Enhancing the biomass and docosahexaenoic acid-rich lipid accumulation of Schizochytrium sp. in propionate wastewater.

In order to find a more effective way to obtain docosahexaenoic acid (DHA) rich lipid from Schizochytrium sp., a widespread propionate wastewater (PW) is used. PW is a common industrial and domestic wastewater, and transforming it into valuable products is a potential treatment method. Schizochytrium sp. is a rapidly growing oleaginous organism, which has been used commercially for DHA production. Herein, PW is completely used for DHA production by Schizochytrium sp. by genetic engineering and fermentation optimization, which can alleviate the increasingly tense demand for water resources and environmental pollution caused by industrial wastewater. Firstly, the methylmalonyl-CoA mutase (MCM) was overexpressed in Schizochytrium sp. to enhance the metabolism of propionate, then the engineered strain of overexpressed MCM (OMCM) can effectively use propionate. Then, the effects of PW with different concentration of propionate were investigated, and results showed that OMCM can completely replace clean water with PW containing 5 g L-1 propionate. Furthermore, in the fed-batch fermentation, the OMCM obtained the highest biomass of 113.4 g L-1 and lipid yield of 64.4 g L-1 in PW condition, which is 26.8% and 51.7% higher than that of wild type (WT) in PW condition. Moreover, to verify why overexpression of MCM can promote DHA and lipid accumulation, the comparative metabolomics, ATP production level, the antioxidant system, and the transcription of key genes were investigated. Results showed that ATP induced by PW condition could drive the synthesis of DHA, and remarkably improve the antioxidant capacity of cells by enhancing the carotenoids production. Therefore, PW can be used as an effective and economical substrate and water source for Schizochytrium sp. to accumulate biomass and DHA.

Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation.

Maturity-onset diabetes of the young type 3 (MODY3) is a specific type of diabetes mellitus with inherited impairment of the islet ß cell function due to the mutation in the hepatocyte nuclear factor 1α (HNF1α) gene. It is a rare condition and easily misdiagnosed as T1DM or T2DM. In this study, the clinical features of two unrelated Chinese MODY3 probands were described and analyzed. Next-generation sequencing was performed to identify the mutated genes, and Sanger sequencing was employed to verify the location of the pathogenic variant in the related family members. It was found that proband 1 inherited a start codon mutation c.2T>C (p.Met1?) in exon 1 of the HNF1α gene from his affected mother, and proband 2 inherited a frameshift mutation c.1136_1137del (p.Pro379fs) in exon 6 of the HNF1α gene also from her affected mother. Proband 1 and proband 2 differed in islet dysfunction, complications, and treatments due to their different disease durations and levels of hemoglobin A1c (HbA1c). The findings of this study demonstrate that early identification of MODY and diagnosis through genetic testing are critical for the treatment of the patient.

Cisatracurium besylate rescues Mycobacterium Tuberculosis-infected macrophages from necroptosis and enhances the bactericidal effect of isoniazid.

OBJECTIVE: Tuberculosis is the leading killer among the chronic single-source infectious diseases. Mycobacterium tuberculosis can induce necrotic-dominant multiple modes of cell death in macrophages, which accelerates bacterium dissemination and expands tissue injury in host lungs. Mining drugs to counteract Mycobacterium tuberculosis-induced cell death would be beneficial to tuberculosis patients. METHODS: In this study, the protective drug was screened out from the FDA-approved drug library in Mycobacterium tuberculosis-infected macrophages with CCK-8 assay. The death mode regulated by the drug was identified using transcriptomic sequencing, cytomorphological observation, and in the experimental mouse Mycobacterium tuberculosis-infection model. The functional mechanism was explored using western blot, co-immunoprecipitation, and DARTS assay. The intracellular bacterial survival was detected using colony forming unit assays. RESULTS: Cisatracurium besylate was identified to be highly protective for the viability of macrophages during Mycobacterium tuberculosis infection via inhibiting necroptosis. Cisatracurium besylate prevented RIPK3 to be associated with the executive molecule MLKL for forming the necroptotic complex, resulting in the inhibition of MLKL phosphorylation and pore formation on cell membrane. However, Cisatracurium besylate did not interfere with the association between RIPK3 with its upstream kinase RIPK1 or ZBP1 but regulated RIPK3 autophosphorylation. Moreover, Cisatracurium besylate significantly inhibited the expansion of intracellular Mycobacterium tuberculosis both in vitro and in vivo, which also displayed a strong auxiliary bacteriostatic effect to support the therapeutic efficacy of isoniazid and rifampicin, the first-line anti-tubercular drugs. CONCLUSION: Cisatracurium besylate performs anti-Mycobacterium tuberculosis and anti-necroptotic roles, which potentiates its application to be an adjuvant drug for antituberculosis therapy to assist the battle against drug-resistant tuberculosis.

Evaluation of bacterial and fungal communities during the fermentation of pine needle.

To improve the quality and organoleptic properties of fermented pine needle, the physiological parameters and microbial communities must be explored. In this study, high-throughput sequencing was used to explore bacterial and fungal communities during the fermentation process of pine needle after adding starter culture of 0.8% activated dry yeast and Lactobacillus fermentum CECT5716 and Bifidobacterium Breve M-16 V. During the fermentation, the total flavonoid (from 0.049 to 111.404 mg/L) and polyphenol (from 19.412 to 183.399 mg/L) contents increased rapidly from 0 to 15 days. The total sugar increased from 0 to 3 days fermentation with a range from 3.359 mg/mL to 45.502 mg/mL in yeast fermentation stage, and reached the maximum value on day 3. The content of total acid (39.167 g/L) and amino acid nitrogen (1.185 g/L) gradually increased during the entire fermentation process and reached a maximum on day 7 of bacterial fermentation. Firmicutes and Proteobacteria phyla were the predominant bacteria in all time periods. At the genus level, well-known Lactobacillus was the most abundant bacterial strain on day 3, followed by Gluconobacter. The Acetobacter constituted more than 50% of the total bacterial abundance on day 1, but it decreased with the fermentation process. Exploration of fermented pine needle microbial community structure will expand the knowledge about their microbiota to manipulate the microbial community and improve their quality and organoleptic properties using different microbial recipes.

Efficient aerobic denitrification without nitrite accumulation by Pseudomonas mendocina HITSZ-D1 isolated from sewage sludge.

A highly efficient aerobic denitrifying microbe was isolated from sewage sludge by using a denitrifier enrichment strategy based on decreasing carbon content. The microbe was identified as Pseudomonas mendocina HITSZ-D1 (hereafter, D1). Investigation of the conditions under which D1 grew and denitrified revealed that it performed good growth and nitrate removal performance under a wide range of conditions. In particular, D1 rapidly removed all types of inorganic nitrogen without accumulation of the intermediate products nitrite and nitrous oxide. Overall, D1 showed a total nitrogen removal efficiency >96% at a C/N ratio of 8. The biotransformation modes and fates of three typical types of inorganic nitrogen were also assessed. Moreover, D1 had significantly higher denitrification efficiency and enzyme activities than other aerobic denitrifying microbes (Paracoccus denitrificans, Pseudomonas aeruginosa, and Pseudomonas putida). These results suggest that D1 has great potential for treating wastewater containing high concentrations of nitrogen.

A Modified Small Intestinal Submucosa Patch with Multifunction to Promote Scarless Repair and Reinvigoration of Urethra.

To reconstruct and restore the functions of the male urethra is a challenging task for urologists. The acellular matrix graft currently used in the clinics is mono-functional and may cause a series of complications including stricture, fibrosis, and stone formation. As a result, such graft materials cannot meet the increasing demand for multifunctionality in the field of urethral tissue engineering. In this context, a multifunctional urethral patch is designed for the repair of urethral defects by mixing protocatechualdehyde (PCA) with small intestinal submucosa (SIS) under an alkalin condition to allow cross linking. As shown, the PCA/SIS patch possesses excellent biocompatibility, antioxidant activity, and anti-inflammatory property. More importantly, this patch can remarkably promote the adhesion, proliferation, and directional extension of rabbit bladder epithelial mucous cells (R-EMCs) as well as rabbit bladder smooth muscle cells (R-SMCs), and upregulate the expression of cytokeratin in the EMCs and contractile protein in the SMCs in vitro. In vivo experiments also confirm that the PCA/SIS patch can significantly enhance scarless repair of urethral defects in rabbits by facilitating smooth muscle regeneration, reducing excessive collagen deposition, and accelerating re-epithelialization and neovascularization. Taken together, the newly developed multifunctional PCA/SIS patch provides a promising candidate for urethral regeneration.

Effect of self-determination theory-based integrated creative art (SDTICA) program on older adults with mild cognitive impairment in nursing homes: Study protocol for a cluster randomised controlled trial.

BACKGROUND: The cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes. METHODS: The study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up. DISCUSSION: This study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI. TRIAL REGISTRATION: The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022.

Motion Decoupling Network for Intra-Operative Motion Estimation Under Occlusion.

In recent intelligent-robot-assisted surgery studies, an urgent issue is how to detect the motion of instruments and soft tissue accurately from intra-operative images. Although optical flow technology from computer vision is a powerful solution to the motion-tracking problem, it has difficulty obtaining the pixel-wise optical flow ground truth of real surgery videos for supervised learning. Thus, unsupervised learning methods are critical. However, current unsupervised methods face the challenge of heavy occlusion in the surgical scene. This paper proposes a novel unsupervised learning framework to estimate the motion from surgical images under occlusion. The framework consists of a Motion Decoupling Network to estimate the tissue and the instrument motion with different constraints. Notably, the network integrates a segmentation subnet that estimates the segmentation map of instruments in an unsupervised manner to obtain the occlusion region and improve the dual motion estimation. Additionally, a hybrid self-supervised strategy with occlusion completion is introduced to recover realistic vision clues. Extensive experiments on two surgical datasets show that the proposed method achieves accurate motion estimation for intra-operative scenes and outperforms other unsupervised methods, with a margin of 15% in accuracy. The average estimation error for tissue is less than 2.2 pixels on average for both surgical datasets.

Cellular immunotherapy combined with platinum-based chemotherapy prolongs survival for non-small cell lung cancer patients.

Platinum-based chemotherapy is the primary treatment option for advanced non-small cell lung cancer (NSCLC) patients without a driver gene mutation, but its efficacy is still modest. Through a potential synergistic effect, autologous cellular immunotherapy (CIT) composed of cytokine-induced killer (CIK, natural killer (NK), and T cells) might enhance it. NK cells exhibited in vitro cytotoxicity toward lung cancer cells (A549 cells) following platinum therapy. Using flow cytometry, the expression of MICA, MICB, DR4, DR5, CD112, and CD155 on lung cancer cells was assessed. In this retrospective cohort study, there were included 102 previously untreated stage IIIB/IV NSCLC patients ineligible for tyrosine kinase inhibitor (TKI) target therapy who received either chemotherapy alone (n = 75) or combination therapy (n = 27). The cytotoxicity of NK cells for A549 cells was increased obviously and a time-dependent enhancement of this effect was also observed. After platinum therapy, the levels of MICA, MICB, DR4, DR5, CD112, and CD155 on the surface of A549 cells were increased. In the combination group, the median PFS was 8.3 months, compared to 5.5 months in the control group (p = 0.042); the median overall survival was 18.00 months, compared to 13.67 months in the combined group (p = 0.003). The combination group had no obvious immune-related adverse effects. The combination of NK cells with platinum showed synergistic anticancer effects. Combining the two strategies increased survival with minor adverse effects. Incorporating CIT into conventional chemotherapy regimens may improve NSCLC treatment. However, additional evidence will require multicenter randomized controlled trials.

CM3-SII polysaccharide obtained from Cordyceps militaris ameliorates hyperlipidemia in heterozygous LDLR-deficient hamsters by modulating gut microbiota and NPC1L1 and PPARα levels.

Accumulating evidence has demonstrated that polysaccharides derived from edible fungi have lipid-lowering effects in mice. However, the lipid metabolism mechanisms in mice and humans are different. We have previously elucidated the structural characteristics of the alkali-extracted polysaccharide CM3-SII obtained from Cordyceps militaris. This study aimed to investigate whether CM3-SII could ameliorate hyperlipidemia in a heterozygous low-density lipoprotein receptor (LDLR)-deficient hamster model of hyperlipidemia. Our data demonstrated that CM3-SII significantly decreased total plasma cholesterol, non-high-density lipoprotein cholesterol, and triglyceride levels in heterozygous LDLR-deficient hamsters. Unlike ezetimibe, CM3-SII could enhance the concentration of plasma apolipoprotein A1 and the expression of liver X receptor α/ATP-binding cassette transporter G8 mRNA pathway and suppress the expression of Niemann-Pick C1-like 1, which help to reduce cholesterol levels further. Moreover, the results of molecular docking analysis demonstrated that CM3-SII could directly bind to Niemann-Pick C1-like 1 with high affinity. The triglyceride-lowering mechanisms of CM3-SII were related to its downregulation of sterol regulatory element-binding protein 1c and upregulation of peroxisome proliferator-activated receptor α. Importantly, CM3-SII increased the abundance of Actinobacteria and Faecalibaculum and the ratio of Bacteroidetes/Firmicutes. Thus, CM3-SII attenuated hyperlipidemia by modulating the expression of multiple molecules involved in lipid metabolism and the gut microbiota.

Epidemiological investigation of the status of myopia in children and adolescents in Fujian Province in 2020.

PURPOSE: The 2020 epidemiological investigation of myopia in children and adolescents in Fujian Province' aimed to provide reference guidelines for the prevention and control of myopia. The purpose of the present study was to address shortfalls in the epidemiological survey of myopia in Fujian and provide a basis for government decision making. STUDY DESIGN: A cross-sectional and epidemiological investigation METHODS: Based on their levels of economic development and other economic factors, three cities in Fujian Province (Fuzhou, Xiamen, Longyan) were chosen through cluster random sampling and epidemiological investigation. Final analysis included 41,906 cases. Examinations including visual acuity and mydriatic optometry were performed on all subjects. RESULTS: The overall proportion of myopia was 63.35% in boys and 70.55% in girls living in Fujian in 2020. The proportions of myopia in Xiamen and Longyan were similar; both cities showed a higher proportion of myopic cases than Fuzhou. The proportion of girls with myopia was higher than boys. The proportion of primary and middle school students with myopia was higher in economically developed regions compared with underdeveloped regions. The proportion of urban students with myopia was higher than in suburban students. Analysis showed that the prevalence of myopia increased with age. Interestingly, the prevalence of myopia was higher in children born in June and August than in children born in other months. CONCLUSION: Children and adolescents in Fujian have a high rate of myopia which increases as the school grade increases. The better the economic conditions are, the higher the myopic rate. In addition, the myopic rate is higher in girls in and students born in June and August. The government, schools, hospitals, and parents should be alerted to this issue and coordinate to control the risk of myopia exacerbation and improve eyesight conditions of students in Fujian Province.

Bacteria-Driven Tumor Microenvironment-Sensitive Nanoparticles Targeting Hypoxic Regions Enhances the Chemotherapy Outcome of Lung Cancer.

Background: Chemotherapy still plays a dominant role in cancer treatment. However, the inability of conventional chemotherapeutic drugs to reach the hypoxic zone of solid tumors significantly weakens their efficacy. Bacteria-mediated drug delivery systems can be an effective targeting strategy for improving the therapeutic outcomes in cancer. Anaerobic bacteria have the unique ability to selectively transport drug loads to the hypoxic regions of tumors. Methods: We designed a Bifidobacterium infantis (Bif)-based biohybrid (Bif@PDA-PTX-NPs) to deliver polydopamine (PDA)-coated paclitaxel nanoparticles (PTX-NPs) to tumor tissues. Results: The self-driven Bif@PDA-PTX-NPs maintained the toxicity of PTX as well as the hypoxic homing tendency of Bif. Furthermore, Bif@PDA-PTX-NPs significantly inhibited the growth of A549 xenografts in nude mice, and prolonged the survival of the tumor-bearing mice compared to the other PTX formulations without any systemic or localized toxicity. Conclusion: The Bif@PDA-PTX-NPs biohybrids provide a new therapeutic strategy for targeted chemotherapy to solid tumors.

[Surgical treatment for ipsilateral femoral neck and shaft fracture].

OBJECTIVE: To retrospectively analyze efficacy of single structure internal fixation and double structure internal fixation in the treatment of ipsilateral femoral shaft and neck fracture, and analyze their indications. METHODS: From June 2015 to December 2020, 21 patients with ipsilateral femoral shaft and femoral neck fracture were treated, including 14 males and 7 females, aged 23 to 69 years old with an average of(38.1±12.9) years old. According to different femoral shaft fracture sites, some patients were fixed with cephalomedullary implant for both femoral neck and the femoral shaft(single structure, InterTan or PFNA Ⅱ), some patients were fixed with cannulated screws for the femoral neck and a retrograde locking nail for the femoral shaft (dual structure), and postoperative function and complications were recorded during follow-up. In 10 cases of single-structure fixation, the femoral necks were all basicervical fractures, and the femoral shaft fractures were located in the proximal isthmus;11 cases were double-structure fixation, 9 cases in 11 were basal type of femoral neck, 2 cases in 11 were neck type, and the femoral shaft fractures were located in the isthmus and the distal isthmus. RESULTS: All patients were followed up for 12 to 27 months. No femoral head necrosis, deformity, delay or nonunion occurred in the patients with single-structure fixation, and no delayed union or nonunion occurred in femoral shaft fractures;At the final follow-up, Harris score of patients with single-structure fixation was 91.8±4.1, with 8 cases were excellent and 2 cases were good. The fractures of patients with dual-structure fixation achieved good union without femoral head necrosis, except 1 case of femoral shaft fracture had delayed union;At the final follow-up, Harris score of patients with dual-structure fixation was 92.4±5.9, 7 cases were excellent, 3 cases were good, and 1 case was fair. CONCLUSION: Good reduction and fixation is the key to the treatment of such fractures. Both the single-structure fixation and the dual-structure fixation are good methods, and it should be selected according to the locations of femoral shaft and femoral neck fractures. Single-structure fixation is a good choice for femoral shaft fractures located at the proximal isthmus and basal femoral neck fractures. For isthmus and distal femoral shaft fractures combined with ipsilateral femoral neck fractures, dual-structure fixation is recommended.

Colorectal cancer survivors' experiences of return-to-work: A meta-synthesis of qualitative studies.

INTRODUCTION: This review is to explore the relevant experience of colorectal cancer survivors' return-to-work, reintegrating and analyzing the promoting factors and obstacles of colorectal cancer survivors' return-to-work. METHODS: This review followed PRISMA List. Databases including the Cochrane Library, PubMed, Web of Science, EM base, CINAHL, APA PsycInfo, Wangfang Database, CNKI and CBM from inception to October 2022 were searched to collect qualitative studies in the experience of colorectal cancer survivors' return-to-work. Article selection and data extraction were conducted by two researchers used the Joanna Briggs Institute Critical Appraisal Tool for qualitative researches (2016) in Australia. RESULTS: Seven studies were included, the thirty-four themes distilled from the literature were grouped into eleven new categories and summed into two integrated findings: (1) facilitators to return-to-work for colorectal cancer survivors: desire and expectation for return-to-work and social dedication, economic needs, support and tolerance from employers and colleagues, work suggestions provided by professionals, health insurance policy of the workplace. (2) obstacles to return-to-work for colorectal cancer survivors: physical problems, psychological barriers, lack of family support, negative attitudes of employers and colleagues, limited information and resources available from professionals, Imperfection of related policies. CONCLUSION: This study shows that colorectal cancer survivors' return-to-work is influenced by many factors. We should pay attention to and avoid obstacles, help colorectal cancer survivors recover their physical functions and maintain a positive psychological state, improve the social support for colorectal cancer survivors to return-to-work, so as to achieve comprehensive rehabilitation as soon as possible.

Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model.

Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1ß production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk-/- mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis.

Peer Supporters' Experience of Supporting Cancer Patients: A Meta-synthesis.

BACKGROUND: With the widespread use of peer support in the cancer field, more and more cancer survivors are becoming supporters. However, they may bear a huge psychological burden in the peer support project. There has been little effort to analyze supporters' experiences from a meta-perspective. OBJECTIVE: The aims of this study were to review the literature on the experience of patients serving as peer supporters, integrate qualitative data to explore the experiences of supporters participating in peer support programs, and provide suggestions for future researchers. INTERVENTIONS/METHODS: China Knowledge Network, Wanfang Database, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, CINAHL, and PsycINFO were searched. Titles, abstracts, and full texts were screened. Included articles (n = 10) underwent data extraction, the Joanna Briggs Institute Critical Appraisal Tool for qualitative researches (2016) quality evaluation, and thematic synthesis. RESULTS: The literature ultimately included 10 studies from which 29 themes were distilled and grouped into 2 main categories: benefits and challenges of peer support for supporters. CONCLUSIONS: Peer supporters will not only gain social support, growth, and recovery but also experience various challenges when providing peer support. Both supporters' and patients' experiences of participating in peer support programs deserve the attention of researchers. Researchers need to be rigorous in controlling the implementation of peer support programs to help supporters gain and overcome challenges. IMPLICATIONS FOR PRACTICE: Future researchers can use study findings to better develop peer support programs. More peer support projects are needed to explore a standardized peer support training guide.

Synergistic effects of lipopolysaccharide and rotenone on dopamine neuronal damage in rats.

INTRODUCTION: The etiology of Parkinson's disease (PD) is still unknown. Until now, oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. However, the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear. METHODS: The changes in motor behavior, dopamine (DA) neurons quantification and their mitochondrial respiratory chain, glial cells activation and secreted cytokines, Nrf2 signaling pathway, and redox balance in the brain of rats were evaluated. RESULTS: Lipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, DA neuron damage, activation of glial cells, and release of related mediators, activation of Nrf2 signaling and destruction of oxidative balance. In addition, further studies indicated that after ROT-induced oxidative stress caused direct damage to DA neurons, LPS-induced inflammatory effects had stronger promoting neurotoxic effects on the above aspects. CONCLUSIONS: Neuroinflammation and oxidative stress synergistically aggravated DA neuronal loss. Furtherly, oxidative stress followed by neuroinflammation caused more DA neuronal loss than neuroinflammation followed by oxidative stress.

Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review.

Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers.

Bioactive ECM-Loaded SIS Generated by the Optimized Decellularization Process Exhibits Skin Wound Healing Ability in Type I Diabetic Rats.

Patients with diabetes have 15-25% chance for developing diabetic ulcers as a severe complication and formidable challenge for clinicians. Conventional treatment for diabetic ulcers is to surgically remove the necrotic skin, clean the wound, and cover it with skin flaps. However, skin flap often has a limited efficacy, and its acquisition requires a second surgery, which may bring additional risk for the patient. Skin tissue engineering has brought a new solution for diabetic ulcers. Herein, we have developed a bioactive patch through a compound culture and the optimized decellularization strategy. The patch was prepared from porcine small intestinal submucosa (SIS) and modified by an extracellular matrix (ECM) derived from urine-derived stem cells (USCs), which have low immunogenicity while retaining cytokines for angiogenesis and tissue regeneration. The protocol included the optimization of the decellularization time and the establishment of the methods. Furthermore, the in vitro mechanism of wound healing ability of the patch was investigated, and its feasibility for skin wound healing was assessed through an antishrinkage full-thickness skin defect model in type I diabetic rats. As shown, the patch displayed comparable effectiveness to the USCs-loaded SIS. Our findings suggested that this optimized decellularization protocol may provide a strategy for cell-loaded scaffolds that require the removal of cellular material while retaining sufficient bioactive components in the ECM for further applications.