The Analysis of Serum Klotho Protein Level and Related Gene Polymorphism in Osteoporotic Fracture of Elderly Patients with Osteoporosis.

Objective: Klotho protein level are reported to play important roles in the osteoporosis. To investigate the correlation between serum Klotho protein level and related gene (Klotho G395-A gene) polymorphism and osteoporotic fracture in elderly patients with osteoporosis. Methods: A total of 62 elderly patients with osteoporosis admitted to the Department of Orthopedics of our hospital from January 2021 to June 2022 were included in the study group. Another 62 elderly patients without osteoporosis who underwent a physical examination at the same time were selected as the control group. Patients in the study group were divided into group A (n = 23, osteoporotic fracture) and group B (n = 39, osteoporotic fracture) according to the occurrence of osteoporotic fracture. Serum Klotho protein level was detected in all patients, and its related gene (Klotho G395-A gene) polymorphism was analyzed. After fasting in the morning (fasting for more than 8 hours), 3-5 ml venous blood was collected and immediately placed in a centrifuge tube. Serum was separated and serum Klotho protein level was measured by enzyme-linked immunosorbent assay kit. Polymorphism typing was performed by Taqman allele-specific hybridization analysis. At the same time, general information (gender, age, body mass index, systolic blood pressure, diastolic blood pressure, glycated glucose protein, low-density lipoprotein cholesterol, bone mineral density) was collected. The differences in general data, serum Klotho protein level and Klotho G395-A gene polymorphism between the study group and the control group were analyzed. Spearman analysis was used to analyze the correlation between general data, serum Klotho protein level and Klotho G395-A gene and osteoporotic fracture. Logistic analysis was used to analyze the independent risk factors of osteoporotic fracture. Results: There was no significant difference of the sex, systolic blood pressure (SBP), diastolic blood pressure (DBP), Klotho G395-A genotype GG and alleles A and G between the study group and the control group. There was significant difference of body mass index (BMI), glycated glucose protein, low-density lipoprotein cholesterol (LDL-C), bone mineral density, serum Klotho protein level and Klotho G395-A genotype AA and AG were between the study group and the control group. Gender, age, glycated glucose protein and Klotho G395-A genotype AA were positively correlated with osteoporotic fracture (P < .05), while bone mineral density was negatively correlated with osteoporotic fracture (P < .05). There was no correlationship between the serum Klotho protein level and the incidence of osteoporotic fracture (P > .05). Logistic analysis showed that age, bone mineral density and Klotho G395-A genotype AA were independent risk factors for osteoporotic fracture. Conclusion: The level of serum Klotho protein and related gene polymorphisms are both related to osteoporotic fracture in elderly patients with osteoporosis. It is significant to reduce the incidence of osteoporotic fractures. In future, more experiments are needed to explore the underlying mechanism.

Enantioselective Fluorescence Recognition of Free α-Amino Acids by Ion-Type Ammonium Salt-Based Sensors.

Optically pure amino acids have extensive applications in pharmaceuticals, pesticides, food, materials, and other fields. Enantiomers recognition of chiral amino acids using optical methods with synthetic chiral sensors has attracted extensive attention. Most reported sensors typically identify guests by covalent or hydrogen bonding or hydrophobic interaction with amino acids and their derivatives. In this paper, a series of ion-type quaternary ammonium salt-based enantioselective fluorescent sensors were synthesized for chiral recognition of free α-amino acids via electrostatic interaction. The fluorescence intensity ratios ID/IL (ID, IL, fluorescence intensity of sensor when treated with D- or L-amino acid) were up to 2.1 and enantioselective fluorescence enhancement ratios ef (ef=[IL-I0]/[ID-I0] or [ID-I0]/[IL-I0]. (I0, fluorescence intensity of the sensor)) were up to 5.0. Among them, sensor 3 showed best enantioselective recognition performance toward tryptophan (Trp), and L-Trp significantly quenched the fluorescence of sensor 3, but D-Trp greatly enhanced the fluorescence of sensor 3, its ID/IL was 2.11 and ef was 1.8. The mechanistic investigation by NMR spectrum revealed that a tight three-point interaction, including electrostatic interaction, hydrogen bond, and π-π stacking, between sensor 3 and D-Trp was formed.

Modified lateral approach combined with medial percutaneous approach versus triceps tongue-shaped flap approach and bilateral triceps brachii approach for pin fixation in treatment of irreducible displaced pediatric supracondylar humeral fractures.

To evaluate the clinical outcomes of the modified lateral approach combined with the medial percutaneous approach (MLACMPA) versus the triceps tongue-shaped flap approach (TTSFA) and the bilateral triceps brachii approach (BTBA) in the treatment of irreducible displaced supracondylar humeral fractures (SHFs) in children. Between March 2000 and July 2022, a total of 135 children who underwent open reduction and Kirschner wire cross internal fixation for irreducible displaced SHFs caused by trauma were retrospectively analyzed. According to the surgical approach, the patients were assigned to the TTSFA group (n = 36), the BTBA group (n = 40) and the MLACMPA group (n = 59). The duration of surgery, intraoperative blood loss, incision length, and elbow range of motion were compared. The 3 groups were similar in terms of mean age, sex distribution, and time from injury to operation. The duration of surgery, intraoperative blood loss, incision length and postoperative elbow range of motion in the MLACMPA group were significantly superior to those in the TTSFA group and BTBA group (P < .05). Compared the use of the TTSFA or the BTBA, using the MLACMPA for pin fixation in the treatment of irreducible displaced pediatric SHFs could significantly shorten the duration of surgery, reduce the operation trauma, facilitate earlier functional exercise of joints after operation and yield better elbow function.

Differences and Correlations of Anxiety, Sleep Quality, and Pressure-Pain Threshold between Patients with Chronic Low Back Pain and Asymptomatic People.

Background: Chronic low back pain (CLBP) is a clinically common and expensive disease. Patients frequently take sick leaves because of pain and dysfunction, and their unpleasant life and work experiences cause psychological depression and anxiety and affect their quality of life. Sleep disturbance is a common problem among patients with low back pain (LBP) with more than 50% complaining about poor sleep quality. This study aimed to explore the correlations between anxiety, sleep quality, and pressure-pain threshold (PPT) and their differences between patients with CLBP and asymptomatic people. Methods: Forty patients with CLBP and 40 asymptomatic people were recruited. Relevant data, including State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, and PPT, were individually and independently collected by blinded physiotherapists with a practicing certificate and then statistically analyzed. An independent sample t-test was used to determine the intergroup differences between patients with CLBP and asymptomatic populations. Pearson correlation coefficient was employed for correlation analysis. Results: The CLBP group had significantly higher anxiety scores (41.64 ± 9.88 vs. 36.69 ± 8.31; t = -2.496, p=0.015) than the asymptomatic group. A significant difference was found in the total score of the Pittsburgh Sleep Quality Index (6.41 ± 2.43 vs. 5.09 ± 2.18; t = -2.628, p=0.010) but not in the trait anxiety (44.00 ± 7.83 vs. 42.67 ± 9.51; t = -0.695, p=0.489) of the two groups. State-Trait Anxiety Inventory showed a low to moderate negative correlation with PPT. No remarkable correlation was observed between Pittsburgh Sleep Quality Index and PPT. Conclusions: Patients with CLBP showed considerably worse state anxiety and sleep quality than asymptomatic people; however, no substantial difference in PPT was found between the two groups. The results suggest that in clinical practice, the focus should include pain and related social and psychological factors. CLBP treatment could be considered from multiple perspectives and disciplines.This trial is registered with Chinese Clinical Trial Registry (Trial registration: ChiCTR-TRC-13003701).

Traditional Chinese Acupressure Massage of the Quadriceps Femoris Can Relieve Flexion Pain after Undergoing Total Knee Arthroplasty.

Objective: To reduce the pain of quadriceps during knee flexion after total knee arthroplasty and increase range motion of knee flexion. Design: Three-month prospective before/after quality improvement project. Setting. Department of Bone and Joint Surgery. Participants. A total of 80 patients who met the surgical indications were admitted to the outpatient department for surgery. They were randomly grouped by computer in advance, and the patients were divided into two groups according to the time of admission, each with 40 cases. Intervention. The intervention group performed routine rehabilitation exercises and received quadriceps acupoint massages for 20 minutes twice a day for two consecutive weeks. The control group performed routine rehabilitation exercises, such as gentle quadriceps massage for 20 minutes twice a day for two consecutive weeks. Main Outcome Measures. PPT (pressure pain threshold) of quadriceps femoris/VAS (visual analog scale) of knee flexion and motion of knee flexion. Results: The VAS score, range of motion, and tenderness threshold during flexion were significantly better in the intervention group than in the control group at 1, 2, and 4 weeks after surgery. But the VAS score, range of motion, and tenderness threshold did not significantly differ between groups at 12 weeks after surgery. Conclusion: Acupoint massage of the quadriceps femoris can relieve early flexion pain in patients after total knee arthroplasty. The trial was registered at clinical trials.gov.

Direct Aerobic α-Hydroxylation of Arylacetates for the Synthesis of Mandelates.

Aerobic α-hydroxylation of α-methylene esters has proven challenging due to overoxidation and hydrolysis of the materials. In this article, KOtBu-promoted TBAB-catalyzed α-hydroxylation of α-methylene aryl esters using O2 as the oxygen source has been developed. Both low reaction temperature and catalyst TBAB are keys to success. This reaction provides an environmentally friendly and low-cost approach to mandelates, which are valuable building blocks and widely present in pharmaceuticals.

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells.

OBJECTIVE: To investigate the role of PI3K/AKT signaling pathway in nucleus pulposus (NP) cells. METHODS: Nucleus pulposus (NP) cells were isolated from SD rat, and thereafter, passage three (P3) NP cells were divided into the following experimental groups: control, PI3K/AKT agonist IGF-1 (25 ng/ml, 50 ng/ml, and 100 ng/ml), and PI3K/AKT inhibitor LY294002 (5 µM, 10 µM, and 20 µM). Flow cytometry and BrdU cell proliferation assays were performed to assess apoptosis and the proliferation rate of NP cells. Western blot analysis was performed to examine the protein expression level of Col II, Col X, Aggrecan, and MMP13. RESULTS: PI3K/AKT inhibitor LY294002 increased the rate of apoptosis in NP cells when compared to the control and decreased the proliferation rate when compared to control. Moreover, LY294002 decreased the protein expression level of Col-II and Aggrecan in NP cells. At the same time, LY294002 increased the protein expression level of MMP13 and Col-X in NP cells. Through activating PI3K/AKT, IGF-1 increased the proliferation rate when compared to control and decreased the rate of apoptosis when compared to control. Additionally, IGF-1 decreased the protein expression level of MMP13 and Col-X and increased Col-II and Aggrecan in NP cells. CONCLUSION: The inhibition of PI3K/AKT signaling pathway accelerated the apoptosis of NP cells and facilitated the extracellular matrix degradation. However, the activation of PI3K/AKT pathway partly prevented the NP cell from apoptosis and promoted their proliferation. Meanwhile, its activation also delayed the loss of extracellular matrix.

Effect of Transversus abdominis muscle training on pressure-pain threshold in patients with chronic low Back pain.

BACKGROUND: Therapeutic training is the most commonly used treatment methods for chronic low back pain (CLBP), and the use of a pressure biofeedback unit for transversus abdominis muscle (TrA) training is one of the core muscle training methods. The study aim of this research is to explore the effects of different intensities (sham training, low-intensity and high-intensity) of TrA muscle training on people with CLBP in pressure-pain threshold (PPT). METHODS: A total of 45 patients with CLBP were recruited, of whom 44 were included in the analysis. Fifteen, 14, and 15 were included in the sham training group, the low-intensity group, and the high-intensity group, respectively. A pressure biofeedback unit was used in performing a one-time TrA training intervention involving 30 times of 180 mmHg TrA contraction training at high intensity for 10 min and 15 times of 100 mmHg TrA contraction training at low intensity for 5 min. The sham training group completed comfort exercises and did not undergo training. The evaluation indicators were as follows: PPT, short-form McGill pain questionnaire, and body surface pain radiation. RESULTS: High-intensity training could activate more waist core muscles than low-intensity training. Significant changes on PPT (units: kgf) were observed in the following four muscles immediately after high-intensity training: iliopsoas [0.69 (0.13-1.25) 95% CI, p = 0.020]; quadratus lumborum [0.84 (0.23-1.45) 95% CI, p = 0.012]; erector spinae [0.66 (0.18-1.15) 95% CI, p = 0.011]; transversus abdominis [0.70 (0.26-1.14) 95% CI, p = 0.004], and in three muscles after low-intensity training: quadratus lumborum [0.61 (0.17-1.05) 95% CI, p = 0.009]; transversus abdominis [0.14 (from - 0.15 to 0.43) 95% CI, p = 0.022]; piriformis [0.55 (0.13-0.98) 95% CI, p = 0.014]. The change in body surface pain radiation immediately after exercise was [- 10.87 (from - 17.51 to - 4.22) 95% CI, p = 0.003] for high-intensity training and [- 5.21 (from - 9.40 to - 1.03) 95% CI, p = 0.019] for low-intensity training. CONCLUSIONS: TrA training could increase the PPT of the waist core muscles and reduce the radiation range of waist pain. The benefits of high-intensity training are higher than those of low-intensity training. TRIAL REGISTRATION: ChiCTR-TRC-13003701 . Registered 18 October 2013. Code of ethical approval: 2018069.

Development of C2-Symmetric Chiral Spirocyclic Phase-Transfer Catalysts: Synthesis and Application to Asymmetric Alkylation of Glycinate Schiff Base.

A class of C2-symmetric chiral spirocyclic phase-transfer catalysts based on tetramethyl-1,1'-spirobiindane scaffold was synthesized from commercially available bisphenol A in 12 steps with 22-25% total yields, which features a more rigid and stable backbone and smaller dihedral angles and can be easily modified. These catalysts show high catalytic performance in the asymmetric alkylation of tert-butyl glycinate Schiff base at only 2 mol % catalyst loading, giving the target products with up to 92% yield and 98% ee.

Copper(I)-Catalyzed Aerobic Oxidation of α-Diazoesters.

A practical Cu-catalyzed oxidation of α-diazoesters to α-ketoesters using molecular oxygen as an oxidant has been developed. Both electron-poor and electron-rich aryl α-diazoesters are suitable substrates and provide the α-ketoesters in good yields. In this oxidative system, α-diazo-ß-ketoesters are also compatible as substrates but unexpectedly furnish α-ketoesters via C-C bond cleavage, rather than the vicinal tricarbonyl products.

Dendritic cells aggregate inflammation in experimental osteoarthritis through a toll-like receptor (TLR)-dependent machinery response to challenges.

AIMS: Dendritic cells (DCs) and Toll-like receptor (TLR) participate in mediating inflammation process. However, the functional role of TLR expressed on DCs in osteoarthritis (OA) development has not been defined yet. The purpose of this study was to investigate the role and mechanism of TLR and DCs in the progression of experimental osteoarthritis (OA). MATERIALS AND METHODS: Experimental OA model was induced by iodoacetate injection. Expressions of toll-like receptors in DCs of OA mice were detected by qRT-PCR and flow cytometry. TLR agonists lipopolysaccharide (LPS) and R848 or TLR antagonist FP7 were used, and the levels of TLRs and inflammatory cytokines were examined by qRT-PCR and ELISA. KEY FINDINGS: The expression levels of TLR family members were increased in DCs derived from synovial fluid of OA mice compared with the sham mice. In vitro, OA mice-derived DCs had increased production of inflammatory cytokine after TLR agonists LPS and R848 challenge, while TLR challenges did not affect DCs maturation. Inhibition of TLR by TLR antagonist FP7 blocked TLR challenges-induced increased inflammation in DCs. In mice, administration of FP7 attenuated LPS-induced inflammatory response and OA condition. SIGNIFICANCE: Increased TLR expression in OA-derived DCs contributes to the inflammation condition and potentially acts as a therapeutic target for osteoarthritis.

Oxidative α-Trichloromethylation of Tertiary Amines: An Entry to α-Amino Acid Esters.

α-Trichloromethylation of tertiary amines with trimethyl(trichloromethyl)silane by oxidative coupling, using DDQ as an oxidant, has been realized. The reaction is instantaneous, is scalable, and tolerates a broad range of functional groups and heteroarenes. The trichloromethylated products can be easily converted into ß,ß-dichloroamines, enamines, and α-amino acid esters under operationally simple conditions. This methodology provides an efficient alternative to the poisonous cyanation reactions for the synthesis of carboxylic acid and their derivatives.

Quantitative and In-Depth Survey of the Isotopic Abundance Distribution Errors in Shotgun Proteomics.

Accuracy is an important metric when mass spectrometry (MS) is used in large-scale quantitative proteomics research. For MS-based quantification by extracting ion chromatogram (XIC), both the mass and intensity dimensions must be accurate. Although much research has focused on mass accuracy in recent years, less attention has been paid to intensity errors. Here, we investigated signal intensity measurement errors systematically and quantitatively using the natural properties of isotopic distributions. First, we defined a normalized isotopic abundance error model and presented its merits and demerits. Second, a comprehensive survey of the isotopic abundance errors using data sets with increasing sample complexities and concentrations was performed. We examined parameters such as error distribution, relationships between signal intensities within one isotopic cluster, and correlations between different peak errors in isotopic profiles. Our data demonstrated that the high resolution MS platforms might also generate large isotopic intensity measurement errors (approximately 20%). Meanwhile, this error can be reduced to less than 5% using a novel correction algorithm, which is based on the theoretical isotopic abundance distribution. Finally, a nonlinear relationship was observed as the abundance error decreased in isotopic profiles with higher intensity. Our findings are expected to provide insight into isotopic abundance recalibration in quantitative proteomics.

Effects of haze particles and fog droplets on NLOS ultraviolet communication channels.

The performance of non-line-of-sight ultraviolet (UV) scattering communication depends largely on atmospheric parameters. In this paper, we consider haze, fog, two common types of aerosols, and introduce the density and size of aerosols as variables to study the channel path loss for the UV scattering communications. We modify a Monte-Carlo based multiple-scattering model and provide fitting functions to replace the complex calculations of Mie theory, which can be used to obtain the atmospheric coefficients and phase functions for the aerosols. Simulation results reveal that, given fixed elevation angles, the channel path loss is related to both communication range, the aerosol density, and size of aerosols. For a short communication range, an increase of aerosol density can reduce the path loss, which improves the performance of UV scattering communication. However, when the communication range is extended, the path loss will fall first and then rise with density of aerosols. This phenomenon also occurs for an increase of fog drop size. The density or size of aerosols that has the lowest path loss is inversely proportional to the communication range.

Chiral Primary Amine/Palladium Dual Catalysis for Asymmetric Allylic Alkylation of ß-Ketocarbonyl Compounds with Allylic Alcohols.

An efficient dual catalytic system composed of a chiral primary amine and a palladium complex was developed to promote the direct asymmetric allylic alkylation (AAA) of ß-ketocarbonyl compounds. In particular, the synergistic dual catalytic system enabled the AAA reaction of challenging acyclic aliphatic ketones, such as ß-ketocarbonyl compounds and 1,3-diketones.

Catalytic Asymmetric Oxidative α-C-H N,O-Ketalization of Ketones by Chiral Primary Amine.

A highly enantioselective primary amine catalyzed α,α-bis-functionalization of ß-ketocarbonyls and cyclohexanones is described. This transformation employs N-hydroxycarbamates as both nitrogen and oxygen sources under aerobic oxidative conditions to furnish chiral N,O-ketals with high yields and enantioselectivities.

Copper-catalyzed aerobic autoxidation of N-hydroxycarbamates probed by mass spectrometry.

We present herein a mechanistic investigation by nanoelectrospray ionization mass spectrometry of copper-catalyzed aerobic oxidative processes involved in the N-nitrosocarbonyl aldol reaction of N-hydroxycarbamates. Protonated amine and copper as charge-tags aided the detection of reaction intermediates, which verified the enamine mechanism together with a competing enol process. Our experimental results reveal that the copper-catalyzed aerobic oxidation of N-hydroxycarbamates may proceed through an autoxidation catalytic mechanism in which a CbzNHO(.) radical abstracts a hydrogen from the bound N-hydroxycarbamate to release the nitroso intermediate through a bimolecular hydrogen-atom transfer. In this process, the chiral diamine also works as a ligand for copper to facilitate the aerobic oxidative step. The dual role of the chiral vicinal diamine as both an aminocatalyst and a bidentate ligand was finally uncovered.

Functional Proteomics Study Reveals SUMOylation of TFII-I is Involved in Liver Cancer Cell Proliferation.

SUMOylation has emerged as a new regulatory mechanism for proteins involved in multiple physiological and pathological processes. However, the detailed function of SUMOylation in liver cancer is still elusive. This study reveals that the SUMOylation-activating enzyme UBA2 is highly expressed in liver cancer cells and clinical samples. Silencing of UBA2 expression could to some extent suppress cell proliferation. To elucidate the function of UBA2, we used a large scale proteomics strategy to identify SUMOylation targets in HepG2 cells. We characterized 827 potential SUMO1-modified proteins that were not present in the control samples. These proteins were enriched in gene expression processes. Twelve candidates were validated as SUMO1-modified proteins by immunoprecipitation-Western blotting. We further characterized SUMOylated protein TFII-I that was identified in this study and determined that TFII-I was modified by SUMO1 at K221 and K240. PIAS4 was an E3 ligase for TFII-I SUMOylation, and SENP2 was responsible for deSUMOylating TFII-I in HepG2 cells. SUMOylation reduced TFII-I binding to its repressor HDAC3 and thus promoted its transcriptional activity. We further show that SUMOylation is critical for TFII-I to promote cell proliferation and colony formation. Our findings contribute to understanding the role of SUMOylation in liver cancer development.

Asymmetric α-benzoyloxylation of ß-ketocarbonyls by a chiral primary amine catalyst.

The direct asymmetric α-benzoyloxylation of ß-ketocarbonyls catalyzed by a chiral primary amine is described herein. This protocol demonstrates excellent enantioselectivity for a broad range of substrates, which allows convenient access to highly enantioenriched α-hydroxy-ß-ketocarbonyls.