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Facial nerve injury caused by traffic accidents or operations may reduce the quality of life in patients, and recovery following the injury presents unique clinical challenges. Glial cell-derived neurotrophic factor (GDNF) is important in nerve regeneration; however, soluble GDNF rapidly diffuses into body fluids, making it difficult to achieve therapeutic efficacy. In this work, we developed a rat tail derived collagen conduit to connect nerve defects in a simple and safe manner. GDNF was immobilized in the collagen conduits via chemical conjugation to enable controlled release of GDNF. The GDNF delivery system prevented rapid diffusion from the site without impacting bioactivity of GDNF; degradation of the collagen conduit was inhibited owing to the chemical conjugation. The artificial nerve conduit was then used to examine facial nerve regeneration across a facial nerve defect. Following transplantation, the artificial nerve conduits degraded gradually without causing dislocations and serious inflammation, with good integration into the host tissue. Functional and histological tests indicated that the artificial nerve conduits were able to guide the axons to grow through the defect, reaching the distal stumps. The degree of nerve regeneration in the group that was treated with the artificial nerve conduit approached that of the autograft group, and exceeded that of the other conduit grafted groups. Statement of significance In this study, we developed artificial nerve conduits consisting of GDNF immobilized on collagen, with the aim of providing an environment for nerve regeneration. Our results show that the artificial nerve conduits guided the regeneration of axons to the distal nerve segment. GDNF was immobilized stably in the artificial nerve conduits, and therefore retained a sufficient concentration at the target site to effectively promote the regeneration process. The artificial nerve conduits exhibited good biocompatibility and facilitated nerve regeneration and functional recovery with an efficacy that was close to that of an autograft, and better than that of the other conduit grafted groups. Our approach provides an effective delivery system that overcomes the rapid diffusion of GDNF in body fluids, promoting peripheral nerve regeneration. The artificial nerve conduit therefore qualifies as a putative candidate material for the fabrication of peripheral nerve reconstruction devices. [ABSTRACT FROM AUTHOR]

In contrast to the released/circulating membrane vesicles (extracellular vesicles), cell-bound membrane vesicles are poorly identified and characterized. In this study, cell-bound membrane vesicles on human umbilical vein endothelial cells (HUVECs) and human hepatoma HepG-2 cells were investigated. We identified that cell-bound membrane vesicles are not co-localized with the major markers for extracellular vesicles (e.g. phosphatidylserine, CD63, CD107α, CD31, and DNA fragments for the three well-known types of extracellular vesicles) and for intracellular organelles with similar sizes (e.g. MitoTracker and LAMP1/LAMP3 for mitochondria and multivesicular bodies or lysosomes, respectively). The data imply that cell-bound membrane vesicles are neither the precursors of extracellular vesicles nor a false structure pushed up by an intracellular organelle but probably a novel unknown structure in the plasma membrane. Moreover, we revealed that cell-bound membrane vesicles are resistant to various detergents including but probably not limited to Triton X-100, SDS, and saponin. We further characterized that these unique vesicles are soluble in organic solvents (e.g. chloroform-methanol mixture and ethanol) which can be prevented by a lipid-stabilizing fixative (e.g. OsO 4 ) and that they are co-localized with, but do not monopolize, the major markers (e.g. caveolin-1 and GM1) for lipid rafts (a nano-sized detergent-resistant domains in the plasma membrane). The data imply that cell-bound membrane vesicles contain the lipid component and lipid rafts. Involvement of other specific unknown components might explain the detergent resistance of cell-bound membrane vesicles. Further research will mainly depend on the establishment of an effective approach for isolation/purification of these vesicles from the plasma membrane. [ABSTRACT FROM AUTHOR]

Introducing neural stem/progenitor cells (NS/PCs) for repairing facial nerve injuries could be an alternative strategy for nerve gap reconstruction. However, the lack of success associated with current methods of applying NS/PCs to neurological disease is due to poor engraftment following transplantation into the host tissue. In this work, we developed rat-tail collagen-based nerve conduits to repair lengthy facial nerve defects, promoting NS/PC proliferation in the natural nerve conduits with anchored bFGF to improve the therapeutic effects of cell transplantation. In vitro studies showed that heparinized collagen prevented leakage of bFGF and NS/PCs expended in the rat-tail collagen gel with the anchored bFGF. The natural nerve conduits were implanted to connect 8-mm facial nerve defects in rats. The repair outcomes including vibrissae movements, electrophysiological tests, immunohistochemistry and remyelination analysis of regenerated nerve were evaluated. At 12 weeks after implantation, only natural nerve conduits treated group showed Hoechst labeled NS/PCs. Besides, the natural nerve conduit significantly promoted functional recovery and nerve growth, which was similar to those of the gold standard, an autograft. The animal experiment results suggesting that the natural nerve conduits were valuable for facial nerve reconstruction. Statement of Significance Neural stem/progenitor cells (NS/PCs) were beneficial for the treatment of nervous system diseases. However, after transplantation, the beneficial was limited because the number of living NS/PCs decreased rapidly due to insufficient signaling molecules, such as growth factors, in the microenvironments surrounding transplanted cells. In the present study, we constructed collagen-based nerve conduit with anchored bFGF to achieve higher numbers of NS/PCs for repairing facial nerve injury. Compared with other methods involving neutral salt treatment or dialysis, the fabrication method of collagen scaffolds was simple, low-cost and safe, requiring a relatively short time to prepare. At 12 weeks after transplantation, the functional and histological results of natural nerve conduits treated group showed significant similarities to the gold standard method of nerve autografting. [ABSTRACT FROM AUTHOR]

This paper summarizes the changing biomass yields in the Yellow Sea large marine ecosystem (YSLME) in recent years and discusses the causes of such changes, including overfishing and climate changes. Meanwhile, two kinds of adaptive management strategies are recommended to support the biomass yields in YSLME, including resource-conservation-based capture fisheries (e.g. closed season/areas, stock enhancement etc.) and environmentally friendly aquaculture (e.g. integrated multi-trophic aquaculture, IMTA). [ABSTRACT FROM AUTHOR]

While circulating/plasma membrane vesicles have been extensively characterized, due to the lack of effective methods cell-bound membrane vesicles are poorly understood including their shape and correlation with the intracellular cytoskeleton. In this study, we focused on cell-bound membrane vesicles and individual vesicle-derived pits on endothelial cells by using confocal microscopy and atomic force microscopy (AFM). For the first time, we found that cell-bound membrane vesicles are hemisphere-shaped and that the actin cortical filaments/network lies at the cytosolic opening of a vesicle instead of being closely attached to the inner side of the vesicle membrane. This structure of cell-bound membrane vesicles may be beneficial to their movement in, or release from, the plasma membrane of cells due to less membrane–cytoskeleton coupling to be broken therefore probably minimizing energy consumption and time usage. Further study indicates that TNF-α activation induced a significant increase in average number/size of cell-bound vesicles and the local disruption of the actin network at the cytosolic opening of cell-bound vesicles. [ABSTRACT FROM AUTHOR]

Biomaterial and regenerative medical research has diversified and developed rapidly. A biological scaffold consisting of an extracellular matrix (ECM) functions not only as a supportive material but also as a regulator of cellular functions. Although decellularized scaffolds have been widely applied for the repair of non-central nervous system (CNS) tissues, their efficacy in the CNS has not been extensively investigated. In this report, we describe a dynamic decellularization protocol that combined intracardial perfusion and a series of treatments to effectively remove the cellular components from the cerebellum, which is a unique and relatively simple CNS structure. The resulting cerebellar scaffold retained neurosupportive proteins and growth factors and, when tested with neural stem cells (NSCs) in vitro, was found to be cytocompatible and to stimulate the proliferation and migration of these cells. NSCs that were cultured in vitro on the scaffold differentiated into neurons and astrocytes, as indicated by their expression of βIII-tubulin and glial fibrillary acidic protein (GFAP). Through subcutaneous and intracranial implantation experiments, this preliminary study demonstrated the in vivo biocompatibility of the cerebellar scaffold and indicated its potential for future applications. Thus, our study demonstrated that the cerebellar ECM scaffold provided tissue-specific advantages for regenerative medical applications. [ABSTRACT FROM AUTHOR]

Acupuncture is considered as an effective alternative treatment for post-stroke depression because of its low side effects and easy availability. However, it usually depends on the skills and experience of doctors to choose which acupuncture methods for specific parts. This study compared the effectiveness of different frequently-used acupuncture methods for specific parts in treating post-stroke depression patients by using network meta-analysis. We searched eight databases including China National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese Biomedical Database (CBM), VIP Chinese Science, the Cochrane Library, Embase, PubMed and Web of Science from the date of database inception to November 29, 2020 to identify eligible RCTs. The trial registers in ClinicalTrials.gov , World Health Organization, and Cochrane trials were searched as a supplement. The effective rate was extracted from the included RCTs as primary outcomes after screening. The network meta-analysis was performed by Review Manager 5.3, Stata14.0, and R 3.6.3. 51 studies were included, which contained 3966 participants among 12 interventions. Based on the ranking probability, scalp acupuncture plus conventional acupuncture was considered to be the most effective method, followed by auricular acupuncture, eye acupuncture, eye acupuncture plus drug, auricular acupuncture plus drug, auricular acupuncture plus conventional acupuncture, scalp acupuncture, scalp acupuncture plus drug, abdominal acupuncture, conventional acupuncture plus drug, drug, conventional acupuncture. 12 acupuncture methods may be effective and safe in improving the condition of patients with PSD. Higher quality randomized controlled trials need sufficient evidence because the overall quality of included trials can only be classified as low quality. This study is registered with PROSPERO (CRD42020177099). • A network meta-analysis on different acupuncture methods for post-stroke depression. • Acupuncture may be effective and safe in treating post-stroke depression patients. • Scalp plus conventional acupuncture is better for post-stroke depression than others. [ABSTRACT FROM AUTHOR]

This paper summarizes the changing states of the food resources in the Yellow Sea Large Marine Ecosystem under multiple stressors from 1958 to 2015, including the changing states of biomass yields, species composition, trophic level and biodiversity. The results show that the changing trends were contrary to expectation. There were no significant declines in biomass yields, trophic level and biodiversity after the 1980s. The major decline observed occurred before the 1980s. However, the species composition changed a lot, that is, over the past half century there were two different types of species shift in YSLME under multiple stresses. One was from demersal, high value species to pelagic, lower value species shift during 1958–59 to 1998–2000, and the other was from pelagic, lower value species to demersal, low value species shift during 1998–2000–2014-15. For future sustainable development, it is still necessary to further strengthen adaptive management. [ABSTRACT FROM AUTHOR]

MicroRNA-543 (miR-543) has been suggested as an important regulator of the development and progression of various cancer types. However, the role and biological function of miR-543 in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we found that miR-543 expression was significantly increased in tumor tissues from ccRCC patients and ccRCC cell lines. We found that overexpression of miR-543 markedly promoted the proliferation and invasion of ccRCC cells, whereas suppression of miR-543 had the opposite effects. Krüppel-like factor 6 (KLF6) was identified as a target gene of miR-543. Furthermore, we found that miR-543 negatively regulates the expression of KLF6 and p21 in ccRCC cells. Overexpression of KLF6 markedly attenuated the oncogenic effect of miR-543 overexpression. Moreover, knockdown of KLF6 significantly reversed the antitumor effect of miR-543 inhibition. Overall, our results demonstrate that miR-543 promotes the proliferation and invasion of ccRCC cells by targeting KLF6 and suggest that miR-543 may serve as a potential therapeutic target for treatment of ccRCC. [ABSTRACT FROM AUTHOR]

Oxidative stress is considered as major culprit for neurodegenerative diseases and triggers cognitive and memory impairments. The present study mainly aimed to study the protective effects and underlying mechanisms of aloin on d -galactose (d -gal) induced ageing mice. Our results demonstrated that chronic administration of d -gal (150 mg kg−1) in mice caused spontaneous and cognitive impairments, as determined by open-field test and Morris water-maze test. Aloin treatment significantly ameliorated histopathological damage, attenuated the microglia activation and reduced levels of inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in the hippocampus. Moreover, it effectively suppressed the level of reactive oxygen species (ROS) and increased antioxidant enzymes activities. Further data showed that these protective effects were accompanied by inhibition of the activation of nuclear factor kappa B and the phosphorylation of p38 and ERK. In conclusion, the present study suggests that aloin can ameliorate d -gal induced oxidative stress, cognitive impairment and inflammation, possibly via mediating the ERK, p38 and NF-κB signaling pathways. • Aloin ameliorates d -gal induced spontaneous and cognitive impairments. • Aloin ameliorates d -gal induced oxidative stress and inflammation in brain of d -gal induced mice. • Aloin inhibited ERK, p38 and NF-κB signal in brain of d -gal induced mice. [ABSTRACT FROM AUTHOR]

The Pacific decadal oscillation (PDO) has been identified as an important driver for fluctuation of fish populations on the eastern Pacific Ocean. However, the relationship between changes in fish population and climate oscillations on a decadal time scale in the Northwest Pacific is still unclear due to the lack of reliable long-term time series data. In the present study, a time series of Engraulis japonicus (Japanese anchovy) populations was reconstructed using the density of sedimentary fish scales in the Yellow Sea basin. E . japonicus populations and the PDO index showed similar patterns on a decadal time scale. Our results confirm that climate is a major driver of ecological changes on a decadal time scale, and indicate that suitable sea water temperature might be the main forcing of anchovy migration. This work also demonstrates the potential of predicting changes in fish population based on climate records. [ABSTRACT FROM AUTHOR]

The Yellow Sea (YS) is a semi-enclosed marginal sea in the West Pacific. As part of the China GLOBEC-IMBER program, the present study set out to investigate the mechanisms involved in the seasonal patterns of phytoplankton biomass and community structure in the southern YS. During four cruises in April and October 2006, and March and August 2007, the phytoplankton spring bloom, the Yellow Sea Warm Current (YSWC) and the Yellow Sea Cold Water Mass (YSCWM) were the most remarkable biogeochemical events in the study area, involving significantly different phytoplankton communities. During cold seasons nutrient-rich water was observed, coincident with the occurrence of the YSWC, which is considered to be warm and saline water from the northward Kuroshio branch current (Cheju Warm Current). However, low Chl a concentrations (< 0.6 mg m − 3 ) and a high relative abundance of prasinophytes (29% of Chl a , average value of the euphotic zone, and the same below) were observed in the YSWC area in March. During April a spring bloom occurred with very high concentrations of Chl a (7.69 mg m − 3 ) and fucoxanthin (1.98 mg m − 3 ), and was dominated by diatoms. The mechanism and processes of the spring bloom in the central YS are very complex and possibly unique, and the YSWC affects the distribution of nutrients and hydrological environment for phytoplankton growth. Low Chl a biomass (0.2 mg m − 3 ) and a low contribution of diatoms, but a high contribution of cyanobacteria (36%) were observed in the stratified central YS in August when the YSCWM prevailed, and a high relative abundance of chrysophytes (38%) was observed in October when the YSCWM was decaying. In a word, significant seasonal variations of phytoplankton biomass and community structure were observed in the central rather than the coastal area. These results were considered as the physical–chemical–biological characteristics of the unique ecosystem in the central YS. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility, safety, and efficiency of bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer.Materials and Methods: We reviewed retrospectively the records of 65 patients who underwent inguinal lymph nodes dissection (ILND) for penile cancer from January 2012 to May 2019. Treatments included open ILND (OILND, 19 patients), video-endoscopic inguinal lymphadenectomy (VEIL) using single laparoscopy (S-VEIL, 24 patients), and VEIL using double laparoscopies (D-VEIL, 22 patients). We evaluated the peri-operative and short-term oncological outcomes of the three groups.Results: The mean operative time of D-VEIL (105.91 ± 10.87 minutes) was significantly shorter than the other two groups, OILND shorter than S-VEIL (160.47 ± 13.74 minutes, 191.67 ± 17.80 minutes, respectively) (P < 0.001). Intraoperative blood loss in the S-VEIL and D-VEIL groups were 53.54 ± 8.78 and 48.41 ± 13.22 ml, respectively; they were significantly lower than that of the OILND group (99.74 ± 9.64 ml; P < 0.001). The numbers of unilateral and total lymph nodes harvested were similar in all groups. The complication rates in the S-VEIL group (4.2%) and the D-VEIL group (4.5%) were significantly lower than that in the OILND group (63.2%; P < 0.001). Compared with open surgery (13.53 ± 1.74 days for hospitalization; 11.37 ± 1.92 days for the left side of drain, 11.95 ± 1.84 days for the right side), the two VEIL groups had significantly shorter drainage tube residence time (7.42 ± 2.02 and 7.32 ± 1.52 days, respectively for the left side; 7.63 ± 1.81 and 7.27 ± 1.58 days, respectively for the right side), shorter postoperative hospitalization (9.46 ± 1.64 and 9.00 ± 1.83 days, respectively) (P < 0.001). There were no statistically significant differences in rates of regional recurrence and short-term survival among the three groups.Conclusion: Bilateral inguinal lymphadenectomy using double laparoscopies simultaneously can provide adequate oncological outcomes safely and efficiently, and carry significantly lower morbidity than OILND, at a median follow-up of 33.5 months. It is a more time-saving surgical approach for penile cancer patients who need bilateral ILND. [ABSTRACT FROM AUTHOR]

Abstract: Growth hormone (GH) is a polypeptide which is an important regulator of development and somatic growth in teleosts, and may be associated with the mechanisms which drive sexual growth dimorphism in the Half-smooth tongue sole (Cynoglossus semilaevis). In this study, the full length gh cDNA was cloned from C. semilaevis by homology cloning and the rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR). The full-length gh cDNA is 826bp and contains an open reading frame (ORF) of 603bp encoding a protein of 200 amino acids (AA). The precursor of gh consists of a 17 amino-acid signal peptide followed by a 183 amino-acid mature polypeptide. GH gene sequences obtained from female and male adults consist of 3428bp and 3371bp, respectively, each of which includes six exons and five introns, and the difference in the GH gene size was mainly caused by the microsatellites. When 14 tissues from females, normal males and extra-large male adults were analyzed for sex-specific tissue expression, the gh mRNA was found to be predominantly expressed in the pituitary, and the expression levels in females were 3.6 times as much as those in normal males, while the mRNA expression in extra-large males was 1.7 times as much as those in normal males. Sex differences in gh mRNA expression during development were also examined by using a full-sib family of C. semilaevis, and the gh mRNA was detected at all of the 12 time points sampled from 10 to 380days-old. A significant increase in gh mRNA was detected starting in 80day old fish and was then followed by a drop to very low levels starting at 230day old fish. Differential expression indicated that the gh expression level in females was significantly higher than males (P <0.01) at all of the stages except for 10days-old. Two microsatellite loci were identified in the second intron of the GH gene. Using these two polymorphic markers to genotype 224 individuals, there was no significant difference between the females and males in the Bohai Sea, the Yellow Sea and the hatchery samples. [Copyright &y& Elsevier]

Abstract: The Bohai Sea (BHS), located at the western boundary of the NW Pacific, is a shallow semienclosed sea with an area of about 77×103 km2 and average depth of 18m, surrounded by fast-developing economic zones and populous lands. Through the Bohai Strait, the BHS connects to the Yellow Sea, one of the 50 large marine ecosystems in the world ocean. The hydrographic conditions there are substantially influenced by river discharges, wind–tide–thermohaline circulation, stratification in summer, and mixing in winter. During the period of 1960–1996, temperature, salinity, dissolved inorganic nitrogen, and the N:P ratio increased from 0.005 to 0.013°C year−1, 0.04 to 0.13 year−1, 0.45 to 0.61μmolL−1 year−1, and 1.27 to 1.40year−1, respectively; while dissolved oxygen, phosphorus, silicon, and the Si:N ratio decreased from −1.59 to −2.30μmolL−1 year−1, −0.007 to −0.011μmolL−1 year−1, −0.385 to −0.602μmolL−1 year−1, and −0.064 to −0.324year−1, respectively. These changes were primarily caused by a reduced freshwater inflow. Since 1985, the concentrations of P and Si, and the Si:N ratio, have dropped to near-critical levels for diatom growth, while the N:P ratio has been below the Redfield ratio. These changes not only have had an influence on phytoplankton production, but also can decrease recruitment of the Penaeid prawn (Penaeus chinensis) and change fish community structure and diversity. [Copyright &y& Elsevier]

• Shikonin ameliorates D-gal induced cognitive impairment. • Shikonin ameliorates D-gal induced oxidative stress, astrocyte activation and neuronal damage in brain of D-gal induced mice. • Shikonin inhibited MAPK and NF-κB signaling pathway in brain of D-gal induced mice. Oxidative stress acts as the major causative factor for various age‐associated neurodegenerative diseases, triggering cognitive and memory impairments. In the present study, the underlying neuroprotective mechanism governing how shikonin acts against D-galactose (D-gal)-induced memory impairment, neuroinflammation and neuron damage was examined. The results revealed that chronic administration of D-gal [150 mg/kg intraperitoneally (i.p.)] in mice caused cognitive and memory impairments, as determined by Morris water-maze test. Shikonin treatment, however, alleviated D‐gal-induced memory impairment and reversed the D‐gal-induced neural damage and apoptosis. Furthermore, western blotting and the results of morphological analysis revealed that shikonin treatments markedly reduced D‐gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein (GFAP) detection, and downregulating other inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Moreover, shikonin treatment led to inhibition of the activation of nuclear factor‐κB (NF‐κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs), preventing neurodegeneration. Hence, taken together, the results of the present study suggested that shikonin attenuated D‐gal-induced memory impairment, neuroinflammation and neurodegeneration, possibly via the NF‐κB/mitogen-activated protein kinase (MAPK) pathway. Our data suggest that shikonin could be a promising, endogenous and compatible antioxidant candidate for age‐associated neurodegenerative diseases, including Alzheimer's disease. [ABSTRACT FROM AUTHOR]