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For the parameter estimation problem in research related to the fractional-order chaotic systems (FOCSs), a modified optimization algorithm based on Salp Swarm Algorithm (SSA) was developed in this paper. The proposed algorithm introduced several improvements on SSA: adding a grouping step, introducing “betrayal” behavior, and improving the update method of the followers. We applied multiple classical optimization algorithms to conduct the parameter estimation experiments on the fractional-order Lorenz chaotic system (Lorenz-FOCS) and the fractional-order Financial chaotic system (Financial-FOCS). In addition, we explored the impact of searching space on parameters estimation through experiments. The experimental results confirmed the feasibility of the modified Salp Swarm Algorithm (MSSA). The MSSA performed better than the SSA and other classical optimization algorithms in terms of the estimation accuracy and convergence rate.

Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ‐binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO‐1 (PDZ) proteins. In this study, we demonstrated that the PDZ protein membrane‐associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) inhibited the Wnt/β‐catenin pathway, and subsequently cervical cancer (CC) cell migration and invasion, via decreasing β‐catenin levels. By reducing MAGI3 protein levels, HPV18 E6 promoted CC cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 was preferentially associated with the downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in CC. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in CC progression., By reducing the level of MAGI3 protein, HPV18 E6 promotes cervical cancer cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 is preferentially associated with downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in cervical cancer. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in cervical cancer progression.

This article examines the relationship between golf activities and tourist perceptions and intentions using data from 592 golf tourists on Hainan Island, China. The results obtained from structural equation modeling show that the attractiveness of the destination can improve the identity of the location, and both factors significantly increase the travel intentions of golf tourists (i.e. revisit intentions and word-of-mouth recommendations). The results also show that place identity has significant mediating effects between destination attractiveness and travel intentions. In addition, the results reveal that the disposable income of golf tourists has significant moderating effects on the attractiveness of the destination, the identity of the destination, and the intention to revisit. This study has some important economic implications for golf destination management. Golf course managers can improve the attractiveness of the destination and strengthen the identity of the location to enhance the behavioral intentions of golf tourists.

This work investigates the effect of circABCC4 on the proliferation, migration, and invasion of colorectal cancer SW620 cells; circABCC4’s regulation of miR-216a-3p is also studied. qRT-PCR was used to measure the levels of circABCC4 and miR-216a-3p in colorectal cancer and adjacent tissues. The human colorectal cancer SW620 cells were transfected with different constructs of circABCC4 or miR-216a-3p or both to study their interactions and combined effects on cell behavior. A dual-luciferase reporter experiment tested the targeted relationship between circABCC4 to miR-216a-3p. Furthermore, the behaviors of SW620 cells, such as cell viability, migration, and invasion, were investigated. Also, the proteins related to cell behaviors were investigated with western blotting. Our results showed that colorectal cancer tissues had a higher level of circABCC4 but a lower level miR-216a-3p. The increased level of circABCC4 and the reduced level of miR-216a-3p had analogous influences on the behaviors of SW620 cells, resulting in reduced cell proliferation, migration, and invasion; the levels of related protein were also decreased. Moreover, we found that disrupting miR-548c-3p could reverse the influence of inhibiting circABCC4 on SW620 cells. In addition, the dual-luciferase reporter assay results confirmed the targeting of miR-216a-3p by circABCC4. These data demonstrate that the silencing of circABCC4 may inhibit the proliferation, migration, and invasion of colorectal cancer cells by upregulating miR-548c-3p.

To investigate the associations between weekly alcohol consumption and the risk and surgical outcome of Chronic Rhinosinusitis (CRS).A case-control study.The study population consisted of 1095 CRS patients and 909 healthy collected from the first affiliated hospital of Zhengzhou University between May 2018 and December 2019.Unconditional multivariate logistic regression analysis and Cox proportional hazards regression analysis were performed to estimate the association of alcohol consumption with the risk and surgical outcomes of CRS. Odds ratios (OR) or hazard ratio (HR) with 95% confidence intervals (CI) were calculated separately. The Kruskal-Wallis test was used to explore the possible molecular mechanisms.As compared with nondrinkers, the multivariable-adjusted OR (95% CI) values of current drinkers consuming 7.5-22 drinks and22 drinks per week were 2.158 (1.249-3.729) and 5.373 (2.912-9.911), respectively. The rate of mucosal epithelialization after CRS surgery for patients who drank 7.5-22 drinks and22 drinks per week was lower than that of nondrinkers [HR (95% CI) = 0.487 (0.351-0.675) and 0.252 (0.184-0.346), respectively]. The association of alcohol consumption with the risk and surgical outcome of CRS was dose dependent (p .01). Alcohol consumption increased the risk of CRS and extended the time of mucosal epithelialization after CRS surgery by possibly increasing serum IgE levels (p .05).Higher alcohol consumption of7.5 drinks per week was an independent risk factor for CRS and extended the time of mucosal epithelialization after surgery. As a potential underlying mechanism, alcohol consumption increases serum IgE levels.

BackgroundMuch observational research reported that tea consumption decreases the risk of osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) which are the three major bone disorders. However, the observed correlation is inconclusive. To determine the causal relationship between genetically predicted tea intake and OA, RA, and OP, we performed a two-sample Mendelian randomization (MR) study based on large samples.MethodsThe European population’s genome-wide association meta-analysis (GWAS) dataset identified SNPs associated with tea consumption was obtained from Neale Lab’s analysis of UK Biobank data that comprised 349,376 participants of European ancestry. We extracted genetic data for knee OA (17,885 controls and 4,462 cases), hip OA (50,898 controls and 12,625 cases), and RA (43,923 controls and 14,361 cases) from the UK Biobank and OP cases (93083 controls and 1,175 cases) from FinnGen Data Freeze 2. A MR study was conducted to examine the effect of selected single nucleotide polymorphisms (SNPs) and OA, RA, and OP risk. Several sensitivity analyses were performed with weighted median and inverse-variance weighted methods for estimating the causal effects.ResultsIn this MR study, the genetically predicted per one cup increase of tea consumption was not associated with knee OA (OR 1.11,95% CI: 0.79–1.55) using IVW with random effect. Genetic predisposition to tea consumption was not associated with hip OA (OR: 1.20, 95% CI: 0.84–1.71), RA (OR: 1.24 95% CI: 0.81–1.91), and OP (OR: 1.11, 95% CI: 0.89, 1.39). Following the sensitivity analysis, there was no potential pleiotropy.ConclusionAccording to our study, According to our study, there was no statistical power to confirm a causal relationship between tea consumption and the risk of knee OA, hip OA, RA, and OP.

PurposeUnstable femoral shaft fractures (UFSFs) in children aged 5–11 years remain challenging due to their intrinsic instability. The aim of this study was to evaluate the clinical and radiographic outcomes of UFSF in children aged 5 to 11 years managed by the combined use of ESIN and temporary EF.MethodsChildren with UFSF (long oblique and comminuted) treated by ESIN and temporary EF were retrospectively reviewed. Sex, age at injury, side involved, type of fracture, presence or absence of associated lesions or neurovascular complications, type of treatment, time from trauma to surgery, duration of surgery, radiation exposure and length of postoperative immobilization were collected from the medical charts. Radiological and functional outcomes were evaluated according to Beaty's and Flynn's criteria, respectively.ResultsA total of 28 consecutive patients with closed or open (Gustilo type I or II) UFSF were reviewed (18 boys and 10 girls). The mean age at injury was 8.7 ± 1.6 years (range, 5–11); the average weight was 38.1 ± 7.6 kg (range, 26–55). The mean hospital stay was 3.7 ± 1.4 days (range, 2–7), and the mean time to EF and ESIN removal was 6.5 ± 1.1 weeks (range, 4–8) and 9.4 ± 1.6 months (range, 6–12), respectively. Twenty-seven out of 28 patients had excellent radiographic outcomes according to Beaty's criteria, and 24/28 had excellent functional outcomes according to Flynn's criteria. Overall, 4 complications (14.3%) were recorded. No statistically significant correlation was found between complication rates and sex, age, weight or fracture characteristics (P < 0.05).ConclusionsThe combined use of ESIN and temporary EF provides good clinical and radiological outcomes in children with UFSF aged between 5 and 11 years, with a reduced complication rate.

Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.

Problem definition: Many small businesses (suppliers) use web platforms (retailers) to sell their products on a consignment basis. Suppliers are often financially constrained, which affects their profits. Academic/practical relevance: We derive the equilibrium terms of the loan that a retailer will offer to a supplier in a consignment selling environment and their implications for supply chain efficiency. Our model is inspired by the lending program initiated by a major web platform owner. Methodology: We formulate and solve a Stackelberg game. The retailer sets loan terms that may include a debt seniority requirement. The supplier may either accept the retailer’s offer or borrow only from the bank or rely solely on its own capital. A competitively priced bank loan is the supplier’s default option. Results: There exist parameter values for which the on-equilibrium loan terms include retailer debt seniority as well as parameter values that do not. In the latter case, the supplier makes the bank the senior lender. The retailer’s debt seniority choice depends on the supplier’s working capital. When the retailer chooses to be the senior lender, its loan terms may induce the supplier to produce more than the first-best quantity. Managerial implications: Direct financing under equilibrium loan terms weakly improves the expected profits of both the retailer and the supplier. However, it may induce the supplier to produce less than or equal to or greater than the first-best production quantity. Loan limits serve to reduce overproduction.

Nucleosomal histones are barriers to the DNA repair process particularly at DNA double-strand breaks (DSBs). However, the molecular mechanism by which these histone barriers are removed from the sites of DNA damage remains elusive. Here, we have generated a single specific inducible DSB in the cells and systematically examined the histone removal process at the DNA lesion. We found that histone removal occurred immediately following DNA damage and could extend up to a range of few kilobases from the lesion. To examine the molecular mechanism underlying DNA damage-induced histone removal, we screened histone modifications and found that histone ADP-ribosylation was associated with histone removal at DNA lesions. PARP inhibitor treatment suppressed the immediate histone eviction at DNA lesions. Moreover, we examined histone chaperones and found that the FACT complex recognized ADP-ribosylated histones and mediated the removal of histones in response to DNA damage. Taken together, our results reveal a pathway that regulates early histone barrier removal at DNA lesions. It may also explain the mechanism by which PARP inhibitor regulates early DNA damage repair.

Group running has become a popular social phenomenon in China. Yet there is a limited understanding of running as a social and communal experience, with most of the previous studies being conducted...

Large micron-sized Y3Al5O12:Ce3+ phosphors were successfully synthesized by a cost-effective method using eutectic mixtures of YF3–AlF3 as the molten-salt flux for high-power laser diodes applications. The crystallinity, morphology, particle size, thermal quenching properties of the phosphors were measured, respectively. The phosphor particle size increased with increasing amount of flux, and the medium size (D50) could reach 40 μm when adding 25 wt% YF3–AlF3. The phosphors with larger particle size did not only exhibit superior optical performances but also excellent thermal-quenching characteristics, leading to a lower surface temperature and a higher radiant efficiency when excited by a high-power laser.

The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control due to the fact that their teeth share highly conserved and well-characterized developmental processes and their developmental tempo vary notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrate that the dental mesenchyme dominates the tooth developmental tempo and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3K-Akt intracellular signaling, and impelled the transition of the cell cycle from G1- to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo and the dental mesenchymal FGF8 could be a pivotal factor in controlling developmental pace in a non-cell-autonomous manner during mammalian odontogenesis.

Semiconducting minerals are ubiquitous in soil and their association with microbes often affects the environment. In this study, the impacts of zinc sulfide (ZnS, used as a model compound for semiconducting sphalerite) on As/Fe mobility of flooded tailing soils under dark and intermittent illumination conditions were elucidated for the first time. Microbial reductive dissolution of As(V) and Fe(III) was more pronounced under intermittent illumination than under dark conditions. In ZnS-amended soils, release of As(III) and Fe(II) was 1.3 and 1.7 times higher, respectively, under intermittent illumination than the highest concentrations released from soils amended with acetate alone under dark conditions (12741.1 ± 714.3 μg/L and 37.9 ± 2.3 mg/L, respectively). However, under dark conditions in ZnS-amended soil, the release of As(III) and Fe(II) was 0.8 and 0.7 times that of the highest concentrations released from soils amended with acetate under dark conditions, respectively. Treatment with ZnS potentially decreased the abundance of several metal-reducing bacteria (e.g., Bacillus, Geobacter, Clostridium, and Desulfitobacterium), which resulted in lower As/Fe reduction than for the acetate alone treatment under dark conditions. However, under intermittent illumination, the excited mineral photoholes were scavenged by humic/fulvic acids, and photoelectrons were synchronously separated and participated in the microbial electron chain. The fortification provided by the photoelectrons subsequently boosted As/Fe reduction, even though there was a lower abundance of metal-reducing bacteria. Hence, this study provides an in-depth understanding of the impacts of semiconducting minerals on the fates of metal pollutants, microbial diversity, and the bioavailability of dissolved organic matter in flooded soils.

Nanosized titanium dioxide (TiO2) is a naturally existing nanoscale semiconducting mineral, and its co-occurrence with microbes may elicit differential environmental effects. In this study, the imp...

By the ordered tree inclusion we will check whether a pattern tree P can be included in a target tree T, where the order of siblings in both P and T matters. This problem has many applications in practice, such as retrieval of documents, data mining, and RNA structure matching. In this paper, we propose an efficient algorithm for this problem. Its time complexity is bounded by ${\text{O}(\vert }T\vert \cdot \;min\{h_{P}{,\;\vert \text{leaves(}}P)\vert \})$O(|T|·min{hP,|leaves(P)|}), with ${\text{O}(\vert }T\vert + \vert P\vert)$O(|T|+|P|) space being used, where hP (hT) represents the height of P (resp., T) and leaves (P) stands for the set of the leaves of P. Up to now the best algorithm for this problem needs $\Theta (\vert T\vert \cdot \vert leaves(P)\vert)$Θ(|T|·|leaves(P)|) time and ${\text{O}(\vert }P\vert + \vert T\vert)$O(|P|+|T|) space. Extensive experiments have been done, which show that the new algorithm can perform much better than the existing ones in practice.

The orange-spotted grouper, Epinephelus coioides, is a marine protogynous hermaphrodite fish of commercial importance. There are many examples of sex change species among marine fish, but the molecular basis for the sex change is still unknown. Gonadal expression patterns of the dmrts and foxls genes in E. coioides have pointed to sexual dimorphism in this species and it has been shown that mRNA levels of dmrts and foxls to vary significantly during reproduction cycles. The steroid 17α-methyltestosterone was used to induce sex reversal in these fish, during which dmrts and foxls levels changed significantly and subsequently reverted to normal when 17α-methyltestosterone was withdrawn. Interestingly, the expression of dmrt2b and dmrt3 was not affected by this steroid. We speculate that the role of foxl2 in reproduction may be conserved via regulation of early differentiation of the ovary by the hypothalamus-pituitary-gonad axis, and dmrt2 may have a significant role in premature ovarian differentiation and maintenance in E. coioides. dmrt1 and foxl3 played a role in the development of the testes and are believed to be potential male regulatory genes.

The karyotype of most birds has remained considerably stable during more than 100 million years’ evolution, except for some groups, such as parrots. The evolutionary processes and underlying genetic mechanism of chromosomal rearrangements in parrots, however, are poorly understood. Here, using chromosome-level assemblies of three parrot genomes (monk parakeet, blue-fronted amazon, budgerigar), we uncovered frequent chromosome fusions and fissions among parrots, with most of them being lineage-specific. In particular, at least 12 chromosomes recurrently experienced inter-chromosomal fusions in different parrot lineages. Two conserved vertebrate genes, ALC1 and PARP3, with known functions in the repair of double-strand breaks and maintenance of genome stability, were specifically lost in parrots. The loss of ALC1 was associated with multiple deletions and an accumulation of CR1-psi, a novel subfamily of transposable elements (TEs) that recently amplified in parrots, while the loss of PARP3 was associated with an inversion. Additionally, the fusion of the ZW sex chromosomes and chromosome 11 has created a pair of neo-sex chromosomes in the ancestor of parrots, and the chromosome 25 has been further added to the sex chromosomes in monk parakeet. The newly formed neo-sex chromosomes were validated by our chromosomal painting, genomic and phylogenetic analyses. Transcriptome profiling for multiple tissues of males and females did not reveal signals of female-specific selection driving the formation of neo-sex chromosomes. Finally, we identified one W-specific satellite repeat that contributed to the unusual enlargement of the W chromosome in monk parakeet. Together, the combination of our genomic and cytogenetic analyses highlight the role of TEs and genetic drift in promoting chromosome rearrangements, gene loss and the evolution of neo-sex chromosome in parrots.

In deep exploration, astronomical images are often contaminated by noise when they are transmitted to the earth by satellites. In addition, the existing compression methods are difficult to compress the image with a lower compression sampling ratio, resulting in longer image data transmission time. Donoho proposed a new sampling theory named compressed sensing (CS) in 2006, which can recover a high quality image only using a few information of original image. In this paper, CS method is employed to solve the problem of astronomical image compression, meanwhile, the CS recovery denoising algorithm based curvelet is proposed for astronomical image denoising. The experimental results show that the compression performance of CS method is superior to the famous JPEG and JPEG-2000 compression method, it can compress the high resolution astronomical image with a lower compression sampling ratio. Meanwhile, the proposed algorithm can effectively remove more noise from the noisy image, and preserves more detailed features.

supplement_material for Mediating and moderating effects in golf tourism: Evidence from Hainan Island by Huimin Song, Jamie M Chen and Yibin Chen in Tourism Economics

In this study, Na doped TiO2 (Na-TiO2) was successfully prepared using metal–organic framework (MIL-125(Ti)) as precursor. Then, the as-prepared Na-TiO2 was inserted into the interlayer between the electron transport layers and perovskite layer. As a result, the interface contact between layers has been improved effectively, leading to the enhancement of optoelectronic performance of perovskite solar cells. Compared with the traditional device, the Na-TiO2 decorated device exhibited higher quality perovskite layer with lower trap state density, higher conductivity, and better electron’s extraction and transmission. Power conversion efficiency of solar cell increased form pristine device of 17.21 % to 20.49 % with excellent reproducibility under 100 mW·cm2 illumination. The result illustrated a novel and facile method for promoting the performance of PSCs.

Engineering of functional vascularized liver tissues holds great promise in addressing donor organ shortage for transplantation. Whole organ decellularization is a cell removal method that retains the native vascular structures of the organ such that it can be anastomosed with the recipient circulation after recellularization with healthy cells. However, a main hurdle to successful implantation of bioengineered organ is the inability to efficiently re-endothelialize the vasculature with a functional endothelium, resulting in blood clotting which is the primary cause of failure in early transplant studies. Here, we present an efficient approach for enhancing re-endothelialization of decellularized rat liver scaffolds by conjugating the REDV cell-binding domain to improve attachment of endothelial cells (EC) on vascular wall surfaces. In order to facilitate expression and purification of the peptide, REDV was fused with elastin-like peptide (ELP) that confers thermally triggered aggregation behavior to the fusion protein. After validating the adhesive properties of the REDV-ELP peptide, we covalently coupled REDV-ELP to the blood vasculature of decellularized rat livers and seeded EC using perfusion of the portal vein. We showed that REDV-ELP increased cell attachment, spreading and proliferation of EC within the construct resulting in uniform endothelial lining of the scaffold vasculature. We further observed that REDV-ELP conjugation dramatically reduced platelet adhesion and activation. Altogether, our results demonstrate that this method allowed functional re-endothelialization of liver scaffold and show great potential toward the generation of functional bioengineered liver for long-term transplantation. Statement of Significance There is a critical need for novel organ replacement therapies as the grafts for transplantation fall short of demand. Recent advances in tissue engineering, through the use of decellularized scaffolds, have opened the possibility that engineered grafts could be used as substitutes for donor livers. However, successful implantation has been challenged by the inability to create a functional vasculature. Our research study reports a new strategy to increase efficiency of endothelialization by increasing the affinity of the vascular matrix for endothelial cells. We functionalized decellularized liver scaffold using elastin-like peptides grafted with REDV cell binding domain. We showed that REDV-ELP conjugation improve endothelial cell attachment and proliferation within the scaffold, demonstrating the feasibility of re-endothelializing a whole liver vasculature using our technique.

Mesothelin (MSLN) is a tumor-associated antigen over-expressed on the cell surface of various malignant tumor cells, including majority of mesothelioma and ovarian cancer. MSLN-directed therapy has been intensively studied in preclinical and clinical settings. However, the clinical efficacy and safety of mesothelin-targeted therapy remains to be demonstrated. To identify a safe and effective target for CAR-T cell therapy in solid tumors, we used artificial intelligent platform developed with public and private RNA transcription database to identify cancer-associated antigens caused by alternative spicing. One of interesting targets is an alternative spicing isoform from MSLN. Human MSLN transcript has at least three isoforms. The isoform 1 is the predominant transcript detected in normal and tumor tissues and has been a promising target for cancer immunotherapy. The isoform 2 is the minor transcript using alternatively spliced exons producing 8 additional amino acids insertion compared to isoform 1. The isoform 3 produces a truncated and soluble MSLN. Our data demonstrated that MSLN isoform 2 is specifically expressed in ovarian cancers but not normal tissues, confirmed by Q-PCR studies. Furthermore, we generated mouse hybridoma antibodies specifically targeting MSLN isoform 2. The antibody specificity was screened and confirmed by ELISA-based reaction to MSLN isoform 2-specific peptide and flow cytometry-based binding to 293T cells overexpressing MSLN isoform 2 but not isoform 1 proteins. We further detected the endogenous MSLN isoform 2 expression in human mesothelioma cell line NCI H226 and further confirmed MSLN isoform 2 expression on human primary mesothelioma and ovarian cancer tissue but not normal tissues by immunohistochemistry staining. To study if targeting MSLN isoform 2 with chimeric antigen receptor (CAR) can control the tumor growth, we made CAR retrovirus construct and showed that genetically modified allogenic gamma-delta T cells expressing CAR for MSLN isoform 2 can kill human mesothelioma cells in vitro and in vivo. In summary, we have demonstrated that MSLN isoform 2 is a tumor-specific antigen, which can be targeted for CAR-T cell therapy. Citation Format: Xiaohong Wang, Yibin Chen, Anupama Gopisetty, Leonardo Mirandola, Lucia Piccotti, Quynh Nguyen, Maurizio Chiriva-Internati. Mesothelin isoform 2 is a novel target for allogenic CARγδT cell therapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1534.

With H2O as the solvent and NaI as the supporting electrolyte, a green and efficient electrochemical route has been developed to synthesize arylsulfonamides via I2 electrogenerated in situ at a graphite anode to promote the reaction of sodium sulfinates with aromatic or aliphatic primary and secondary amines. The target products could be obtained in good to excellent yields at room temperature.

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch‐like enoyl-coenzyme A hydratase (ECH)‐associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

Liver is a highly metabolically active organ that has high oxygen and nutrient demands. Even though a healthy liver has the capacity to regenerate, damage to the organ may result in mortality if the hepatic function is not supported. Because the current treatment methods for liver failure are limited, tissue engineering has offered tools to develop alternative treatment options. One common aspect of tissue engineering approaches for liver regeneration is the use of either synthetic or natural materials to provide an environment that mimics the physiological conditions and architecture of the organ. Here, we provide background on the extracellular environment in the liver and summarize materials and fabrication methods used for scaffold fabrication that support liver regeneration.

Engineered liver grafts for transplantation with sufficient hepatic function have been developed both in small and large animal models using the whole liver engineering approach. However, repopulation of the bile ducts in the whole liver scaffolds has not been addressed yet. In this study, we show the feasibility of repopulating the bile ducts in decellularized rat livers. Biliary epithelial cells were introduced into the bile ducts of the decellularized liver scaffolds with or without hepatocytes in the parenchymal space. The recellularized grafts were cultured under perfusion for up to 2 days and histological analysis revealed that the biliary epithelial cells formed duct-like structures, with the viable hepatocyte mass residing in the parenchymal space, in an arrangement highly comparable to the native tissue. The grafts were viable and functional as confirmed by both albumin and urea assay results and the gene expression analysis of biliary epithelial cells in recellularized liver grafts. This study provides the proof-of-concept results for rat liver grafts co-populated with parenchymal and biliary epithelial cells.

Minerals are ubiquitous in the natural environment and have close contact with microorganisms. In various scenarios, microorganisms that harbor extracellular electron transfer (EET) capabilities have evolved a series of beneficial strategies through the mutual exchange of electrons with extracellular minerals to enhance survival and metabolism. These electron exchange interactions are highly relevant to the cycling of elements in the epigeosphere and have a profound significance in bioelectrochemical engineering applications. In this review, we summarize recent advances related to the effects of different minerals that facilitate the EET process and discuss the underlying mechanisms and outlooks for future applications. The promotional effects of minerals arise from their redox-active ability, electrical conductivity and photocatalytic capability. In mineral-promoted EET processes, various responses have concurrently arisen in microorganisms, such as stretching of electrically conductive pili (e-pili), upregulated expression of outer-membrane cytochromes (Cyts) and production of specific enzymes, and secretion of extracellular polymeric substances (EPSs). This review synthesizes the understanding of electron exchange mechanisms between microorganisms and minerals and highlights potential applications in development of renewable energy production and pollutant remediation, which are topics of particular significance to future exploitation of biotechnology.

Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear. Here, we describe a new method to utilize discarded livers to make transplantable new liver grafts. We show that marginal donor livers damaged due to warm ischemia could be treated with machine perfusion to yield 39 million viable hepatocytes per gram of liver, similar to fresh livers, and these cells could be used to repopulate decellularized liver matrix (DLM) scaffolds to make transplantable liver grafts. The hepatocytes from recovered livers sustained their characteristic epithelial morphology while they exhibited slightly lower protein synthesis functions both in plate cultures and in recellularized liver grafts. The dampened protein synthesis was attributed to residual endoplasmic reticulum stress found in recovered cells. The results here represent a unique approach to reengineer transplantable liver grafts solely from discarded organs.