Hippo pathway regulation by phosphatidylinositol transfer protein and phosphoinositides.

The Hippo pathway plays a key role in development, organ size control and tissue homeostasis, and its dysregulation contributes to cancer. The LATS tumor suppressor kinases phosphorylate and inhibit the YAP/TAZ transcriptional co-activators to suppress gene expression and cell growth. Through a screen of marine natural products, we identified microcolin B (MCB) as a Hippo activator that preferentially kills YAP-dependent cancer cells. Structure-activity optimization yielded more potent MCB analogs, which led to the identification of phosphatidylinositol transfer proteins α and ß (PITPα/ß) as the direct molecular targets. We established a critical role of PITPα/ß in regulating LATS and YAP. Moreover, we showed that PITPα/ß influence the Hippo pathway via plasma membrane phosphatidylinositol-4-phosphate. This study uncovers a previously unrecognized role of PITPα/ß in Hippo pathway regulation and as potential cancer therapeutic targets.

XGBoost in the Prediction of 28-Day Mortality in Critical Elderly Patients with Hip Fracture: A MIMIC-IV Cohort Study.

Background: The impact of hip fracture on older adults is significant, including increased mortality, reduced activity levels and abilities and reduced quality of life。 Hip fractures often occur in the elderly and increase the risk of death. The purpose of this study is to analyze the risk factors associated with 28-day mortality in elderly patients with severe hip fractures using two models, XG Boost and multivariate logistic regression, and to compare the predictive value of the two models. Methods: MIMIC database is a powerful tool to provide clinical data to clinical researchers. The database was established in 2003 with funding from the National Institutes of Health by the Computational Physiology Laboratory at the Massachusetts Institute of Technology, Beth Israel Deaconess Medical Center (BIDMC) at Harvard Medical School, and Philips Medical. Patients with severe hip fractures in the elderly were included based on the MIMIC-IV database and were divided into a death group and a survival group based on the death 28 days after admission to the ICU. Baseline data differences between the two groups of patients were compared, and risk factors associated with 28-day mortality in severe elderly patients with hip fractures were analyzed using XG Boost and multivariate logistic regression models, respectively. The predictive power of the two models was compared using receiver operation characteristics curves. Results: 287 elderly patients with severe hip fractures were included, including 43 cases (15.0%) in the death group and 244 cases (85.0%) in the survival group. Logistic regression analysis showed that advanced age, male, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), high sepsis-related organ failure (SOFA) score, high heart rate, high white blood cell count, high creatinine, high mean arterial pressure, and high hemoglobin levels were associated with 28-day mortality after admission to the ICU, while the higher the mean arterial pressure and the hemoglobin level, the lower the risk of death. Although the rate of using mechanical ventilation and receiving blood transfusion in the death group was higher than that in the survival group, neither of them reached statistical significance. The XG Boost model shows that the top 5 factors associated with 28-day mortality are Sequential organ failure score (SOFA) score (31 points), chronic heart failure (20 points), chronic structural pulmonary disease (18 points), age (17 points), and male (15 points). The higher the mean arterial pressure and the hemoglobin level, the lower the risk of death. The area under the ROC curve predicted by the multivariate logistic regression model for mortality risk was 0.729 (95% CI: 0.701-0.783), and the Jordan index was 0.412. The area under the ROC curve predicted by the XG Boost model for mortality risk was 0.804 (95% CI: 0.720-0.837), and the Jordan index was 0.492. Conclusion: The ability of the XG Boost model to predict the 28-day mortality risk in elderly patients with severe hip fractures is better than the multivariate logistic regression model, which will help healthcare professionals provide more support for elderly patients with hip fracture.

Effective doses of midazolam oral solution for the prevention of preoperative anxiety in paediatric patients.

BACKGROUND: More than 60% children exhibit anxiety before undergoing an anesthetic-surgical procedure, particularly among pre-school paediatric patients. Oral midazolam can provide procedural sedation for children prior to anesthesia. However, extemporaneous solutions of midazolam are usually prepared from injectable drug solutions, leading to inconsistent efficacy due to variable preparation methods. Xiaoerjing® is the first commercially available oral formulation of midazolam for procedural sedation in children in China. Despite the recommended dosage range of 0.25-0.5 mg/kg, its effective dose is still largely unknown. AIM: To determine the 95% effective dose (ED95) of midazolam oral solution (Xiaoerjing®) for alleviating preoperative anxiety in children prior to mask induction of general anesthesia. DESIGN: The study included 61 children between the ages of 1 and 6 years undergoing elective surgery under general anesthesia. The first patient received a single dose of 0.5 mg/kg midazolam oral solution, which was adjusted for subsequent patients using the biased coin design method based on their response to the previous dose. Doses were increased or decreased at the rate of 0.1 mg/kg. An effective response was defined as having a modified Ramsay sedation score ≥3a, separation anxiety score ≤2, and mask acceptance score ≤2 during inhalational anesthesia induction. RESULTS: Fifty-six children were included in the final analysis. Of those, sedation was successful in 50 patients, with a median separation time of 15 (IQR: 25) min. Midazolam oral solution has an ED95 of 0.8254 mg/kg (95% CI: 0.6915-0.8700 mg/kg) for relieving preoperative anxiety in children. No adverse events occurred following drug administration. CONCLUSION: Midazolam oral solution is a safe and effective medication for relieving preoperative anxiety in children. The ED95 of a single oral dose of midazolam oral solution is 0.8254 mg/kg (95% CI: 0.6915-0.8700 mg/kg).

Recent advances in the routes and catalysts for ethanol synthesis from syngas.

Ethanol, as one of the important bulk chemicals, is widely used in modern society. It can be produced by fermentation of sugar, petroleum refining, or conversion of syngas (CO/H2). Among these approaches, conversion of syngas to ethanol (STE) is the most environmentally friendly and economical process. Although considerable progress has been made in STE conversion, control of CO activation and C-C growth remains a great challenge. This review highlights recent advances in the routes and catalysts employed in STE technology. The catalyst designs and pathway designs are summarized and analysed for the direct and indirect STE routes, respectively. In the direct STE routes (i.e., one-step synthesis of ethanol from syngas), modified catalysts of methanol synthesis, modified catalysts of Fischer-Tropsch synthesis, Mo-based catalysts, noble metal catalysts and multifunctional catalysts are systematically reviewed based on their catalyst designs. Further, in the indirect STE routes (i.e., multi-step processes for ethanol synthesis from syngas via methanol/dimethyl ether as intermediates), carbonylation of methanol/dimethyl ether followed by hydrogenation, and coupling of methanol with CO to form dimethyl oxalate followed by hydrogenation, are outlined according to their pathway designs. The goal of this review is to provide a comprehensive perspective on STE technology and inspire the invention of new catalysts and pathway designs in the near future.

Tuning C1 /C2 Selectivity of CO2 Electrochemical Reduction over in-Situ Evolved CuO/SnO2 Heterostructure.

Heterostructured oxides with versatile active sites, as a class of efficient catalysts for CO2 electrochemical reduction (CO2 ER), are prone to undergo structure reconstruction under working conditions, thus bringing challenges to understanding the reaction mechanism and rationally designing catalysts. Herein, we for the first time elucidate the structural reconstruction of CuO/SnO2 under electrochemical potentials and reveal the intrinsic relationship between CO2 ER product selectivity and the in situ evolved heterostructures. At -0.85 VRHE , the CuO/SnO2 evolves to Cu2 O/SnO2 with high selectivity to HCOOH (Faradaic efficiency of 54.81 %). Mostly interestingly, it is reconstructed to Cu/SnO2-x at -1.05 VRHE with significantly improved Faradaic efficiency to ethanol of 39.8 %. In situ Raman spectra and density functional theory (DFT) calculations reveal that the synergetic absorption of *COOH and *CHOCO intermediates at the interface of Cu/SnO2-x favors the formation of *CO and decreases the energy barrier of C-C coupling, leading to high selectivity to ethanol.

Long non-coding RNA BZRAP1-AS1 silencing suppresses tumor angiogenesis in hepatocellular carcinoma by mediating THBS1 methylation.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer associated with a high mortality. Long non-coding RNAs (lncRNAs) have recently emerged as regulators in the development and progression of several cancers, and therefore represent an opportunity to uncover new targets for therapy. In the present study, we aimed to investigate the potential effect of lncRNA BZRAP1-AS1 on the angiogenesis of HCC. METHODS: Microarray-based data analysis was initially employed to screen genes and lncRNAs that are differentially expressed in HCC and the candidate BZRAP1-AS1 was identified as a hit. The expression of BZRAP1-AS1 and thrombospondin-1 (THBS1) in HCC tissues and cells were then determined using RT-qPCR. The gene methylation level was measured by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) assays. Next, the interactions between BZRAP1-AS1, DNA methyltransferase 3B (DNMT3b), and THBS1 were assessed by RIP, RNA pull-down and ChIP assays. Finally, the roles of BZRAP1-AS1, DNMT3b and THBS1 in angiogenesis in vitro as well as tumorigenesis in vivo were evaluated by a battery of the gain- and loss-of function experiments. RESULTS: BZRAP1-AS1 was identified as a highly expressed lncRNA in HCC tissues and cells. Down-regulation of BZRAP1-AS1 in HCC cells inhibited HUVEC proliferation, migration and angiogenesis. By interacting with DNMT3b, BZRAP1-AS1 induced methylation of the THBS1 promoter and inhibited the transcription of THBS1, resulting in promoted angiogenesis of HUVECs. Moreover, silencing of BZRAP1-AS1 repressed the angiogenesis as well as the tumor growth of HCC in vivo via up-regulating THBS1. CONCLUSION: This study provides evidence that angiogenesis in HCC is hindered by silencing of BZRAP1-AS1. Thus, BZRAP1-AS1 may be a promising marker for the treatment of HCC.

Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy.

The nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3' end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci ("TT foci") are not stress granules but instead are a mRNP granule containing poly(A)(+) mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3' end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus.

Vertical MoSe2-MoO x p-n heterojunction and its application in optoelectronics.

The hybrid n-type 2D transition-metal dichalcogenide (TMD)/p-type oxide van der Waals (vdW) heterojunction nanosheets consist of 2D layered MoSe2 (the n-type 2D material) and MoO x (the p-type oxide) which are grown on SiO2/Si substrates for the first time via chemical vapor deposition technique, displaying the regular hexagon structures with the average length dimension of sides of ∼8 µm. Vertical MoSe2-MoO x p-n heterojunctions demonstrate obviously current-rectifying characteristic, and it can be tuned via gate voltage. What is more, the photodetector based on vertical MoSe2-MoO x heterojunctions displays optimal photoresponse behavior, generating the responsivity, detectivity, and external quantum efficiency to 3.4 A W-1, 0.85 × 108 Jones, and 1665.6%, respectively, at V ds = 5 V with the light wavelength of 254 nm under 0.29 mW cm-2. These results furnish a building block on investigating the flexible and transparent properties of vdW and further optimizing the structure of the devices for better optoelectronic and electronic performance.

Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics.

10.8 kW spectral beam combination of eight all-fiber superfluorescent sources and their dispersion compensation.

We report an 8-element spectral beam combination of Yb-doped all fiber superfluorescent sources around 1070 nm wavelength. Each source consists of a 60 mW front-end and a 1.5 kW three-stage fiber amplifier chain. The eight output beamlets are spectrally combined using a home-made polarization-independent multilayer dielectric reflective diffraction grating. 10.8 kW output power is achieved with an efficiency of 94%. Besides, both theoretical and experimental studies of dual grating dispersion compensation scheme have been performed, which is proved to be a prospective way for high brightness spectral beam combination.

[Application of Image Plate in Quality Assurance of Medical Accelerator].

Objective: To explore the value of Computed Radiography(CR) in quality control for the medical linear accelerator. Methods: By using both CR and autoradiography film respectively, we tested the alignment of light fields with radiation fields, colimator rotation with center, couch rotation with center and multi-leave colimators(MLC) position accuracy of medical linear accelerator. Each tests were carried out ten times repetitive colection. Then compared the differences between this two methods. Results: There were no significant difference between CR and autoradiography film in the same grup(P>0.05). Conclusion: CR can be used in quality control for the medical linear accelerator since it can meet quality control requirements of radiotherapy.

Schottky Junctions with Bi@Bi2MoO6 Core-Shell Photocatalysts toward High-Efficiency Solar N2-to-Ammonnia Conversion in Aqueous Phase.

The photocatalytic nitrogen reduction reaction (NRR) in aqueous solution is a green and sustainable strategy for ammonia production. Nonetheless, the efficiency of the process still has a wide gap compared to that of the Haber-Bosch one due to the difficulty of N2 activation and the quick recombination of photo-generated carriers. Herein, a core-shell Bi@Bi2MoO6 microsphere through constructing Schottky junctions has been explored as a robust photocatalyst toward N2 reduction to NH3. Metal Bi self-reduced onto Bi2MoO6 not only spurs the photo-generated electron and hole separation owing to the Schottky junction at the interface of Bi and Bi2MoO6 but also promotes N2 adsorption and activation at Bi active sites synchronously. As a result, the yield of the photocatalytic N2-to-ammonia conversion reaches up to 173.40 µmol g-1 on core-shell Bi@Bi2MoO6 photocatalysts, as much as two times of that of bare Bi2MoO6. This work provides a new design for the decarbonization of the nitrogen reduction reaction by the utilization of renewable energy sources.

DPPA2/4 Promote the Pluripotency and Proliferation of Bovine Extended Pluripotent Stem Cells by Upregulating the PI3K/AKT/GSK3ß/ß-Catenin Signaling Pathway.

Developmental pluripotency-associated 2 (DPPA2) and DPPA4 are crucial transcription factors involved in maintaining pluripotency in humans and mice. However, the role of DPPA2/4 in bovine extended pluripotent stem cells (bEPSCs) has not been investigated. In this study, a subset of bEPSC-related differentially expressed genes (DEGs), including DPPA2 and DPPA4, was identified based on multiomics data (ATAC-seq and RNA-seq). Subsequent investigations revealed that double overexpression of DPPA2/4 facilitates the reprogramming of bovine fetal fibroblasts (BFFs) into bEPSCs, whereas knockout of DPPA2/4 in BFFs leads to inefficient reprogramming. DPPA2/4 overexpression and knockdown experiments revealed that the pluripotency and proliferation capability of bEPSCs were maintained by promoting the transition from the G1 phase to the S phase of the cell cycle. By activating the PI3K/AKT/GSK3ß/ß-catenin pathway in bEPSCs, DPPA2/4 can increase the nuclear accumulation of ß-catenin, which further upregulates lymphoid enhancer binding factor 1 (LEF1) transcription factor activity. Moreover, DPPA2/4 can also regulate the expression of LEF1 by directly binding to its promoter region. Overall, our results demonstrate that DPPA2/4 promote the reprogramming of BFFs into bEPSCs while also maintaining the pluripotency and proliferation capability of bEPSCs by regulating the PI3K/AKT/GSK3ß/ß-catenin pathway and subsequently activating LEF1. These findings expand our understanding of the gene regulatory network involved in bEPSC pluripotency.

Trace Metal(loid) Migration from Road Dust to Local Vegetables and Tree Tissues and the Bioaccessibility-Based Health Risk: Impacts of Vehicle Operation-Associated Emissions.

Traffic activities release large amounts of trace metal(loid)s in urban environments. However, the impact of vehicle operation-associated emissions on trace metal(loid) enrichment in road dust and the potential migration of these trace metal(loid)s to the surrounding environment remain unclear. We evaluated the contamination, sequential fraction, and bioaccessibility of trace metal(loid)s in urban environments by assessing their presence in road dust, garden vegetables, and tree tissues, including bark and aerial roots, at a traffic-training venue impacted by vehicle operation emissions and, finally, calculated the bioaccessibility-based health risk. The results indicated a significant accumulation of trace metal(loid)s in road dust, with the highest lead (Pb), cadmium (Cd), and antimony (Sb) concentrations in the garage entrance area due to higher vehicle volumes, frequent vehicle starts and stops, and lower speeds. Aerial roots exposed to hill start conditions exhibited the highest Pb, Zn, and Sb levels, potentially caused by high road dust resuspension, confirming that this tree tissue is an appropriate bioindicator. Sequential extraction revealed high percentages of carbonate-, Fe/Mn oxide-, and organic/sulphide-associated fractions of Pb, copper (Cu), and zinc (Zn) in road dust, while most Cd, Cr, Ni, and Sb occurred as residual fractions. According to the potential mobilizable fractions in sequential extraction, the in vitro gastrointestinal method could be more suitable than the physiologically based extraction test to evaluate the bioaccessibility-related risk of traffic-impacted road dust. The bioaccessibility-based health risk assessment of the road dust or soil confirmed no concern about noncarcinogenic risk, while the major risk originated from Pb although leaded gasoline was prohibited before the venue establishment. Furthermore, the cancer risks (CRs) analysis showed the probable occurrence of carcinogenic health effects from Cd and Ni to adults and from Cd, Cr, and Ni to children. Furthermore, the Cd and Pb concentrations in the edible leaves of cabbage and radish growing in gardens were higher than the recommended maximum value. This study focused on the health risks of road dust directly impacted by vehicle emissions and provides accurate predictions of trace metal(loid) contamination sources in the urban environment.

Experimental study on the repair of peripheral nerve injuries via simultaneously coapting the proximal and distal ends of peripheral nerves to the side of nearby intact nerves.

Introduction: Peripheral nerve defect is a difficult disease to treat in clinical practice. End-to-side anastomosis is a useful method to treat it. At present, the end-to-side anastomosis method does not involve the proximal nerve, which results in a waste of proximal donor nerves, and even the formation of traumatic neuromas at the proximal end. The patients suffer from traumatic neuralgia and the curative effect is unsatisfactory. Methods: In this study, an improved end-to-side anastomosis technique was proposed in this study: both the proximal and distal ends of the damaged common peroneal nerve were sutured to an adjacent normal tibial nerve. Moreover, the possible role and mechanism of the proposed technique were explained at the physiological and anatomical levels. In this study, a 10 mm common peroneal nerve defect was made in SD rats, and the rats were randomly divided into three groups. In Group I, the distal end of the common peroneal nerve was attached end-to-side to the fenestrated tibial nerve adventitia, and the proximal end was ligated and fixed in the nearby muscle. In Group II, the tibial nerve adventitia was fenestrated and the epineurial end-to-end anastomosis surgery was performed to suture the proximal and distal ends of the common peroneal nerve. Rats in Group III were taken as control and received sham operation. Twelve weeks after the operation, the recovery of the repaired nerve and distal effector functions were examined by the sciatic functional index, electrophysiology, osmic acid staining, the muscle wet weight ratio, and the muscle fiber cross-sectional area. Results: It was found that these results in Group II were similar to those in Group III, but better than those in Group I. Through retrograde tracing of neurons and Electrophysiological examination in Group II, the study also found that the proximal common peroneal nerve also could establish a connection with tibialis anterior, even gastrocnemius. Discussion: Therefore, it is inferred that fostering both the proximal and distal ends of defective peripheral nerves on normal peripheral nerves using the end-to-side anastomosis technique is a more effective approach to repairing injured nerves.

Salermide up-regulates death receptor 5 expression through the ATF4-ATF3-CHOP axis and leads to apoptosis in human cancer cells.

Sirtuins (a class III histone deacetylase) have emerged as novel targets for cancer therapy. Salermide, a reverse amide compound that inhibits Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2), has been shown to induce apoptosis in human cancer cells. The mechanism underlying cellular apoptotic signalling by salermide remains unclear. In this study, we show that salermide up-regulates the expression of death receptor 5 (DR5) in human non-small cell lung cancer (NSCLC) cells. Blocking DR5 expression by gene silencing technology results in a decrease in activated forms of several pro-apoptotic proteins (caspase-8, caspase-9, caspase-3, PARP). Increasing DR5 protein expression correlates with salermide-induced apoptosis in human NSCLC cells. We discovered that IRE-1α, Bip, activating transcription factor 3 (ATF4), activating transcription factor 3 (ATF3) and C/EBP homologous protein (CHOP) are induced by salermide, which suggests that DR5-dependent apoptosis is induced by endoplasmic reticulum stress. Moreover, knockdown of Sirt1 and Sirt2 expression resulted in up-regulation of ATF4, CHOP and DR5. Transfected NSCLC cells with ATF4, ATF3 or CHOP siRNA results in a decline in pro-apoptotic proteins (such as caspase-8, caspase-9, caspase-3 and PARP) despite salermide treatment. We demonstrate that salermide induces expression of ATF4, and ATF4 up-regulates ATF3 and subsequently modulates CHOP. This suggests that DR5 is modulated by the ATF4-ATF3-CHOP axis in NSCLC after Sirt1/2 inhibition or salermide treatment. This study highlights the importance of DR5 up-regulation in apoptosis induced by Sirt1/2 inhibition and elucidates the underlying mechanism in human NSCLC cells.

The Role of Structural Deterioration and Biomechanical Changes of the Necrotic Lesion in Collapse Mechanism of Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a crippling disease which is due to a lack of effective therapeutic measures. Its natural progression is rapid, the internal bone structure of the femoral head changes dramatically, and the subsequent fractures and collapse cause severe hip pain and loss of hip function. Femoral head collapse is a critical turning point in the development of ONFH and is related to the prognosis of patients. Early prevention and intervention help to preserve the hip joint and delay femoral head collapse. However, the mechanism of collapse still needs to be further studied because it is affected by different complex factors. This review discusses the underlying causes of femoral head collapse from two aspects: structural degradation and regional changes of biomechanical properties in the necrotic femoral head.

Anderson-Type Polyoxometalate-Assisted Synthesis of Defect-Rich Doped 1T/2H-MoSe2 Nanosheets for Efficient Seawater Splitting and Mg/Seawater Batteries.

Designing high-performance hydrogen evolution reaction (HER) catalysts is crucial for seawater splitting. Herein, we demonstrate a facile Anderson-type polyoxometalate-assisted synthesis route to prepare defect-rich doped 1T/2H-MoSe2 nanosheets. As demonstrated, the optimized defect-rich doped 1T/2H-MoSe2 nanosheets display low overpotentials of 116 and 274 mV to gain 10 mA cm-2 in acidic and simulated seawater for the HER, respectively. A magnesium (Mg)/seawater battery was fabricated with the defect-rich doped 1T/2H-MoSe2 nanosheet cathode, displaying the highest power density of up to 7.69 mW cm-2 and stable galvanostatic discharging over 24 h. The theoretical and experimental investigations show that the superior HER and battery performances of the heteroatom-doped MoSe2 nanosheets are attributed to both the improved intrinsic catalytic activity (effective activation of water and favorable subsequent hydrogen desorption) and the abundant active sites, benefiting from the favorable catalytic factors of the doped heteroatom, 1T phase, and defects. Our work presents an intriguing structural modulation strategy to design high-performance catalysts toward both HER and Mg/seawater batteries.

3D gel-printed porous magnesium scaffold coated with dibasic calcium phosphate dihydrate for bone repair in vivo.

BACKGROUND: /Objective: The treatment of bone defect has always been a difficult problem in orthopedic clinic. The search for alternative biodegradable implants is a hot topic. The development of biodegradable magnesium scaffolds for the treatment of bone defects has long been a goal of the public. METHODS: In this study, we proposed a porous magnesium scaffold prepared by 3D gel printing and surface modification with an additional calcium phosphate coating and use of its strength, degradability and slow degradation rate in a bone graft substitute material. The porous magnesium granular scaffold was prepared by 3D gel printing technology and modified by DCPD (Dibasic Calcium Phosphate Dihydrate) coating. The biocompatibility, degradation rate, and osteogenic ability of the scaffold were evaluated in vitro and in vivo. RESULTS: The biocompatibility, in vivo degradation and bone defect healing response of the implants were investigated. Porous magnesium scaffolds were successfully prepared, and the strength of sintered scaffolds reached 5.38 â€‹MPa. The degradation rates of scaffolds were significantly reduced after coating with DCPD. The cell compatibility evaluation showed that DCPD-coated Mg scaffold was suitable for cell proliferation. In vivo biosafety monitoring showed that scaffold implantation did not cause an increase in Mg ion concentration in vivo, and no toxic damage was detected in the liver or kidney. Micro-CT and pathological results showed that a large amount of new bone was formed at 6 weeks. At 12 weeks, approximately 52% of the scaffold volume remained. At 24 weeks, osteogenesis, which was stimulated by some residual scaffold, still can be observed. In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives. CONCLUSION: In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The translational potential of this article is to make use of the advantages of 3D gel printing technology with higher efficiency and lower cost compared with SLM and SLS technologies, and use pure magnesium powder as raw material to prepare degradable porous magnesium metal scaffolds, opening up a new technical route for the preparation of degradable porous magnesium scaffolds which are made for bone defect regeneration in the future.

Core Decompression with Local Administration of Zoledronate and Enriched Bone Marrow Mononuclear Cells for Treatment of Non-Traumatic Osteonecrosis of Femoral Head.

OBJECTIVE: To investigate the efficacy and safety of core decompression (CD) with local administration of zoledronate and enriched bone marrow mononuclear cells (BMMCS) for the treatment of non-traumatic osteonecrosis of femoral head (ONFH). METHODS: A total of 17 patients (30 hips) diagnosed with stage II and III ONFH according to the 2019 revised Association for Research on Osseous Circulation (ARCO) staging criteria from 2012 to 2014 were retrospectively reviewed. The patients received the following therapy: the BMMCs and zoledronate were injected into the necrotic zone, respectively, along with CD. The mean age of the patients was 36.8 years; 14 were men and three were women. All patients included had non-traumatic ONFH and a minimum follow-up of 5 years, which ended when total hip arthroplasty (THA) was performed. Imaging modalities, including plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI) were taken pre- and postoperatively. Harris hip score (HHS) was used to evaluate the functional outcomes of femoral head necrosis. Kaplan-Meier analysis was adopted to determine the probability of survivorship with THA as the end point in this series of patients. The correlation between radiological progression or THA and related risk factors were further analyzed. All complications were recorded. RESULTS: With THA as the follow-up endpoint, All patients were followed up for an average of 69.1 ± 20.5 months (range, 18-95 months). Preoperative imaging found six hips (20%) at ARCO stage II, 14 hips (46.7%) at stage IIIA, 10 hips (33.3%) at stage IIIB. Fourteen hips (46.7%) shown progression radiologically, while six hips (20%) underwent TKA among these patients with hip preservation. The cumulative survival was 80% (95% CI, 0.608-905) at 5 years with THA as the end point. HHS improved from 63.3 ± 8.7 preoperatively to 74.6 ± 20.6 postoperatively (P = 0.000). Radiological progression was found to be associated with ARCO stage, Japanese Investigation Committee (JIC) type, and corticosteroid exposure (P = 0.047; P = 0.012; P = 0.031). However, no correlation was found between conversion to THA and the known risk factors. No major complication was reported, with only four patients complaining about general weakness and muscle soreness, and all disappeared within 2-3 days. CONCLUSIONS: The novel treatment modality could relieve pain, delay the progression of collapse, which might be an effective and safe method for hip preservation of early and mid-term ONFH. However, the effect of this method may be related to ARCO stage, JIC type, and corticosteroid exposure.