Synthesis and Characterization of Newly Designed and Highly Solvatochromic Double Squaraine Dye for Sensitive and Selective Recognition towards Cu2.

Synthesis and characterization of a novel and zwitterionic double squaraine dye (DSQ) with a unique D-A-A-D structure is being reported. Contrary to the conventional mono and bis-squaraine dyes with D-A-D and D-A-D-A molecular frameworks reported so far, DSQ dye demonstrated strong solvatochromism allowing for the multiple ion sensing using a single probe by judicious selection of the suitable solvent system. The DSQ dye exhibited a large solvatochromic shift of about 200 nm with color changes from the visible to NIR region with metal ion sensitivity. Utilization of a binary solvent consisted of dimethylformamide and acetonitrile (1:99, v/v), highly selective detection of Cu2+ ions with the linearity range from 50 µM to 1 nM and a detection limit of 6.5 × 10-10 M has been successfully demonstrated. Results of the Benesi-Hildebrand and Jobs plot analysis revealed that DSQ and Cu2+ ions interact in the 2:1 molecular stoichiometry with appreciably good association constant of 2.32 × 104 M-1. Considering the allowed limit of Cu2+ ions intake by human body as recommended by WHO to be 30 µM, the proposed dye can be conveniently used for the simple and naked eye colorimetric monitoring of the drinking water quality.

Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat.

Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone.

The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: The standard for early traumatic brain injury (TBI) seizure prophylaxis is phenytoin (PHT). Levetiracetam (LEV) has been proposed as an alternative to PHT. The aim of this study was to evaluate the safety and efficacy of LEV on TBI seizure when compared with PHT. METHODS: A search was carried out based on the databases from Pubmed, Embase and the Cochrane database up to May 2015. The relative risk (RR) and the relevant 95% confidence intervals (CI) were determined. RESULTS: Eight observational studies and one randomized controlled trial involving 2035 cases were included. The results indicated that no significant differences in terms of overall seizure (RR = 0.90; 95% CI = 0.51-1.53; p = 0.68), early seizure (RR = 1.06; 95% CI = 0.37-3.07; p = 0.92) and late seizure (RR = 1.10; 95% CI = 0.43-2.79; p = 0.85) occurrence. However, LEV was associated with a lower adverse drug reaction rate (RR = 0.43; 95% CI = 0.23-0.81; p = 0.01). Moreover, there were no significant differences in terms of mortality, length of ICU or hospital stay between groups. CONCLUSIONS: The meta-analysis suggests that LEV appears to have a similar efficacy to PHT on TBI. A better safety profile of LEV is supported by this analysis.

Lithium Chloride Modulates Adipogenesis and Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells.

BACKGROUND/AIMS: Lithium chloride (LiCl) has long been used as a psychiatric medication; however, its role in the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains largely unknown. The aim of this study is to explore the effect of LiCl on the differentiation of BMSCs. METHODS: The roles of LiCl in osteogenic and adipogenic processes were observed using alizarin red staining and oil red O staining, respectively. The effects of LiCl on the Wnt and Hedgehog (Hh) pathways were investigated. RESULTS: Our data showed that LiCl effectively promoted osteogenesis and inhibited adipogenesis by simultaneously affecting the Wnt and Hh pathways. CONCLUSION: These results suggest that LiCl influences the differentiation of BMSCs directly through the Wnt and Hh pathways and thus may be a candidate drug for the treatment of osteoporosis.

Studies toward the total synthesis of Itralamide B and biological evaluation of its structural analogs.

Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 µM). Preliminary studies disapproved the proposed stereochemistry of itralamide. In this paper, we will provide a full account of the total synthesis of four stereoisomers of itralamide B and the results derived from biological tests of these structural congeners.

Neurogenin 2 enhances the neuronal differentiation of skin-derived precursors.

Skin-derived precursors (SKPs), a novel stem cell population isolated from mammalian skin, can differentiate into neural and mesodermal lineages. Cell therapy using SKPs seems like a promising approach for the treatment of neural diseases, however, the low efficiency of neuronal differentiation limited their clinical application. In the present study, we transfected neurogenin 2 (Ngn2), a member of the bHLH transcription factor family, into SKPs by lentivirus. Morphological analysis, immunocytochemistry, Western blot, and electrophysiological analysis were performed to identify the cells derived from SKPs following 7-14 d neural induction. The results of immunocytochemistry staining showed that expression of neuronal markers, including MAP2, NF and NeuN were significantly elevated compared with those in GFP-SKPs and parental SKPs. Western blot confirmed the increased expression of NF-M and NeuN in Ngn2-SKPs-derived cells. Moreover, electrophysiological analysis showed that Ngn2-SKPs-derived neurons also acquired voltage-gated Na+ channels, which were absent in GFP-SKPs. Furthermore, western blot showed that Ngn2 enhanced the expression of Delta-like1, which reduced the level of Hes1 and suppressed Notch pathway. Therefore, overexpression of Ngn2 enhanced the neural differentiation of SKPs, probably through cis-inhibiting of Notch signal pathway.

Contribution of transforming growth factor α polymorphisms to nonsyndromic orofacial clefts: a HuGE review and meta-analysis.

We performed a meta-analysis of the association of transforming growth factor α gene (TGFA) polymorphisms with the risk of cleft lip with or without cleft palate (CL/P) or cleft palate (CP). In total, data from 29 studies were pooled for the following 3 polymorphisms: TGFA/TaqI, TGFA/BamHI, and TGFA/RasI in the TGFA gene. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A significantly increased CL/P or CP risk was observed in persons carrying a C2 allele at the TaqI polymorphism (odds ratio (OR) = 1.70, 95% confidence interval (CI): 1.41, 2.05) compared with those with a C1 allele (OR = 1.57, 95% CI: 1.23, 2.01). For the TGFA/BamHI polymorphism, carriers of the minor A1 allele had an estimated relative decrease in CL/P risk (OR = 0.44, 95% CI: 0.30, 0.64). These associations remained significant when only high-quality studies were included. However, no significant association was observed between the TGFA/RasI variant and CL/P risk. In summary, this meta-analysis provided a robust estimate of the positive association of the TGFA/TaqI polymorphism with both CL/P and CP and suggests that persons with an A1 allele may have a markedly decreased risk of CL/P.

Development of a Predictive Nomogram Model for Early Deep Vein Thrombosis in Postoperative Spontaneous Intracerebral Hemorrhage Patients.

Background: This study explores risk determinants for participants' lower extremities deep vein thrombosis (DVT) in the perioperative phase after spontaneous intracerebral hemorrhage (SICH), thereby informing more effective clinical prevention and treatment strategies. Methods: During the period spanning October 2021 to March 2024, clinical data from 96 participants who received surgical treatment for spontaneous cerebral hemorrhage was analyzed in a retrospective study. Participants were classified into DVT and negative-DVT groups within the first week post-surgery. We used univariate logistic regression and multivariate logistic regression analyses to assess the impact of various clinical variables on DVT. A nomogram model was constructed to forecast the occurrence of early DVT following SICH surgery. The model's performance was assessed and validated using receiver operating characteristic (ROC) curves and bootstrap resampling. Results: Among the 96 participants, 46 developed DVT. Significant differences were noted in age, D-dimer levels, fibrinogen degradation products, Caprini scores, and total surgical bleeding volume between the groups. Multivariate analysis revealed that Caprini score (the values of OR, 95% CI, and P are 1.962, 1.124-3.424, and 0.018, respectively) and total surgical bleeding volume (the values of OR, 95% CI, and P are 1.010, 1.002-1.018, and 0.017, respectively) were risk variables contributing to DVT occurrence. The area under the receiver operating characteristic curve was 0.918 (95% CI, 0.821-0.988). The calibration curve showed good prediction accuracy. Conclusion: The Caprini score and total surgical bleeding volume are meaningful self-reliant risk variables contributing to DVT occurrence in postoperative participants with SICH. We have created a straightforward and efficient model to predict early DVT post-SICH surgery. This model serves as a valuable clinical tool for evaluating individual risk and enhancing decision-making processes.

Flexible liquid metal-based microfluidic strain sensors with fractal-designed microchannels for monitoring human motion and physiological signals.

With the rapid advancement of wearable electronics, there is an increasing demand for high-performance flexible strain sensors. In this work, a flexible strain sensor based on liquid metal (LM)-integrated into a microfluidic device is developed with Peano-type fractal structure design. Compared with the microfluidic sensors with straight and wavy microchannels, the sensor with Peano-shaped channels shows lower hysteresis and improved stretchability. Furthermore, the increase of the fractal order can further improve the sensing performances. The third-order Peano sensor exhibits excellent mechanical and electrical properties, including high tensile capability (490.3%), minimal hysteresis (DH = 0.86%), ultra-low detection limit (0.1%), low overshoot, rapid response time (117 ms), as well as good stability and durability. By adding two independent and perpendicular straight channels to the Peano sensing unit, the feasibility of multi-directional strain recognition is demonstrated. To further improve the sensitivity of the Peano-shaped sensor, a multi-layer Peano sensor is developed, exhibiting remarkably enhanced sensitivity while maintaining low hysteresis. Overall, the developed LM-based microfluidic strain sensors enrolling Peano fractal geometry hold high potential for various wearable electronics applications.

Antibacterial and Osteogenic Dual-Functional Micronano Composite Scaffold Fabricated via Melt Electrowriting and Solution Electrospinning for Bone Tissue Engineering.

The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

Adipose-derived stem cell exosomes ameliorate traumatic brain injury through the NLRP3 signaling pathway.

The exosomes of mesenchymal stem cells have immunoregulatory properties and can effectively mitigate secondary neuroinflammation due to traumatic brain injury (TBI). In this study, we found that adipose-derived stem cell exosomes (ADSCs-Exo) could reduce the inflammatory response after traumatic brain injury by reducing NLRP3 inflammasome secretion by microglial. ADSCs-Exo were monitored by Western blot and electron microscopy. An in-vitro lipopolysaccharide (LPS)-caused primary microglia model and a TBI rat model were constructed. Functional recovery was examined using the modified neurological severity score and foot fault tests. Inflammasome inactivation in LPS-stimulated microglial, ADSCs-Exo can reduce the secretion of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α. Compared with PBS-processed controls, the sensorimotor functional recovery was significantly improved by exosome treatment after injury at 14-35 days. Additionally, NLRP3 inflammasome was stimulated within 24 h after TBI. ADSCs-Exo application led to remarkable down-expression of NLRP3 and caspase-1. ADSCs-Exo can ameliorate LPS-induced inflammatory activation by reducing microglial pro-inflammatory cytokines. Moreover, the neuroprotective effect of ADSCs-Exo may be partially attributed to the inhibition thereof on the formation of NLRP3-mediated inflammasome. Such findings imply a potential function of ADSCs-Exo in treating TBI.

ATNet: A Defect Detection Framework for X-ray Images of DIP Chip Lead Bonding.

In order to improve the production quality and qualification rate of chips, X-ray nondestructive imaging technology has been widely used in the detection of chip defects, which represents an important part of the quality inspection of products after packaging. However, the current traditional defect detection algorithm cannot meet the demands of high accuracy, fast speed, and real-time chip defect detection in industrial production. Therefore, this paper proposes a new multi-scale feature fusion module (ATSPPF) based on convolutional neural networks, which can more fully extract semantic information at different scales. In addition, based on this module, we design a deep learning model (ATNet) for detecting lead defects in chips. The experimental results show that at 8.2 giga floating point operations (GFLOPs) and 146 frames per second (FPS), mAP0.5 and mAP0.5-0.95 can achieve an average accuracy of 99.4% and 69.3%, respectively, while the detection speed is faster than the baseline yolov5s by nearly 50%.

Research progress on the role and mechanism of miR-671 in bone metabolism and bone-related diseases.

Bone metabolism consists of bone formation and resorption and maintains a dynamic balance in vivo. When bone homeostasis is broken, it can manifest as osteoarthritis (OA), rheumatoid arthritis (RA), osteosarcoma (OS), etc. MiR-671, an important class of non-coding nucleotide sequences in vivo, is regulated by lncRNA and regulates bone metabolism balance by regulating downstream target proteins and activating various signaling pathways. Based on the structure and primary function of miR-671, this paper summarizes the effect and mechanism of miR-671 in bone-related inflammation and cancer diseases, and prospects the application possibility of miR-671, providing reference information for targeted therapy of bone-related disorders.

Study on Filtration Performance of PVDF/PUL Composite Air Filtration Membrane Based on Far-Field Electrospinning.

At present, the situation of air pollution is still serious, and research on air filtration is still crucial. For the nanofiber air filtration membrane, the diameter, porosity, tensile strength, and hydrophilicity of the nanofiber will affect the filtration performance and stability. In this paper, based on the far-field electrospinning process and the performance effect mechanism of the stacked structure fiber membrane, nanofiber membrane was prepared by selecting the environmental protection, degradable and pollution-free natural polysaccharide biopolymer pullulan, and polyvinylidene fluoride polymer with strong hydrophobicity and high impact strength. By combining two kinds of fiber membranes with different fiber diameter and porosity, a three-layer composite nanofiber membrane with better hydrophobicity, higher tensile strength, smaller fiber diameter, and better filtration performance was prepared. Performance characterization showed that this three-layer composite nanofiber membrane had excellent air permeability and filtration efficiency, and the filtration efficiency of particles above PM 2.5 reached 99.9%. This study also provides important reference values for the preparation of high-efficiency composite nanofiber filtration membrane.

Prognostic potential of lncRNA RHPN1-AS1 in glioma.

Expression level of long non-coding RNA (lncRNA) RHPN1-AS1 in glioma tissues was detected to determine potential risk factors influencing prognosis of glioma. This study aimed to clarify the molecular mechanisms underlying tumorigenesis of glioma and thus to improve therapeutic efficacy of glioma. RHPN1-AS1 levels in glioma tissues (n=105) and normal brain tissues (n=105) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between RHPN1-AS1 level and pathological indicators of glioma patients was analyzed. Glioma patients were followed up for 5 years. Overall survival (OS) and relapse-free survival (RFS) in glioma patients were tested by Kaplan-Meier and log-rank method. Potential factors influencing prognosis of glioma were analyzed by Cox regression model. RHPN1-AS1 was upregulated in glioma tissues. Its level was correlated to histological grade, Karnofsky (KPS) score and postoperative recurrence of glioma patients, rather than sex, age, pathological and tumor size. Glioma patients expressing high level of RHPN1-AS1 suffered worse OS and RFS than those with low level. Advanced histological grade, KPS score <80 and high level of RHPN1-AS1 were considered to be risk factors influencing postoperative prognosis of glioma. High level of RHPN1-AS1 is an independent risk factor for poor prognosis of glioma, which may be utilized as a prognostic hallmark.

A Bayesian network meta-analysis of 5 different fusion surgical procedures for the treatment of lumbar spondylolisthesis.

Lumbar fusion has been widely used to treat lumbar spondylolisthesis, which can be classified into 5 types according to its approach, including posterolateral fusion (PLF), posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), posterolateral fusion plus anterior lumbar interbody fusion (PLFplusALIF), and posterolateral fusion plus posterior lumbar interbody fusion (PLFplusPLIF). Theoretically, each approach has its own advantages and disadvantages, however, no studies are available to compare them.A network meta-analysis (NMA) was performed in this study and the results were illustrated by the mean difference (MD) or odds ratio (OR). Meanwhile, the preferable treatments were indicated using the surface under the cumulative ranking curve (SUCRA). All data were analyzed and graphs were plotted using R 3.4.1.A total of 28 literatures were included in this meta-analysis. PLIF was the most effective treatment for pain relief. Conversely, TLIF was the most effective method for reducing vertebral slippage. For patients with isthmic spondylolisthesis (IS), PLIF performed the best in terms of Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) score, fusion rate, blood loss, and complication rate. For patients with degenerative spondylolisthesis (DS), TLIF was the best from the points of view of VAS, complication rate, and vertebral slippage reduction.PLIF and TLIF are identified as the optimal treatments for all lumbar spondylolisthesis cases, among which, PLIF may be the preferred choice for pain relief, while TLIF can offer the best outcomes in terms of vertebral slippage reduction. Furthermore, TLIF has displayed the best clinical outcomes and tolerability for DS patients.

Therapeutic effect of beta-blocker in patients with traumatic brain injury: A systematic review and meta-analysis.

OBJECTIVE: ß-Blocker exposure has been shown to reduce mortality in traumatic brain injury (TBI); however, the efficacy of ß-blockers remains inconclusive. Therefore, a meta-analysis was conducted in this paper to evaluate the safety and efficacy of ß-blocker therapy on patients with TBI. METHODS: The electronic databases were systemically retrieved from construction to February 2017. The odds ratio (OR), mean difference (MD) and 95% confidence intervals (CI) were determined. RESULTS: A total of 13 observational cohort studies involving 15,734 cases were enrolled. The results indicated that ß-blocker therapy had remarkably reduced the in-hospital mortality (OR 0.33; 95% CI 0.27-0.40; p<0.001). However, ß-blocker therapy was also associated with increased infection rate (OR 2.01; 95% CI 1.50-2.69; p<0.001), longer length of stay (MD=7.40; 95% CI=4.39, 10.41; p<0.001) and ICU stay (MD=3.52; 95% CI=1.56, 5.47; p<0.001). In addition, ß-blocker therapy also led to longer period of ventilator support (MD=2.70; 95% CI=1.81, 3.59; p<0.001). CONCLUSION: The meta-analysis demonstrates that ß-blockers are effective in lowering mortality in patients with TBI. However, ß-blocker therapy has markedly increased the infection rate and requires a longer period of ventilator support, intensive care management as well as length of stay.

Lamotrigine versus valproic acid monotherapy for generalised epilepsy: A meta-analysis of comparative studies.

PURPOSE: The standard for generalized epilepsies (GE) monotherapy in treatment is valproic acid (VPA) and lamotrigine (LTG) has been proposed as an alternative to VPA. This study aimed to evaluate the safety and efficacy of LTG on GE seizure in comparison with VPA. METHOD: A search was conducted based on the databases from Pubmed, Embase and the Cochran database up to February 2017. The relative risk odds ratios (ORs) and the relevant 95% confidence intervals (CI) were determined. RESULTS: Five randomized controlled trials and four observational cohort studies involving 1732 cases were included. The results indicated that VPA was significantly superior to LTG for the outcome rate to treatment withdrawal for any reason and seizure freedom. The ORs and 95% CI of VPA versus LTG for withdrawal after 12- and 24-month treatment were 0.39(0.27, 0.56) and 0.50(0.14, 1.75), respectively, and were 3.51(2.68, 4.59) and 8.58(5.40, 13.63)for 12- and 24- month seizure free intervals, respectively. Moreover, the risk of adverse effects (OR (95%CI); 1.11(0.61-2.01)) was not significantly different between the two groups. However, the treatment withdrawal due to lack of seizure control were in the LTG group (OR (95%CI); 0.15(0.10-0.23)), while the treatment withdrawal due to intolerable side effects were in the VPA group (OR (95%CI); (1.75(1.10-2.80)). CONCLUSIONS: The meta-analysis suggests that VPA appears to be a better choice in controlling seizure following GE. However, therapy should be switched to alternative monotherapy if an adequate trial of VPA monotherapy is not effective and intolerable, especially in young women.