Dioscin induces osteosarcoma cell apoptosis by upregulating ROS-mediated P38 MAPK signaling.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Many patients with osteosarcoma readily develop resistance to chemotherapy and have an extremely dismal prognosis. Dioscin, a saponin, is known to exhibit potent anticancer activities and induce cellular death of a variety of cancer types. However, the inhibitory effect of dioscin on osteosarcoma cells and its underlying mechanisms have not been fully elucidated. We investigated the responses of human U2-OS and MG63 osteosarcoma cells to dioscin with regard to proliferation, apoptosis, migration, and invasion, and studied the effect of dioscin on MAPK-related proteins by western blot analysis assays. Dioscin inhibited osteosarcoma cell proliferation, migration, and invasion. Moreover, it induced osteosarcoma cell apoptosis via reactive oxygen species (ROS)-dependent apoptotic signaling. N-acetylcysteine, a reactive oxygen species inhibitor, suppressed dioscin-induced apoptosis, indicating that ROS play an essential role in dioscin-induced apoptosis. Western blot analysis assays showed that p38 MAPK was upregulated after dioscin treatment, and that dioscin induced apoptosis by upregulating ROS-mediated p38 MAPK signaling. Our study suggests that dioscin possesses antitumor activities against human osteosarcoma cells, inhibits osteosarcoma cell proliferation, migration and invasion, and induces osteosarcoma cell apoptosis through upregulating ROS-mediated p38 MAPK signaling. This study may provide a new therapeutic strategy and potential clinical applications for the treatment of osteosarcoma.

Combined evaluation of coronary artery disease and high-sensitivity cardiac troponin T for prediction of adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: This study was performed to investigate the clinical significance of combined evaluation of both coronary artery disease (CAD) and high-sensitivity cardiac troponin T (hs-cTnT) for prediction of major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM). METHODS: We performed clinical evaluations, including coronary artery imaging and hs-cTnT measurement, in 162 patients with HCM. RESULTS: The patients were followed up for a median period of 3.7 years (interquartile range 2.4-5.6 years; total of 632.3 person-years [PYs]), during which time MACEs occurred in 24 (14.8%) patients. The incidence of MACEs was 6.4 and 2.7 per 100 PYs for patients with CAD and normal coronary arteries, respectively; similarly, the incidence was 5.8 and 2.1 per 100 PYs in patients with an elevated hs-cTnT concentration (> 14.0 ng/L) and a normal hs-cTnT concentration, respectively. The multivariate analysis suggested that CAD and an elevated hs-cTnT concentration tended to be positively associated with MACEs. When the groups were allocated according to these two markers, the patients were divided into four groups, which further improved the predictive values. The incidence of MACEs was 10.4 per 100 PYs in the CAD and elevated hs-cTnT group, which was much higher than the incidence in all other groups (range, 2.0-3.5 per 100 PYs). With the normal coronary arteries and normal hs-cTnT group serving as a reference, the adjusted hazard ratio was 5.0 (95% confidence interval 1.0-23.8; P = 0.046) for the CAD and elevated hs-cTnT group. In addition, the subgroup analysis showed similar findings among the patients without severe CAD. CONCLUSIONS: In patients with HCM, combined evaluation of both CAD and hs-cTnT might facilitate more reliable prediction of MACEs than evaluation of a single marker. These may serve as clinically useful markers to guide risk management.

Evaluation of parallel endplate osteotomy for severe rigid spinal deformities: a retrospective analysis of 36 cases with a minimum 2-year follow-up.

BACKGROUND: To report on the technique and results of parallel endplate osteotomy (PEO) for severe rigid spinal deformity. METHODS: We retrospectively reviewed the clinical data of 36 patients with severe rigid spinal deformities who underwent PEO between July 2016 and December 2018 and who were followed up for at least 24 months. RESULTS: Following PEO, the kyphosis and scoliosis correction rates reached 77.4 ± 14.0% and 72.2 ± 18.2%, respectively. The median intraoperative estimated blood loss was 1500 mL and the median operative time was 6.8 h. The SF-36 scores of physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional and mental health changed from 62 ± 28, 51 ± 26, 49 ± 29, 35 ± 30, 53 ± 28, 45 ± 30, 32 ± 34 and 54 ± 18 at baseline to 81 ± 16, 66 ± 41, 72 ± 40, 64 ± 44, 75 ± 25, 71 ± 46, 66 ± 34 and 76 ± 28 at 12 months postoperatively, 82 ± 32, 67 ± 42, 81 ± 30, 71 ± 41, 80 ± 30, 74 ± 36, 68 ± 35 and 85 ± 33 at 18 months postoperatively, and 86 ± 21, 83 ± 33, 88 ± 26, 79 ± 39, 86 ± 36, 86 ± 48, 80 ± 47 and 91 ± 39 at 24 months postoperatively, respectively. CONCLUSIONS: PEO is an effective technique for successful correction of spinal deformities. At the two-year follow-up visit, all patients achieved better clinical results based on the SF-36 scores.

Protection of L1 nerve roots by pre-relieve tension in parallel endplate osteotomy for severe rigid thoracolumbar spine deformity.

BACKGROUND: This is a retrospective study of the use of parallel endplate osteotomy (PEO) for correction of severe rigid thoracolumbar spine deformity. METHODS: From July 2016 to January 2019, 12 patients with severe rigid thoracolumbar spine deformity underwent PEO on T12 or L1 vertebrae were studied. RESULTS: Following PEO at T12 or L1, the mean kyphosis and scoliosis correction rates reached 77.0 ± 8.9% and 75.5 ± 8.0%, respectively and the intraoperative estimated blood loss was 1950 ± 1050 mL, and the mean operative time was 6.98 ± 4.02 h. The SF-36 scores of physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional and mental health changed from 63 ± 28, 50 ± 25, 50 ± 30, 34 ± 19, 53 ± 28, 45 ± 30, 30 ± 36 and 54 ± 18 at baseline to 83 ± 18, 69 ± 19, 72 ± 12, 66 ± 21, 75 ± 15, 72 ± 22, 66 ± 34 and 76 ± 12 at 1 year postoperatively, 83 ± 8, 68 ± 32, 83 ± 17, 73 ± 17, 82 ± 18, 76 ± 26, 70 ± 37 and 88 ± 12 at 18 months postoperatively, 86 ± 6, 83 ± 33, 90 ± 16, 81 ± 16, 89 ± 14, 88 ± 25, 83 ± 17 and 94 ± 10 at 24 months postoperatively, respectively (P < 0.01). Three patients had symptoms of L1 nerve root injury, as reflected by lower limb weakness and inner thigh numbness on knee extension and hip flexion, which was further confirmed by electromyography. CONCLUSIONS: PEO is easier to operate, and the spinal cord and nerve root are under direct vision and can effectively and safely correct severe rigid thoracolumbar spine deformity with satisfactory clinical results. However, it is important to identify, separate and protect L1 nerve roots during surgery in cases where patients have symptoms of back pain, muscle weakness and leg numbness on the convex side after surgery.

A successful pregnancy in a patient with secondary hypertension caused by adrenal adenoma: a case report.

BACKGROUND: Secondary hypertension is a rare complication in pregnancy that causes poor outcomes, such as preeclampsia, premature delivery, intrauterine growth retardation, stillbirths, spontaneous abortion or intrauterine death. Cushing's disease caused by an adrenal adenoma is rare during pregnancy and may be overlooked by obstetricians and physicians, but can lead to hypertension, diabetes mellitus and an increased risk of fetal and maternal morbidity. Approximately 200 cases have been reported in the literature. Here, we report the successful management of a pregnant patient with Cushing's syndrome due to an adrenal adenoma. CASE PRESENTATION: The 35-year-old Chinese female had no individual or family medical history of hypertension, and did not exhibit chronic kidney disease, diabetes mellitus, autoimmune and common endocrine diseases. Her blood pressure was elevated from the 16th week of gestation and was not controlled by 30 mg nifedipine twice a day. Examination in our department revealed her 24 h urinary free cortisol (24 h UFC) level was 1684.3 µg/24 h (normal range: 20.26-127.55 µg/24 h) and plasma adrenocorticotropic hormone was < 1.00 ng/L in three independent measurements (normal range: 5-78 ng/L). Ultrasonography demonstrated a mass (2.9 cm × 2.8 cm) in the right side of the adrenal gland. Magnetic resonance imaging without contrast showed a 3.2 cm diameter mass in the right-side of the adrenal gland. Other medical tests were normal. Laparoscopic adrenalectomy was performed at the 26th week of gestation by a urological surgeon in the West China Hospital. Histopathology revealed an adrenocortical adenoma. After surgery, the patient accepted glucocorticoid replacement therapy. The remaining trimester continued without complication and her blood pressure was normal at the 32nd week of gestation without antihypertensive therapy. The patient gave birth to a healthy boy at the 40th week of gestation. CONCLUSIONS: Cushing's syndrome caused by adrenal adenoma is rare during pregnancy. This unique case suggested that analysis of the UFC level and circadian rhythm of plasma cortisol provides a suitable strategy to diagnose Cushing's syndrome during pregnancy. Laparoscopic surgical resection in the second trimester provides a reasonable approach to treat pregnant patients exhibiting Cushing's syndrome caused by an adrenal adenoma.

Effects of commercial premix vitamin level on sternum growth, calcification and carcass traits in meat duck.

The present study was conducted to investigate the effects of dietary vitamin level on sternum growth, calcification and carcass traits in meat duck. A total of 432 1-d-old mixed-sex Cherry Valley ducks (216 males and 216 females) were randomly allocated and fed low-vitamin level diet (70% NRC vitamin regimen), high-vitamin level diet (DSM vitamin regimen) or medium-vitamin level diet (50% low-vitamin level diet and 50% high-vitamin level diet). Sternum and serum were harvested after 49 d of feeding. Compared with the low-vitamin level group, dietary high-vitamin level increased body weight (BW) at d 49 (p = 0.029) but did not alter all parameters of carcass trait (p > 0.05). Medium- and high-vitamin level increased sternum defatted weight, density, ash and calcium (Ca) concentration (p < 0.05). Meanwhile, the medium and high-vitamin level group significantly decreased the relative proportions of the keel cartilage at 49 d (p < 0.05) and decreased the sternum length and height (p < 0.05) in meat ducks at 49 d. Likewise, high-vitamin level improved serum Ca and phosphate (P) content (p < 0.05) and declined serum Alkaline phosphatase (ALP) activity (p = 0.003) compared with the low-vitamin level group. Our study indicates that high-vitamin level did not affect the examined carcass traits; however, high-vitamin level improved growth performance and sternum calcification.

The prevalence of hyperuricemia and its correlates in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China.

BACKGROUND: Hyperuricemia is a common and serious public health problem. There has been no broad epidemiological survey of hyperuricemia in China, especially in Tibetan area. This study was therefore investigated the prevalence of hyperuricemia and its correlated factors among people aged 18-85 years in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China. METHODS: We carried out a cross-sectional study among 3093 participants in Ganzi Tibetan Autonomous Prefecture using questionnaires in face-to-face interviews, anthropometric measurements and biochemical tests. We included 1416 subjects with complete data including serum uric acid and medical history to analyze the prevalence of hyperuricemia and correlated factors. Hyperuricemia was defined as a fasting serum uric acid level higher than 420 µmol/L in men and 360 µmol/L in women. RESULTS: The overall crude prevalence of hyperuricemia was 37.2%, and was greater in men than women (41% vs 34.4%, P = 0.011). The age-adjusted prevalence was 33.0%. Characteristics linked to hyperuricemia were farmers-herdsmen (OR: 1.749, 95% CI: 1.022-2.992), low to moderate education level (low OR:1.57, 95% CI: 1.102-2.237; moderate OR: 1.86, 95% CI: 1.167-2.963), current drinking (OR: 1.795, 95% CI: 1.193-2.702), hypertension (OR: 1.48, 95% CI: 1.091-2.006), higher body mass index (1 unit increase) (OR: 1.116, 95% CI: 1.077-1.156) and higher serum creatinine (1 unit increase) (OR: 1.046, 95% CI: 1.034-1.059). Serum uric acid was positively related to triglycerides and total cholesterol and negatively related to high density lipoprotein cholesterol in all subjects. Hyperuricemia was a risk factor for high triglyceride ((OR: 2.13, 95% CI: 1.156-3.9266) and high total cholesterol (OR: 2.313, 95% CI: 1.364-3.923) in men and for high low-density lipoprotein cholesterol (OR: 2.696, 95% CI: 1.386-5.245) in women. CONCLUSION: There is a high prevalence of hyperuricemia in Ganzi Tibetan Autonomous Prefecture. The government needs to prevent and manage hyperuricemia in this area.

Intermedin Ameliorates Atherosclerosis by Increasing Cholesterol Efflux Through the cAMP-PKA Pathway in Macrophage RAW264.7 Cell Line.

BACKGROUND The aim of this study was to explore the role of intermedin and its mechanism in cholesterol efflux of macrophage THP-1 and RAW264.7 cell lines in atherosclerosis (AS). MATERIAL AND METHODS ApoE-/- mice were fed with a high-fat diet, and the concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The lipidoses of the aortic sinus were analyzed by hematoxylin and eosin staining, and the cAMP level was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of ATP-binding cassette transporter (ABCA1) were tested by real-time PCR and Western blot analysis. RESULTS IMD decreased serum TC and LDL-C, and increased serum HDL-C level in apoE-/- mice and attenuated AS plaque areas. In vitro, IMD increased intracellular cAMP concentration in a dose-dependent manner in THP-1 and RAW264.7 cell lines, which enhanced the expression of ABCA1 and increased cholesterol efflux rate. However, this effect was inhibited by PKAI in the RAW 264.7 cell line but not in the THP-1 cell line. CONCLUSIONS IMD can ameliorate the development of AS in ApoE-/- mice and regulate cholesterol balance in the RAW264.7 cell line through the cAMP-PKA pathway.

Investigation of the relationship between arterial stiffness and sleep architecture in patients with essential hypertension.

A change in sleep architecture might increase the risk of hypertension and worsen target organs. This study thus aimed to study the features of sleep architecture and examine its relationship with pulse wave velocity (PWV), a measure of arterial stiffness, in patients with essential hypertension and healthy people aged 45-65 years (n = 106). We collected data on demographics, the serum index, overnight polysomnography, vascular testing and ambulatory blood pressure in addition to measuring arterial stiffness and monitoring sleep respiration. We found that patients with hypertension had longer sleep latency and shorter duration. Their sleep efficiency and the ratio of N3 in non-rapid eye movement (NREM) and rapid eye movement were lower, while the micro-arousal index (MI), N1 and N2 in NREM, and the apnea-hypopnea index were higher than normal people in controls. PWV raised with a decrease in N3 and an increase in the MI. In summary, there were notable changes in sleep architecture and with a decrease in N3 and increase in MI can accelerate arterial stiffness and then worsen target organ damage in patients with hypertension.

Association of dietary live microbe intake with frailty in US adults: evidence from NHANES.

OBJECTIVE: Diets rich in live microbes can bring various health benefits. However, the association between dietary live microbe intake and frailty has not been studied. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. A total of 11,529 participants were included. Sanders et al. classified the level of live microbes in foods into low (<104 CFU/g), medium (104-107 CFU/g), or high (>107 CFU/g). With the methodology of Sanders et al. and dietary questionnaire data, participants were divided into three groups: (1) low dietary live microbe intake group (only low-level foods), (2) medium dietary live microbe intake group (medium but not high-level foods), and (3) high dietary live microbe intake group (any high-level foods). Additionally, foods with medium and high live microbe content were aggravated as MedHi. Frailty index ≥0.25 is defined as frailty. The weighted logistic regression analysis was conducted to examine the relationship between the intake of dietary live microbe and frailty. The restricted cubic splines (RCS) were employed to detect the nonlinear relationships. RESULTS: In the fully adjusted model, participants with high dietary intake of live microbe had a significantly lower risk of frailty than those with low dietary intake of live microbe (OR = 0.67, 95% CI: 0.56, 0.79). For every 100 grams of MedHi food consumed, the risk of frailty decreased by 11% (OR = 0.89, 95% CI: 0.85, 0.92) after adjusting all covariates. The RCS indicated the existence of non-linear relationships. For those who consumed less than 100 grams of MedHi, increasing MedHi intake may significantly reduce the risk of frailty, but after exceeding 100 grams, the curve gradually levels off. CONCLUSIONS: Our results suggested that increasing dietary live microbe intake was associated with a lower risk of frailty. However, more research is needed to verify this.

Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative condition that results in dyskinesia, with oxidative stress playing a pivotal role in its progression. Antioxidant peptides may thus present therapeutic potential for PD. In this study, a novel cathelicidin peptide (Cath-KP; GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog ( Kaloula pulchra). Structural analysis using circular dichroism and homology modeling revealed a unique αßß conformation for Cath-KP. In vitro experiments, including free radical scavenging and ferric-reducing antioxidant analyses, confirmed its antioxidant properties. Using the 1-methyl-4-phenylpyridinium ion (MPP +)-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, Cath-KP was found to penetrate cells and reach deep brain tissues, resulting in improved MPP +-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1 (Sirt1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Both focal adhesion kinase (FAK) and p38 were also identified as regulatory elements. In the MPTP-induced PD mice, Cath-KP administration increased the number of tyrosine hydroxylase (TH)-positive neurons, restored TH content, and ameliorated dyskinesia. To the best of our knowledge, this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress. These findings expand the known functions of cathelicidins, and hold promise for the development of therapeutic agents for PD.

FS145, the first flea-derived disintegrin, inhibits angiogenesis through specifically binding integrin αvß3.

FS145, a protein containing a WGD motif, was previously described from the salivary transcriptome of the flea Xenopsylla cheopis. Nevertheless, its biological function and complete structure are still uncertain. Herein, FS145 was confirmed to adopt a common αßß structure with the WGD motif exposed on its surface and located right at the top of a loop composed of residues 72-81. Furthermore, FS145 dose-dependently inhibited the proliferation, adhesion, migration, and tube formation of HUVECs by not only binding to integrin αvß3 but also by subsequently inactivating the FAK/Src/MAPK pathway along with the reduction of the expression of MMP-2, MMP-9, VEGFA, bFGF, Ang2, Tie2, HIF-1α, and FAK. Moreover, FS145 also inhibited aortic vessel sprout and showed strong anti-angiogenic activities as assessed ex vivo, by employing the rat aortic ring assay, chick embryo chorioallantoic membrane, and zebrafish embryo models. Altogether, our results suggest that FS145 suppresses angiogenesis ex vivo and in vitro by blocking integrin αvß3. The current study reveals the first anti-angiogenesis disintegrin with WGD motif from invertebrates and provides a beneficial pharmacological activity to inhibit abnormal angiogenesis.

Androcin 18-1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction.

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18-1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18-1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18-1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18-1 in drug development for glioblastoma treatment.

Intermedin induces autophagy and attenuates hypoxia-induced injury in cardiomyocytes by regulation of MALAT1/ULK1.

Myocardial infarction is a predominant cause of cardiovascular diseases with high incidence and death rate worldwide. Although growing evidence has suggested that IMD has significant protective influences on the cardiovascular system, the molecular regulatory mechanism of IMD in hypoxia-induced injury caused by myocardial infarction is urgent to be elucidated. In the present study, we found hypoxia led to a noteworthy enhancement in IMD expression and IMD alleviated hypoxia-induced myocardial injury of NRCMs. Furthermore, IMD was proved to inhibit hypoxia-induced injury by regulating MALAT1. Our findings suggested MALAT1 positively regulated the mRNA and protein expression level of ULK1 and hypoxia induced autophagy of NRCMs. MALAT1 stimulated autophagy to block hypoxia-induced cell injury in NRCMs via upregulation of ULK1 expression. Autophagy suppression abolished the protective capability of IMD overexpression against hypoxia-induced myocardial injury in NRCMs. In a word, our study shed light on the central mechanism of IMD in preventing hypoxia-induced injury caused by myocardial infarction. We confirmed IMD induced autophagy and attenuated hypoxia-induced injury in cardiomyocytes via MALAT1/ULK1, which may contribute to designing effective therapeutic approaches of myocardial infarction.

Mortality Risk in Older People Who Drank Alcohol in the Past by Varying Duration of Alcohol Abstention.

INTRODUCTION: This study aims to explore the mortality risk in older people who drank alcohol in the past by varying the duration of alcohol abstention. METHODS: In total, 31,999 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (Waves 1998, 2000, 2002, 2005, 2008, 2011, 2014) were included. Duration of alcohol abstention was assessed by designed questions, and the study outcome was all-cause mortality. Cox proportional hazard models were used to examine the association. Analyses occurred from 2022 to 2023. RESULTS: During a follow-up of 140,974.8 person-years, all-cause mortality occurred in 24,257 participants. Mortality significantly increased by 23% (adjusted hazard ratio=1.23, 95% CI=1.14, 1.33, p<0.001), by 17% (adjusted hazard ratio=1.17, 95% CI=1.06, 1.31, p=0.003), and by 17% (adjusted hazard ratio=1.17, 95% CI=1.07, 1.28, p=0.001) in people who drank alcohol in the past with ≤5 years, 5-10 years, 10-20 years of alcohol abstention, respectively, compared with that among those who drink alcohol at present. After 20 years of alcohol abstention, the increased mortality risk disappeared (adjusted hazard ratio=1.06, 95% CI=0.97, 1.15, p=0.204). Stratified and sensitivity analysis revealed similar results. In addition, compared with the risk of all-cause mortality among people who never drink alcohol, the risk of all-cause mortality in those who drank alcohol in the past also significantly increased in the following 20 years after they stop drinking, and then the increased risk disappeared afterward. CONCLUSIONS: An increased risk of all-cause mortality in older people who drank alcohol in the past was observed, which disappeared after 20 years of alcohol abstention.

Formation and Applications in Electronic Devices of Lattice-Aligned Gallium Oxynitride Nanolayer on Gallium Nitride.

Gallium nitride (GaN), a promising alternative semiconductor to Si, is widely used in photoelectronic and electronic technologies. However, the vulnerability of the GaN surface is a critical restriction that hinders the development of GaN-based devices, especially in terms of device stability and reliability. In this study, this challenge is overcome by converting the GaN surface into a gallium oxynitride (GaON) epitaxial nanolayer through an in situ two-step "oxidation-reconfiguration" process. The O plasma treatment overcomes the chemical inertness of the GaN surface, and sequential thermal annealing manipulates the kinetic-thermodynamic reaction pathways to create a metastable GaON nanolayer with a wurtzite lattice. The GaN-derived GaON nanolayer is a tailored structure for surface reinforcement and possesses several advantages, including a wide bandgap, high thermodynamic stability, and large valence band offset with a GaN substrate. These physical properties can be further leveraged to enhance the performance of GaN-based devices in various applications, such as power systems, complementary logic integrated circuits, photoelectrochemical water splitting, and ultraviolet photoelectric conversion.

TLR2-mediated NF-κB signaling pathway is involved in PPV1-induced apoptosis in PK-15 cells.

Porcine parvovirus 1 (PPV1) mainly induces severe reproductive failure in pregnant swine, and causes huge economic losses to the swine industry. Cell apoptosis induced by PPV1 infection has been identified the major cause of reproductive failure. However, the molecular mechanism was not fully elucidated. In this study, the potential mechanism of PPV1 induced apoptosis in PK-15 cells was investigated. Our results showed that PPV1 induced apoptosis in PK-15 cells. Further studies revealed toll-like receptor 2 (TLR2) was involved in the PPV1-mediated apoptosis. TLR2 siRNA significantly decreased the apoptosis. Finally, our study showed NF-κB was activated by TLR2 during PPV1-induced apoptosis. The activation of NF-κB signaling was demonstrated by the phosphorylation of p65, p65 nuclear translocation and degradation of inhibitor of kappa B α (IκBα). Together, these results provided evidence that the recognition between PPV1 and PK-15 cells was mainly through TLR2, and then induction of the NF-κB signaling pathway activation, which further induces apoptosis. Our study could provide information to understand the molecular mechanisms of PPV1 infection.

Peptide TK-HR from the Skin of Chinese Folk Medicine Frog Hoplobatrachus Rugulosus Accelerates Wound Healing via the Activation of the Neurokinin-1 Receptor.

Wound healing is a complex process and remains a considerable challenge in clinical trials due to the lack of ideal therapeutic drugs. Here, a new peptide TK-HR identified from the skin of the frog Hoplobatrachus rugulosus was tested for its ability to heal cutaneous wounds in mice. Topical application of TK-HR at doses of 50-200 µg/mL significantly accelerated wound closure without causing any adverse effects in the animals. In vitro and in vivo investigations proved the regulatory role of the peptide on neutrophils, macrophages, keratinocytes, and vein endothelial cells involved in the inflammatory, proliferative, and remodeling phases of wound healing. Notably, TK-HR activated the MAPK and TGF-ß-Smad signaling pathways by acting on NK1R in RAW264.7 cells and mice. The current work has identified that TK-HR is a potent wound healing regulator that can be applied for the treatment of wounds, including diabetic foot ulcers and infected wounds, in the future.

The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}.

INTRODUCTION: Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30-60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. METHODS AND ANALYSIS: This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6-10 am) or a bedtime (6-10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. DISCUSSION: Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. TRIAL REGISTRATION: ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}.