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L-tryptophan has been used as a feed additive for swine and poultry and as a nutrient supplement for humans. However, some impurities in l-tryptophan have been reported as causative components of eosinophilia-myalgia syndrome. Therefore, from a safety perspective, it is important to analyze meat samples for these impurities. This study aims to develop an analytical method for the simultaneous detection of l-tryptophan impurities in meat products using LC–MS/MS. Among the various impurities, detection methods for (S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid (5-hydroxytryptophan) (HTP), 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA), 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]-indole-2-carboxylic acid (PIC), and 1,1′-ethylidenebistryptophan (EBT) and 2-(3-indoylmethyl)-l-tryptophan (IMT) were developed. The developed method allowed simultaneous determination of these four impurities in 5 min. No interferences from the matrix were observed, and the method showed good sensitivity to each analyte. The method detection limit and limit of quantification in meat matrices were below 11.2 and 35.7 μg/kg, respectively.

Water beads are small, colorful toys that swell over the time in water. We report 2 cases of intestinal obstruction by unwitnessed ingestion of water beads. The diagnosis of each case was made by exploratory laparoscopy or comprehensive ultrasonography. The water beads were removed surgically in both cases. Since their ingestion can cause intestinal obstruction, water beads should not be allowed as toys for children.

Background and Objectives: With the emergence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), it has become necessary to identify the implant shell type patients have received. Therefore, an immediate, reliable method for identifying a breast implant shell type is essential. Evidence-based research and applying a real-world technique that identifies the surface topographic information of the inserted breast implants, without surgery, has become of paramount importance for breast implant physicians. Methods and Materials: A review of the medical records of 1901 patients who received 3802 breast implants and subsequently received an ultrasound-assisted examination was performed. All patients received not only a breast cancer examination but also a high-resolution ultrasonography (HRUS) assisted examination of the device at a single center between 31 August 2017 and 31 December 2022. Results: Most patients had breast implants within 10 years (77.7%) of the examination. Of the 3802 implants screened, 2034 (53.5%) were identified with macro-textured shell topography in ultrasonography. A macrotextured shell type implant was used in 53.5% of cases and a smooth type in 42.7% of cases. Seventy-three (1.9%) breast implant shell types could not be identified due to ruptures. However, 250 breast implant shell types could be identified despite rupture cases (6.5%). Conclusions: HRUS was found to be a useful and reliable image modality for identifying various surface shell types of breast implants. The shell type information would be helpful to patients who lack information about their breast implants and are concerned about BIA-ALCL.

Aucubin is an iridoid glycoside that displays various pharmacological actions including antioxidant activity. However, there are few reports available on the neuroprotective effects of aucubin against ischemic brain injury. Thus, the aim of this study was to investigate whether aucubin protected against damage to hippocampal function induced by forebrain ischemia-reperfusion injury (fIRI) in gerbils, and to examine whether aucubin produced neuroprotection in the hippocampus against fIRI and to explore its mechanisms by histopathology, immunohistochemistry, and Western analysis. Gerbils were given intraperitoneal injections of aucubin at doses of 1, 5, and 10 mg/kg, respectively, once a day for seven days before fIRI. As assessed by the passive avoidance test, short-term memory function following fIRI significantly declined, whereas the decline in short-term memory function due to fIRI was ameliorated by pretreatment with 10 mg/kg, but not 1 or 5 mg/kg, of aucubin. Most of the pyramidal cells (principal cells) of the hippocampus died in the Cornu Ammonis 1 (CA1) area four days after fIRI. Treatment with 10 mg/kg, but not 1 or 5 mg/kg, of aucubin protected the pyramidal cells from IRI. The treatment with 10 mg/kg of aucubin significantly reduced IRI-induced superoxide anion production, oxidative DNA damage, and lipid peroxidation in the CA1 pyramidal cells. In addition, the aucubin treatment significantly increased the expressions of superoxide dismutases (SOD1 and SOD2) in the pyramidal cells before and after fIRI. Furthermore, the aucubin treatment significantly enhanced the protein expression levels of neurotrophic factors, such as brain-derived neurotrophic factor and insulin-like growth factor-I, in the hippocampal CA1 area before and after IRI. Collectively, in this experiment, pretreatment with aucubin protected CA1 pyramidal cells from forebrain IRI by attenuating oxidative stress and increasing neurotrophic factors. Thus, pretreatment with aucubin can be a promising candidate for preventing brain IRI.

Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.

Autograft or metal implants are routinely used in skeletal repair but can fail to provide a long-term clinical resolution, emphasising the need for a functional biomimetic tissue engineering alternative. An attractive sustainable opportunity for tissue regeneration would be the application of human bone waste tissue for the synthesis of a material ink for 3D bioprinting of skeletal tissue.The use of human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate micro-environment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. Extrusion-based deposition was mediated by the blending of human bone-ECM (B) with nanoclay (L, Laponite®) and alginate (A) polymer, to engineer a novel material ink (LAB). The inclusion of nanofiller and polymeric material increased the rheological, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularisation following implantation in anex vivochick chorioallantoic membrane (CAM) model. Addition of bone morphogenetic protein-2 (BMP-2) with HBMSCs further enhanced vascularisation together with mineralisation after only 7 days.The current study demonstrates the synergistic combination of nanoclay with biomimetic materials, (alginate and bone-ECM) to support the formation of osteogenic tissue bothin vitroandex vivoand offers a promising novel 3D bioprinting approach to personalised skeletal tissue repair.Graphical AbstractEngineering nanoclay-based bone ECM novel bioink for bone regeneration. Human bone trabecular tissue was demineralised, decellularised and blended with nanoclay (Laponite®) and alginate after digestion. The resulting ink was investigated for printability following rheological and filament fusion investigation. The microstructural arrangement of the blends was examined together with viability and functionality of bioprinted HBMSCs. Finally, the ability of the novel blend to support drug release ex vivo in a CAM model was determined confirming the potential of the bone ECM ink to support bone formation.

Localized surface plasmon resonance-enhanced Cd-free blue electroluminescent devices integrated with ZnSeTe quantum dots and AuAg alloy nanoparticles were demonstrated.

The subchronic toxicity of oral L-tryptophan produced by fermentation with metabolically engineered

Multi-organ dysfunction following cardiac arrest is associated with poor outcome as well as high mortality. The kidney, one of major organs in the body, is susceptible to ischemia and reperfusion; however, there are few studies on renal ischemia and reperfusion injury (IRI) following the return of spontaneous circulation (ROSC) after cardiac arrest. Risperidone, an atypical antipsychotic drug, has been discovered to have some beneficial effects beyond its original effectiveness. Therefore, the aim of the present study was to investigate possible therapeutic effects of risperidone on renal IRI following cardiac arrest. Rats were subjected to cardiac arrest induced by asphyxia for five minutes followed by ROSC. When serum biochemical analyses were examined, the levels of serum blood urea nitrogen, creatinine, and lactate dehydrogenase were dramatically increased after cardiac arrest, but they were significantly reduced by risperidone administration. Histopathology was examined using hematoxylin and eosin staining. Histopathological injury induced by cardiac arrest was apparently attenuated by risperidone administration. Furthermore, alterations in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and anti-inflammatory cytokines (interleukin-4 and interleukin-13) were examined by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokine immunoreactivities were gradually and markedly increased and decreased, respectively, in the kidneys following cardiac arrest; however, risperidone administration after cardiac arrest significantly attenuated the increased pro-inflammatory cytokine immunoreactivities and the decreased anti-inflammatory cytokine immunoreactivities. Collectively, our current results revealed that, in rats, risperidone administration after cardiac arrest protected kidneys from IRI induced by cardiac arrest and ROSC through anti-inflammatory effects.

Autophagy dysregulation and lysosomal dysfunction are critical in Parkinson’s disease. However, the cause and pathogenic signaling of the lysosomal functional deficiency is unknown. Here, we report on the role of zinc as a link between mitochondrial damage and lysosomal depletion. A mitochondrial toxin, 1-methyl-4 phenylpyridinium (MPP⁺), increased reactive oxygen species (ROS) and intracellular zinc ([Zn2+]i), causing lysosomal membrane permeabilization (LMP) and cell death. Supporting this, antioxidant or zinc chelator significantly reduced MPP⁺-induced LMP and neuronal death, whereas lysosomal protease inhibitors attenuated neuronal death but not ROS and [Zn2+]i. Whereas H₂O₂ toxicity was almost completely attenuated in Metallothionein-3 (MT-3) knock-out (KO) astrocytes, zinc overload- or MPP⁺-induced toxicity increased in MT-3 KO astrocyte cultures, suggesting that MT-3 modulates excessive zinc rather than providing a source of zinc after MPP⁺ treatment. Next, mitochondria-deficient Rho 0 cells were used to determine whether mitochondria are a source of zinc. No increase in ROS, [Zn2+]i, LMP, or MPP⁺ toxicity was observed in Rho 0 cells compared to wild-type cells, suggesting that increased ROS and [Zn2+]i by MPP⁺ originated from mitochondria. Taken together, we suggest that LMP is induced by the release of zinc after mitochondrial damage, eventually leading to neuronal death and lysosomal deficiency. Conduct of future studies will be needed to determine whether zinc is involved in MPP+-induced blocking of autophagic flux and accumulation of α-synuclein.

Isolating a large quantity of high-quality human islets is a prerequisite for diabetes research. Human islets are typically isolated from the pancreases of brain-dead donors, making research difficult due to low availability. Pancreas tissue discarded after surgical resection may be a good alternative source of islet cells. To test this hypothesis, we isolated islets from discarded surgical specimens and evaluated the islet yield and quality as well as islet cell preparations. Eighty-two segmental pancreases were processed using the Ricordi automated method, and islet yield and quality were investigated. The mean age of patients was 54.6, and the cohort included 32 diabetes patients. After purification, partially resected pancreases yielded an average of 59,593 ± 56,651 islet equivalents (IEQs) and 2546 IEQ/g of digested pancreas, with 71.5 ± 21% purity. Multivariate analysis revealed that diabetes (p = 0.0046) and the lobe used (p = 0.0156) significantly altered islet yield. Islets transplanted into diabetic mice displayed good viability and in vitro glucose responses, DNA/RNA quality, mitochondrial function, and glucose control, even though these results were dependent on islet quality. Isolated cells also maintained high viability and function even after cryopreservation. Our findings indicate that pancreatic tissue discarded after surgery can be a valuable source of islets for diabetes research.

The past decade has seen a growing appreciation for the role of the innate immune response in mediating repair and biomaterial directed tissue regeneration. The long-held view of the host immune/inflammatory response as an obstacle limiting stem cell regenerative activity, has given way to a fresh appreciation of the pivotal role the macrophage plays in orchestrating the resolution of inflammation and launching the process of remodelling and repair. In the context of bone, work over the past decade has established an essential coordinating role for macrophages in supporting bone repair and sustaining biomaterial driven osteogenesis. In this review evidence for the role of the macrophage in bone regeneration and repair is surveyed before discussing recent biomaterial and drug-delivery based approaches that target macrophage modulation with the goal of accelerating and enhancing bone tissue regeneration.

This paper aims to investigate the effectiveness of the process-genre approach on EFL learners’ writing improvement. A total of 48 Chinese college freshmen students participated in this study, and they were divided into high-level (n=20) and low-level (n=28) groups. All the participants were instructed by the same teacher in the College English class for 14 weeks, during which they were taught how to compose in three writing genres: narration, exposition, and argumentation. After comparing the writing scores of pre- and post-tests from both groups, it can be concluded that the processgenre approach is helpful in enhancing the EFL learners’ writing competence because both groups of students had significantly improved their writing abilities. Besides, both group learners attained a salient achievement in expository writing after they were trained by the process-genre approach. Compared with the high-level learners, the low-level learners made larger progress in all three writing genres. It indicates that enough teaching time and teacher’s scaffolding systems are crucial for the learners’ writing development.

Clonorchis sinensis is the most common fish-borne intestinal parasite in Korea. The aim of the present investigation was to survey the status of C. sinensis infection and analyze associated risk factors in residents of Haman-gun, Gyeongsangnam-do. A total of 5,114 residents from 10 administrative towns/villages voluntarily agreed to participate in the study, which comprised fecal examination, a questionnaire survey for risk factors, ultrasonography, and enzymelinked immunosorbent assay for cancer biomarker detection in the blood. We detected C. sinensis eggs in 5.3% of the subjects. By region, Gunbuk-myeon had the highest number of residents with C. sinensis eggs. The infection rate and intensity were higher in male than in female residents. Based on the risk factor questionnaire, infection was highly associated with drinking, a history of C. sinensis infection, and the practice of eating of raw freshwater fish. Extension of the bile duct, infection intensity, and cancer biomarker detection significantly correlated with the presence of eggs in the study population. In conclusion, the development of feasible, long-term control policies and strategies for the elimination of C. sinensis in Korea is still required.

In contrast to a substantial progress of heavy metal-free green and red emitters exclusively from indium phosphide (InP) quantum dots (QDs), the development of non-Cd blue QDs remains nearly unexpl...

Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function. As well as their utility as physical cross-linkers, clays have been explored for sustained localization of biomolecules to promote in vivo tissue regeneration. To date, both biomolecule-clay and polymer-clay nanocomposite strategies have utilised the negatively charged clay particle surface. As such, biomolecule-clay and polymer-clay interactions are set in competition, potentially limiting the functional enhancements achieved. Here, we apply specific bisphosphonate interactions with the positively charged clay particle edge to develop self-assembling hydrogels and functionalized clay nanoparticles with preserved surface exchange capacity. Low concentrations of nanoclay are applied to cross-link hyaluronic acid polymers derivatised with a pendant bisphosphonate to generate hydrogels with enhanced mechanical properties and preserved protein binding able to sustain, for over six weeks in vivo, the localized activity of the clinically licensed growth factor BMP-2., Nanoclays have been used in composites and for drug delivery but have suffered from a trade-off in properties when used for both. Here the authors report on the use of bisphosphonate interactions with nanoclay edges to made drug loaded composites without compromising materials properties or drug loading.

Obesity is a serious problem in modern society and its prevalence continues to increase worldwide, resulting in metabolic disorder related diseases. D-allulose, a sugar substitute, boasts a near-zero calorie value and regulates lipid accumulation. However, the molecular mechanism of D-allulose at the cellular level has not been fully elucidated. In this study, we investigated the effect of D-allulose on 3T3-L1 adipocyte differentiation. D-allulose inhibits differentiation of 3T3-L1 preadipocytes into mature adipocytes, as examined by Oil Red O staining. The mRNA levels of genes involved in lipogenesis, including fatty acid synthase (FAS) and adipocyte fatty acid-binding protein (aP2), were significantly decreased and intracellular triglyceride (TG) content was markedly reduced with D-allulose treatment. We also monitored the activity of major adipogenic transcription factors–CREB, SREBP-1c, and PPARψ–using 3T3-L1 reporter cell lines that were constructed to secrete Gaussia luciferase upon binding of a transcription factor to its DNA binding element. Collectively, D-allulose suppresses adipocyte differentiation and lipid accumulation through regulating adipogenic transcription factors and may have anti-obesity potential.

Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and/or death in the spinal cord as well as the brain. Hypothermic therapy is reported to protect neurons from damage and improve hindlimb paralysis after resuscitation in a rat model of CA induced by asphyxia. In this study, we investigated roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the lumbar spinal cord protected by therapeutic hypothermia in a rat model of asphyxial CA. Male Sprague-Dawley rats were subjected to seven minutes of asphyxial CA (induced by injection of 2 mg/kg vecuronium bromide) and hypothermia (four hours of cooling, 33 ± 0.5 °C). Survival rate, hindlimb motor function, histopathology, western blotting, and immunohistochemistry were examined at 12, 24, and 48 h after CA/ROSC. The rats of the CA/ROSC and hypothermia-treated groups had an increased survival rate and showed an attenuated hindlimb paralysis and a mild damage/death of motor neurons located in the anterior horn of the lumbar spinal cord compared with those of the CA/ROSC and normothermia-treated groups. In the CA/ROSC and hypothermia-treated groups, expressions of cytoplasmic and nuclear Nrf2 and HO-1 were significantly higher in the anterior horn compared with those of the CA/ROSC and normothermia-treated groups, showing that cytoplasmic and nuclear Nrf2 was expressed in both motor neurons and astrocytes. Moreover, in the CA/ROSC and hypothermia-treated group, interleukin-1β (IL-1β, a pro-inflammatory cytokine) expressed in the motor neurons was significantly reduced, and astrocyte damage was apparently attenuated compared with those found in the CA/ROSC and normothermia group. Taken together, our results indicate that hypothermic therapy after CA/ROSC attenuates CA-induced hindlimb paralysis by protecting motor neurons in the lumbar spinal cord via activating the Nrf2/HO-1 signaling pathway and attenuating pro-inflammation and astrocyte damage (reactive astrogliosis).

Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends neuroprotective effects against cerebral or forebrain injury induced by ischemia and reperfusion. However, research on protective effects against ischemia and reperfusion cerebellar injury induced by cardiac arrest (CA) and the return of spontaneous circulation has been poor. Rats were assigned to four groups as follows: (Groups 1 and 2) sham asphyxial CA and vehicle- or oxcarbazepine-treated, and (Groups 3 and 4) CA and vehicle- or oxcarbazepine-treated. Vehicle (0.3% dimethyl sulfoxide/saline) or oxcarbazepine (200 mg/kg) was administered intravenously ten minutes after the return of spontaneous circulation. In this study, CA was induced by asphyxia using vecuronium bromide (2 mg/kg). We conducted immunohistochemistry for calbindin D-28kDa and Fluoro-Jade B histofluorescence to examine Purkinje cell death induced by CA. In addition, immunohistochemistry for 4-hydroxy-2-nonenal (4HNE) was carried out to investigate CA-induced oxidative stress, and immunohistochemistry for Cu, Zn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) was performed to examine changes in endogenous antioxidant enzymes. Oxcarbazepine treatment after CA significantly increased the survival rate and improved neurological deficit when compared with vehicle-treated rats with CA (survival rates ≥ 63.6 versus 6.5%), showing that oxcarbazepine treatment dramatically protected cerebellar Purkinje cells from ischemia and reperfusion injury induced by CA. The salvation of the Purkinje cells from ischemic injury by oxcarbazepine treatment paralleled a dramatic reduction in 4HNE (an end-product of lipid peroxidation) and increased or maintained the endogenous antioxidant enzymes (SOD1 and SOD2). In brief, this study shows that therapeutic treatment with oxcarbazepine after CA apparently saved cerebellar neurons (Purkinje cells) from CA-induced neuronal death by attenuating oxidative stress and suggests that oxcarbazepine can be utilized as a therapeutic medicine for ischemia and reperfusion brain (cerebellar) injury induced by CA.

The present study examines the extent to which key competence and learning competence in particular are promoted in the high school English classes attended by Chinese students. Eight hundred and thirty five college freshmen at a comprehensive four-year university in Jilin Province were surveyed on their experiences in high school English classes. In part 1 of the survey, we found that high school English instruction in China tends to be exam-focused rather than emphasizing the development of key competences. In part 2 of the survey, we found that three aspects of learning competence – attitudes toward learning English, meta-cognitive awareness concerning one’s own English learning, and knowledge about English language instruction – are not consistently instilled in high school English classes. Virtually no differences between ethnic majority and minority students were observed in survey. We believe that because English instruction in Chinese high schools is exam-oriented so that instructors do not have enough time to enhance learning competences. Our conclusion is that reform of instructional methods needs to include greater attention to the aspects of learning competence.