULTS: The expression of rhythm genes in normal rats showed a certain rhythm at 6 time points, while the expression of rhythm genes in model rats decreased, and the gene rhythm returned to normal after isorhynchophylline treatment. Cosine analysis of 12 neurotransmitters in hypothalamus showed that there were 6 rhythmic neurotransmitters in the normal group, while in the model group, 4 of the 6 neurotransmitters lost their rhythmicity, and the rhythmicity returned to normal after isorhynchophylline intervention. Compared with the normal group, the expression of ERK protein in the model group increased significantly and decreased after isorhynchophylline treatment. CONCLUSION: The mechanism of isorhynchophylline treating hypertension is not only the regulation of serum neurotransmitters rhythm, but also acting on rhythm genes in the feedback loop of the central biological clock.

Comparison of the Effects of Acute Appendicitis and Chronic Cholecystitis on Intestinal Mucosal Function During Surgery.

OBJECTIVE: The objective of this study is to explore the effect of acute appendicitis and chronic cholecystitis on inflammatory factors and intestinal mucosal function during operation. METHODS: This was a prospective cohort study. Forty-four patients including those who underwent elective cholecystectomy (Group A, n = 22) or emergency appendectomy (Group B, n = 22) were recruited. Before anesthesia and after surgery, arterial blood was collected for the measurement of plasma indices associated with inflammation or intestinal permeability. RESULTS:  Both the tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) levels were higher in Group B than in Group A (P < 0.05). The preoperative IL-10 level was higher in Group A than in Group B (P = 0.036), while after surgery, the opposite relationship was observed (P = 0.020). There were no intergroup or intragroup differences for D-Lac. The postoperative lipopolysaccharide (LPS) and human syndecan-1 (Sdc-1) levels were lower than the corresponding preoperative value (P < 0.05) in the two groups. Both the preoperative Sdc-1 and fatty acid binding protein (FABP2) levels in Group A were higher than the corresponding levels in Group B (P < 0.05). CONCLUSIONS: The study suggested that chronic cholecystitis had more severe damage to intestinal mucosal function than acute appendicitis. It is necessary to strengthen the protection of intestinal mucosa during the perioperative period.

Sexually Dimorphic Gene Expression in X and Y Sperms Instructs Sexual Dimorphism of Embryonic Genome Activation in Yellow Catfish (Pelteobagrus fulvidraco).

Paternal factors play an important role in embryonic morphogenesis and contribute to sexual dimorphism in development. To assess the effect of paternal DNA on sexual dimorphism of embryonic genome activation, we compared X and Y sperm and different sexes of embryos before sex determination. Through transcriptome sequencing (RNA-seq) and whole-genome bisulfite sequencing (WGBS) of X and Y sperm, we found a big proportion of upregulated genes in Y sperm, supported by the observation that genome-wide DNA methylation level is slightly lower than in X sperm. Cytokine-cytokine receptor interaction, TGF-beta, and toll-like receptor pathways play important roles in spermatogenesis. Through whole-genome re-sequencing (WGRS) of parental fish and RNA-seq of five early embryonic stages, we found the low-blastocyst time point is a key to maternal transcriptome degradation and zygotic genome activation. Generally, sexual differences emerged from the bud stage. Moreover, through integrated analysis of paternal SNPs and gene expression, we evaluated the influence of paternal inheritance on sexual dimorphism of genome activation. Besides, we screened out gata6 and ddx5 as potential instructors for early sex determination and gonad development in yellow catfish. This work is meaningful for revealing the molecular mechanisms of sex determination and sexual dimorphism of fish species.

Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration.

BACKGROUND: Icariin (ICA), a main active ingredient of Herba Epimedium, could promote bone formation, inhibit bone resorption and alleviate inflammatory responses. The aim of this study was to investigate the effect of ICA on the inhibition of bacteria associated with peri-implantitis, and fabricate a calcium phosphate cement (CPC) with ICA-loaded gelatin microspheres (GMs) as a local drug delivery system efficiently promoting bone formation and alleviating inflammation. RESULTS: In this study, ICA exhibited antibacterial activity against P. gingivalis with a MIC value of 1 × 10-4 mol/L. When the concentration of ICA was 0.5 mM, the encapsulation efficiency of GMs reached the maximum value of 76.26 ± 3.97%. GMs with ICA revealed a controlled release profile, 0.5 mM ICA exhibited a higher ICA release profile than the other groups during a 21 d monitoring span. The results of SEM and XRD demonstrated successful fabrication of a calcium phosphate cement with ICA-loaded GMs. ICA released from CPC/GMs (ICA) was slower than ICA released from GMs within 10 days. CPC/GMs (ICA) exhibited antibacterial activity against P. gingivalis, but the antibacterial rate of CPC/GMs (ICA) was only 17.15 ± 6.06%. In addition, CPC/GMs (ICA) promoted the proliferation of BMSCs and significantly stimulated the differentiation and maturation of BMSCs. In vivo, H&E and Masson staining experiments demonstrated that CPC/GMs (ICA) exhibited better capacity for bone regeneration than CPC/GMs and CPC, and the expression of TNF-α and IL-1ß in the tissue around CPC/GMs (ICA) was significantly lower than CPC/GMs and CPC in IHC staining (P < 0.05). CONCLUSION: In this study, ICA exhibited limited antibacterial activity against bacteria associated with peri-implantitis. A composite material of calcium phosphate cement with ICA-loaded gelatin microspheres was developed, which not only promoting osteoinductivity and bone formation, but also alleviating inflammation, demonstrating its potential as a promising bone substitute material for treatment of peri-implantitis.

Design and fabrication of a focus-tunable liquid cylindrical lens based on electrowetting.

In this study, a focus-tunable liquid cylindrical lens based on electrowetting was designed and fabricated. The cylindrical cavity usually used in common electrowetting zoom spherical lenses was replaced by a 20 mm × 10 mm × 8 mm cuboid cavity, in which the interface of two liquids formed a toroid owing to the electrowetting effect. The proposed liquid cylindrical lens can serve as either a converging or diverging lens with the response time under 110 ms by changing the supplied voltage. The zoom lens we fabricated worked stably under 0-110 V voltage for a long time, guaranteeing that the focal length of the liquid cylindrical lens can range within (-∞, -148.36 mm) ∪ (697.21 mm, +∞). By combining the liquid lens that we designed with a simple fixed cylindrical lens, a cylindrical lens system with an arbitrary focal length suitable for various tasks in beam manipulation can be realized.

Component Characterization, In Vitro Activities and Molecular Mechanism of Cydonia oblonga Mill. against Diabetic.

Cydonia Oblonga Mill. is widely distributed in Turkey, Uzbekistan and China and commonly used by the food industry to produce jam, jelly and candies. The aim of this study was to investigate the in vitro antidiabetic activity and anti-diabetic mechanism of Cydonia Oblonga Mill. fruit (COMF). The chemical compositions were further characterized in COMF by UPLC-Q-Orbitrap/MS and 65 components including 22 flavonoids, 16 organic acids, 11 polyphenols, 5 amino acids, 3 pentacyclic triterpenoids and 8 other compounds were identified. The antioxidant activity by DPPH scavenging method and α-glucosidase inhibitory activity were tested. Furthermore, we detected the effects of COMF extract on the proliferation activity of HUVECs, cell viability of HUVECs under H2O2-induced oxidative stress, and NO production. Then, molecular docking activity and α-glucosidase inhibitory activity of seven key flavonoid components selected by bioinformatics analysis and literature in the COMF were studied. Among them, quercetin showed potent inhibitory activity, kaempferol, isorhamnetin, luteolin and apigenin demonstrated moderate inhibitory activity, while rutin and epicatechin exhibited poor inhibitory activity. Subsequently, the effects of quercetin, kaempferol, isorhamnetin, leteolin and apigenin on the gene expression levels of AKT1, IL-6 and VEGFA were verified by real-time fluorescence quantification (RT-qPCR). Molecular biology result showed that different active ingredients can significantly recover the levels of AKT1, IL-6 and VEGFA in HUVECs injured by high glucose.