Hybrid aluminum nitride and silicon devices for integrated photonics.

Aluminum nitride has advantages ranging from a large transparency window to its high thermal and chemical resistance, piezoelectric effect, electro-optic property, and compatibility with the complementary metal-oxide-semiconductor fabrication process. We propose a hybrid aluminum nitride and silicon platform for integrated photonics. Hybrid aluminum nitride-silicon basic photonic devices, including the multimode interferometer, Mach-Zehnder interferometer, and micro-ring resonator, are designed and fabricated. The measured extinction ratio is > 22 dB and the insertion loss is < 1 dB in a wavelength range of 40 nm for the Mach-Zehnder interferometer. The extinction ratio and intrinsic quality factor of the fabricated micro-ring resonator are > 16 dB and 43,300, respectively. The demonstrated hybrid integrated photonic platform is promising for realizing ultralow-power optical switching and electro-optic modulation based on the piezoelectric and electro-optic effects of aluminum nitride thin films.

Influence of Nutritional Status on Prognosis of Stroke Patients With Dysphagia.

Context: Stroke is an acute cerebrovascular disease and a neurological disorder that occurs due to a cerebral arterial embolism and rupture. Acute stroke is often accompanied by dysphagia, which reduces patients' intake of food and nutrients, decreases their nutritional status, and affects their quality of life. Objective: The study intended to identify the demographic and clinical characteristics of stroke patients with dysphagia and to explore the relationship of those characteristics to nutritional status and prognosis. Methods: The research team retrospectively collected the clinical data of patients to compare the nutritional status and prognoses of patients with different demographic and clinical characteristics. Setting: The study took place in the Department of Neurology at the First People's Hospital of Shenyang in Shenyang, China. Participants: Participants were 789 stroke patients with dysphagia who had been admitted to the general ward of the neurology departments of hospitals of Grade 3 or higher in Northeast China between January 2019 and September 2020. Based on the results of the Nutrition Risk Screening (NRS-2002) and Subjective Global Assessment (SGA) scales at baseline, participants were enrolled in this study. Outcome Measures: The outcomes were the correlations between participants' demographic and clinical characteristics and their nutritional statuses and prognoses. The Modified Rankin Scale (mRS) was used to evaluate the prognosis of the patients at seven days and three months after participants' enrollment in the study. Using the SPSS 26.0, a t test, chi-square test, and F test were performed to analyze and verify the presence of fundamental differences in baseline characteristics between participants with good nutrition and those with poor nutrition. Also, a statistical correlation analysis was performed. Results: The study showed that participants with different nutritional levels had statistically significant differences in the presence or absence of infections and body temperature and scores on the Standardized Swallowing Assessment (SSA) and National Institutes of Health Stroke Scale (NIHSS), with all P < .001. At baseline seven days after enrollment, the prognoses of participants were significantly different for different previous histories of stroke (P < .001), family history of stroke (P = .005), presence or absence of infections (P < .001), body temperature (P < .001), and SSA (P < .001) and NIHSS (P < .001) scale scores. At three months after enrollment, the prognoses of participants were significantly different for previous history of stroke (P = .003), different body temperatures (P < .001), presence or absence of infections(P < .001), and SSA (P < .001) and NIHSS (P < .001) scale scores. Age, gender, family history of stroke, smoking, alcohol consumption, previous history of stroke, education level, SSA scale score, NIHSS scale score, body mass index (BMI), body temperature, and infection were adjusted in the model. Nutritional status as classified by NRS-2002 and SGA was significantly correlated with prognosis (P < .001). The prognosis of stroke patients with dysphagia was associated with nutritional status by unconditional logistic regression. Conclusion: The prognosis of stroke patients with dysphagia is related to their nutritional status. A better nutritional status indicates the better prognosis, and vice versa. In clinical treatment, attention should be paid to use of a nutritional intervention.

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy-lysosome mediated OCT4A degradation.

Capsaicin (CAP) is a well-known anti-cancer agent. Recently, we reported capsaicin-induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose-dependently decreased the sphere formation capacity of ATC cells. The stemness-inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP-induced OCT4A degradation was reversed by autophagy inhibitors 3-MA and chloroquine, BAPTA-AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium-dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.

Network Pharmacological Study of Achyranthis bidentatae Radix Effect on Bone Trauma.

PURPOSE: Bone trauma is a clinical condition that afflicts the majority of the world's population. For the management of bone trauma, the underlying mechanisms of the drugs effective for bone healing are deemed necessary. Achyranthis bidentatae Radix (ABR) is a popular alternative medicine recommended in the treatment of bone trauma and injury, yet its mechanism of action persists to be vague. This study was conducted for the evaluation of the mode of action of ABR through network pharmacology in treating bone trauma. METHODS: An extensive survey of published works led to the development of a drug-target database, after which multiple protein targets for bone trauma were discerned. The protein-protein interaction network was developed by utilizing the STITCH database and gene ontology (GO) enrichment analysis using Cytoscape and ClueGO. Moreover, docking studies were performed for revealing the affinity of various ingredients with IL6. RESULTS: The extensive literature survey yielded the presence of 176 components in ABR, and 151 potential targets were acquired. Scrutinization of these targets revealed that 21 potential targets were found to be associated with bone trauma. Out of which, some remarkable targets such as IL6, MAPK14, MAPK8, SRC, PTGS2, and MMP2 were observed to be associated in the functional interaction of ABR. According to docking results, several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have the lowest docking scores (range between -6 and -7). CONCLUSIONS: The results of the study elucidated that ABR can positively be utilized for the management of bone trauma, which can be mediated by multiple molecular mechanisms such as ERBB2 signaling pathway, positive regulation of oxidoreductase activity, JNK cascade pathway, multicellular organism metabolic process, T cell costimulation, and the positive regulation of MAPK activity. The findings also suggest that several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have good affinity with IL6, suggesting the promising potential of ABR in treating bone trauma, likely through IL6.

Diallyl trisulphide, a H2 S donor, compromises the stem cell phenotype and restores thyroid-specific gene expression in anaplastic thyroid carcinoma cells by targeting AKT-SOX2 axis.

It is widely accepted that anaplastic thyroid carcinoma (ATC), a rare, extremely aggressive malignant, is enriched by cancer stem cells (CSCs), which are closely related to the pathogenesis of ATC. In the present study, we demonstrated that diallyl trisulphide (DATS), a well-known hydrogen sulphide (H2 S) donor, suppressed sphere formation and restored the expression of iodide-metabolizing genes in human ATC cells, which were associated with H2 S generation. Two other H2 S donors, NaHS and GYY4137, could also suppress the self-renewal properties of ATC cells in vitro. Compared with normal thyroid tissues and papillary thyroid carcinomas (PTCs), the elevated expressions of SOX2 and MYC, two cancer stem cell markers, in ATCs were validated in the combined Gene Expression Omnibus (GEO) cohort. DATS decreased the expression of SOX2, which was mediated by H2 S generation. Furthermore, knockdown of AKT or inhibition of AKT by DATS led to a decrease of SOX2 expression in ATC cells. AKT knockdown phenocopied restoration of thyroid-specific gene expression in ATC cells. Our data suggest that H2 S donors treatment can compromise the stem cell phenotype and restore thyroid-specific gene expression of ATC cells by targeting AKT-SOX2 pathway, which may serve as a therapeutic strategy to intervene the CSC progression of ATC.

Targeting optimal time for hyperbaric oxygen therapy following carbon monoxide poisoning for prevention of delayed neuropsychiatric sequelae: A retrospective study.

OBJECTIVES: Delayed neuropsychiatric sequelae (DNS) are serious complications of carbon monoxide poisoning; neuropsychiatric disorders can occur within a few days of recovery from acute poisoning. Hyperbaric oxygen therapy (HBOT) has been the main treatment of carbon monoxide (CO) poisoning and was recommended as the treatment choice for CO poisoning by the American Undersea and Hyperbaric Medical Society and the Tenth European Consensus Conference on Hyperbaric Medicine of the European Underwater and Baromedical Society. However, the optimal timing for commencing HBOT in patients with CO poisoning remains unknown. We therefore conducted a retrospective study in an attempt to target the optimal time of HBOT for DNS prevention. METHODS: A retrospective review of patient files/medical records was conducted on all patients with CO poisoning admitted to the Emergency Department of Linkou Chang-Gung Memorial Hospital, Taiwan between January 1, 2009 and December 31, 2015. A total of 279 patients who received HBOT were eligible for further DNS detection. DNS was defined as the presence of one of the following neurological, cognitive, or psychological sequelae that were documented in the medical record during hospital stay or outpatient clinic follow-up for at least 6 months. A multivariable logistic regression analysis was employed to identify potential determinants of DNS after receiving HBOT for CO poisoning. A receiver operating characteristic (ROC) curve was used to analyse the influence of duration from CO exposure to HBOT on DNS development. RESULTS: A Glasgow coma score of <9 (odds ratio [OR], 3.20; 95% confidence interval [CI], 1.19-8.60) and a longer duration from CO exposure to HBOT (OR, 1.06; 95% CI, 1.03-1.09) were associated with a higher risk of DNS. By contrast, the presence of multiple victims from the same incident was associated with a lower risk of DNS. The ROC curve for the duration between CO exposure and HBOT in predicting DNS development demonstrated an area under the curve of 0.638 (95% CI, 0.575-0.698). The optimal cut-off point according to the Youden index was 22.5 h, with a sensitivity of 41.7% and a specificity of 85.9%. We also stratified the duration from CO exposure to HBOT into 5 intervals (< 6 h, 6-11 h, 12-23 h, 24-47 h and ≥ 48 h) and revealed a trend of increasing DNS risk with time. CONCLUSIONS: We identified several potential predictors of DNS in patients with CO poisoning who received HBOT. Multivariable logistic regressions further revealed that longer duration from CO exposure to HBOT, loss of consciousness, and the presence of multiple victims were independent predictors of DNS development. HBOT should be performed as early as possible and preferably within 22.5 h after CO poisoning.

Neuroprotective effects of Ginkgo biloba extract and Ginkgolide B against oxygen-glucose deprivation/reoxygenation and glucose injury in a new in vitro multicellular network model.

Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract (GBE) against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B (GB), against oxygen-glucose deprivation/reoxygenation and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein (Na-F), and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.

[Therapeutic effect of Artemisia argyi on oral ulcer in rats].

OBJECTIVE: To determine bacteriostatic abilities of Artemisia argyi extracts, and to explore the effect of Artemisia argyi extracts on oral ulcer in rats.
 Methods: We extracted the mixture of Artemisia argyi volatile oils and water-extraction by leaching method and evaluated the anti-microbial effect of Artemisia argyi extracts on common oral floras in vitro. The rat cheeks were burnt by NaOH to establish the models of oral ulcer. The curative effects of crude drug of Artemisia argyi extracts at 2.0, 1.0, 0.5 g/mL on oral ulcer in rats were evaluated by measuring the oral ulcer healing time. Serum TNF-α level and expression of proliferating cell nuclear antigen (PCNA) were analyzed by ELASA and immunohistochemical staining.
 Results: Artemisia argyi extracts obviously inhibited the Staphylococcus aureus and Streptococcus. NaOH-made oral ulcer in rats were successfully established. The crude drug at 2.0 and 1.0 g/mL obviously reduced healing time, significantly inhibited the release of TNF-α, and improved the PCNA level in the ulcer tissues (All P<0.01). The extracts obviously reduced the local inflammatory reaction and promoted tissue repair of oral ulcer.
 Conclusion: Artemisia argyi extracts promote tissue repair of oral ulcer via inhibiting bacterial growth, reducing the release of TNF-α and improving the PCNA level.

Regulation of the Phenylpropanoid Pathway: A Mechanism of Selenium Tolerance in Peanut (Arachis hypogaea L.) Seedlings.

To clarify the mechanisms of selenium (Se) tolerance in peanut seedlings, we grew peanut seedlings with sodium selenite (0, 3, and 6 mg/L), and investigated the phenylpropanoids metabolism in seedling roots. The results showed that selenite up-regulated the expression of genes and related enzyme activities involving in the phenylpropanoids biosynthesis cascade, such as phenylalanine ammonia-lyase, trans-cinnamate-4-hydroxylase, chalcone synthase, chalcone isomerase, and cinnamyl-alcohol dehydrogenase. Selenite significantly increased phenolic acids and flavonoids, which contributed to the alleviation of selenite-induced stress. Moreover, selenite enhanced the formation of endodermis in roots, which may be attributed to the up-regulation of lignin biosynthesis mediated by the selenite-induced changes of H2O2 and NO, which probably regulated the selenite uptake from an external medium. Accumulation of polyphenolic compounds via the phenylpropanoid pathway may be one of the mechanisms of the increasing selenite tolerance in plants, by which peanut seedlings survived in seleniferous soil, accompanied by accumulation of Se.

Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice.

Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) were reduced and the high density lipoprotein cholesterol level (HDL-C) was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions.

Enhanced hypoxia-inducible factor (HIF)-1α stability induced by 5-hydroxymethyl-2-furfural (5-HMF) contributes to protection against hypoxia.

We first reported the role of 5-hydroxymethyl-2-furfural (5-HMF) against hypoxia. Here, we studied the mechanism by using oxygen-dependent degradation domain (ODD)-Luc mice, which are a useful model to probe the stabilization of hypoxia-inducible factor 1α (HIF-1α). Compared with three other compounds that have been reported to have a role in stabilizing HIF-1α, 5-HMF caused stronger bioluminescence, which is indicative of HIF-1α stability in the brain and kidney of ODD-Luc mice. We further demonstrated that the HIF-1α protein accumulated in response to 5-HMF in the brains and kidneys of these mice, as well as in PC12 cells. Additionally, 5-HMF promoted the nuclear translocation of HIF-1α and the transcriptional activity of HIF-1, which was evaluated by detecting vascular endothelial growth factor (VEGF ) mRNA expression. These results suggest that 5-HMF stabilized HIF-1α and increased its activity. Considering the role of proline hydroxylases (PHDs) in negatively regulating HIF-1α stability, we explored whether 5-HMF interacts with the substrates and cofactors of PHDs, such as 2-oxoglutarate (2-OG), Fe(2+) and vitamin C (VC), which affects the activity of PHDs. The result revealed that 5-HMF did not interact with Fe(2+) or 2-OG but interacted with VC. This interaction was confirmed by subsequent experiments, in which 5-HMF entered into cells and reduced the VC content. The enhanced stability of HIF-1α by 5-HMF was reversed by VC supplementation, and the improved survival of mice caused by 5-HMF under hypoxia was abrogated by VC supplementation. Thus, we demonstrated for the first time that 5-HMF increases HIF-1α stability by reducing the VC content, which mediates the protection against hypoxia.

Two new steroidal saponins from Selaginella uncinata (Desv.) Spring and their protective effect against anoxia.

Four steroidal saponins were isolated from the anti-anoxic fraction of the 60% EtOH extract of Selaginella uncinata, including two new compounds, (3ß, 7ß, 12ß, 25R)-spirost-5-ene-3, 7, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-ß-D-glucopyranoside (1), (2α, 3ß, 12ß, 25R)-spirost-5-ene-2, 3, 12-triol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-ß-D-glucopyranoside (2) and two known compounds, (3ß, 12ß, 25R)-spirost-5-ene-3,12-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-O-ß-D-glucopyranoside, (3), (1α, 3ß, 25R)-spirost-5-ene-2-diol-3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl(1→4)]-O-ß-D-glucopyranoside (4). The four compounds showed potent protective effect against anoxia in the anoxic PC12 cells assay, among which compounds 1 and 2 were the most active. To our knowledge, this is the first study to report the steroidal saponins in the plant S. uncinata and demonstrate their protective effect against anoxia in PC12 cell assay.

New 3',8''-linked biflavonoids from Selaginella uncinata displaying protective effect against anoxia.

Seven 3',8''-linked bioflavonoids, including one new compound, (2''S)-2'', 3''-dihydroamentoflavone-4'-methyl ether and six known compounds: (2S)-2,3- dihydroamentoflavone-4'-methyl ether, (2S,2''S)-2,3,2'',3''-tetrahydroamento- flavone-4'-methyl ether, (2S,2''S)-tetrahydroamentoflavone, (2S)-2,3-dihydro- amentoflavone and (2''S)-2'',3''-dihydroamentoflavone (6) and amentoflavone, were isolated from the 60% ethanolic extract of Selaginella uncinata (Desv.) Spring. The structures of these compounds were elucidated mainly by analysis of their 1D and 2D NMR spectroscopic data, and their absolute configurations were determined by circular-dichroism (CD) spectroscopy. All the seven compounds showed protective effect against anoxia in the anoxic PC12 cells assay, in which compound 6 displayed particularly potent activity.

[Anti-hypoxia protective role of the effective component extracted from angelia injection].

AIM: To investigate anti-hypoxia protective roles of the effective component extracted from angelia injection using hypoxia injury model in mice and ECV304 cells separately. METHODS: The survival time of mice was observed separately under normobaric and hypobaric hypoxia. The activity of ECV304 cells was tested by MTT assay, and the mortality rate was examined by Trypan blue exclusion assay to evaluate the pharmacodynamic effects. RESULTS: After exposed to hypoxia the survival time of mice was increased in medicine groups,compared with the control groups (P < 0.05). The cell survival rate was decreased and the cell mortality rate was increased after cells were exposed to hypoxia,while the cell survival rate was significantly increased (P < 0.01), and the cell mortality rate was significantly decreased (P < 0.1) in the medicine groups compared with the control groups. CONCLUSION: The effective component extracted from angelia injection can protect against the injury induced by hypoxia.

Involvement of increased stability of mitochondrial membrane potential and overexpression of Bcl-2 in enhanced anoxic tolerance induced by hypoxic preconditioning in cultured hypothalamic neurons.

The effects of hypoxic preconditioning (HP) on changes in mitochondrial membrane potential (MMP) and Bcl-2 expression in cultured hypothalamic neurons after severe anoxia were investigated. In the HP group, hypothalamic neurons, after a 4-day culture, were preconditioned daily under a hypoxic condition (1% O(2), 10 min) for 8 days; subsequently, the HP neurons and those in the control group (similarly cultured, but without HP) were exposed to 6 h of severe anoxia (0% O(2)). The preconditioned neurons had a higher survival rate and a lower lactate dehydrogenase leakage, compared with the control group. Although HP did not prevent the degradation of MMP during severe hypoxia, preconditioned neurons exhibited a higher level of MMP than that of the control group. Increased expression of Bcl-2 was also observed in the preconditioned hypothalamic neurons. These results suggest that HP enhances the hypoxic tolerance of hypothalamic neurons, and the underlying mechanisms may be related to the increased stability of MMP and the overexpression of Bcl-2 induced by HP.

[Relationship between enhanced anoxic tolerance induced by hypoxic preconditioning and Na+, K+ currents in cultured hypothalamic cells].

AIM: To investigate the relationship between enhanced anoxic tolerance induced by hypoxic preconditioning and Na+, K+ currents. METHODS: After hypoxic preconditioning and acute anoxia the I(Na), I(K) were measured in cultured hypothalamic cells by patch-clamp whole cell recording technique. RESULTS: The amplification of Na+ currents did not been significantly changed, but the amplification of K+ currents was in hypoxic preconditioning neurons; acute anoxia lead to the inhibition of Na+, K+ currents in the two groups, while Na+, K+ currents in non-preconditioned control group were inhibited severity than hypoxic preconditioning group. CONCLUSION: It is presumed enhanced anoxia tolerance induced by hypoxic preconditioning may be related to the opening of K+ channels.