Microneedles containing Cucumaria frondosa polysaccharides and 3-acetylaconitine exert analgesic, anti-inflammatory and chondroprotective activity for knee osteoarthritis.

3-Acetylaconitine (AAC) is a commercially analgesic drug for arthritis, however, due to its narrow safety range, its clinical application is limited. The objective of the study was to investigate the combined effect of Cucumaria frondosa polysaccharide (CFP) and AAC in microneedles on knee osteoarthritis (KOA). The characterization of microneedles was conducted and a rat model of monosodium iodoacetate (MIA)-induced KOA was established to evaluate the anti-inflammatory and analgesic activity in this study. The inhibitory effects on cartilage degradation and synovial inflammation were determined by morphological observation of the knee joint, pathological and imaging results. The von Frey pain threshold and hind limb weight bearing test were used to evaluate the effect of microneedles on pain relief. The results showed that microneedles had the mechanical strength to penetrate the skin and dissolved well in the skin for drug delivery within 30 min after patch administration. Furthermore, AAC-MN and CFP-AAC-MN both played roles in relieving pain, reducing cartilage degeneration and inhibiting synovial inflammation in KOA. In summary, CFP combined with AAC loading into microneedles exhibited higher skin penetration and more advantages in inhibiting cartilage damage and inflammation compared to AAC alone.

A Biodegradable Shape Memory Polyurethane Film as a Postoperative Anti-adhesion Barrier for Minimally Invasive Surgery.

Postoperative adhesions commonly form in various tissues, resulting in serious implications and an increased risk of secondary surgery. The application of anti-adhesion films as physical barriers has proven effective in reducing adhesion incidence and severity. However, existing anti-adhesion films require manual deployment during minimally invasive surgery, posing inconvenience and possibility of further injury. To address these limitations, we have developed an intelligent anti-adhesion film based on shape memory polyurethane. In this work, a linear shape memory polyurethane (ISO2-PU), incorporating hexamethylene isocyanate and isosorbitol as hard segments and poly(D, L-lactic acid) macrodiol as soft segments, was fabricated into an anti-adhesion film. The favorable shape memory effect of the ISO2-PU film ensures its convenient delivery and automatic unfolding, as revealed by a simulation experiment for endoscopic surgical implantation. Furthermore, the glass transition temperature (Tg) close to body temperature endows the ISO2-PU film with good mechanical compliance, thus ensuring a reliable fit with the wounded tissue to avoid undesired folding. Finally, in vivo experiments using a rat cecal abdominal wall injury model demonstrated that the combination of reliable fit, appropriate degradation rate, and good cytocompatibility promises the ISO2-PU film with high anti-adhesion efficacy. This work validates the concept of shape memory anti-adhesion barrier and expands future directions for advanced anti-adhesion biomaterials. STATEMENT OF SIGNIFICANCE: Postoperative adhesions are a common complication that occurs widely after various surgeries. This work developed an intelligent anti-adhesion film based on a linear shape memory polyurethane (ISO2-PU). This film is featured with remarkable shape memory effect and mechanical compliance at body temperature, appropriate degradability, and good cytocompatibility. These merits ensure convenient delivery and smart unfolding of ISO2-PU film during minimally invasive surgery and favorable postoperative anti-adhesion efficacy. The results validate the concept of shape memory anti-adhesion barrier and paves a way for designing next-generation anti-adhesion biomaterials.

Effects of visual neuroplasticity training on visual perception, visual quality, and macular blood flow in patients with strabismus.

PURPOSE: To observe the effects of visual neuroplasticity training on visual perception, visual quality, and macular blood flow in patients with concomitant strabismus postoperatively. METHODS: In total, 108 patients underwent binocular strabismus correction operation, and some patients underwent neuroplasticity training. All patients underwent clinical ophthalmic examination, including measurement of best-corrected visual acuity, spherical equivalent, axis length, optical coherence tomography angiography, optical quality analysis system, and visual perception examinations. RESULTS: A total of 78 patients received neuroplasticity training for 1 month postoperatively, and 30 patients did not receive training. All patients underwent a visual perception examination preoperatively and at 1 day, 1 week, and 1 month postoperatively. Macular blood flow and visual quality were examined preoperatively and at 1 month postoperatively. Postoperative visual perception was better than preoperative visual perception (P < 0.05). After neuroplasticity training, the visual perception of the trained subjects was better than that of the untrained subjects (P < 0.05), and the blood flow in the macular area of the trained patients was lower than that of the untrained subjects (P < 0.05). The visual quality of the untrained subjects was lower than that of the trained patients (P < 0.05). CONCLUSIONS: Visual inspection system could accurately evaluate binocular visual perception in patients with concomitant strabismus. After surgical alignment of the strabismus patient, training can stimulate and integrate the formation of stereovision in a short period of time, maintain the visual quality of patients after surgery, and provide conditions for the formation of binocular visual signals and binocular stereovision, but in the short term, it will lead to the decrease of macular blood vessel density and perfusion density. However, the long-term effects of training have not been proven.

The Pd (II) Reduction Mechanisms in Bacillus megaterium Y-4 Revealed by Proteomic Analysis.

Many studies have been conducted on the microbial reduction of Pd (II) to palladium nanoparticles (Pd-NPs) due to the environmental friendliness, low cost, and the decreased toxicity of Pd (II) ions. In this study, we investigate the reduction mechanism of Pd (II) by Bacillus megaterium Y-4 through proteomics. The data are available via ProteomeXchange with identifier PXD049711. Our results revealed that B. megaterium Y-4 may use the endogenous electron donor (NAD(P)H) generated by nirB, tdh, and fabG and reductase to reduce Pd (II) to Pd-NPs. The expression levels of fabG, tdh, gudB, and rocG that generate NAD(P)H were further increased, and the number of reduced Pd-NPs was further increased with the exogenous electron donor sodium formate. Endogenous electron mediators such as quinones and flavins in B. megaterium Y-4 can further enhance Pd (II) reduction. The findings provided invaluable information regarding the reduction mechanism of Pd (II) by B. megaterium Y-4 at the proteome level.

The effect of different angle kappa on higher-order aberrations after small incision lenticule extraction.

This study aimed to compare higher-order aberrations (HOAs) after small incision lenticule extraction (SMILE) in patients with different angle kappa. This is a retrospective report in which 341 right eyes of 341 patients who were subjected to SMILE, which used coaxially sighted corneal light reflex (CSCLR) as the treatment zone centered, treated by the same experienced surgeon (LHB) for correction of myopia and myopic astigmatism, preoperative and postoperative spherical equivalent (SE), angle kappa, total higher-order aberrations (total HOA), spherical aberration (SA), vertical coma (VC), horizontal coma (HC), oblique trefoil (OT), and horizontal trefoil (HT), were compared. SMILE showed outstanding performance in terms of safety, efficacy, and predictability. In addition, a comparison of preoperative and postoperative HOAs exhibited the difference of total HOA (P < 0.01), SA (P < 0.01), VC (P < 0.01), and HC (P < 0.01), which was statistically significant; however, for OT and HT with the longer follow-up time, the statistical difference gradually decreased. For stratification of angle kappa into groups based on decantation, angle kappa was divided into three major groups: r < 0.1 mm, 0.1 ≤ r < 0.2 mm, and r ≥ 0.2 mm; the changes of SA (F = 4.127, P = 0.021) and OT (F = 3.687, P = 0.031) exhibited significant difference after 1 year of SMILE. We performed a correlation analysis of all preoperative and postoperative parameters, and the results indicated that the preoperative total HOA was negatively correlated with preoperative cylindrical diopter (DC), and postoperative total HOA, SA, and coma were affected by spherical diopter (DS) and SE. Moreover, we also found a significant difference of SA and VC in the early postoperative with preoperative. SA was positively correlated with Y values and r of 1 year after SMILE. All of the analyzed parameters in the three groups, except for the trefoil, gradually increased over time; however, the trefoil could gradually stabilize over time. We also divided angle kappa into four groups by quadrants; the result showed that the effects of higher-order aberrations were markedly different from the various quadrants. Patients with large angle kappa were able to increase VC and SA postoperatively, and higher HOAs were more significant in patients with high myopia. The differences in quadrants exhibited a diversity of HOAs; this could be attributed to the corneal surface reestablishment and the alteration of angle kappa, but the trend was not apparent. Although all patients displayed increased HOAs after SMILE, the potential application of CSCLR as the treatment zone centered still showed excellent safety, efficacy, and predictability.

Advantage effect of Dalbergia pinnata on wound healing and scar formation of burns.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia pinnata, as a natural and ethnic medicine in China, has been used for burns and wounds with a long history, which has the effect of invigorating blood and astringent sores. However, there were no reports on the advantage activity of burns. AIM OF STUDY: The purpose of this study was to screen out the best active extract part of Dalbergia pinnata and investigate its therapeutic effect on wound healing and scar resolution. MATERIALS AND METHODS: Rat burn model was established and the healing effects of extracts from Dalbergia pinnata on burn wounds were evaluated by the percentage of wound contraction and period of epithelialization. Histological observation, immunohistochemistry, immunofluorescence and ELISA were used for the examination of inflammatory factors, TGF-ß1, neovascularization and collagen fibers through the period of epithelialization. In addition, the effect of the optimal extraction site on fibroblast cells was evaluated by cell proliferation and cell migration assays. The extracts of Dalbergia pinnata were analyzed by UPLC-Q/TOF-MS or GC-MS technique. RESULTS: Compared to the model group, there were better wound healing, suppressed inflammatory factors, more neovascularization as well as newly formed collagen in the ethyl acetate extract (EAE) and petroleum ether extract (PEE) treatment groups. The ratio of Collagen I and Collagen III was lower in the EAE and PEE treatment groups, suggesting a potential for reduced scarring. Furthermore, EAE and PEE could repair wounds by up-regulating TGF-ß1 in the early stage of wound repair and down-regulating TGF-ß1 in the late stage. In vitro studies showed that both EAE and PEE were able to promote NIH/3T3 cells proliferation and migration compared with the control group. CONCLUSIONS: In this study, EAE and PEE were found to significantly accelerate wound repair and might have an inhibitory effect on the generation of scars. It was also hypothesized that the mechanism might be related to the regulation of TGF-ß1 secretion. This study provided an experimental basis for the development of topical drugs for the treatment of burns with Dalbergia pinnata.

Polysaccharides from Ostrea rivularis rebuild the balance of gut microbiota to ameliorate non-alcoholic fatty liver disease in ApoE-/- mice.

The purpose of this study was to investigate the preventive effects of polysaccharide from Ostrea rivularis (ORP) on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in mice and the underlying mechanism. The results showed that NAFLD model group mice had significant fatty liver lesions. ORP could significantly reduce TC, TG and LDL level, and increase HDL level in serum of HFD mice. Besides, it could also reduce the contents of serum AST and ALT and alleviate pathological changes of fatty liver disease. ORP could also enhance the intestinal barrier function. 16sRNA analysis showed that ORP could reduce the abundance of Firmicutes and Proteobacteria and the ratio of Firmicutes/ Bacteroidetes at the phylum level. These results suggested that ORP could regulate the composition of gut microbiota in NAFLD mice, enhance intestinal barrier function, reduce intestinal permeability, and finally delay the progress and reduce the occurrence of NAFLD. In brief, ORP is an ideal polysaccharide for prevention and treatment of NAFLD, which can be developed as functional food or candidate drugs.

Synchronous bio-degradation and bio-electricity generation in a Microbial Fuel Cell with aged and fresh leachate from the identical subtropical area.

Seasonal leachate from both sealed and operating landfill in the identical district were employed as the sole substrate in the Microbial Fuel Cell (MFC) to evaluate the power output performance and aqueous organic waste disposal. The electrical performance was characterized to study the power generation, while the Chemical Oxygen Demand (COD) removal ratio and Coulombic Efficiency (CE) were calculated to illustrate the substrate disposal effect. In addition, Scanning Electron Microscope (SEM) on the operated anode was conducted to preliminarily explain the microbial community difference, and the phylogenetic tree constructed on the cultivated microorganism was an insight into the dominant bacteria suitable for leachate degradation. It was found that the MFCs inoculated with seasonal leachate from both sealed and operating landfill could generate electricity successfully. Although the fresh leachate-inoculated MFCs had better electrical output performance (22.7-25.6 W/m3 versus 6.61-7.48 W/m3) and COD removal efficiency (55.8%∼61.7% versus 47.7%∼51.4%), the CEs were only 4.3%∼7.6%, which were lower than the aged leachate inoculated group (5.9%∼11.3%). Based on the SEM images and the phylogenetic tree of the operated anode, the composition impacts on the microbial community and power output performance were verified, which was instructive for the leachate disposal in the MFC.

Engineering a vitamin B12 high-throughput screening system by riboswitch sensor in Sinorhizobium meliloti.

BACKGROUND: As a very important coenzyme in the cell metabolism, Vitamin B12 (cobalamin, VB12) has been widely used in food and medicine fields. The complete biosynthesis of VB12 requires approximately 30 genes, but overexpression of these genes did not result in expected increase of VB12 production. High-yield VB12-producing strains are usually obtained by mutagenesis treatments, thus developing an efficient screening approach is urgently needed. RESULT: By the help of engineered strains with varied capacities of VB12 production, a riboswitch library was constructed and screened, and the btuB element from Salmonella typhimurium was identified as the best regulatory device. A flow cytometry high-throughput screening system was developed based on the btuB riboswitch with high efficiency to identify positive mutants. Mutation of Sinorhizobium meliloti (S. meliloti) was optimized using the novel mutation technique of atmospheric and room temperature plasma (ARTP). Finally, the mutant S. meliloti MC5-2 was obtained and considered as a candidate for industrial applications. After 7 d's cultivation on a rotary shaker at 30 °C, the VB12 titer of S. meliloti MC5-2 reached 156 ± 4.2 mg/L, which was 21.9% higher than that of the wild type strain S. meliloti 320 (128 ± 3.2 mg/L). The genome of S. meliloti MC5-2 was sequenced, and gene mutations were identified and analyzed. CONCLUSION: To our knowledge, it is the first time that a riboswitch element was used in S. meliloti. The flow cytometry high-throughput screening system was successfully developed and a high-yield VB12 producing strain was obtained. The identified and analyzed gene mutations gave useful information for developing high-yield strains by metabolic engineering. Overall, this work provides a useful high-throughput screening method for developing high VB12-yield strains.

Bexarotene protects against traumatic brain injury in mice partially through apolipoprotein E.

Bexarotene has been proved to have neuroprotective effects in many animal models of neurological diseases. However, its neuroprotection in traumatic brain injury (TBI) is still unknown. This study aims to explore the neuroprotective effects of bexarotene on TBI and its possible mechanism. Controlled cortical impact (CCI) model was used to simulate TBI in C57BL/6 mice as well as APOE gene knockout (APOE-KO) mice. After CCI, mice were daily dosed with bexarotene or vehicle solution intraperitoneally. The motor function, learning and memory, inflammatory factors, microglia amount, apoptosis condition around injury site and main side-effects were all measured. The results showed that, after CCI, bexarotene treatment markedly improved the motor function and spatial memory in C57BL/6 compare to APOE-KO mice which showed no improvement. The inflammatory cytokines, microglia amount, cell apoptosis rate, and protein of cleaved caspase-3 around the injury site were markedly upregulated after TBI in both C57BL/6 and APOE-KO mice, and all these upregulation were significantly mitigated by bexarotene treatment in C57BL/6 mice, but not in APOE-KO mice. No side-effects were detected after consecutive administration. Taken together, bexarotene inhibits the inflammatory response as well as cell apoptosis and improves the neurological function of mice after TBI partially through apolipoprotein E. This may make it a promising candidate for the therapeutic treatment after TBI.