State of energy estimation of lithium-ion battery based on long short-term memory optimization Adaptive Cubature Kalman filter.

State of energy (SOE) is an important parameter to ensure the safety and reliability of lithium-ion battery (LIB) system. The safety of LIBs, the development of artificial intelligence, and the increase in computing power have provided possibilities for big data computing. This article studies SOE estimation problem of LIBs, aiming to improve the accuracy and adaptability of the estimation. Firstly, in the SOE estimation process, adaptive correction is performed by iteratively updating the observation noise equation and process noise equation of the Adaptive Cubature Kalman Filter (ACKF) to enhance the adaptive capability. Meanwhile, the adoption of high-order equivalent models further improves the accuracy and adaptive ability of SOE estimation. Secondly, Long Short-term Memory (LSTM) is introduced to optimize Ohmic internal resistance (OIR) and actual energy (AE), further improving the accuracy of SOE estimation. Once again, in the process of OIR and AE estimation, the iterative updating of the observation noise equation and process noise equation of ACKF were also adopted to perform adaptive correction and enhance the adaptive ability. Finally, this article establishes a SOE estimation method based on LSTM optimized ACKF. Validate the LSTM optimized ACKF method through simulation experiments and compare it with individual ACKF methods. The results show that the ACKF estimation method based on LSTM optimization has an SOE estimation error of less than 0.90% for LIB, regardless of the SOE at 100%, 65%, and 30%, which is more accurate than the SOE estimation error of ACKF alone. It can be seen that this study has improved the accuracy and adaptability of LIB's SOE estimation, providing more accurate data support for ensuring the safety and reliability of lithium batteries.

Serum 25-hydroxyvitamin D level and erectile dysfunction: a causal relationship? Findings from a two-sample Mendelian randomization study.

Background: Serum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain. Objective: Conduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk. Method: Genome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method. Result: There were 103 SNPs utilized as instrumental variables (p < 5 × 10-8). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, p = 0.5772). There was no heterogeneity and pleiotropy in the statistical models. Conclusion: The present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.

Biodegradable Zn-2Cu-0.5Zr alloy promotes the bone repair of senile osteoporotic fractures via the immune-modulation of macrophages.

Delayed bone-healing of senile osteoporotic fractures remains a clinical challenge due to the alterations caused by aging in bone and immune systems. The novel biomaterials that address the deficiencies in both skeletal cells and immune systems are required to effectively treat the bone injuries of older patients. Zinc (Zn) has shown promise as a biodegradable material for use in orthopedic implants. To address the bone-healing deficiencies in elderly patients with bone injuries, we developed a biodegradable Zn-based alloy (Zn-2Cu-0.5Zr) with enhanced mechanical properties, including a yield strength of 198.7 MPa and ultimate tensile strength of 217.6 MPa, surpassing those of pure Zn and Zn-2Cu alloys. Cytotoxicity tests conducted on bone marrow mesenchymal stem cells (BMSCs) and MC3T3-E1 cells demonstrated that the extracts from Zn-2Cu-0.5Zr alloy exhibited no observable cytotoxic effects. Furthermore, the extracts of Zn-2Cu-0.5Zr alloy exhibited significant anti-inflammatory effects through regulation of inflammation-related cytokine production and modulation of macrophage polarization. The improved immune-osteo microenvironment subsequently contributed to osteogenic differentiation of BMSCs. The potential therapeutic application of Zn-2Cu-0.5Zr in senile osteoporotic fracture was tested using a rat model of age-related osteoporosis. The Zn-2Cu-0.5Zr alloy met the requirements for load-bearing applications and accelerated the healing process in a tibial fracture in aged rats. The imaging and histological analyses showed that it could accelerate the bone-repair process and promote the fracture healing in senile osteoporotic rats. These findings suggest that the novel Zn-2Cu-0.5Zr alloy holds potential for influencing the immunomodulatory function of macrophages and facilitating bone repair in elderly individuals with osteoporosis.

Transient acceleration waveform replication of electro-hydraulic systems using convex combined adaptive controller with input shaping technique.

Electro-hydraulic systems are extensively utilized to generate desired acceleration waveforms to provide a vibration environment for testing the performance and reliability of objects in various industrial applications. However, as electro-hydraulic systems are often affected by some inevitable drawbacks resulted from hydraulic nonlinearities, unwanted dynamic variations and disturbances, the generated acceleration waveform is generally far behind the expectation. In this paper, a convex combined adaptive controller with input shaping technique is proposed for enhancing the transient acceleration waveform replication accuracy of electro-hydraulic systems. The proposed controller is comprised of a three variable controller at the bottom level, an input shaping technique controller at the middle level, and a convex combined adaptive controller at the upper level. The three variable controller is firstly utilized for the establishment of a fundamental closed-loop acceleration control system, and then the input shaping technique controller is constructed by introducing an offline designed inverse prefilter utilizing the multi-innovation recursive least squares algorithm and the zero magnitude error tracking algorithm. The convex combined adaptive controller at the upper level is comprised of two individual adaptive filters with high and low step sizes, which provides the merits of fast convergence rate and high tracking accuracy, and it is further exploited to address for system's dynamic variations, model uncertainties and unexpected perturbations. Comparative experiments of the proposed controller with a manually generated random waveform and a recorded earthquake waveform as the testing inputs are conducted on a typical electro-hydraulic test bench, and the corresponding results demonstrate the feasibility and superiority of the proposed controller in improving the transient acceleration waveform replication performance of electro-hydraulic systems.

Evaluation of modified clear Twin Block aligner in treating adolescents with skeletal class II malocclusion: A two-centre cephalometric study.

INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and the development of non-alcoholic steatohepatitis (NASH) might cause irreversible hepatic damage. Hyperlipidemia (HLP) is the leading risk factor for NAFLD. This study aims to illuminate the causative contributor and potential mechanism of Kallistatin (KAL) mediating HLP to NAFLD. 221 healthy control and 253 HLP subjects, 62 healthy control and 44 NAFLD subjects were enrolled. The plasma KAL was significantly elevated in HLP subjects, especially in hypertriglyceridemia (HTG) subjects, and positively correlated with liver injury. Further, KAL levels of NAFLD patients were significantly up-regulated. KAL transgenic mice induced hepatic steatosis, inflammation, and fibrosis with time and accelerated inflammation development in high-fat diet (HFD) mice. In contrast, KAL knockout ameliorated steatosis and inflammation in high-fructose diet (HFruD) and methionine and choline-deficient (MCD) diet-induced NAFLD rats. Mechanistically, KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI-58) by LRP6/Gɑs/PKA/GSK3ß pathway through down-regulating peroxisome proliferator-activated receptor γ (PPARγ) and up-regulating kruppel-like factor four (KLF4), respectively. CGI-58 is bound to NF-κB p65 in the cytoplasm, and diminishing CGI-58 facilitated p65 nuclear translocation and TNFα induction. Meanwhile, hepatic CGI-58-overexpress reverses NASH in KAL transgenic mice. Further, free fatty acids up-regulated KAL against thyroid hormone in hepatocytes. Moreover, Fenofibrate, one triglyceride-lowering drug, could reverse hepatic steatosis by down-regulating KAL. These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis.

This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

Novel fluorescence strategy based on G-quadruplex structure-switching aptamer for enrofloxacin detection in food and environmental samples.

Enrofloxacin (ENR) is widely used in the prevention and treatment of animal infectious diseases, so it is necessary to strengthen the residue detection of this drug in animal-derived food and water environments. In this work, for the first time, we engineered assembly a split ENR aptamer into the G-quadruplex (G4) region to form a new aptamer (G4-ENRA) that provides a more sensitive signal-reporting function while retaining target-specific recognition ability of the aptamer. This rational design effectively overcomes the issue of difficulty in identification probe development. Under the optimized conditions, a response range of 0.05-20 µM and limit of detection of 26.7 nM were obtained by directly detecting fluorescence signals, displaying a comparative advantage over the previously reported methods. Moreover, this method demonstrated satisfactory performance for the ENR detection in various real food and environmental samples, with the detection recoveries ranging from 95.87 % to 104.36 %, illustrating promising applicability prospects.

Experimental investigation of thermal performance of vertical multitube cylindrical latent heat thermal energy storage systems.

The multitube design in the shell-and-tube type latent heat thermal energy storage (LHTES) system has received intensive attention due to its promising benefits in enhancing heat storage efficiency. In this paper, single and multi-tube shell LHTES systems were experimentally investigated. First, this study experimentally compared the thermal characteristics between a multiple-tube heat exchanger (MTHX) and a single-tube heat exchanger (STHX). The STHX's geometrical parameters coincided with a virtual cylindrical domain in the MTHX, being similar to the single-tube model formulated by simplifying the numerical solution to investigate the MTHX. The experimental data was then used to validate the simplified numerical model commonly used in the literature that converted the multi-tube problem to a single-tube model by formulating a virtual cylindrical domain for each tube in the MTHX system. The results showed that there was a noticeable difference in the thermal characteristics between the actual STHX and the virtual cylindrical STHX domain in the MTHX system. The comparison indicated that the simplified numerical model could not accurately reflect the thermal performance of the MTHX system. An experimental study or three-dimensional numerical modelling was required for the thermal analysis of the multi-tube problems. Second, the effect of tube number in the MTHX was experimentally investigated. It was found that an increase in tube number boosted both charging and discharging rates without inhibiting the natural convection. The five-tube configuration decreased the total charging and discharging duration by 50% compared to the two-tube one. Finally, the effect of heat transfer fluid (HTF) operating parameters on the system performance was evaluated on the five-tube MTHX system. The results revealed that the adoption of higher HTF temperature considerably improved the charging performance. The charging time decreased by up to 41% with the HTF temperature increasing from 70 to 80 °C. Meanwhile, a variation in the HTF flow rate from 5 to 20 L/min showed a more pronounced influence on charging than on discharging due to the different dominant heat transfer mechanisms.

Advances and prospects of natural dietary polyphenols as G-quadruplex stabilizers in biomedical applications.

G-quadruplexes (G4s) have arrested continuous interest in cancer research, and targeting G4s with small molecules has become an ideal approach for drug development. Plant-based dietary polyphenols have attracted much attention for their remarkable anti-cancer effects. Studies have suggested that polyphenols exhibit interesting scaffolds to bind G4s, which can effectively downregulate the proto-oncogenes by stabilizing those G4 structures. Therefore, this review not only summarizes studies on natural dietary polyphenols (including analogs) as G4 stabilizers, but also reveals their anti-cancer activities. Furthermore, the structural and antioxidant insights of polyphenols with G4s are discussed, and future development is proposed. These insights may pave the way for the development of the next generation of anti-cancer drugs targeting nucleic acids.

Correlates of Bullying Behavior Among Children and Adolescents in Physical Education: A Systematic Review.

Background and Objective: Bullying is notably prevalent among children and adolescents, especially within the context of physical education (PE) environments. Understanding the underlying factors that trigger bullying behavior is essential in designing strategies to prevent bullying and formulating more effective interventions in PE. There is a lack of integrated findings regarding the wide range of correlates of bullying behavior among children and adolescents within the PE context. Therefore, this systematic review aimed to synthesize the correlates of bullying behavior among children and adolescents within the context of PE. Methods: We conducted a systematic search across four databases (EBSCOhost, PubMed, Scopus, Web of Science) for relevant studies published before August 2023. Two reviewers independently examined the articles, assessed their methodological quality, and performed data extraction. Results: A total of 23 articles met the inclusion criteria. It is found that demographic, physical movement, physical appearance, psycho-cognitive, teacher-related, and contextual factors emerged as six prominent influential factors affecting adolescent bullying behavior. Specifically, demographic factors mainly encompassed age and gender; physical movement factors primarily include physical activity, sedentary behavior, physical exercise, and sports competence; physical appearance factors primarily include being overweight, too thin, too tall, or too short; psycho-cognitive factors chiefly involved cognitive empathy, motivation, enjoyment of physical activity; teacher-related factors primarily comprised activity choices, teachers competence, controlling style, autonomy support; and contextual factors primarily cover desolate climate, perceived caring climate, strong sense of competition and winning setting. Conclusion: The results indicate that bullying is a complex and multifaced behavior primarily determined by demographic, physical movement, physical appearance, psycho-cognitive, teacher-related, and contextual factors. Future studies need to enhance the diversity of research samples and comparative studies on the factors influencing bullying behavior among children and adolescents in different countries. Additionally, a more extensive range of intervention studies addressing bullying behavior among children and adolescents is warranted.

[Identification and the Related Molecular Mechanism of B(A)04 Allele].

OBJECTIVE: To investigate the identification and molecular biological mechanism of a case of B(A)04 allele. METHODS: The ABO blood groups of the proband and his nine family members were analyzed serologically and DNA sequencing was used to accurately determine the genotypes of these ten specimens. The cartoon models of local active center of enzymes of the GTA,GTB and the GTB mutant were constructed to explore the possible molecular mechanism leading to abnormal enzyme-catalyzed A antigen synthesis. RESULTS: The serological results suggested that the ABO blood groups of the proband, his elder brother and his maternal grandmother were AweakB or B(A); the ABO blood group of his mother was type AB, his uncle and elder aunt were type B, and his father was type O. ABO blood group gene sequencing results showed that 6 out of 10 members of the family carried the B(A)04 allele. Molecular structure models suggested that the spatial distance of critical amino acid residues in the catalytic center of the GTB mutant enzyme was greater than that of GTB, which might cause the enzyme to abnormally catalyze the synthesis of A antigen. CONCLUSION: The characteristics of serological reactions of B(A) blood subgroup are complicated, and its identification needs to be combined with molecular biology and pedigree investigation. It is speculated that the B(A) phenotype may be associated with a larger volume of the catalytic center in the GTB mutant.

Kallistatin Deficiency Induces the Oxidative Stress-Related Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells: A Novel Protagonist in Age-Related Macular Degeneration.

Purpose: Retinal pigment epithelium (RPE) dysfunction induced by oxidative stress-related epithelial-mesenchymal transition (EMT) of RPE is the primary underlying mechanism of age-related macular degeneration (AMD). Kallistatin (KAL) is a secreted protein with an antioxidative stress effect. However, the relationship between KAL and EMT in RPE has not been determined. Therefore we aimed to explore the impact and mechanism of KAL in oxidative stress-induced EMT of RPE. Methods: Sodium iodate (SI) was injected intraperitoneally to construct the AMD rat model and investigate the changes in RPE morphology and KAL expression. KAL knockout rats and KAL transgenic mice were used to explain the effects of KAL on EMT and oxidative stress. In addition, Snail overexpressed adenovirus and si-RNA transfected ARPE19 cells to verify the involvement of Snail in mediating KAL-suppressed EMT of RPE. Results: AMD rats induced by SI expressed less KAL in the retina, and KAL knockout rats showed RPE dysfunction spontaneously where EMT and reactive oxygen species (ROS) production increased in RPE. In contrast, KAL overexpression attenuated EMT and ROS levels in RPE, even in TGF-ß treatment. Mechanistically, Snail reversed the beneficial effect of KAL on EMT and ROS reduction. Moreover, KAL ameliorated SI-induced AMD-like pathological changes. Conclusions: Our findings demonstrated that KAL inhibits oxidative stress-induced EMT by downregulating the transcription factor Snail. Herein, KAL knockout rats may be an appropriate animal model for observing spontaneous RPE dysfunction for AMD-like retinopathy, and KAL may represent a novel therapeutic target for treating dry AMD.

Platelet mitochondria, a potent immune mediator in neurological diseases.

Dysfunction of the immune response is regarded as a prominent feature of neurological diseases, including neurodegenerative diseases, malignant tumors, acute neurotraumatic insult, and cerebral ischemic/hemorrhagic diseases. Platelets play a fundamental role in normal hemostasis and thrombosis. Beyond those normal functions, platelets are hyperactivated and contribute crucially to inflammation and immune responses in the central nervous system (CNS). Mitochondria are pivotal organelles in platelets and are responsible for generating most of the ATP that is used for platelet activation and aggregation (clumping). Notably, platelet mitochondria show marked morphological and functional alterations under heightened inflammatory/oxidative stimulation. Mitochondrial dysfunction not only leads to platelet damage and apoptosis but also further aggravates immune responses. Improving mitochondrial function is hopefully an effective strategy for treating neurological diseases. In this review, the authors discuss the immunomodulatory roles of platelet-derived mitochondria (PLT-mitos) in neurological diseases and summarize the neuroprotective effects of platelet mitochondria transplantation.

Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth.

Sphingosine kinases (SphK), including SphK1 and SphK2, are important enzymes promoting progression of prostate cancer. SKI-178 is a novel and highly potent SphK1/2 dual inhibitor. We here tested the potential anti-prostate cancer cell activity of SKI-178. Bioinformatics analyses and results from local tissues demonstrated that that both SphK1 and SphK2 are upregulated in human prostate cancer tissues. Ectopic overexpression of SphK1 and SphK2, by lentiviral constructs, promoted primary prostate cancer cell proliferation and migration. In primary human prostate cancer cells and immortalized cell lines, SKI-178 potently inhibited cell viability, proliferation, cell cycle progression and cell migration, causing robust cell death and apoptosis. SKI-178 impaired mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production and ATP depletion.SKI-178 potently inhibited SphK activity and induced ceramide production, without affecting SphK1/2 expression in prostate cancer cells. Further, SKI-178 inhibited Akt-mTOR activation and induced JNK activation in prostate cancer cells. Contrarily, a constitutively-active Akt1 construct or the pharmacological JNK inhibitors attenuated SKI-178-induced cytotoxicity in prostate cancer cells. In vivo, daily intraperitoneal injection of a single dose of SKI-178 potently inhibited PC-3 xenograft growth in nude mice. SphK inhibition, ceramide production, ATP depletion and lipid peroxidation as well as Akt-mTOR inactivation and JNK activation were detected in PC-3 xenograft tissues with SKI-178 administration. Together, targeting SphK1/2 by SKI-178 potently inhibited prostate cancer cell growth in vitro and in vivo.

[A reflectional insight into orthodontic theoretical renovation and technological innovation].

Orthodontics, among other specialties in dentistry, remains most dynamic and vigorous in upgrading and reforming its fundamental doctrines and clinical technologies. Orthodontic specialty in China has played a leading role in recent years in reshaping fundamental theories and in creating cutting-edge therapeutic modalities. The newly developed diagnostic classification system, a complementary addition to that of Angle's, not only defines the natures, but also identifies the developmental mechanisms of malocclusions. Orthopedic therapy aiming to relocate the mandible before correcting the dentition is emerging as an indispensable treatment mode to malocclusions concurring with mandibular deviation. Whilst correlations exist between malocclusion and TMD susceptibility and incidence, the specifically designed orthopedic and orthodontic approaches have proven effective in managing cases inflicted by TMD conditions. Innovative efforts that create the GS products, have redefined the clear appliances much more beyond merely clear aligners, thus further pushing the boundaries of both the indications and clinical use for clear appliances.

Metal-organic Zn-zoledronic acid and 1-hydroxyethylidene-1,1-diphosphonic acid nanostick-mediated zinc phosphate hybrid coating on biodegradable Zn for osteoporotic fracture healing implants.

Zn and its alloys are increasingly under consideration for biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for osteoporotic bone fracture healing, due to their uneven degradation mode, burst release of zinc ions, and insufficient osteo-promotion and osteo-resorption regulating properties. In this study, a type of Zn2+ coordinated zoledronic acid (ZA) and 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) metal-organic hybrid nanostick was synthesized, which was further mixed into zinc phosphate (ZnP) solution to mediate the deposition and growth of ZnP to form a well-integrated micro-patterned metal-organic/inorganic hybrid coating on Zn. The coating protected noticeably the Zn substrate from corrosion, in particular reducing its localized occurrence as well as suppressing its Zn2+ release. Moreover, the modified Zn was osteo-compatible and osteo-promotive and, more important, performed osteogenesis in vitro and in vivo of well-balanced pro-osteoblast and anti-osteoclast responses. Such favorable functionalities are related to the nature of its bioactive components, especially the bio-functional ZA and the Zn ions it contains, as well as its unique micro- and nano-scale structure. This strategy provides not only a new avenue for surface modification of biodegradable metals but also sheds light on advanced biomaterials for osteoporotic fracture and other applications. STATEMENT OF SIGNIFICANCE: Developing appropriate biodegradable metallic materials is of clinical relevance for osteoporosis fracture healing, whereas current strategies are short of good balance between the bone formation and resorption. Here, we designed a micropatterned metal-organic nanostick mediated zinc phosphate hybrid coating modified Zn biodegradable metal to fulfill such a balanced osteogenicity. The in vitro assays verified the coated Zn demonstrated outstanding pro-osteoblasts and anti-osteoclasts properties and the coated intramedullary nail promoted fracture healing well in an osteoporotic femur fracture rat model. Our strategy may offer not only a new avenue for surface modification of biodegradable metals but also shed light on better understanding of new advanced biomaterials for orthopedic application among others.

N-cadherin cleavage: A critical function that induces diabetic retinopathy fibrosis via regulation of ß-catenin translocation.

Retinal fibrosis is a severe pathological change in the late stage of diabetic retinopathy and is also the leading cause of blindness. We have previously revealed that N-cadherin was significantly increased in type 1 and type 2 diabetic mice retinas and the fibrovascular membranes from proliferative diabetic retinopathy (PDR) patients. However, whether N-cadherin directly induces retinal fibrosis in DR and the related mechanism is unknown. Here, we investigated the pathogenic role of N-cadherin in mediating retinal fibrosis and further explored the relevant therapeutic targets. We found that the level of N-cadherin was significantly increased in PDR patients and STZ-induced diabetic mice and positively correlated with the fibrotic molecules Connective Tissue Growth Factor (CTGF) and fibronectin (FN). Moreover, intravitreal injection of N-cadherin adenovirus significantly increased the expression of FN and CTGF in normal mice retinas. Mechanistically, overexpression of N-cadherin promotes N-cadherin cleavage, and N-cadherin cleavage can further induce translocation of non-p-ß-catenin in the nucleus and upregulation of fibrotic molecules. Furthermore, we found a novel N-cadherin cleavage inhibitor, pigment epithelial-derived factor (PEDF), which ameliorated the N-cadherin cleavage and subsequent retinal fibrosis in diabetic mice. Thus, our findings provide novel evidence that elevated N-cadherin level not only acts as a classic EMT maker but also plays a causative role in diabetic retinal fibrosis, and targeting N-cadherin cleavage may provide a strategy to inhibit retinal fibrosis in DR patients.

Translational albumin nanocarrier caging photosensitizer for efficient cancer photodynamic therapy.

It still remains a great challenge to efficiently treat malignant cancers which severely threaten human health. Photodynamic therapy (PDT) as a localized therapeutic modality has improved the therapeutic efficacy via chemical damage through reactive oxygen species (ROS). However, their efficacy is severely hampered by insufficient targeted delivery of photosensitizers owing to the lack of suitable carrier with facile preparation process and the clinical applicability. Herein, we applied clinically approved human serum albumin as the nanoreactor to encapsulate photosensitizers Chlorin e6 (Ce6) for enhancing their tumor accumulation and subsequently potent PDT effect against bladder cancer models. Albumin-loaded Chlorin e6 nanoparticles (CA-NPs) with rational nanoscale size exhibit increased reactive oxygen species production and excellent resistance to photobleaching. Moreover, CA-NPs could be efficiently internalized by tumor cells and locate in the lysosome, while they rapidly translocate to cytosol after irradiation to induce remarkable cytotoxicity (IC50 ∼5.8 µg/ml). Furthermore, CA-NPs accumulate effectively in tumor tissue to afford total eradication of murine bladder tumor after single injection. More importantly, we also evidence the superior PDT effect in fresh human bladder tumor tissues via abundant reactive oxygen species generation and subsequent cell apoptosis. These findings demonstrate that human serum albumin acts as a universal tool to load small organic photoactivatable molecule with remarkable effectiveness and readiness for clinical translation.

Meckel's Diverticulum with Multiple Sprouts at the Tip in a Child.

Background: Meckel's diverticulum (MD) is usually a simple tubular-shaped diverticulum. Case report: We describe a MD with multiple complex terminal sprouts in a child found incidentally during an appendectomy for appendicitis. The MD was resected, and the child recovered well. Conclusion: MD may show multiple sprouts. There was no additional clinical consequence in this child with the malformed MD.