Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS).

Background: Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. Objective: To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. Methods: FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Results: Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Conclusion: Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.

Apelin Receptor Homodimerisation Inhibits Hippocampal Neuronal Autophagy via G Protein-Dependent Signalling in Vascular Dementia.

Vascular dementia (VD), a progressive vascular cognitive impairment, is characterised by the presence of cerebral hypoperfusion, increased blood-brain barrier permeability, and white matter lesions. Although current treatment strategies primarily focus on risk factors such as hypertension, diabetes, and heart disease, efficient and targeted therapies are lacking and the underlying mechanisms of VD remain unclear. We previously discovered that Apelin receptors (APJ), which are G protein-coupled receptors (GPCRs), can homodimerize and generate signals that are distinct from those of APJ monomers in VD rats. Apelin-13 reduces the level of APJ homodimers and leads to the proliferation of endogenous neural stem cells in the hippocampal dentate gyrus area, suggesting that it has a neuroprotective role. In this study, we established a rat and cellular oxygen-glucose deprivation/reoxygenation VD model to investigate the impact of APJ homodimerisation on autophagy. We found that APJ homodimers protect against VD by inhibiting autophagy through the Gαq and PI3K/Akt/mTOR pathways upon Gαi signalling, both in vivo and in vitro. This discovery provides a promising therapeutic target for chronic cerebral ischaemia-reperfusion diseases and an experimental foundation for the development of drugs that target APJ homodimers.

Comparing musculoskeletal and connective tissue disorder risks of teriparatide and abaloparatide in osteoporosis: an analysis based on FDA adverse event reporting system (FAERS).

BACKGROUND: Osteoporosis (OP), characterized by low bone mass and increased fracture risk, is a prevalent skeletal disorder. Teriparatide (TP) and abaloparatide (ABL) are anabolic agents that may reduce fracture incidence, but their impact on musculoskeletal and connective tissue disorders (MCTD) risk is uncertain. RESEARCH DESIGN AND METHODS: A retrospective, observational disproportionality analysis was conducted utilizing FAERS data from Q1 2004 to Q3 2023, where TP or ABL was identified as the primary suspect drug. Multiple data mining algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to detect MCTD safety signals. RESULTS: A total of 366,747 TP-related and 422,377 ABL-related cases were identified, predominantly among female patients aged ≥45 years. The top specific AEs involved musculoskeletal, connective tissue, and administration site disorders. Comparative analysis revealed a higher frequency of AEs related to the nervous, cardiovascular, and gastrointestinal systems for ABL compared to TP. Both drugs exhibited strong signals for arthralgia, limb pain, back pain, muscle spasms, bone pain, muscle pain, and muscle weakness. CONCLUSION: The analysis suggests a potential MCTD risk with TP and ABL treatment in OP patients, highlighting the need for AE monitoring and management in clinical practice. This contributes to a better understanding of the safety profiles of these anabolic medications.

Global Trends in Research of Programmed Cell Death in Osteoporosis: A Bibliometric and Visualized Analysis (2000-2023).

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

Electrostatic Self-Assembly Synthesis of Pd/In2O3 Nanocatalysts with Improved Performance Toward CO2 Hydrogenation to Methanol.

CO2 hydrogenation to methanol has emerged as a promising strategy for achieving carbon neutrality and mitigating global warming, in which the supported Pd/In2O3 catalysts are attracting great attention due to their high selectivity. Nonetheless, conventional impregnation methods induce strong metal-support interaction (SMSI) between Pd and In2O3, which leads to the excessive reduction of In2O3 and the formation of undesirable PdIn alloy in hydrogen-rich atmospheres. Herein, we innovatively synthesized Pd/In2O3 nanocatalysts by the electrostatic self-assembly process between surface-modified composite precursors with opposite charges. And the organic ligands concurrently serve as Pd nanoparticle protective agents. The resultant Pd/In2O3 nanocatalyst demonstrates the homogeneous distribution of Pd nanoparticles with controllable sizes on In2O3 supports and the limited formation of PdIn alloy. As a result, it exhibits superior selectivity and stability compared to the counterparts synthesized by the conventional impregnation procedure. Typically, it attains a maximum methanol space-time yield of 0.54 gMeOH h-1gcat -1 (300 °C, 3.5 MPa, 21,000 mL gcat -1 h-1). Notably, the correlation characterization results reveal the significant effect of small-size, highly dispersed Pd nanoparticles in mitigating MSI. These results provide an alternative strategy for synthesizing highly efficient Pd/In2O3 catalysts and offer a new insight into the strong metal-support interaction.

Identification and functional analysis of perforin 1 from largemouth bass (Micropterus salmoides).

In this study, we present the first cloning and identification of perforin (MsPRF1) in largemouth bass (Micropterus salmoides). The full-length cDNA of MsPRF1 spans 1572 base pairs, encoding a 58.88 kDa protein consisting of 523 amino acids. Notably, the protein contains MACPF and C2 structural domains. To evaluate the expression levels of MsPRF1 in various healthy largemouth bass tissues, real-time quantitative PCR was employed, revealing the highest expression in the liver and gut. After the largemouth bass were infected by Nocardia seriolae, the mRNA levels of MsPRF1 generally increased within 48 h. Remarkably, the recombinant protein MsPRF1 exhibits inhibitory effects against both Gram-negative and Gram-positive bacteria. Additionally, the largemouth bass showed a higher survival rate in the N. seriolae challenge following the intraperitoneal injection of rMsPRF1, with observed reductions in the tissue bacterial loads. Moreover, rMsPRF1 demonstrated a significant impact on the phagocytic and bactericidal activities of largemouth bass MO/MΦ cells, concurrently upregulating the expression of pro-inflammatory factors. These results demonstrate that MsPRF1 has a potential role in the immune response of largemouth bass against N. seriolae infection.

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects.

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. The primary obstacle lies in the absence of an optimal delivery system, which significantly hampers the immunogenicity of DNA vaccines. We conduct a comprehensive analysis of the current status and limitations of DNA vaccines by focusing on both viral and non-viral DNA delivery systems, as they play crucial roles in the exploration of novel DNA vaccines. We provide an evaluation of their strengths and weaknesses based on our critical assessment. Additionally, the review summarizes the most recent advancements and breakthroughs in pre-clinical and clinical studies, highlighting the need for further clinical trials in this rapidly evolving field.

Effect of Tooth Mobility on the Accuracy of Conventional Impressions: A Pilot Study.

PURPOSE: To study the influence of tooth mobility on the accuracy of conventional impressions. MATERIALS AND METHODS: In total, 10 patients with mobile anterior teeth and 10 healthy patients were treated with conventional impressions and intraoral digital impressions. The digital impression group was recorded as standard data, the mobile teeth group was recorded as the experimental group, and the healthy anterior teeth group was recorded as the control group. We imported digital impression and irreversible hydrocolloid impression files into Geomagic Wrap and marked reference points to execute N-point alignment, then we recorded the coordinates. Paired-samples t test was used to analyze whether the point coordinates of mobile teeth were statistically significant (a = .05). One-way ANOVA was used to analyze whether there was a relationship between coordinate differences and tooth mobility in the distal, coronal, and buccal directions (a = .05). RESULTS: In the buccal and coronal directions, the difference was statistically significant between the conventional and digital impression groups. In the buccal direction, the accuracy differences of I-degree and II-degree mobile teeth were 0.149 mm and 0.401 mm, respectively. In the coronal direction, the differences were 0.128 mm and 0.233 mm, respectively. Meanwhile, ANOVA analysis showed that there was a relationship between point coordinate difference and tooth mobility in the buccal and coronal directions. CONCLUSIONS: Conventional impressions can influence the accuracy of mobile tooth impressions. Therefore, digital impressions should be adopted for mobile teeth impressions.

Evaluating the performance of low-frequency variant calling tools for the detection of variants from short-read deep sequencing data.

Detection of low-frequency variants with high accuracy plays an important role in biomedical research and clinical practice. However, it is challenging to do so with next-generation sequencing (NGS) approaches due to the high error rates of NGS. To accurately distinguish low-level true variants from these errors, many statistical variants calling tools for calling low-frequency variants have been proposed, but a systematic performance comparison of these tools has not yet been performed. Here, we evaluated four raw-reads-based variant callers (SiNVICT, outLyzer, Pisces, and LoFreq) and four UMI-based variant callers (DeepSNVMiner, MAGERI, smCounter2, and UMI-VarCal) considering their capability to call single nucleotide variants (SNVs) with allelic frequency as low as 0.025% in deep sequencing data. We analyzed a total of 54 simulated data with various sequencing depths and variant allele frequencies (VAFs), two reference data, and Horizon Tru-Q sample data. The results showed that the UMI-based callers, except smCounter2, outperformed the raw-reads-based callers regarding detection limit. Sequencing depth had almost no effect on the UMI-based callers but significantly influenced on the raw-reads-based callers. Regardless of the sequencing depth, MAGERI showed the fastest analysis, while smCounter2 consistently took the longest to finish the variant calling process. Overall, DeepSNVMiner and UMI-VarCal performed the best with considerably good sensitivity and precision of 88%, 100%, and 84%, 100%, respectively. In conclusion, the UMI-based callers, except smCounter2, outperformed the raw-reads-based callers in terms of sensitivity and precision. We recommend using DeepSNVMiner and UMI-VarCal for low-frequency variant detection. The results provide important information regarding future directions for reliable low-frequency variant detection and algorithm development, which is critical in genetics-based medical research and clinical applications.

The Effect of the Hip Flexion Angle in Osteonecrosis of the Femoral Head Based on China-Japan Friendship Hospital Classification - A Finite Element Study.

OBJECTIVE: The alteration in the mechanical environment of the necrotic area is the primary cause of the collapse observed in osteonecrosis of the femoral head (ONFH). This study aims to evaluate the biomechanical implications of the China-Japan Friendship Hospital (CJFH) classification system and hip flexion angles on the necrotic area in ONFH using finite element analysis (FEA). The goal is to provide valuable guidance for hip preservation treatments and serve as a reference for clinical diagnosis and therapeutic interventions. METHODS: Hip tomography CT scan data from a healthy volunteer was used to create a 3D model of the left hip. The model was preprocessed and imported into Solidworks 2018, based on the CJFH classification. Material parameters and boundary conditions were applied to each fractal model in ANSYS 21.0. Von Mises stresses were calculated, and maximum deformation values were obtained to evaluate the biomechanical effects of the load on the necrotic area and post-necrotic femur, as well as assess each fractal model's collapse risk. RESULTS: (1) At the same hip flexion angle, maximum deformation followed this order: M Type < C Type < L Type. The L3 type necrotic area experienced the most significant deformation at 0, 60, and 110° angles (1.121, 1.7913, and 1.8239 mm respectively). (2) Under the same CJFH classification, maximum deformation values increased with hip flexion angle (0 < 60 < 110°), suggesting a higher risk of collapse at larger angles. (3) Von Mises stress results showed that the maximum stress was not located in the necrotic area but near the inner and outer edge of the femoral neck, indicating decreased stiffness and strength of the subchondral bone after osteonecrosis. CONCLUSION: The study found that femoral head collapse risk was higher when the necrotic area was located in the lateral column under the same stress load and flexion angle. Mechanical properties of the necrotic area changed, resulting in decreased bone strength and stiffness. Large-angle hip flexion is more likely to cause excessive deformation of the necrotic area; thus, ONFH patients should reduce or avoid large-angle hip flexion during weight-bearing training in rehabilitation activities.

Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head.

PURPOSE: Steroid-induced necrosis of the femoral head (SONFH) is a refractory orthopedic hip disease occurring in young and middle-aged people, with glucocorticoids being the most common cause. Previous experimental studies have shown that cell pyroptosis may be involved in the pathological process of SONFH, but its pathogenesis in SONFH is still unclear. This study aims to screen and validate potential pyroptosis-related genes in SONFH diagnosis by bioinformatics analysis to further elucidate the mechanism of pyroptosis in SONFH. METHODS: There were 33 pyroptosis-related genes obtained from the prior reviews. The mRNA expression was downloaded from GSE123568 dataset in the Gene Expression Omnibus (GEO) database, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples. The pyroptosis-related differentially expressed genes involved in SONFH were identified with "affy" and "limma" R package by intersecting the GSE123568 dataset with pyroptosis genes. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the pyroptosis-related differentially expressed genes involved in SONFH were conducted by "clusterProfiler" R package and visualized by "GOplot" R package. Then, the correlations between the expression levels of the pyroptosis-related differentially expressed genes involved in SONFH were confirmed with "corrplot" R package. Moreover, the protein-protein interaction (PPI) network was analysed by using GeneMANIA database. Next, The ROC curve of pyroptosis-related differentially expressed genes were analyzed by "pROC" R package. RESULTS: A total of 10 pyroptosis-related differentially expressed genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 20 upregulated genes and 10 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 10 pyroptosis-related differentially expressed genes involved in SONFH were particularly enriched in cysteine-type endopeptidase activity involved in apoptotic process, positive regulation of interleukin-1 beta secretion and NOD-like receptor signaling pathway. Correlation analysis revealed significant correlations among the 10 differentially expressed pyroptosis-related genes involved in SONFH. The PPI results demonstrated that the 10 pyroptosis-related differentially expressed genes interacted with each other. Compared to non-SONFH samples, these pyroptosis-related differentially expressed genes had good predictive diagnostic efficacy (AUC = 1.000, CI = 1.000-1.000) in the SONFH samples, and NLRP1 had the highest diagnostic value (AUC: 0.953) in the SONFH samples. CONCLUSIONS: There were 10 potential pyroptosis-related differentially expressed genes involved in SONFH were identified via bioinformatics analysis, which might serve as potential diagnostic biomarkers because they regulated pyroptosis. These results expand the understanding of SONFH associated with pyroptosis and provide new insights to further explore the mechanism of action and diagnosis of pyroptosis associated in SONFH.

Plasma lipids, alcohol intake frequency and risk of Osteoarthritis: a Mendelian randomization study.

BACKGROUD: Plasma lipids and alcohol intake frequency have been reported to be associated with the risk of osteoarthritis (OA). However, it remains inconclusive whether plasma lipids and alcohol intake frequency play a role in the development of OA. METHODS: The study employed a comprehensive genome-wide association database to identify independent genetic loci strongly linked to plasma lipids and alcohol intake frequency, which were used as instrumental variables. The causal association between plasma lipids, alcohol intake frequency, and the risk of OA was then analyzed using two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (ORs) as the evaluation criteria. RESULTS: A total of 392 SNPs were included as instrumental variables in this study, including 32 for total cholesterol (TC), 39 for triglycerides (TG), 170 for high-density lipoproteins (HDL), 60 for low-density lipoproteins (LDL), and 91 for alcohol intake frequency. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome, with the IVW method as the primary analysis method and other MR analysis methods complementing IVW. The results of this study showed that four exposure factors were causally associated with the risk of OA. TC obtained a statistically significant result for IVW (OR = 1.207, 95% CI: 1.018-1.431, P = 0.031); TG obtained a statistically significant result for Simple mode (OR = 1.855, 95% CI: 1.107-3.109, P = 0.024); LDL obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 1.363, 95% CI: 1.043-1.781, P = 0.023; WME: OR = 1.583, 95% CI: 1.088-2.303, P = 0.016; Weighted mode: OR = 1.521, 95% CI: 1.062-2.178, P = 0.026). Three statistically significant results were obtained for alcohol intake frequency with IVW, WME and Weighted mode (IVW: OR = 1.326, 95% CI: 1.047-1.678, P = 0.019; WME: OR = 1.477, 95% CI: 1.059-2.061, P = 0.022; Weighted mode: OR = 1.641, 95% CI: 1.060-2.541, P = 0.029). TC, TG, LDL, and alcohol intake frequency were all considered as risk factors for OA. The Cochran Q test for the IVW and MR-Egger methods indicated intergenic heterogeneity in the SNPs contained in TG, HDL, LDL, and alcohol intake frequency, and the test for pleiotropy indicated a weak likelihood of pleiotropy in all causal analyses. CONCLUSIONS: The results of two-sample Mendelian randomization analysis showed that TC, TG, LDL, and alcohol intake frequency were risk factors for OA, and the risk of OA increased with their rise.

Impact of Sulfur Fumigation on the Chemistry of Dioscoreae Rhizoma (Chinese Yam).

Dioscoreae Rhizoma (Chinese yam; derived from the rhizome of Dioscorea opposita Thunb.) (DR), commonly consumed as a food or supplement, is often sulfur-fumigated during post-harvest handling, but it remains largely unknown if and how sulfur fumigation impacts the chemistry of DR. In this study, we report the impact of sulfur fumigation on the chemical profile of DR and then the molecular and cellular mechanisms potentially involved in the chemical variations induced by sulfur fumigation. The results show that sulfur fumigation significantly and specifically changed the small metabolites (molecular weight lower than 1000 Da) and polysaccharides of DR at both qualitative and quantitative levels. Multifaceted molecular and cellular mechanisms involving chemical transformations (e.g., acidic hydrolysis, sulfonation, and esterification) and histological damage were found to be responsible for the chemical variations in sulfur-fumigated DR (S-DR). The research outcomes provide a chemical basis for further comprehensive and in-depth safety and functional evaluations of sulfur-fumigated DR.

Effect of different occlusal forces on the accuracy of interocclusal records of loose teeth.

BACKGROUND: This study aimed at investigating the effect of loose teeth on the accuracy of occlusal records by comparing the differences in the number of occlusal contact points, occlusal contact area and the centre of the occlusal contact region under different occlusal forces in patients with periodontitis. OBJECTIVE: The effects of different occlusal forces on the occlusal contact point (OCP), occlusal contact area (OCA) and the centre of occlusal contact region (OCC) of loose teeth. METHODS: Occlusal training was performed on the 30 patients who completed periodontal serial treatment. One doctor took the occlusal records with silicone rubber and the T-scan system; the patients were digitally scanned intraorally by a technician. The data of the healthy teeth were recorded as the control group, and the data of the loose teeth were recorded as the experimental group. Then, we used Image J to measure the numbers of OCP and OCA and Auto CAD to calculate the coordinates of OCC. A paired t test was used to analyse whether the differences in OCP, OCA and OCC were statistically significant when the occlusal forces were different. RESULTS: The OCA of all three experimental methods increased under heavy occlusal force (p < .01), and the silicone rubber OCA increased the most. The OCC of all three experimental methods was shifted in the buccal and mesial (p < .01). And the occlusal records obtained by the T-scan system showed a low correlation between the differences of OCA and OCC. CONCLUSION: Whether the teeth were loose or not, the OCA increased under heavy occlusal forces. For patients with loose teeth, the OCC was shifted towards the buccal under heavy occlusal force.

Engineered geranyl diphosphate methyltransferase produces 2-methyl-dimethylallyl diphosphate as a noncanonical C6 unit for terpenoid biosynthesis.

Terpenoids constitute the largest class of natural products with complex structures, essential functions, and versatile applications. Creation of new building blocks beyond the conventional five-carbon (C5) units, dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate, expands significantly the chemical space of terpenoids. Structure-guided engineering of an S-adenosylmethionine-dependent geranyl diphosphate (GPP) C2-methyltransferase from Streptomyces coelicolor yielded variants converting DMAPP to a new C6 unit, 2-methyl-DMAPP. Mutation of the Gly residue at the position 202 resulted in a smaller substrate-binding pocket to fit DMAPP instead of its native substrate GPP. Replacement of Phe residue at the position 222 with a Tyr residue contributed to DMAPP binding via hydrogen bond. Furthermore, using Escherichia coli as the chassis, we demonstrated that 2-methyl-DMAPP was accepted as a start unit to generate noncanonical trans- and cis-prenyl diphosphates (C5n+1) and terpenoids. This work provides insights into substrate recognition of prenyl diphosphate methyltransferases, and strategies to diversify terpenoids by expanding the building block portfolio.

Sox11b regulates the migration and fate determination of Müller glia-derived progenitors during retina regeneration in zebrafish.

The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development. However, its function in retina regeneration remains elusive. Here we report that Sox11b, a zebrafish Sox11 homolog, regulates the migration and fate determination of Müller glia-derived progenitors (MGPCs) in an adult zebrafish model of mechanical retinal injury. Following a stab injury, the expression of Sox11b was induced in proliferating MGPCs in the retina. Sox11b knockdown did not affect MGPC formation at 4 days post-injury, although the nuclear morphology and subsequent radial migration of MGPCs were altered. At 7 days post-injury, Sox11b knockdown resulted in an increased proportion of MGPCs in the inner retina and a decreased proportion of MGPCs in the outer nuclear layer, compared with controls. Furthermore, Sox11b knockdown led to reduced photoreceptor regeneration, while it increased the numbers of newborn amacrines and retinal ganglion cells. Finally, quantitative polymerase chain reaction analysis revealed that Sox11b regulated the expression of Notch signaling components in the retina, and Notch inhibition partially recapitulated the Sox11b knockdown phenotype, indicating that Notch signaling functions downstream of Sox11b. Our findings imply that Sox11b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish, which may have critical implications for future explorations of retinal repair in mammals.

A polysaccharide from native Curcuma kwangsiensis and its mechanism of reversing MDSC-induced suppressive function.

A purified polysaccharide nCKAP-2 was prepared from Curcuma kwangsiensis and characterized. Structural analyses revealed that nCKAP-2 contains a high-branched arabinan composed of mono-substituted (O-5, 17.07 %) and di-substituted (O-2,5, 16.67 %) (1 â†’ 3)-α-Araf residues. Bioactive test showed that nCKAP-2 significantly reversed the suppression function of myeloid-derived suppressor cells (MDSCs) on T cells. Further study revealed that treatment of MDSCs with nCKAP-2 could induce apoptotic cell death at the G0/G1 phase via the intrinsic pathway as suggested from the up-regulation of cleaved caspase 3 and 9, cleaved PARP, and Bax and the down-regulation of Bcl-xl. This apoptotic process was mainly mediated by the TLR4-NF-κB signaling pathway. Additionally, the down-regulation of ROS level of MDSCs after nCKAP-2 treatment involved in this process. Summarily, we explain how nCKAP-2 reverses the MDSC-induced suppressive function on T cells, and provide a scientific basis for the clinical application and development of C. kwangsiensis.

3D Hierarchical Porous Fe/Ni-P-B as Practical Bifunctional Electrode for Alkaline Water Electrolysis.

Bifunctional electrodes for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are extremely attractive as they can simplify the water electrolysis system. Here, a general and scalable strategy to prepare stable and efficient bifunctional electrode was reported, based on a novel hierarchical porous structure constructed by conductive electrocatalyst. The method involved the construction of 3D monolithic structure and its surface reconstruction by chemical etching process. This strategy produced an advanced 3D hierarchical porous Fe/Ni-P-B@MS electrode containing well-defined macropores (>100 µm) at the inter-wire space and mesopores (<100 nm) distributed uniformly over the entire catalyst surface. This highly efficient bifunctional electrode required only 79 and 279 mV to reach 100 mA cm-2 toward HER and OER in 1.0 m KOH. An alkaline electrolyzer consisting of this electrode provided 100 mA cm-2 at a low cell voltage of 1.61 V and survived at large current density of 800 mA cm-2 for over 140 h without apparent degradation. This work provides a new perspective for the rational design of transition metal-based bifunctional electrodes with outstanding performance.

Integrating trace ruthenium cluster with cobalt boride toward superior overall water splitting in neutral media.

Cobalt boride which is an active bifunctional water splitting catalyst in alkaline media shows poor activity in neutral media. We found that trace ruthenium (Ru) cluster deposition (80 µg·cm-2) on cobalt boride by simple wet chemical reduction method can dramatically improve both its hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activity in neutral solution. The electron transfer from Co-B to Ru may result in the easier water dissociation step so as to facilitate the catalytic process. The resulting Ru@Co-B/Ni binder-free electrode could supply 10 mA cm-2 at overpotentials of 56 mV for HER and 280 mV for OER in 0.5 M phosphate buffer electrolyte. This work proposed a fruitful approach to advance the water splitting performance of transition metal boride in neutral media.

In situ synthesis of ZnS nanoparticles onto cellulose/chitosan sponge for adsorption-photocatalytic removal of Congo red.

Developing an efficient and sustainable approach for removing dyes from wastewater remains a challenge. Herein, we report a facile and reliable strategy to create ZnS nanoparticles (NPs) supported by cellulose/chitosan sponge (ZnCCSs) via hydrothermal decomposition of xanthates and in situ synthesis of ZnS NPs. ZnCCSs demonstrate high porosity, low bulk density, outstanding compressibility, and uniformly immobilized ZnS NPs. Benefiting from the affinity sites of polysaccharide sponge skeleton and highly exposed ZnS NPs, ZnCCSs show an excellent synergistic effect of adsorption and photocatalytic degradation performances in removing Congo red pollutants. By regulating the structure through the ratio of components, ZnCCSs show a high removal ratio of 96.53% and excellent stability after reusability cycles. The adsorption and degradation behavior and the photodegradation mechanism are also investigated through trapping experiments. This study provides a promising way of removing dye contaminants through a combination of various mechanisms.