Colonoscopy polyp classification via enhanced scattering wavelet Convolutional Neural Network.

Among the most common cancers, colorectal cancer (CRC) has a high death rate. The best way to screen for colorectal cancer (CRC) is with a colonoscopy, which has been shown to lower the risk of the disease. As a result, Computer-aided polyp classification technique is applied to identify colorectal cancer. But visually categorizing polyps is difficult since different polyps have different lighting conditions. Different from previous works, this article presents Enhanced Scattering Wavelet Convolutional Neural Network (ESWCNN), a polyp classification technique that combines Convolutional Neural Network (CNN) and Scattering Wavelet Transform (SWT) to improve polyp classification performance. This method concatenates simultaneously learnable image filters and wavelet filters on each input channel. The scattering wavelet filters can extract common spectral features with various scales and orientations, while the learnable filters can capture image spatial features that wavelet filters may miss. A network architecture for ESWCNN is designed based on these principles and trained and tested using colonoscopy datasets (two public datasets and one private dataset). An n-fold cross-validation experiment was conducted for three classes (adenoma, hyperplastic, serrated) achieving a classification accuracy of 96.4%, and 94.8% accuracy in two-class polyp classification (positive and negative). In the three-class classification, correct classification rates of 96.2% for adenomas, 98.71% for hyperplastic polyps, and 97.9% for serrated polyps were achieved. The proposed method in the two-class experiment reached an average sensitivity of 96.7% with 93.1% specificity. Furthermore, we compare the performance of our model with the state-of-the-art general classification models and commonly used CNNs. Six end-to-end models based on CNNs were trained using 2 dataset of video sequences. The experimental results demonstrate that the proposed ESWCNN method can effectively classify polyps with higher accuracy and efficacy compared to the state-of-the-art CNN models. These findings can provide guidance for future research in polyp classification.

Effect of Xuefu zhuyu oral liquid on tension-type headache: A randomized clinical trial.

BACKGROUND: Tension-type headache (TTH) is the most common neurological disorder worldwide, incurring immense social and economic costs and affecting quality of life. However, due to adverse reactions and inadequate effectiveness, there is still an unmet need for treatment. Xuefu zhuyu oral liquid (XZOL) is a Chinese patent medicine widely used for TTH in China, but evidence of its efficacy remains scant. PURPOSE: The aim of this study was to assess the efficacy and safety of XZOL for TTH patients. METHODS: This multicenter, double-blind, randomized placebo-controlled trial enrolled 174 patients with TTH in six centers in China from March 2020 to October 2021. Patients were randomly assigned to receive XZOL or a matched placebo for 4weeks. The primary outcome was the change in the mean headache intensity as measured by a visual analogue scale (VAS) from baseline to the end of treatment (Week 4). Secondary outcomes were the change in VAS from baseline to Week 12, the area-under-the-headache curve (AUC), response rate, number of headache days, average headache duration, rescue medication use proportion, etc. RESULTS: Of the 174 patients who were randomized, 160 completed the study. There was no significant difference in the mean change in VAS from baseline to the end of treatment between the XZOL group and the placebo group (-0.29; (95 % CI:0.81 to 0.23; p = 0.279) in the full analysis set (FAS), while there were statistically significant results (-0.9; 95 % CI:1.47 to -0.33; p = 0.002) in the per-protocol set (PPS). There were no significant differences in any of the secondary outcomes. The incidence of adverse events was similar in the two groups. CONCLUSION: XZOL may be an alternative option to relieve pain for TTH patients with high compliance in clinical practice. However, XZOL did not improve headache measurements in the FAS population.

Medicinal activities of Tualang honey: a systematic review.

Natural products derived from various sources, including plants, have garnered significant interest as alternative therapeutic options. Among these, Tualang honey, extracted from the nectar of Tualang trees (Koompassia excelsa (Becc.) Taub.), has a long history of traditional use due to its therapeutic properties. This review aims to examine the pharmacological activities of Tualang honey, encompassing both in vitro and in vivo studies. A systematic search was conducted in multiple databases, including PubMed, Springer, Scopus, Wiley, and Science Direct, up until December 2022 to identify relevant studies on the pharmacological activities of Tualang honey. Two independent reviewers were involved in article selection, followed by data extraction and assessment of methodological quality using Syrcle's risk of bias tool. 123 articles were included, collectively describing the pharmacological activities of Tualang honey, including antimicrobial, anticancer, anti-inflammatory, antioxidant, antinociceptive, neuroprotective effects, and others. Tualang honey has significant promise as an alternative treatment option for treating a wide range of pathological diseases due to its wide range of pharmacological properties. Tualang honey's diverse array of pharmacological actions indicates its potential for multiple medicinal uses.

Comparative efficacy of unilateral biportal endoscopic and full-endoscopic posterior cervical foraminotomy in the treatment of cervical spondylotic radiculopathy: a retrospective analysis.

OBJECTIVE: The aim of this study was to compare the clinical efficacy of the full-endoscopic posterior cervical foraminotomy (FE-PCF) and the unilateral biportal endoscopic posterior cervical foraminotomy (UBE-PCF) in the treatment of cervical spondylotic radiculopathy (CSR). METHODS: Patients who underwent posterior cervical spine surgery in our hospital from January 2020 to December 2022 were retrospectively analyzed. According to the surgical method, the patients were divided into two groups: FE-PCF group and UBE-PCF group. Perioperative data included operation time, Intraoperative blood loss and postoperative hospital stay were collected. The Visual Analog Scale (VAS)-arm, VAS-neck, and Neck Diability Index (NDI) was used to evaluate the clinical outcomes at preoperative, postoperative 1 week and Last follow-up. Serum creatine phosphokinase (CPK) and C-reactive protein (CRP) levels were recorded to evaluate surgical invasiveness. RESULTS: A total of 160 patients were included, including 89 cases of FE-PCF and 71 cases of UBE-PCF. The demographic and preoperative data showed no significant differences between the two groups (P > 0.05). The mean operating time was significantly shorter in the UBE-PCF group compared to FE-PCF group (P < 0.05). Serum CRP and CPK levels of the two groups both exhibited a pattern of rising and then falling, peaking one day following surgery and decreasing to near normal values three days after the operation. Compared with preoperative, both groups showed significant improvement in postoperative VAS and NDI scores, with a statistically significant difference (P < 0.05). However, the differences in results between the groups were not significant. CONCLUSIONS: Both UBE-PCF and FE-PCF are secure and efficient methods for treating CSR by continuous visualization. UBE-PCF offers predictable and adequate decompression within a reduced surgical duration, facilitated by its separate observation and operation channels.

Tough and stretchable ionic polyurethane foam for use in wearable devices.

Developing tough and conductive materials is crucial for the fields of wearable devices. However, soft materials like polyurethane (PU) are usually non-conductive, whereas conductive materials like carbon nanotubes (CNTs) are usually brittle. Besides, their composites usually face poor interfacial interactions, leading to a decline in performance in practical use. Here, we develop a stretchable PU/CNTs composite foam for use as a strain sensor. A cationic chain extender is incorporated to afford PU cationic groups and to regulate its mechanical properties, whose tensile strength is up to 12.30 MPa and breaking strain exceeds 1000%, and which shows considerable adhesion capability. Furthermore, porous PU foam is prepared via a salt-templating method and carboxylic CNTs with negative groups are loaded to afford the foam conductivity. The obtained foam shows high sensitivity to small strain (GF = 5.2) and exhibits outstanding long-term cycling performance, which is then used for diverse motion detection. The strategy illustrated here should provide new insights into the design of highly efficient PU-based sensors.

Monoterpene indole glycoalkaloids from the hook-bearing branches of Uncaria rhynchophylla.

Twelve monoterpene indole glycoalkaloids, comprising of three new ones, 19-epi-rhynchophylloside A (1), 7-epi-rhynchophylloside A (2), and 7-epi-anthocephalusine A (3), were isolated from the hook-bearing branches of Uncaria rhynchophylla. The structures and absolute configurations of 1-3 were elucidated by analysis of MS, NMR, ECD, and single-crystal X-ray diffraction or TDDFT-ECD calculations. Glycoalkaloids 1 and 3 showed significant immunosuppressive activity against the proliferation of B lymphocyte induced by LPS with broad selective index.

Paricalcitol ameliorates diabetic nephropathy by promoting EETs and M2 macrophage polarization and inhibiting inflammation by regulating VDR/CYP2J2 axis.

Previous studies have shown that paricalcitol (PA) has a protective effect on the kidneys. However, the exact molecular mechanism by which PA affects diabetic nephropathy (DN) progression remains uncertain. PBMCs of patients with DN were isolated, and CYP2J2 and VDR levels were detected by qPCR. Pearson correlation analysis was utilized to detect the relationship between uACR and CYP2J2 and VDR and between CYP2J2 and VDR. The protective effects of PA on DN have been examined by TUNEL, HE staining, ELISA, and Flow cytometry assays in STZ-induced mice. Moreover, THP-1 cells were stimulated with HG/LPS for in vitro studies. ELISA, qPCR, western blot, and Flow cytometry assays were utilized to assess the effects of PA on DN progression by regulating CYP2J2. The interaction between CYP2J2 and VDR was analyzed by CHIP-qPCR and luciferase experiments. CYP2J2 and VDR levels were downregulated and uACR level was upregulated in DN patients. CYP2J2 and VDR were positively correlated in PBMCs. Both CYP2J2 and VDR are inversely correlated with uACR. Moreover, after PA treatment, 11, 12-EET levels increased, inflammatory factor levels decreased, and M2 macrophage polarization was promoted in STZ-induced mice and HG/LPS-triggered THP-1 cells. Depletion of CYP2J2 and VDR decreased 11, 12-EET level, enhanced inflammatory factor levels, and inhibited M2 macrophage polarization, which were reversed by CYP2J2 overexpression in HG/LPS-treated cells. Furthermore, VDR bound to the CYP2J2 promoter and promoted CYP2J2 transcriptional expression. The present work pointed out a new use for PA to inhibit DN progression by increasing EET level, inhibiting inflammatory response, and inducing M2 macrophage polarization via regulating the VDR/CYP2J2 axis.

Gelatin Methacrylic Acid Hydrogel-Based Nerve Growth Factors Enhances Neural Stem Cell Growth and Differentiation to Promote Repair of Spinal Cord Injury.

Background: The challenge in treating irreversible nerve tissue damage has resulted in suboptimal outcomes for spinal cord injuries (SCI), underscoring the critical need for innovative treatment strategies to offer hope to patients. Methods: In this study, gelatin methacrylic acid hydrogel scaffolds loaded with nerve growth factors (GMNF) were prepared and used to verify the performance of SCI. The physicochemical and biological properties of the GMNF were tested. The effect of GMNF on activity of neuronal progenitor cells (NPCs) was investigated in vitro. Histological staining and motor ability was carried out to assess the ability of SCI repair in SCI animal models. Results: Achieving nerve growth factors sustained release, GMNF had good biocompatibility and could effectively penetrate into the cells with good targeting permeability. GMNF could better enhance the activity of NPCs and promote their directional differentiation into mature neuronal cells in vitro, which could exert a good neural repair function. In vivo, SCI mice treated with GMNF recovered their motor abilities more effectively and showed better wound healing by macroscopic observation of the coronal surface of their SCI area. Meanwhile, the immunohistochemistry demonstrated that the GMNF scaffolds effectively promoted SCI repair by better promoting the colonization and proliferation of neural stem cells (NSCs) in the SCI region and targeted differentiation into mature neurons. Conclusion: The application of GMNF composite scaffolds shows great potential in SCI treatment, which are anticipated to be a potential therapeutic bioactive material for clinical application in repairing SCI in the future.

From banked human cord blood to induced pluripotent stem cells: New opportunities and promise in induced pluripotent stem cell banking (Review).

Umbilical cord blood (CB) is a valuable source of haematopoietic stem/progenitor cells (HSCs) and is known for the therapeutic use of these cells in treating blood disorders. However, challenges such as a high running cost and the increasing availability of treatment alternatives have made the effort to sustain CB banks difficult. This prompts the need to revisit the current CB banking initiatives to retain the relevance in this ever­changing era parallel to the fast­pacing development of cell­based therapeutic technology. Cellular reprogramming has shown to have successfully converted adult somatic cells into human induced pluripotent stem cells (hiPSCs), which promise wider applications in regenerative medicine, personalized treatment and tissue engineering. CB is the youngest, primitive adult cell source that has not been affected by any prior, acquired disorders. Hence, using CB as a source of candidate cells for generating hiPSCs may be a new opportunity for banking, albeit with challenges. The present review summarizes the rise and fall of CB usage and banking for clinical therapy, the considerations in reprogramming CB into hiPSCs, the safety concerns regarding the use of hiPSC­derived cells in clinical transplantation and the prospect of using CB­derived hiPSCs.

Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.

Alzheimer's Disease (AD), as the most common neurodegenerative disease worldwide, severely impairs patients' cognitive functions. Although its exact etiology remains unclear, the abnormal aggregations of misfolded ß-amyloid peptide and tau protein are considered pivotal in its pathological progression. Recent studies identify ubiquitin-specific protease 11 (USP11) as the key regulator of tau deubiquitination, exacerbating tau aggregation and AD pathology. Thereby, inhibiting USP11 function, via either blocking USP11 activity or lowering USP11 protein level, may serve as an effective therapeutic strategy against AD. Our research introduces IsoLiPro, a unique lithium isobutyrate-L-proline coordination compound, effectively lowers USP11 protein level and enhances tau ubiquitination in vitro. Additionally, long-term oral administration of IsoLiPro dramatically reduces total and phosphorylated tau levels in AD transgenic mice. Moreover, IsoLiPro also significantly lessens ß-amyloid deposition and synaptic damage, improving cognitive functions in these animal models. These results indicate that IsoLiPro, as a novel small-molecule USP11 inhibitor, can effectively alleviate AD-like pathologies and improve cognitive functions, offering promise as a potential multi-targeting therapeutic agent against AD.

Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype.

Uveitis is a vision-threatening disease primarily driven by a dysregulated immune response, with retinal microglia playing a pivotal role in its progression. Although the transcription factor EGR2 is known to be closely associated with uveitis, including Vogt-Koyanagi-Harada disease and Behcet's disease, and is essential for maintaining the dynamic homeostasis of autoimmunity, its exact role in uveitis remains unclear. In this study, diminished EGR2 expression was observed in both retinal microglia from experimental autoimmune uveitis (EAU) mice and inflammation-induced human microglia cell line (HMC3). We constructed a mice model with conditional knockout of EGR2 in microglia and found that EGR2 deficiency resulted in increased intraocular inflammation. Meanwhile, EGR2 overexpression downregulated the expression of inflammatory cytokines as well as cell migration and proliferation in HMC3 cells. Next, RNA sequencing and ChIP-PCR results indicated that EGR2 directly bound to its downstream target growth differentiation factor 15 (GDF15) and further regulated GDF15 transcription. Furthermore, intravitreal injection of GDF15 recombinant protein was shown to ameliorate EAU progression in vivo. Meanwhile, knockdown of GDF15 reversed the phenotype of EGR2 overexpression-induced microglial inflammation in vitro. In summary, this study highlighted the protective role of the transcription factor EGR2 in AU by modulating the microglial phenotype. GFD15 was identified as a downstream target of EGR2, providing a unique target for uveitis treatment.

Design, Synthesis, and Antirheumatoid Arthritis Mechanism of TLR4 Inhibitors.

A total of 12 carbonyl compounds were synthesized, their lipopolysaccharide induced inhibition, and activity of RAW264.7 cells was evaluated. The most active compound 3k inhibited RAW264.7 cells with IC50 value of 1.02 ± 0.08 µM. Compound 3k significantly inhibited the release of TNF-α, IL-1ß, and IL-6 in supernatant for RAW264.7 cells. In vivo collagen-induced arthritis model tests administered orally, compound 3k showed effects similar to those of methotrexate in the positive control group. The preliminary mechanism study showed that compound 3k had an effect on abnormal expression for TLR4, TNF-α, NF-κB protein, and genes related to inflammation signaling pathway in RAW264.7 cells. Meanwhile, compound 3k showed a good affinity for the TLR4 receptor in molecular docking simulation. Therefore, compound 3k may be a promising lead compound for the treatment of rheumatoid arthritis.

Targeting PYK2 with heterobifunctional T6BP helps mitigate MASLD and MASH-HCC progression.

BACKGROUND & AIMS: The mechanisms underlying the regulation of hepatocyte non-receptor tyrosine kinases in metabolic dysfunction-associated steatohepatitis (MASH) remain largely unclear. METHODS: Hepatocyte-specific overexpression or deletion and anti-protein tyrosine kinase 2 beta (PYK2) or anti-TRAF6-binding protein (T6BP) crosslinking were utilised to study fatty liver protection by T6BP. P-PTC, a peptide-proteolysis targeting chimaera, degrades PYK2 to block MASH progression. RESULTS: Since PYK2 activation is promoter signalling in steatohepatitis development, we find that T6BP is a novel and critical suppressor of PYK2 that reduces hepatic lipid accumulation, pro-inflammatory factor release, and pro-fibrosis production by ubiquitin ligase CBL to degrade PYK2. Mechanistic evidence suggests that T6BP directly targets PYK2 and prevents its N-terminal FERM domain-triggered dimerization, disrupting downstream PYK2-JNK signalling hyperactivation. Additionally, T6BP favourably recruits CBL, a particular E3 ubiquitin ligase targeting PYK2, to form a complex and degrade PYK2. T6BP (F1), a core fragment of T6BP, directly blocks N-terminal FERM domain-associated dimerization of PYK2, followed by T6BP-recruiting CBL-mediated PYK2 degradation in a typical T6BP-dependent manner when the tiny fragment is specifically expressed using thyroxine binding globulin (TBG)-ground vectors. This inhibits the progression of MASH, metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC (MASH-HCC), and metabolic syndrome in dietary rodent models. First-ever peptide-proteolysis targeting chimaera (P-PTC) based on the core segment of T6BP as a ligand for targeted recruitment of CBL targeting metabolic disorders like MASH has been devised and validated in animal models. CONCLUSIONS: Our study revealed a previously unknown mechanism: identification of T6BP as a key eliminator of fatty liver strongly contributes to the development of promising therapeutic targets, and the discovery of crucial fragments of T6BP-based pharmacon that interrupt PYK2 dimerization are novel and viable treatments for fatty liver and its advanced symptoms and complications. IMPACT AND IMPLICATIONS: Excessive high-energy diet ingestion is critical in driving steatohepatitis via regulation of hepatocyte non-receptor tyrosine kinases. The mechanisms under lying the regulation of hepatocyte PYK2 in metabolic dysfunction-associated steatohepatitis (MASH) remain largely unclear. Here, we found that T6BP as a critical fatty liver eliminator has a significant impact on the development of promising therapeutic targets. Additionally, vital T6BP-based pharmacon fragments that impede PYK2 dimerization have been found, offering new and effective treatments for advanced fatty liver symptoms and complications.

Comparative efficacy of unilateral biportal and percutaneous endoscopic techniques in unilateral laminectomy for bilateral decompression (ULBD) for lumbar spinal stenosis.

BACKGROUND: Unilateral laminotomy for bilateral decompression (ULBD) has yielded positive results in the treatment of lumbar spinal stenosis (LSS). Unilateral biportal ULBD (UB-ULBD) and percutaneous endoscopic ULBD (PE-ULBD) are gaining popularity because of the progress that has been made in minimally invasive surgery (MIS). The objective of this study was to evaluate and compare the radiographic and clinical results of UB-ULBD and PE-ULBD. METHODS: This study retrospectively enrolled patients who underwent ULBD surgery for LSS. The patients were categorized into two groups on the basis of the surgical method: the UB-ULBD group and the PE-ULBD group. Data on the general demographic data, surgical details, clinical efficacy, radiography and complications were compared between the two groups were compared. The minimum follow-up duration was 12 months. RESULTS: A total of 113 LSS patients who had undergone ULBD at our institution were included, of whom 61 patients underwent UB-ULBD surgery and 52 underwent PE-ULBD surgery. The UB-ULBD group had a significantly shorter operation time (P < 0.05). The facet was significantly better preserved in the UB-ULBD group than in the PE-ULBD group, and the angle of ipsilateral facet joint resection in the UE-ULBD group was significantly smaller (P < 0.05). The ODI score, VAS score and modified Macnab criteria improved postoperatively in both groups. The UB-ULBD group had a 95.08% rate of excellent or good patient outcomes, whereas the PE-ULBD group had a 92.30% rate. CONCLUSION: Both UB-ULBD and PE-ULBD can provide favourable clinical outcomes when used to treat LSS. UB-ULBD is beneficial because of its shorter operation time, smaller angle of ipsilateral facet joint resection and better facet preservation, making it a viable and safe option for treating LSS while ensuring spinal stability.

Choosing Your Endoscopist: A Retrospective Single-Centre Cohort Study.

Background Colorectal cancer is one of the most common internal malignancies affecting Australians, and colonoscopy is widely accepted as a part of comprehensive large bowel assessment. Different specialties perform colonoscopies, most commonly general surgeons and gastroenterologists. Analysing performance outcomes against benchmarks allows insight into inter-specialty differences and enables the improvement of overall service provision and quality. Methods We performed a retrospective single-centre cohort study on 2086 patients undergoing colonoscopies by seven surgeons (S) and nine gastroenterologists (G) between July 2021 and June 2023. Primary outcomes were comparative caecal intubation rates (CIR), photo documentation rates (PDR), documented withdrawal rates (DWR), withdrawal times (WT), and adenoma detection rates (ADR). Secondary outcomes characterised adenoma frequency, optimal WT, and indications for colonoscopies. Results We found significant differences in CIR (S: 94.9%, 990/1043; G: 99%, 1033/1043, P<0.01), PDR (S: 95.9%, 949/990; G: 99.1%, 1024/1033, P<0.01), DWR (S: 17.4%, 181/1043; G: 87.3%, 911/1043, P<0.01), WT >6 minutes (S: 82.3%, 149/181; G: 97.8%, 891/911, P<0.01), and ADR (S: 37.9%, 193/509; G: 59.7%, 421/705, P<0.01). Subgroup analysis revealed adenoma frequency peaked at 50-70 years old and optimal WT was ≥9 minutes. We demonstrated surgeons mainly perform colonoscopies for diverticulitis surveillance, abnormal imaging, post-cancer resections, and rectal bleeding, but gastroenterologists predominantly investigate bowel symptoms, polyp surveillance, positive faecal occult blood test, and anaemia. Conclusion Despite both specialties surpassing national standards in CIR and ADR, there were significant differences in performance indicators. We believe ADR differences could be explained by different indications specialties perform colonoscopies for. Increasing WT ≥9 minutes could improve ADR, and education on the usage of withdrawal timer on endoscopes will improve DWR.

Binaphthyl-based chiral covalent organic frameworks for chiral drug separation.

Separation of racemic drugs is of great importance and interest in chemistry and pharmacology. Here, we report the bottom-up synthesis of the binaphthyl-based chiral covalent organic frameworks (CCOFs), (R)-BHTP-COF. Then, high-performance liquid chromatography (HPLC) columns were prepared using (R)-BHTP-COF as a chiral stationary phase (CSP). Racemic ibuprofen was successfully baseline-separated on (R)-BHTP-COF-based CSP, and achieved excellent selectivity (α = 2.32) and chromatographic resolution (Rs = 3.39) factors. Meanwhile, the separation of six racemic drugs by the (R)-BHTP-COF-packed column exhibited high resolution, selectivity, and durability. The successful applications indicate the great potential of CCOFs as a novel stationary phase for efficient HPLC separation.

Probing the Effect of Alloying Elements on the Interfacial Segregation Behavior and Electronic Properties of Mg/Ti Interface via First-Principles Calculations.

The interface connects the reinforced phase and the matrix of materials, with its microstructure and interfacial configurations directly impacting the overall performance of composites. In this study, utilizing seven atomic layers of Mg(0001) and Ti(0001) surface slab models, four different Mg(0001)/Ti(0001) interfaces with varying atomic stacking configurations were constructed. The calculated interface adhesion energy and electronic bonding information of the Mg(0001)/Ti(0001) interface reveal that the HCP2 interface configuration exhibits the best stability. Moreover, Si, Ca, Sc, V, Cr, Mn, Fe, Cu, Zn, Y, Zr, Nb, Mo, Sn, La, Ce, Nd, and Gd elements are introduced into the Mg/Ti interface layer or interfacial sublayer of the HCP2 configurations, and their interfacial segregation behavior is investigated systematically. The results indicate that Gd atom doping in the Mg(0001)/Ti(0001) interface exhibits the smallest heat of segregation, with a value of -5.83 eV. However, Ca and La atom doping in the Mg(0001)/Ti(0001) interface show larger heat of segregation, with values of 0.84 and 0.63 eV, respectively. This implies that the Gd atom exhibits a higher propensity to segregate at the interface, whereas the Ca and La atoms are less inclined to segregate. Moreover, the electronic density is thoroughly analyzed to elucidate the interfacial segregation behavior. The research findings presented in this paper offer valuable guidance and insights for designing the composition of magnesium-based composites.

Blocking α1 Adrenergic Receptor as a Novel Target for Treating Alzheimer's Disease.

While amyloidopathy and tauopathy have been recognized as hallmarks in Alzheimer's disease (AD) brain, recently, increasing lines of evidence have supported the pathological roles of cerebrovascular changes in the pathogenesis and progression of AD. Restoring or ameliorating the impaired cerebrovascular function during the early phase of the disease may yield benefits against the cognitive decline in AD. In the present study, we evaluated the potential therapeutic effects of nicergoline [NG, a well-known α1 adrenergic receptor (ADR) blocker and vasodilator] against AD through ameliorating vascular abnormalities. Our in vitro data revealed that NG could reverse ß-amyloid1-42 (Aß1-42)-induced PKC/ERK1/2 activation, the downstream pathway of α1-ADR activation, in α1-ADR-overexpressed N2a cells. NG also blocked Aß1-42- or phenylephrine-induced constrictions in isolated rat arteries. All these in vitro data may suggest ADR-dependent impacts of Aß on vascular function and the reversal effect of NG. In addition, the ameliorating impacts of NG treatment on cerebral vasoconstriction, vasoremodeling, and cognitive decline were investigated in vivo in a PSAPP transgenic AD mouse model. Consistent with in vitro findings, the chronic treatment of NG significantly ameliorated the cerebrovascular dysfunctions and Aß plaque depositions in the brain. Moreover, an improved cognitive performance was also observed. Taken together, our findings supported the beneficial effects of NG on AD through adrenergic-related mechanisms and highlighted the therapeutic potential of α1-adrenergic vasomodulators against AD pathologies.

Transcriptome analysis reveals that defects in cell cycle regulation contribute to preimplantation embryo arrest.

Patients with preimplantation embryo arrest (PREMBA) often experience assisted reproductive failure primarily due to the lack of transferable embryos, and the molecular mechanisms underlying PREMBA remain unclear. In our study, the embryos from five women with recurrent preimplantation embryo arrest and three women with tubal factor infertility were used for single-embryo transcriptome sequencing. Meanwhile, the transcriptomes of normal human preimplantation embryos obtained from GSE36552 were utilized to perform a comparative analysis with the transcriptomes of PREMBA embryos. Our results showed dysregulation of the cell cycle phase transition might be a potential pathogenic factor contributing to PREMBA. Through integrated analysis of the differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA), we identified a number of hub genes using the protein-protein interaction network. The top 5 hub genes were as follows: CCNB2, BUB1B, CDC25A, CCNB3, and PLK3. The expression of hub genes was validated in PREMBA embryos and donated embryos using RT-qPCR. The knockdown of Ccnb2 in mouse zygotes led to an increase in embryo fragmentation, a rise in apoptosis, and a reduction in blastocyst formation. Furthermore, silencing the expression of CDC25A in HEK293T cells resulted in a decrease in cell proliferation and an increase in apoptosis, providing further support for our findings. Our findings could predict the development outcomes of preimplantation embryos and be used as potential therapeutic targets to prevent recurrent failures of IVF/ICSI attempts.