Artificial nonenzymatic antioxidant Prussian blue/KGM-BSA nanocomposite hydrogel dressing as ROS scavenging for diabetic wound healing.

The process of diabetic wound healing was influenced by the excessive proliferation of reactive oxygen species (ROS). Therefore, in the process of healing diabetic wounds, it was crucial to removing ROS. This study designed composited nanoparticles: KBP, consisted by Konjac glucomannan, bovine serum albumin, and Prussian blue. Then they were embedded in Konjac glucomannan and hydroxypropyl trimethylammonium chloride chitosan composite hydrogel (KH), The KBP@KH hydrogel finally achieved excellent efficacy in diabetic wound healing. The in vitro and in vivo experiments demonstrated that KPB nanoparticles exhibited favorable ROS scavenging capability and biosafety. The KBP@KH hydrogel not only effectively eliminated ROS from diabetic wounds, but also exhibited excellent wound adaptability. The KBP@KH hydrogel facilitated angiogenesis and suppressed the production of inflammatory factors. Overall, the KBP@KH hydrogel dressing was characterized by its user-friendly nature, safety, and high efficiency.

Heterostructured grafting of NiFe-layered double hydroxide@TiO2 for boosting photoelectrochemical cathodic protection.

Accelerating the oxidation process at photoanode-electrolyte interfaces can prolong the lifetime of photoexcited electrons and improve the efficiency of photoelectrochemical cathodic protection (PECCP) systems without relying on hole scavengers. However, the systematic design of precisely structured heterostructures for efficient photoanodes remains challenging. Here we meticulously engineered a type-II heterostructure featuring precise spatial organization, wherein NiFe-layered double hydroxide nanosheets (NiFe-LDH NSs) were assembled onto annealed TiO2 nanorod arrays (ATNAs), demonstrating their effectiveness in achieving efficient PECCP. The interfacial electronic coupling and appropriate energy alignment between the NiFe-LDH NSs and ATNAs allowed rapid hole extraction from the ATNAs to the NiFe-LDH NSs. Furthermore, the uniform distribution of the NiFe-LDH NSs on top of ATNAs drastically reduced the overpotential of oxygen evolution reactions (OER) from 370 to 200 mV and Tafel slope from 162 to 56 mV dec-1, leading to significantly improved cathodic protection of 304 stainless steel (SS) under extended illumination and interesting post-illumination protection. In addition, with the increase of testing cycles, the as-prepared NiFe-LDH NSs@ATNAs demonstrated a progressively enhanced cathodic protection potential from 0.15 to 0.13 V vs. RHE over 50 cycles. These findings provide important guidelines for the design of future high-efficiency green metal protection through rational photoanode design.

Determination of the total antioxidant capacity of the Chinese tea based on a novel "peroxidase/zirconium phosphonate"composite electrochemical sensor.

In this work, a novel zirconium phosphonate (ZrPR1R2) was prepared by decorating both the aminoethoxy- group (R1) and the carboxypropyl- group (R2) on the zirconium phosphate layers in order to manipulate further the immobilization of the peroxidase (POD), and an antioxidant biosensor with higher sensitivity was constructed by dropping the POD/ZrPR1R2 composite onto the glassy carbon electrode surface. The activity of the POD/ZrPR1R2 composite was detected by Uv-vis spectra. The direct electrochemical behavior, the electrocatalytic response to dissolved oxygen and hydrogen peroxide, as well as the ability to detect total antioxidant capacity in tea sample were investigated by the methods of cyclic voltammetry. The results indicated that the immobilization of POD in ZrPR1R2 nanosheets matrix enhanced the enzymatic activity, and achieved the fast and direct electron transfer between POD and glassy carbon electrode. Moreover, the POD/ZrPR1R2 composite modified electrode show the electrocatalytic response to hydrogen peroxide in the linear range of 8.8×10-8 to 8.8×10-7 mol L-1, with the detection limit of 3.3×10-8 mol L-1. Attributing to the sensitive response to dissolved oxygen, the total antioxidant capacity can be detected directly in the real tea water by this POD/ZrPR1R2 composite modified electrode.

Superalkali-alkaline earthide ion pairs of δ+(AM-HMHC)-AM'δ- (AM = Li, Na and K; AM' = Be, Mg and Ca) possessing large NLO responses and excellent electronic stabilities and alkalide characteristics: a DFT study.

To identify superalkali-alkaline earthide ion pairs, it's theoretically shown that, as a novel class of excess electron superalkali compounds, both chair and boat forms of (AM-HMHC)-AM' (AM = Li, Na, and K; AM' = Be, Mg, and Ca; HMHC = 1,4,7,10,13,16-hexamethyl-1,4,7,10,13,16-hexaazacyclooctadecane) are good candidates. An attractive superalkali-alkaline earthide ion pair in δ+(AM-HMHC)-AM'δ- is firstly exhibited, which possesses alkaline-earthide characteristics and nonlinear optical response superior to similar M+(calix[4]pyrrole)M'- (M = Li, Na, and K; M' = Be, Mg, and Ca) with high stability. The electronic and vibrational second order hyperpolarizabilities and the frequency-dependent first hyperpolarizabilities of δ+(AM-HMHC)-AM'δ- are presented. For each pair of (AM-HMHC)-AM', the boat conformation is preferred to its chair one in the case of Hyper-Rayleigh scattering response (ßHRS). These alkaline earthides suggest prominently high ßHRS up to 2.59 × 104 a.u. (boat forms of δ+(Na-HMHC)-Caδ-). We expect that this work will inspire the preparation and characterization of these new alkaline earthides as high-performance NLO materials.

Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.

Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.

DNA methylation of DKK-1 may correlate with pathological bone formation in ankylosing spondylitis.

OBJECTIVE: To investigate DNA methylation (DNAm) status of dickkopf-associated protein 1 (DKK-1) in ossified hip capsule synovium and serum among patients with ankylosing spondylitis (AS). METHODS: Western blot was applied to detect the level of DKK-1 protein expression in hip joint capsule tissues from four patients with AS as well as four patients with femoral neck fracture (FNF) caused by trauma as control. DKK-1 gene promoter methylation (GPM) was examined by methylation-specific polymerase chain reaction. Reverse transcription-polymerase chain reaction was performed to examine the messenger RNA (mRNA) levels of DKK-1, ß-catenin, and Wnt3a in both tissue and serum. The DNAm status of serum DKK-1 was measured among 36 patients with AS and syndesmophytes (AS + syndesmophytes group), 40 patients with AS but no syndesmophyte (AS group), and 42 healthy individuals (control group). Also, the serum levels of DKK-1 were measured by enzyme-linked immunosorbent assay. The modified New York criteria (mNYC) together with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were adopted to examine the radiographic progression of AS. The receiver operating characteristic (ROC) curve was applied to investigate the diagnostic value of the methylation rate of DKK-1 with regard to radiographic progression. RESULTS: The expressions of DKK-1 protein and mRNA in hip joint capsule tissues of AS patients were significantly lower, while DKK-1 GPM rate, ß-catenin mRNA, and Wnt3a mRNA were markedly higher when compared with FNF group. For serum samples, the DKK-1 methylation rate was significantly higher in AS+ syndesmophytes group in contrast to AS group and healthy controls. Serum levels of DKK-1 protein and mRNA in AS with syndesmophytes group were markedly decreased, while ß-catenin mRNA and Wnt3a mRNA expressions were significantly increased than AS with no syndesmophyte group and the healthy control group. AS patients in Grade 4 showed a significantly higher serum DKK-1 GPM rate than those in Grade 3 based on mNYC. Serum DKK-1 GPM level was markedly and positively correlated with mSASSS. Serum levels of DKK-1 in AS+ syndesmophytes group were markedly lower compared with AS but no syndesmophyte group and healthy controls. ROC curve analysis indicated that serum DKK-1 methylation rate serves as a decent indicator for AS radiographic progression. CONCLUSION: DNAm of DKK-1 may correlate with pathological bone formation in AS, which may provide new strategies for the treatment of AS abnormal bone formation.

Daytime Hypercapnia Impairs Working Memory in Young and Middle-Aged Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) can lead to cognitive impairment, though few studies have so far examined hypercapnia as its causal mechanism, due to the invasive nature of conventional arterial CO2 measurement. The study aims to investigate the effects of daytime hypercapnia on working memory in young and middle-aged patients with OSAHS. Patients and Methods: This prospective study screened 218 patients and eventually recruited 131 patients (aged 25-60 years) with polysomnography (PSG)-diagnosed OSAHS. Using a cut-off of 45mmHg daytime transcutaneous partial pressure of carbon dioxide (PtcCO2), 86 patients were assigned into the normocapnic group and 45 patients into the hypercapnic group. Working memory was evaluated using the Digit Span Backward Test (DSB) and the Cambridge Neuropsychological Test Automated Battery. Results: Compared with the normocapnic group, the hypercapnic group performed worse in verbal, visual, and spatial working memory tasks. PtcCO2≥45mmHg was an independent predictor for lower DSB scores (OR=4.057), lower accuracy in the immediate Pattern Recognition Memory (OR=2.600), delayed Pattern Recognition Memory (OR=2.766) and Spatial Recognition Memory (OR=2.722) tasks, lower Spatial Span scores (OR=4.795), and more between errors in the Spatial Working Memory task (OR=2.734 and 2.558, respectively). Notably, PSG indicators of hypoxia and sleep fragmentation did not predict task performance. Conclusion: Hypercapnia may be plays an important role in working memory impairment in patients with OSAHS, perhaps more so than hypoxia and sleep fragmentation. Routine CO2 monitoring in these patients could prove of utility in clinical practices.

Microfluidic rotating-target device capable of three-degrees-of-freedom motion for efficient in situ serial synchrotron crystallography.

There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1 mg of protein is consumed in collecting a complete dataset.

Melatonin mediates reactive oxygen species homeostasis via SlCV to regulate leaf senescence in tomato plants.

Melatonin (MT) functions in removing reactive oxygen species (ROS) and delaying plant senescence, thereby acting as an antioxidant; however, the molecular mechanism underlying the specific action of MT is unclear. Herein, we used the mutant plants carrying the MT decomposition gene melatonin 3-hydroxylase (M3H) in tomato to elucidate the specific mechanism of action of MT. SlM3H-OE accelerated senescence by decreasing the content of endogenous MT in plants. SlM3H is a senescence-related gene that positively regulates aging. MT inhibited the expression of the senescence-related gene SlCV to scavenge ROS, induced stable chloroplast structure, and delayed leaf senescence. Simultaneously, MT weakened the interaction between SlCV and SlPsbO/SlCAT3, reduced ROS production in photosystem II, and promoted ROS elimination. In conclusion, MT regulates ROS homeostasis and delays leaf aging in tomato plants through SlCV expression modulation.

Efficacy of conbercept after switching from bevacizumab/ranibizumab in eyes of macular edema secondary to central retinal vein occlusion.

AIM: To explore the efficacy of conbercept after switching from bevacizumab/ranibizumab in eyes of central retinal vein occlusion (CRVO) through optical coherence tomography angiography (OCTA). METHODS: Patients with prior treatment of a minimum of three consecutive intravitreal injections of either bevacizumab or ranibizumab, followed by injection of conbercept, were recruited. The minimal follow-up period after switching was 12mo. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), the interval of injections was reviewed. Perfusion density (PD) and vascular length density (VLD) of superficial and deep capillary plexus were acquired from OCTA images before and after switching. RESULTS: Twenty-four eyes were included. CRT significantly decreased from 460.71±153.23 µm (before switching) to 283.92±38.27 µm at the end of follow-up (P<0.001). However, BCVA gained to some extent (from 0.98±0.33 to 0.76±0.42 logMAR) but the difference was not significant (P=0.070). After switching to conbercept the injection interval extended from 5.2±2.3wk to 8.3±3.9wk (P=0.012). At the end of follow-up, PD of deep retinal layer decreased significantly compared with before switching (from 34.62%±5.27% to 33.26%±5.82%, P=0.016), similar result was found in VLD of deep retinal layer but not in PD or VLD in superficial layer. CONCLUSION: In cases of refractory macular edema secondary to CRVO, switching to conbercept improves macular thickness and extends interval of injection. Retinal microvasculature cannot improve with treatment of conbercept.

Can a molecular switch exist in both superalkali electride and superalkalide forms?

To combine both electride and alkalide characteristics in one molecular switch, it is shown herein that the phenalenyl radical and the M3 ring (M3-PHY, M = Li, Na, and K) stacked with parallel and vertical geometries are good candidates. The former geometry is the superalkali electride e-⋯M3+-PHY while the latter geometry is the superalkalide Mδ--M2(1-δ)+-PHY-. The superalkalide Mδ--M2(1-δ)+-PHY- may isomerize to the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K) using suitable long-wavelength irradiation, while the latter may isomerize to the former with suitable short-wavelength irradiation. Also, applying suitable oriented external electric fields can drive the superalkalide Mδ-M2(1-δ)+-PHY- to change into the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K). The differences in the static and dynamic first hyperpolarizability (ß0) values between them were also studied.

Syntheses, structures and magnetic properties of two CoII/NiII isostructural coordination polymers based on an asymmetric semirigid tricarboxylate ligand.

Two new isostructural complexes, namely, poly[aqua[µ3-2-(4-carboxyphenoxy)terephthalato-κ3O1:O4:O4'](1,10-phenanthroline-κ2N,N')cobalt(II)], [Co(C15H8O7)(C12H8N2)(H2O)]n or [Co(µ3-Hcpota)(phen)(H2O)]n, I, and poly[aqua[µ3-2-(4-carboxyphenoxy)terephthalato-κ3O1:O4:O4'](1,10-phenanthroline-κ2N,N')nickel(II)], [Ni(C15H8O7)(C12H8N2)(H2O)]n or [Ni(µ3-Hcpota)(phen)(H2O)]n, II, have been synthesized by solvothermal reactions. Complexes I and II were fully characterized by IR spectroscopy, elemental analyses, thermogravimetric analyses, and powder and single-crystal X-ray diffraction. They both present two-dimensional structures based on [M2(µ-COO)2]2+ (M = CoII or NiII) dinuclear metal units with a fes topology and a vertex symbol (4·82). Interestingly, the positions of the two dimeric metal motifs and the two partially deprotonated Hcpota2- ligands reproduce regular flying butterfly arrangements flipped upside down and sharing wings in the ab plane. Magnetic studies indicate antiferromagnetic interactions (J = -5.21 cm-1 for I and -11.53 cm-1 for II) in the dimeric units, with Co...Co and Ni...Ni distances of 4.397 (1) and 4.358 (1) Å, respectively, that are related to double syn-anti carboxylate bridges.

A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System.

To evaluate outcomes between extraperitoneal robotic single-port radical prostatectomy (epR-spRP) and extraperitoneal robotic multiport radical prostatectomy (epR-mpRP) performed with the da Vinci Si Surgical System, comparison was performed between 30 single-port (SP group) and 26 multiport (MP group) cases. Comparisons included operative time, estimated blood loss (EBL), hospital stay, peritoneal violation, pain scores, scar satisfaction, continence, and erectile function. The median operation time and EBL were not different between the two groups. In the SP group, the median operation time of the first 10 patients was obviously longer than that of the latter 20 patients (P < 0.001). The median postoperative hospital stay in the SP group was shorter than that in the MP group (P < 0.001). The rate of peritoneal damage in the SP group was less than that in the MP group (P = 0.017). The pain score and overall need for pain medications in the SP group were lower than those in the MP group (P < 0.001 and P = 0.015, respectively). Patients in the SP group were more satisfied with their scars than those in the MP group 3 months postoperatively (P = 0.007). At 3 months, the cancer control, recovery of erectile function, and urinary continence rates were similar between the two groups. It is safe and feasible to perform epR-spRP using the da Vinci Si surgical system. Therefore, epR-spRP can be a treatment option for localized prostate cancer. Although epR-spRP still has a learning curve, it has advantages for postoperative pain and self-assessed cosmesis. In the absence of the single-port robotic surgery platform, we can still provide minimally invasive surgery for patients.

[Research on community promotion and application of single acupoint electroacupuncture therapy for lumbar intervertebral disc herniation].

OBJECTIVE: To observe the clinical effect of single acupoint [Yaotu (extra)] electroacupuncture (EA) therapy on lumbar intervertebral disc herniation (LIDH) and its promotion and application in community medical institutions. METHODS: This research adopted a three-level promotion model, and used multi-center collaboration topics as a platform. A total of 240 patients with LIDH were divided into a group A (top three hospital, 80 cases, 3 cases dropped off), a group B (secondary hospital, 80 cases, 8 cases dropped off), and a group C (community health center, 80 cases, 7 cases dropped off). All groups were treated with EA at a single acupoint [Yaotu (extra)] under the guidance of a unified experimental protocol. The EA was given 60 min each time and performed 3 times a week for a total of 2 weeks. The changes of visual analogue scale (VAS) scores of three groups before and after each treatment were compared, and the clinical efficacy was evaluated. RESULTS: Compared with before each treatment, the VAS scores of three groups after each treatment decreased (P<0.05). Except for the second and fifth treatments, the immediate effect in the group A was higher than that in the group B and C (P<0.05). The total effective rate of group A, group B, and group C respectively was 90.9% (70/77), 93.1% (67/72), 86.3% (63/73), and there was no statistically significant difference among the three groups (P>0.05). CONCLUSION: The single acupoint EA therapy has a significant effect in the treatment of LIDH, can quickly relieve the pain symptoms, and has the characteristics of simple operation and easy control, suitable for promotion and application in primary hospitals.

Mechanism and prognostic indicators for explosion-related eye trauma: eye injury vitrectomy study.

PURPOSE: To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis. METHODS: A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6 months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models. RESULTS: The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6 months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wave and projectile were worse than that of ruptured eyes (Fisher's exact = 0.041). The extrusion of iris/lens (OR = 3.20, p = 0.015), PVR-C (OR = 6.08, p = 0.036) and choroid damage (OR = 5.84, p = 0.025) is independent risk factors of unfavourable prognosis for explosion-related eye trauma. CONCLUSION: The extrusion of iris/lens, PVR-C and choroid damage is the independent risk factors for unfavourable outcomes in explosion-related eye trauma. There is a unique injury mechanism in explosion-related eye trauma. SUMMARY STATEMENT: Through the nested case-control study, the extrusion of iris/lens, PVR-C, and choroid damage are the independent risk factors for unfavorable outcomes in explosion-related eye trauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.

Switching from an electride-like molecule to the molecular electride K-F6C6H6 driven by an oriented external electric field.

The exploration of innovative molecular switches has resulted in large developments in the field of molecular electronics. Focusing on a single molecular switch with different forms exhibiting different electride features, potassium-atom-doped all-cis 1,2,3,4,5,6-hexafluorocyclohexane K-F6C6H6 was studied theoretically. It was found that an oriented external electric field can drive excess electron transfer from the region outside of the K atom to that outside of F6C6H6. Subsequently, the electride-like molecule K-F6C6H6 (1) switches into the molecular electride K-F6C6H6e- (3) through another electride-like molecule K-F6C6H6 (2). The static first hyperpolarizabilities (ß0) are increased over 12- and 5-fold when moving from 1 to 2 and 3, respectively. The rise of each ß0 value constitutes an order of magnitude improvement. Between them, the different ß0 values suggest that K-F6C6H6 is a good candidate for use as a multiple-response nonlinear optics switch. The order of the ß0 values of 1-4 for M-F6C6H6 (M = Li and Na) coincide with that of K-F6C6H6, also exhibiting a switch effect.

A novel sample delivery system based on circular motion for in situ serial synchrotron crystallography.

A sample delivery system is one of the key parts of serial crystallography. It is the main limiting factor affecting the application of serial crystallography. At present, although a variety of useful sample delivery systems have been developed for serial crystallography, it still remains the focus of the field to further improve the performance and efficiency of sample delivery. In existing sample delivery technologies, samples are usually delivered in linear motion. Here we show that the samples can also be delivered using circular motion, which is a novel motion mode never tested before. In this paper, we report a microfluidic rotating-target sample delivery device, which is characterized by the circular motion of the samples, and verify the performance of the device at a synchrotron radiation facility. The microfluidic rotating-target sample delivery device consists of two parts: a microfluidic sample plate and a motion control system. Sample delivery is realized by rotating the microfluidic sample plate containing in situ grown crystals. This device offers significant advantages, including a very wide adjustable range of delivery speed, low background noise, and low sample consumption. Using the microfluidic rotating-target device, we carried out in situ serial crystallography experiments with lysozyme and proteinase K as model samples at the Shanghai Synchrotron Radiation Facility, and performed structural determination based on the serial crystallographic data. The results showed that the designed device is fully compatible with the synchrotron radiation facility, and the structure determination of proteins is successful using the serial crystallographic data obtained with the device.

LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis.

BACKGROUND: Radiotherapy is an effective strategy for preventing cancer metastasis, including osteosarcoma. However, cancer radioresistance limits the efficiency of radiotherapy. Therefore, it is essential to investigate the mechanism of osteosarcoma radioresistance. METHODS: The osteosarcoma tissues and adjacent healthy tissues were collected from 53 osteosarcoma patients. The expression of LINC00210, miR-342-3p, and GFRA1 mRNA were determined using qRT-PCR. Cell viability, cell apoptosis, and cell surviving fraction were determined by MTT assay, flow cytometry, and colony formation assay, respectively. Western blot was performed to detect the protein levels. Luciferase assay was conducted to verify the relationship between LINC00210, miR-342-3p, and GFRA1. RESULTS: LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma tissues and cells. The expression of LINC00210 in osteosarcoma was negatively related to miR-342-3p expression and positively associated with GFRA1. Besides, there was a negative correlation between LINC00210 and GFRA1 expression in osteosarcoma. Also, LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma cells exposed to 4 Gy irradiation treatment. Furthermore, either LINC00210 knockdown or miR-342-3p overexpression enhanced the radiosensitivity of osteosarcoma cells. Moreover, LINC00210 increased GFRA1 expression via sponging miR-342-3p. Additionally, LINC00210 knockdown improved the radiosensitivity of osteosarcoma cells by regulating GFRA1 expression via sponging miR-342-3p. CONCLUSION: LINC00210 modulated the radiosensitivity of osteosarcoma cells via the miR-342-3p/GFRA1 axis, making LINC00210 a novel target for improving radiotherapy efficiency in osteosarcoma.

Efficacy and safety of Chinese medicines for vitreous hemorrhage: A protocol for systematic review and meta-analysis.

BACKGROUND: Vitreous hemorrhage (VH) is a common ophthalmic disease with a high rate of blindness, which will seriously affect the quality of life of patients and bring great burden to patients' families and society. The treatment for VH contains medical therapy, lasers, and surgery. At present, there is no recognized western medicine with definite curative effect and little side effect for the treatment of VH. In most cases, PRP is not available to treat VH; intravitreal injection or surgical treatment is adopted as the primary therapy. However, in the long-term treatment, the effect of the above-mentioned treatment is not satisfactory, so many patients choose oral Chinese medicines, which has been widely used in China to treat VH. Numerous clinical trials have demonstrated that Chinese medicines can promote the absorption of VH and improve the visual function of patients. The purpose of this review is to evaluate the efficacy and safety of Chinese medicines in the treatment of VH and inform a decision aid for the clinical encounter between patients and clinicians. Besides, it is beneficial to establish a future research agenda. METHODS: The systematic review will include all of the randomized controlled trials on the efficacy and safety of Chinese medicines for VH. Nine electronic databases, namely PubMed, Web of Science, EMBASE, the Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal database (VIP), and CBM, will be searched normatively on the basis of the rule of each database from the inception to August 31, 2019. We will also search registers of clinical trials, potential gray literature, and conference abstracts. There are no limits on language and publication status. The literature screening, data extraction, and quality assessment will be conducted by 2 reviewers independently. The reporting quality and risk of bias will be assessed by other 2 researchers. Standard of curative effect and total treatment efficacy rate were assessed as the primary outcome. The secondary outcomes will include the curative effect of single symptom and sign, the improvement rate of single auxiliary examination, withdrawal and reduction of western medicines in a course of treatment, maintenance of western medicines after the course of treatment, laboratory efficacy indexes. Meta-analysis will be performed using RevMan5.3 software provided by the Cochrane Collaboration. RESULTS: This study will provide a comprehensive review based on current evidence of Chinese medicines treatment for VH in several aspects, including standard of curative effect, total treatment efficacy rate, the curative effect of single symptom and sign, the improvement rate of single auxiliary examination, withdrawal and reduction of western medicines in a course of treatment, laboratory efficacy indexes, total treatment efficacy, and safety, among others. CONCLUSION: The conclusion of this study will provide evidence to determine whether Chinese medicines are an effective and safe intervention for patients with VH. ETHICS AND DISSEMINATION: It is not necessary to obtain ethical approval for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences and will be shared on social media platforms. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020152321.

A Novel Rhynchophylline Analog, Y396, Inhibits Endothelial Dysfunction Induced by Oxidative Stress in Diabetes Through Epidermal Growth Factor Receptor.

Aims: Endothelial dysfunction appears in early diabetes mellitus partially because of epidermal growth factor receptor (EGFR) abnormal activation and downstream oxidative stress. The aim of this study was to determine whether Y396, a synthesized analog of rhynchophylline, could protect against endothelial dysfunction in diabetes and the underlying molecular mechanism. Results: Y396 could directly target the EGFR and inhibit its phosphorylation induced by high glucose and EGF, downstream translocation to the nucleus of E2F1, and its transcriptional activity and expression of Nox4. Diabetes-induced endothelium malfunction was ameliorated by Y396 treatment through EGFR inhibition. Downstream oxidative stress was decreased by Y396 in the aortas of type 1 diabetes mellitus mice and primary rat aorta endothelial cells (RAECs). Y396 could also ameliorate tunicamycin-induced oxidative stress in the aorta and RAECs. In addition, we again determined the protective effects of Y396 on high-fat diet/streptozotocin-induced type 2 diabetes mellitus. Innovation: This is the first study to demonstrate that Y396, a novel rhynchophylline analog, suppressed high-glucose-induced endothelial malfunction both in vivo and in vitro by inhibiting abnormal phosphorylation of EGFR. Our work uncovered EGFR as a novel therapeutic target and Y396 as a potential therapy against diabetes-induced complication. Conclusion: Y396 could directly bind with EGFR, and inhibit its phosphorylation and downstream E2F1 transcriptional activity. It could also preserve tunicamycin-evoked endothelial dysfunction and oxidative stress. It could protect against diabetes-induced endothelium malfunction in vivo through EGFR inhibition and downstream oxidative stress. Antioxid. Redox Signal. 32, 743-765.