Effects of sodium intake, age, gender, blood sampling time on distribution of plasma aldosterone, renin activity, deoxycorticosterone, cortisol, cortisone, and 24 h urinary aldosterone levels in normotensive individuals based on LC-MS/MS.

PURPOSE: This study aims to analyze the distribution of plasma aldosterone, renin activity, deoxycorticosterone (DOC), cortisol, cortisone, and 24 h urinary aldosterone (24 h-uAld) levels based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: Plasma and 24 h urine were collected from 129 healthy volunteers in Northeast China. The effect of sodium intake, age, gender, blood sampling time on plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio (ARR), DOC, cortisol, cortisone, cortisol to cortisone ratio, and 24 h-uAld were investigated by nonparametric test, multiple linear regression and Harris-Boyd's standard deviate test. RESULTS: There was no significant difference observed in 24 h-uAld, PAC (AM), PRA(AM), ARR (AM), DOC (AM), cortisol (AM), cortisone (AM), and cortisol to cortisone (AM) between high and low sodium intake group. Significant differences were observed between morning and afternoon sampling groups in terms of PAC, ARR, DOC, cortisol, and cortisone. Reference intervals (RIs) of 24 h-uAld, PAC (AM) were recommended to be partitioned by gender. RI of PRA was recommended age stratification. CONCLUSION: We recommend that the same reference interval could be used regardless of sodium intake. Gender is the main influence factor for 24 h-uAld, PAC, and ARR. Age is key influence factor for PRA.

Aggregative Luminescence from CsPbBr3 Perovskite Precursors.

Understanding the properties of the precursor can provide deeper insight into the crystallization and nucleation mechanisms of perovskites, which is vital for the solution-process device performance. In this work, we conducted a detailed investigation into the photophysics properties of all-inorganic perovskite (CsPbBr3) precursors in a broad concentration and various solvents. The precursor gradually transformed from the solution state into the colloidal state and exhibited aggregation-induced emission (AIE) character as the concentration increased. The aggregative luminescence from the precursors originates from the polybromide plumbous that is formed through the coordination of solvent molecules to the lead metal center. Two adducts with monodentate (PbBr2⋅solvent) and bidentate (PbB2⋅2solvent) ligands can be obtained based on the coordination capability, accompanied by a red and green emission with photoluminescence peak at 610 and 565 nm, respectively. Furthermore, the aggregative luminescence intensity and color could be regulated by changing the solvent and precursor ratio. Besides, we discussed the difference between the molecular aggregate in the organic system and the ionic aggregate in the inorganic system. The fluorescence that is sensitive to Pb²âº coordination reported here could be applied to screen perovskite additives and judge the precursor aging.

An Injectable, Self-Healing, Adhesive Multifunctional Hydrogel Promotes Bacteria-Infected Wound Healing.

Bacterial infections have a serious impact on public health. It is urgent to develop antibacterial hydrogels with good biocompatibility to reduce the use of antibiotics. In this study, poly(lipoic acid-co-sodium lipoate)-phytic acid (P(LA-SL)-PA) hydrogels are prepared by a simple mixture of the natural small molecules lipoic acid (LA) and phytic acid (PA) in a mild and green reaction environment. The crosslinking network is constructed through the connection of covalent disulfide bonds as well as the hydrogen bonds, which endow the injectable and self-healing properties. The P(LA-SL)-PA hydrogels exhibit an adjustable compression modulus and adhesion. The in vitro agar plates assay indicates that the antibacterial rate of hydrogels against Escherichia coli and Staphylococcus aureus is close to 95%. In the rat-infected wound model, the P(LA-SL)-PA hydrogels adhere closely to the tissue and promote epithelialization and collagen deposition with a significant effect on wound healing. These results prove that the P(LA-SL)-PA hydrogels could act as effective wound dressings for promoting the healing of infected wounds.

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury.

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100 mg/kg and 0.05 mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.

Facile Solvent-Free Fabrication of All-Small-Molecule Supramolecular Photothermal Bioadhesive for Sutureless Wound Closure.

Achieving underwater adhesion possesses a significant challenge, primarily due to the presence of interfacial water, which restricts the potential applications of adhesives. In this study, we present a straightforward and environmentally friendly one-pot approach for synthesizing a solvent-free supramolecular TPFe bioadhesive composed of thioctic acid, proanthocyanidins, and FeCl3. The bioadhesive exhibits excellent biocompatibility and photothermal antibacterial properties and demonstrates effective adhesion on various substrates in both wet and dry environments. Importantly, the adhesive strength of this bioadhesive on steel exceeds 1.2 MPa and that on porcine skin exceeds 100 kPa, which is greater than the adhesive strength of most reported bioadhesives. In addition, the bioadhesive exhibits the ability to effectively halt bleeding, close wounds promptly, and promote wound healing in the rat skin wound model. Therefore, the TPFe bioadhesive has potential as a medical bioadhesive for halting bleeding quickly and promoting wound healing in the biomedical field. This study provides a new idea for the development of bioadhesives with firm wet adhesion.

Multiple photofluorochromic luminogens via catalyst-free alkene oxidative cleavage photoreaction for dynamic 4D codes encryption.

Controllable photofluorochromic systems with high contrast and multicolor in both solutions and solid states are ideal candidates for the development of dynamic artificial intelligence. However, it is still challenging to realize multiple photochromism within one single molecule, not to mention good controllability. Herein, we report an aggregation-induced emission luminogen TPE-2MO2NT that undergoes oxidation cleavage upon light irradiation and is accompanied by tunable multicolor emission from orange to blue with time-dependence. The photocleavage mechanism revealed that the self-generation of reactive oxidants driving the catalyst-free oxidative cleavage process. A comprehensive analysis of TPE-2MO2NT and other comparative molecules demonstrates that the TPE-2MO2NT molecular scaffold can be easily modified and extended. Further, the multicolor microenvironmental controllability of TPE-2MO2NT photoreaction within polymer matrices enables the fabrication of dynamic fluorescence images and 4D information codes, providing strategies for advanced controllable information encryption.

Aggregation-induced emission photosensitizer for antibacterial therapy of methicillin-resistant Staphylococcus aureus.

A cationic aggregation-induced emission photosensitizer (AIE-PS) MNNPyBB has been reported to have antibacterial effects against both Gram-positive and Gram-negative bacteria. The bacterial kill mechanism has been investigated and elucidated. In a methicillin-resistant Staphylococcus aureus subcutaneous infection model, wound closure has been achieved with normal re-epithelialization and preserved skin morphology.

The Inhibition of Fibrosis and Inflammation in Obstructive Kidney Injury via the miR-122-5p/SOX2 Axis Using USC-Exos.

Background: Fibrosis and inflammation due to ureteropelvic junction obstruction substantially contributes to poor renal function. Urine-derived stem-cell-derived exosomes (USC-Exos) have therapeutic effects through paracrine. Methods: In vitro, the effects of USC-Exos on the biological functions of HK-2 and human umbilical vein endothelial cells were tested. Cell inflammation and fibrosis were induced by transforming growth factor-ß1 and interleukin-1ß, and their anti-inflammatory and antifibrotic effects were observed after exogenous addition of USC-Exos. Through high-throughput sequencing of microRNA in USC-Exos, the pathways and key microRNAs were selected. Then, the antifibrotic and anti-inflammatory effects of exosomal miR-122-5p and target genes were verified. The role of the miR-122-5p/SOX2 axis in anti-inflammatory and antifibrotic effects was verified. In vivo, a rabbit model of partial unilateral ureteral obstruction (PUUO) was established. Magnetic resonance imaging recorded the volume of the renal pelvis after modeling, and renal tissue was pathologically analyzed. Results: We examined the role of USC-Exos and their miR-122-5p content in obstructive kidney injury. These Exos exhibit antifibrotic and anti-inflammatory activities. SOX2 is the hub gene in PUUO and negatively related to renal function. We confirmed the binding relationship between miR-122-5p and SOX2. The anti-inflammatory and antifibrotic effects of miR-122-5p were inhibited, indicating that miR-122-5p has anti-inflammatory and antifibrotic effects by inhibiting SOX2 expression. In vivo, the PUUO group showed typical obstructive kidney injury after modeling. After USC-Exo treatment, the shape of the renal pelvis shown a remarkable improvement, and inflammation and fibrosis decreased. Conclusions: We confirmed that miR-122-5p from USC-Exos targeting SOX2 is a new molecular target for postoperative recovery treatment of obstructive kidney injury.

Alternations in the human skin, gut and vaginal microbiomes in perimenopausal or postmenopausal Vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life. However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P < 0.05). Patients with VLS had a higher abundance of Enterobacter cloacae, Flavobacterium_branchiophilum, Mediterranea_sp._An20, Parabacteroides_johnsoniiand Streptococcus_bovimastitidis on the vulvar skin, while Corynebacterium_sp._zg-913 was less abundant compared to the control group. The relative abundance of Sphingomonas_sp._SCN_67_18, Sphingobium_sp._Ant17, and Pontibacter_sp_BT213 was significantly higher in the gut samples of patients with VLS.Paenibacillus_popilliae,Gemella_asaccharolytica, and Coriobacteriales_bacterium_DNF00809 compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of Bacteroidales_bacterium_43_8, Bacteroides_sp._CAG:20, Blautia_sp._AM28-10, Fibrobacter_sp._UWB16, Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79, and Tolumonas_sp. Additionally, the butyrate-producing bacterium SS3/4 showed a significant difference compared to the controls. The study found a negative relationship between Sphingobium_sp._Ant17 in stool and Skindex-16 (P < 0.05), while Mediterranea_sp._An20 had a positive correlation with Skindex-16 (P < 0.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.

Supramolecular Mimotope Peptide Nanofibers Promote Antibody-Ligand Polyvalent and Instantaneous Recognition for Biopharmaceutical Analysis.

Peptide-based supramolecules exhibit great potential in various fields due to their improved target recognition ability and versatile functions. However, they still suffer from numerous challenges for the biopharmaceutical analysis, including poor self-assembly ability, undesirable ligand-antibody binding rates, and formidable target binding barriers caused by ligand crowding. To tackle these issues, a "polyvalent recognition" strategy employing the CD20 mimotope peptide derivative NBD-FFVLR-GS-WPRWLEN (acting on the CDR domains of rituximab) was proposed to develop supramolecular nanofibers for target antibody recognition. These nanofibers exhibited rapid self-assembly within only 1 min and robust stability. Their binding affinity (179 nM) for rituximab surpassed that of the monomeric peptide (7 µM) by over 38-fold, highlighting that high ligand density and potential polyvalent recognition can efficiently overcome the target binding barriers of traditional supramolecules. Moreover, these nanofibers exhibited an amazing "instantaneous capture" rate (within 15 s), a high recovery (93 ± 3%), and good specificity for the target antibody. High-efficiency enrichment of rituximab was achieved from cell culture medium with good recovery and reproducibility. Intriguingly, these peptide nanofibers combined with bottom-up proteomics were successful in tracking the deamidation of asparagine 55 (from 10 to 16%) on the rituximab heavy chain after 21 day incubation in human serum. In summary, this study may open up an avenue for the development of versatile mimotope peptide supramolecules for biorecognition and bioanalysis of biopharmaceuticals.

Endothelial deubiquinatase YOD1 mediates Ang II-induced vascular endothelial-mesenchymal transition and remodeling by regulating ß-catenin.

Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1-/- mice by administration of Ang II (1 µg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation. Knockout of YOD1 resulted in a notable reduction in EndMT in vascular endothelial cells of Ang II-treated mouse; a similar result was observed in Ang II-treated human umbilical vein endothelial cells (HUVECs). We then conducted LC-MS/MS and co-immunoprecipitation (Co-IP) analyses to verify the binding between YOD1 and EndMT-related proteins, and found that YOD1 directly bound to ß-catenin in HUVECs via its ovarian tumor-associated protease (OTU) domain, and histidine at 262 performing deubiquitination to maintain ß-catenin protein stability by removing the K48 ubiquitin chain from ß-catenin and preventing its proteasome degradation, thereby promoting EndMT of vascular endothelial cells. Oral administration of ß-catenin inhibitor MSAB (20 mg/kg, every other day for four weeks) eliminated the protective effect of YOD1 deletion on vascular endothelial injury. In conclusion, we demonstrate a new YOD1-ß-catenin axis in regulating Ang II-induced vascular endothelial injury and reveal YOD1 as a deubiquitinating enzyme for ß-catenin, suggesting that targeting YOD1 holds promise as a potential therapeutic strategy for treating ß-catenin-mediated vascular diseases.

Design, Synthesis, and Evaluation of Dihydropyrimidine Derivatives as Selective PDE1 Inhibitors for the Treatment of Liver Fibrosis.

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-ß-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.

Single-incision plus one-port laparoscopy surgery versus conventional multi-port laparoscopy surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.

3D-printed piezocatalytic hydrogels for effective antibacterial treatment of infected wounds.

Bacterial-infected wound repair has become a significant public health concern. This study developed a novel 3D-printed piezocatalytic SF-MA/PEGDA/Ag@BT (SPAB) hydrogels were fabricated by using digital light processing. These hydrogels exhibited high consistency, mechanical properties and good biocompatibility. Besides, the SPAB hydrogels exhibited excellent piezocatalytic performance and thus could induce piezoelectric polarization under ultrasound to generate reactive oxygen species (ROS). The SPAB hydrogels possessed an antibacterial rate of 99.23% and 99.96% for Escherichia coli and Staphylococcus aureus, respectively, under 5 min of ultrasonic stimulation (US) in vitro. The US-triggered piezocatalytic performance could increase antibacterial activity and improve the healing process of the infected wound. Therefore, the 3D printed piezocatalytic SPAB hydrogels could be unutilized as wound dressing in the field of bacterial-infected wound repair.

Genomic basis determining root system architecture in maize.

KEY MESSAGE: A total of 389 and 344 QTLs were identified by GWAS and QTL mapping explaining accumulatively 32.2-65.0% and 23.7-63.4% of phenotypic variation for 14 shoot-borne root traits using more than 1300 individuals across multiple field trails. Efficient nutrient and water acquisition from soils depends on the root system architecture (RSA). However, the genetic determinants underlying RSA in maize remain largely unexplored. In this study, we conducted a comprehensive genetic analysis for 14 shoot-borne root traits using 513 inbred lines and 800 individuals from four recombinant inbred line (RIL) populations at the mature stage across multiple field trails. Our analysis revealed substantial phenotypic variation for these 14 root traits, with a total of 389 and 344 QTLs identified through genome-wide association analysis (GWAS) and linkage analysis, respectively. These QTLs collectively explained 32.2-65.0% and 23.7-63.4% of the trait variation within each population. Several a priori candidate genes involved in auxin and cytokinin signaling pathways, such as IAA26, ARF2, LBD37 and CKX3, were found to co-localize with these loci. In addition, a total of 69 transcription factors (TFs) from 27 TF families (MYB, NAC, bZIP, bHLH and WRKY) were found for shoot-borne root traits. A total of 19 genes including PIN3, LBD15, IAA32, IAA38 and ARR12 and 19 GWAS signals were overlapped with selective sweeps. Further, significant additive effects were found for root traits, and pyramiding the favorable alleles could enhance maize root development. These findings could contribute to understand the genetic basis of root development and evolution, and provided an important genetic resource for the genetic improvement of root traits in maize.

Gasless robot-assisted transaxillary hemithyroidectomy (RATH): learning curve and complications.

PURPOSE: Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. METHODS: We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. RESULTS: In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). CONCLUSION: Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.

Boosting Luminescence Efficiency of Near-Infrared-II Aggregation-Induced Emission Luminogens via a Mash-Up Strategy of π-Extension and Deuteration for Dual-Model Image-Guided Surgery.

The simultaneous pursuit of accelerative radiative and restricted nonradiative decay is of tremendous significance to construct high-luminescence-efficiency fluorophores in the second near-infrared wavelength window (NIR-II), which is seriously hindered by the energy gap laws. Herein, a mash-up strategy of π-extension and deuteration is proposed to efficaciously ameliorate the knotty problem. By extending the π-conjugation of the aromatic fragment and introducing an isotope effect to the aggregation-induced emission luminogen (AIEgen), an improved oscillator strength (f), coupled with suppressed deformation and high-frequency oscillation in the excited state, are successively implemented. In this case, a faster rate of radiative decay (kr) and restricted nonradiative decay (knr) are simultaneously achieved. Moreover, the preeminent emissive property of AIEgen in the molecular state could be commendably inherited by the aggregates. The corresponding NIR-II emissive AIEgen-based nanoparticles display high brightness, large Stokes shift, and superior photostability simultaneously, which can be applied for image-guided cancer and sentinel lymph node (SLN) surgery. This work thus provides a rational roadmap to improve the luminescence efficiency of NIR-II fluorophores for biomedical applications.

N6-methylation in the development, diagnosis, and treatment of gastric cancer.

Gastric cancer (GC) ranks third among cancers in terms of mortality rate worldwide. A clear understanding of the mechanisms underlying the genesis and progression of GC will contribute to clinical decision making. N6-methyladenosine (m6A) is the most abundant among diverse mRNA modification types and regulates multiple facets of RNA metabolism. In recent years, emerging studies have shown that m6A modifications are involved in gastric carcinoma tumorigenesis and progression and can potentially be valuable new prospects for diagnosis and prognosis. This article reviews the recent progress regarding m6A in GC.

Unveiling the distinctive ossification patterns of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis using computed tomography three-dimensional reconstruction.

OBJECTIVE: To quantitatively analyze the morphological characteristics of osteophytes in DISH and syndesmophytes in AS, and summarize different ossification patterns to help identify the two diseases. Associated factors for new bone formation would be investigated. METHODS: Fifty patients with DISH and 50 age-, sex-, CT examination site- matched patients with AS were enrolled. Radiographic and clinical data were reviewed. Osteophytes (syndesmophytes) in front of each vertebral body and the corresponding intervertebral disc space were defined as vertebral osteophytes unit (VOU). The volume, angle and location (contralateral, ipsilateral, bilateral) of osteophytes in each VOU were measured and compared between DISH and AS groups. RESULTS: In each VOU, the volume and angle of osteophytes in DISH were significantly larger. The best osteophytes volume and angle cutoff value in predicting DISH was 0.59 cm3 and 40.15°. Contralateral, bilateral, ipsilateral osteophytes were recorded in 59.32%, 36.38%, 4.3% of assessed VOUs in patients with DISH and 64.78%, 29.31%, 5.91% in AS (p<0.001), respectively. As to ipsilateral osteophytes, the volume was inversely correlated with the center of the vertebral body to the center of the descending aorta (DISH: r = -0.45, p= 0.01; AS: r = -0.83, p<0.001). Advanced age, disease duration, smoking and overweight contribute to the progression of osteophytes and syndesmophytes. CONCLUSION: Morphological features of osteophytes are helpful to distinguish DISH with AS. Aortic pulsations inhibit or hinder new bone formation in both DISH and AS. Maintaining normal BMI could postpone osteophytes formation.

Phytochemicals targeting Alzheimer's disease via the AMP-activated protein kinase pathway, effects, and mechanisms of action.

Alzheimer's disease (AD), characterized by cognitive dysfunction and other behavioral abnormalities, is a progressive neurodegenerative disease that occurs due to aging. Currently, effective drugs to mitigate or treat AD remain unavailable. AD is associated with several abnormalities in neuronal energy metabolism, such as decreased glucose uptake, mitochondrial dysfunction, and defects in cholesterol metabolism. Amp-activated protein kinase (AMPK) is an important serine/threonine protein kinase that regulates the energy status of cells. AMPK is widely present in eukaryotic cells and can sense and regulate energy metabolism to maintain energy supply and demand balance, making it a promising target for energy metabolism-based AD therapy. Therefore, this review aimed to discuss the molecular mechanism of AMPK in the pathogenesis of AD to provide a theoretical basis for the development of new anti-AD drugs. To review the mechanisms of phytochemicals in the treatment of AD via AMPK pathway regulation, we searched PubMed, Google Scholar, Web of Science, and Embase databases using specific keywords related to AD and phytochemicals in September 2023. Phytochemicals can activate AMPK or regulate the AMPK pathway to exert therapeutic effects in AD. The anti-AD mechanisms of these phytochemicals include inhibiting Aß aggregation, preventing Tau hyperphosphorylation, inhibiting inflammatory response and glial activation, promoting autophagy, and suppressing anti-oxidative stress. Additionally, several AMPK-related pathways are involved in the anti-AD mechanism, including the AMPK/CaMKKß/mTOR, AMPK/SIRT1/PGC-1α, AMPK/NF-κB/NLRP3, AMPK/mTOR, and PERK/eIF2α pathways. Notably, urolithin A, artemisinin, justicidin A, berberine, stigmasterol, arctigenin, and rutaecarpine are promising AMPK agonists with anti-AD effects. Several phytochemicals are effective AMPK agonists and may have potential applications in AD treatment. Overall, phytochemical-based drugs may overcome the barriers to the effective treatment of neurodegenerative diseases.