Discovery and mechanistic insights into thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines inhibitors targeting tubulin for cancer therapy.

Guided by the X-ray cocrystal structure of the lead compound 4a, we developed a series of thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines demonstrating potent antiproliferative activity against four tumor cell lines. Two analogs, 13 and 25d, exhibited IC50 values around 1 nM and overcame P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). At low concentrations, 13 and 25d inhibited both the colony formation of SKOV3 cells in vitro and tubulin polymerization. Furthermore, mechanistic studies showed that 13 and 25d induced G2/M phase arrest and apoptosis in SKOV3 cells, as well as dose-dependent inhibition of tumor cell migration and invasion at low concentrations. Most notably, the X-ray cocrystal structures of compounds 4a, 25a, and the optimal molecule 13 in complex with tubulin were elucidated. This study identifies thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines as representatives of colchicine-binding site inhibitors (CBSIs) with potent antiproliferative activity.

The Effects of Lentinan on the Hematological and Immune Indices of Dairy Cows.

In this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty Holstein cows to four treatment groups. The treatments consisted of 0, 5, 10, and 15 g/d of LNT. Compared with the control group, the addition of 10 g/d of LNT decreased the content of ALT and IL-8 but simultaneously increased the content of IL-4 in the cows' serum. Supplementation with 10 g/d of LNT decreased the levels of lymphocyte, RDW, ALT, AST, TC, IL-2, and IL-8, but, concurrently, in-creased the levels of granulocytes and IL-4 in their serum. In addition, supplementation with 15 g/d of LNT decreased the levels of RDW, TC, IL-2, and IL-8, but, at the same time, increased the levels of IL-4 and IgM in their serum. For the metabolomic analysis, cows fed with 0 and 10 g/d of LNT were selected. The results showed that 10 metabolites, including reduced nicotinamide riboside and trehalose, were upregulated in the 10 g/d group. These differential metabolites were enriched in tyrosine metabolism and trehalose degradation and altered two metabolic pathways of ubiquinone and other terpene quinone biosynthesis, as well as starch and sucrose metabolism. These findings provide evidence that LNT could be used to reduce the risk of inflammation in dairy cows.

Analysis of Factors Associated with Lumbar Degenerative Disease Complicated by Baastrup's Disease.

OBJECTIVE: To investigate the factors associated with the occurrence of Baastrup's disease (BA) in patients with lumbar degenerative diseases (LDDs). METHODS: A retrospective analysis was conducted on 168 patients with LDDs (including lumbar disc herniation, lumbar spinal stenosis, and lumbar spondylolisthesis) who were treated at our hospital from January 2020 to January 2023, comprising 95 males and 73 females, aged 48-84 years.Patients were divided into two groups based on the presence of Baastrup's disease: those with BA (Group A) and those without BA (Group B).Relevant patient factors were extracted, including age, gender, occupation, smoking history, alcohol consumption history, body mass index, bone density, presence of internal diseases (diabetes, hypertension), lumbar lordosis angle, endplate Modic changes, degree of intervertebral disc degeneration, and facet joint degeneration (Weishaupt grading).Statistical analysis was performed using, Statistical Package for the Social Sciences 26.0 software to compare the differences in these factors between the two groups, and statistically significant results were included in a multivariate logistic regression analysis. RESULTS: Univariate analysis indicated that there were no statistically significant differences between the two groups in terms of gender, smoking history, alcohol consumption history, bone density, presence of internal diseases (diabetes, hypertension), lumbar lordosis angle, and endplate Modic changes (P>0.05),whereas age, occupation, body mass index, degree of intervertebral disc degeneration, and degree of facet joint degeneration showed statistically significant differences (P < 0.05).Multivariate logistic regression analysis revealed that age, degree of intervertebral disc degeneration, and degree of facet joint degeneration were independent risk factors for the occurrence of BA in patients with LDDs (P < 0.05). CONCLUSIONS: BA is relatively common in patients with LDDs, and advanced age, severe intervertebral disc degeneration, and facet joint degeneration are its independent risk factors.

Levels of 91 circulating inflammatory proteins and risk of lumbar spine and pelvic fractures and peripheral ligament injuries: a two-sample mendelian randomization study.

OBJECTIVE: Lumbar spine and pelvic fractures(LPF) are combined with peripheral ligament injuries(PLI), frequently. It has been reported that the site of fracture injury is usually paralleled by the secretion of inflammatory proteins. This study aimed to investigate the causal relationship between 91 circulating inflammatory proteins and LPF and PLI by using a Two-sample Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) associated with 91 circulating inflammatory proteins, as exposures were selected from a large genome-wide association study (GWAS). The genetic variant data for LPF and PLI as outcomes from the FinnGen consortium. The inverse-variance-weighted (IVW) method was utilized as the main analysis for exposures and outcomes. In addition, the final results were reinforced by the methods of MR Egger, weighted median, simple mode, and weighted mode. The sensitivity analyses were used to validate the robustness of results and ensure the absence of heterogeneity and horizontal pleiotropy. MR-Steiger was used to assess whether the causal direction was correct to avoid reverse causality. RESULTS: This study has shown that Beta-nerve growth factor(Beta-NGF) and Interferon gamma(IFN-gamma) are both involved in the occurrence of LPF and PLI, and they are reducing the risk of occurrence(OR:0.800, 95%CI: 0.650-0.983; OR:0.723, 95%CI:0.568-0.920 and OR:0.812, 95%CI:0.703-0.937; OR:0.828, 95%CI:0.700-0.980). Similarly, Axin-1 and Sulfotransferase 1A1 (SULT-1A1) were causally associated with LPF(OR:0.687, 95%CI:0.501-0.942 and OR:1.178,95%CI:1.010-1.373). Furthermore, Interleukin-4(IL-4), Macrophage inflammatory protein 1a(MIP-1a), and STAM binding protein(STAM-BP) were causally associated with PLI(OR:1.236, 95% CI: 1.058-1.443; OR:1.107, 95% CI: 1.008-1.214 and OR:0.759, 95% CI: 0.617-0.933). The influence of heterogeneity and horizontal pleiotropy were further excluded by sensitivity analysis. CONCLUSION: This study provides new insights into the relationship between circulating inflammatory proteins and LPF and PLI, and may provide new clues for predicting this risk.

Artificial-intelligence-based risk prediction and mechanism discovery for atrial fibrillation using heart beat-to-beat intervals.

BACKGROUND: Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning has been used for disease risk prediction; however, it lacks adherence to evidence-based medicine standards. Identifying the underlying mechanisms behind disease risk prediction is important and required. METHODS: We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability. FINDINGS: HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction. CONCLUSIONS: HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors. FUNDING: This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.

Predicting and analysing of the unfavourable outcomes of early applicated percutaneous endoscopic interlaminar discectomy for lumbar disc herniation: development and validation based nomogram.

OBJECTIVE: To predict and analyse the unfavourable outcomes of early applicated percutaneous endoscopic interlaminar discectomy for lumbar disc herniation. METHODS: Information of 426 patients treated by early applicated percutaneous endoscopic interlaminar discectomy (PEID) for lumbar disc herniation (LDH) at our hospital from June 2017 to October 2021 in addition to 17 other features was collected. The risk factors were selected by the least absolute shrinkage and selection operator method (LASSO) regression. Then, a prediction model (nomogram) was established to predict the unfavourable outcomes of using the risk factors selected from LASSO regression. Bootstrap (n = 1000) was used to perform the internal validation, and the performance of the model was assessed by the concordance index (C-index), receiver operating characteristic curve, and calibration curve. The decision curve analysis (DCA) and clinical impact curve (CIC) were used to assess the clinical utility of the model, respectively. RESULTS: Finally, 53 of 426 patients showed unfavourable outcomes. Five potential factors, Modic change, Calcification, Lumbar epidural steroid injection preoperative, Articular process hyperplasia and cohesion, and Laminoplasty technique, were selected according to the LASSO regression, that identified the predictors to establish nomogram model. Meanwhile, the C-index of the prediction nomogram was 0.847, the area under the receiver operating characteristic curve value was 0.847, and the interval bootstrapping (n = 1000) validation C-index was 0.809. The model has good practicability for clinics according to the DCA and CIC. CONCLUSION: This nomogram model has good predictive performance and clinical practicability, which could provide a certain basis for predicting unfavourable outcomes of early applicated PEID for LDH.

A new classification of lumbar Basstrup's disease based on radiographic and clinical symptoms.

OBJECTIVE: To propose a new classification method for lumbar Basstrup's disease based on radiographic and clinical symptoms, and to test its credibility and reproducibility. METHODS: A retrospective analysis of 116 patients with complete data of lumbar Basstrup's disease in our hospital from January 2019 to January 2022, radiological imaging including X-ray, CT and MRI, were divided into two main types according to the number of segments: type I (single segment) and type II (multiple segments), each type was divided into a total of eight subtypes according to the degree of degeneration: Ia, Ib, Ic, Id, IIa, IIb, IIc, IId; it was further divided into 16 subtypes according to the presence or absence of clinical symptoms (i.e. low back pain or/and lower limb neurological symptoms: no 0, yes 1): Ia0, Ia1, Ib0, Ib1, Ic0, Ic1, Id0, Id1; IIa0, IIa1, IIb0, IIb1, IIc0, IIc1, IId0, IId1.The 116 patients with Basstrup's disease were successively typed twice (1 month interval) by five physicians according to the new classification method, and the reliability and reproducibility of the new classification were assessed using the Kappa consistency test. RESULTS: Among 116 patients with lumbar Basstrup's disease: there were 60 cases of type I (single segment), accounting for 51.72%, including Ia 19 cases, Ib 16 cases, Ic 10 cases, and Id 15 cases; there were 56 cases of type II (multiple segments), accounting for 48.28%, including IIa 10 cases, IIb 20 cases, IIc 14 cases, and IId 12 cases. Of the 116 patients, 47 cases had no clinical symptoms (Ia0 16 cases, Ib0 3 cases, Ic0 6 cases, Id0 1 case, IIa0 8 cases, IIb0 2 cases, IIc0 10 cases, IId0 1 case), accounting for 40.52%; 69 cases were accompanied by low back pain or/and lower extremity nerve symptoms (Ia1 3 cases, Ib1 13 cases, Ic1 4 cases, Id1 14 cases, IIa1 2 cases, IIb1 18 cases, IIc1 4 cases, IId1 11 cases), accounting for 59.48%.Five physicians completed two rounds of a total of 1160 typings, with inter-assessor typing agreement of 82.47% (80.17-85.34%) and a mean Kappa value of 0.723 (0.771-0.831); intra-assessor typing agreement of 82.76% (77.59-86.21%) and a mean Kappa value of 0.801 (0.742-0.841). CONCLUSION: The new classification method for lumbar Basstrup's disease based on radiographic and clinical symptoms is simple, practical, with good credibility and reproducibility, and provides some guidance for clinical treatment.

TiO2-modified MoS2 monolayer films enable sensitive NH3 sensing at room temperature.

The research and development of high-performance NH3 sensors are of great significance for environment monitoring and disease diagnosis applications. Two-dimensional (2D) MoS2 nanomaterials have exhibited great potential for building room-temperature (RT) NH3 sensors but still suffer from relatively low sensitivity. Herein, the TiO2-modified monolayer MoS2 films with controllable TiO2 loading contents are fabricated by a facile approach. A remarkable enhancement in the RT NH3 sensing performance is achieved after the n-n hetero-compositing of the TiO2/MoS2 system. The device with 95% surface coverage of TiO2 shows enhanced sensor response, low detection limit (0.5 ppm), wide detection range (0.5-1000 ppm), good repeatability, and superior selectivity against other gases. In situ Kelvin potential force microscopy results revealed that the TiO2 modification not only improved the surface reactivity of the sensing layers but also contributed to the NH3 sensing performance by serving as the "gas-gating" layers that modulated the electron depletion layer and the conductivity of the MoS2 films. Such an n-n hetero-compositing strategy can provide a simple and cost-effective approach for developing high-performance NH3 sensors based on 2D semiconductors.

Adjuvant chemotherapy for pT1-3N0-1 breast cancer patients with HR+, HER2- subtype: a propensity-score matched study with competing risk analysis.

OBJECTIVE: To wholly evaluate the prognostic value of CHT for pT1-3N0-1 breast cancer patients with HR+, HER2- subtype using the Surveillance, Epidemiology, and End Results (SEER) database. METHOD: A total of 126,102 eligible cases diagnosed between January 2010 and December 2018 were included in the SEER database. A propensity-score matched (PSM) study with competing risk analysis was conducted. The Kaplan-Meier method was used to visualize the survival disparities between chemotherapy (CHT) and no CHT groups. The cumulative incidences of different subgroups were compared by Fine-Gray's test. RESULTS: Before PSM, patients in the CHT group had worse OS and CSS (both P < 0.001). After PSM, we were surprised that patients in the CHT group had a better OS than those in the no CHT group (HR 0.74, 95% CI 0.68-0.80, P < 0.001), while no significant survival disparities were observed for CSS (HR 1.00, 95% CI 0.89-1.12, P = 0.952). In the competing risk analysis, the OS disparities between the CHT and no CHT groups were mainly attributed to deaths of other causes (subdistribution HR [95% CI] 0.50 [0.44-0.57]). After adjusting for other competitive risk events, there was no significant difference in cumulative death risk of breast cancer between the CHT and no CHT groups (subdistribution HR [95% CI] 1.01 [0.90-0.1.13]). CONCLUSION: The present study is the first, to our knowledge, to wholly evaluate the prognostic value of CHT for pT1-3N0-1 breast cancer patients with HR+, HER2- subtype using a propensity-score matched study with competing risk analysis. All pT1-3N0-1 breast cancer patients with HR+, HER2- subtype do not benefit from CHT. Genetic testing may be the only effective tool to determine the need for CHT at the present.

Thoracolumbar Osteoporotic Vertebral Compression Fracture Treatment by Unilateral Percutaneous Vertebroplasty Using Curved Diffusion Needle.

Objective: To investigate the clinical effect of unilateral puncture vertebroplasty with curved diffusion needle (CDN) in the treatment of thoracolumbar osteoporotic vertebral compression fracture (OVCFs). Methods: We used the method of a retrospective study. The clinical data of 38 patients with OVCFs treated by unilateral puncture vertebroplasty with curved diffusion needle from January 2021 to January 2022 were analyzed. The operation time and the amount of bone cement injected were recorded to observe the leakage and dispersion of bone cement during the operation and the incidence of vertebral re-fracture at the last follow-up. Visual analog scale (VAS) and Oswestry disability index (ODI) were used to evaluate the pain and functional improvement before and after surgery. Results: All patients successfully completed the operation. The operation time was 31.2 ± 5.1 min, and the bone cement injection volume was 4.8 ± 1.1 ml. During the operation, three patients had bone cement leakage, and the leakage rate was 7.8%. The bone cement dispersion was excellent in 31 cases, among which seven cases were good; the postoperative follow-up time was 3-10 months, with an average of 6.3 months; no vertebral body re-fracture occurred. VAS score and ODI at 1d after the operation and at the last follow-up were significantly improved compared with those before the operation, and the difference was statistically significant (P < 0.05). Also there was a significant difference between the postoperative 1d and the last follow-up (P < 0.05). Conclusions: Unilateral puncture vertebroplasty for the treatment of thoracolumbar OVCFs can obtain good bone cement distribution, safety and does not increase complications, and the clinical effect is satisfactory.

Targeting glutaminase 1 (GLS1) by small molecules for anticancer therapeutics.

Glutaminase-1 (GLS1) is a critical enzyme involved in several cellular processes, and its overexpression has been linked to the development and progression of cancer. Based on existing research, GLS1 plays a crucial role in the metabolic activities of cancer cells, promoting rapid proliferation, cell survival, and immune evasion. Therefore, targeting GLS1 has been proposed as a promising cancer therapy strategy, with several GLS1 inhibitors currently under development. To date, several GLS1 inhibitors have been identified, which can be broadly classified into two types: active site and allosteric inhibitors. Despite their pre-clinical effectiveness, only a few number of these inhibitors have advanced to initial clinical trials. Hence, the present medical research emphasizes the need for developing small molecule inhibitors of GLS1 possessing significantly high potency and selectivity. In this manuscript, we aim to summarize the regulatory role of GLS1 in physiological and pathophysiological processes. We also provide a comprehensive overview of the development of GLS1 inhibitors, focusing on multiple aspects such as target selectivity, in vitro and in vivo potency and structure-activity relationships.

Design, Synthesis, and Biological Evaluation of Heterocyclic-Fused Pyrimidine Chemotypes Guided by X-ray Crystal Structure with Potential Antitumor and Anti-multidrug Resistance Efficacy Targeting the Colchicine Binding Site.

Herein, a series of quinazoline and heterocyclic fused pyrimidine analogues were designed and synthesized based on the X-ray co-crystal structure of lead compound 3a, showing efficacious antitumor activities. Two analogues, 15 and 27a, exhibited favorable antiproliferative activities, which were more potent than lead compound 3a by 10-fold in MCF-7 cells. In addition, 15 and 27a exhibited potent antitumor efficacy and tubulin polymerization inhibition in vitro. 15 reduced the average tumor volume by 80.30% (2 mg/kg) in the MCF-7 xenograft model and 75.36% (4 mg/kg) in the A2780/T xenograft model, respectively. Most importantly, supported by structural optimization and Mulliken charge calculation, X-ray co-crystal structures of compounds 15, 27a, and 27b in complex with tubulin were resolved. In summary, our research provided the rational design strategy of colchicine binding site inhibitors (CBSIs) based on X-ray crystallography with antiproliferation, antiangiogenesis, and anti-multidrug resistance properties.

Is unilateral pedicle screw fixation as effective as bilateral pedicle screw fixation in transforaminal lumbar interbody fusion: a meta-analysis of randomized controlled trials.

PURPOSE: This meta-analysis aimed to investigate whether unilateral pedicle screw fixation (UPSF) is comparable to bilateral pedicle screw fixation (BPSF) in transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative diseases. METHODS: Up to September 2022, established electronic literature databases including PubMed, Web of Science, EMBASE, and the Cochrane Library were systematically searched. Randomized controlled trials (RCTs) published in English that compared the efficacy of UPSF versus BPSF in TLIF were included. The methodological quality was evaluated, relevant data was extracted, and suitable meta-analysis was carried out. Data of fusion rate, complications, cage migration, visual analog scale (VAS), and Oswestry Disability Index (ODI), total blood loss (TBL), operation time, and hospital stay were extracted and analyzed. Pooled mean differences and risk ratio (RR) along with 95% confidence intervals (95% CI) were calculated for the results. RESULTS: Ten RCTs including 614 patients (UPSF = 294, BPSF = 320) were included in our meta-analysis. There were no significant differences in terms of fusion rate, VAS (VAS-BP and VAS-LP), ODI, complications, or hospital stay between UPSF and BPSF groups (P > 0.05, respectively). The UPSF group clearly had the advantage of less blood loss (SMD = -2.99, 95% CI [-4.54, -1.45], P = 0.0001) and operation time (SMD = -2.05, 95% CI [-3.10, -1.00], P = 0.0001). However, UPSF increased cage migration more than BPSF (10.7% vs 4.8%, RR = 2.23, 95% CI [1.07, 4.65], P = 0.03). CONCLUSION: According to the findings of this meta-analysis, UPSF is just as effective as BPSF in TLIF and may reduce blood loss and operation time. Nevertheless, UPSF may result in more cage migration than BPSF.

Discovery and biological evaluation of 4,6-pyrimidine analogues with potential anticancer agents as novel colchicine binding site inhibitors.

Novel 4,6-pyrimidine analogues were designed and synthesized as colchicine binding site inhibitors (CBSIs) with potent antiproliferative activities. Among them, compound 17j has the most potent activities against 6 human cancer cell lines with IC50 values from 1.1 nM to 4.4 nM, which was 76 times higher than the lead compound 3 in A549 cells. The co-crystal structure of 17j in complex with tubulin confirms the key binding mode at the colchicine binding site. Moreover, 17j inhibited the tubulin polymerization in biochemical assays, depolymerized cellular microtubules, induced the G2/M arrest, inhibited the cell migration, and promoted the initiation of apoptosis. In vivo, 17j effectively inhibits primary tumor growth with tumor growth inhibition rates of 42.51% (5 mg/kg) and 65.42% (10 mg/kg) in A549 xenograft model. Taken together, 17j represents a promising new generation of CBSIs.

Genetic Profile and Clinical Characteristics of Brugada Syndrome in the Chinese Population.

BACKGROUND: Brugada syndrome (BrS) is an inheritable arrhythmia syndrome that can lead to sudden cardiac death in patients while the heart structure is normal. However, the genetic background of more than 65% of BrS probands remains unclear. OBJECTIVES: The purpose of this study is to report the variant spectrum in a Chinese cohort with suspected BrS and to analyze their distinct clinical and electrocardiographic features. METHODS: Patients with suspected BrS from Tongji Hospital between 2008 and 2021 were analyzed retrospectively. RESULTS: A total of 79 probands were included in this study. Patients with type 1 BrS electrocardiogram (ECG) had a prolonged QRS duration compared to patients with type 2/3 BrS ECG. Of them, 59 probands underwent genetic testing. Twenty-five patients (42.37%) showed abnormal genetic testing results, and eight of them (13.56%) carried pathogenic/likely pathogenic (P/LP) mutations. Mutation carriers presented much more prominent depolarization and repolarization abnormalities than non-carriers, including a prolonged P-wave duration, QRS duration, QTc interval, decreased QRS amplitude, and deviation of the electrocardiographic axes (T-wave axis and R-wave axis). Furthermore, our study identified four novel P/LP mutations: Q3508X in TTN, A990G in KCNH2, G1220E, and D372H (in a representative pedigree) in SCN5A. CONCLUSIONS: Our study showed the variant spectrum of a suspected Chinese BrS cohort, and we identified four novel P/LP mutations in TTN, KCNH2, and SCN5A.

Synthesis and biological evaluation of a novel c-Myc inhibitor against colorectal cancer via blocking c-Myc/Max heterodimerization and disturbing its DNA binding.

c-Myc is a transcription factor that is aberrantly expressed in the majority of human cancers. Recent studies unveiled that abnormal expression of c-Myc protein is involved in the development of colorectal cancer (CRC). Previously, we reported a novel phenoxy-N-phenylaniline derivative A-42 that can inhibit c-Myc protein and the growth of different CRC cancer cells potently. To look for a better candidate, the structure-activity relationship (SAR) of A ring, D ring and the linker between A and B rings of A-42 was investigated, and a series of compounds were synthesized. Among them, compound B13 was identified as the most active c-Myc inhibitor with cytotoxicity activity against HT29 and HCT116 cells at IC50 0.29 µM and IC50 0.64 µM, respectively, which is superior to that of A-42. According to the bioassays, compound B13 not only can suppress CRC cells proliferation and migration, but also inhibit the binding of c-Myc/Max dimer to DNA, which further interfere with the expression of the relevant proteins of apoptosis pathway. Furthermore, B13 could inhibit HT29 tumor growth in xenograft mouse models potently with tumor growth inhibitions (TGIs) up to 65.49% at dose of 40 mg/kg, which is superior to A-42 (55.82%, 40 mg/kg). Overall, B13 may potentially serve as an effective CRC therapy via blocking c-Myc/Max binding with DNA.

Betaine Reduces Lipid Anabolism and Promotes Lipid Transport in Mice Fed a High-Fat Diet by Influencing Intestinal Protein Expression.

Betaine is more efficient than choline and methionine methyl donors, as it can increase nitrogen storage, promote fat mobilisation and fatty acid oxidation and change body fat content and distribution. Lipid is absorbed primarily in the small intestine after consumption, which is also the basis of lipid metabolism. This study was conducted to establish a mouse model of obesity in Kunming mice of the same age and similar body weight, and to assess the effect of betaine on the intestinal protein expression profile of mice using a proteomic approach. Analysis showed that betaine supplementation reversed the reduction in expression of proteins related to lipid metabolism and transport in the intestine of mice induced by a high-fat diet (HFD). For example, the addition of betaine resulted in a significant upregulation of microsomal triglyceride transfer protein (Mttp), apolipoprotein A-IV (Apoa4), fatty-acid-binding protein 1 (Fabp1) and fatty-acid-binding protein 2 (Fabp2) expression compared to the HFD group (p < 0.05), which exhibited accelerated lipid absorption and then translocation from the intestine into the body's circulation, in addition to a significant increase in Acetyl-CoA acyltransferase (Acaa1a) protein expression, hastening lipid metabolism in the intestine (p < 0.05). Simultaneously, a significant reduction in protein expression of alpha-enolase 1 (Eno1) as the key enzyme for gluconeogenesis in mice in the betaine-supplemented group resulted in a reduction in lipid synthesis in the intestine (p < 0.05). These findings provide useful information for understanding the changes in the protein profile of the small intestine in response to betaine supplementation and the potential physiological regulation of diets' nutrient absorption.

[The effect of axis pedicle and intra-axial vertebral artery on C 2 pedicle screw placement].

Objective: To investigate the influence of axis pedicle and intra-axial vertebral artery (IAVA) alignment on C 2 pedicle screw placement by measuring the data of head and neck CT angiography. Methods: The axis pedicle diameter (D), isthmus height (H), isthmus thickness (T), and IAVA alignment types were measured in 116 patients (232 sides) who underwent head and neck CT angiography examinations between January 2020 and June 2020. Defined the IAVA offset direction by referencing the vertical line through the center of C 3 transverse foramen on the coronal scan, it was divided into lateral (L), neutral (N), and medial (M). Defined the IAVA high-riding degree by referencing the horizontal line through the outlet of the C 2 transverse foramen, it was divided into below (B), within (W), and above (A). The rate of pedicle stenosis, high-riding vertebral artery, and different IAVA types were calculated, and their relationships were analysed. Simulative C 2 pedicle screws were implanted by Mimics 19.0 software, and the interrelation among the rates of pedicle stenosis, high-riding vertebral artery, IAVA types, and vertebral artery injury were analyzed. Results: The rate of C 2 pedicle stenosis was 33.6% (78/232), and the rate of high-riding vertebral artery was 35.3% (82/232). According to the offset direction and the degree of riding, IAVA was divided into 9 types, among which the N-W type (29.3%) was the most, followed by the L-W type (19.0%) and the L-B type (12.9%), accounting for 60.9%. The vertebral artery injury rate of simulative implanted C 2 pedicle screws was 35.3% (82/232). The vertebral artery injury rate in patients with pedicle stenosis and high-riding vertebral artery was significantly higher than that who were not ( P<0.001). The rate of pedicle stenosis, high-riding vertebral artery, and vertebral artery injury were significantly different among IAVA types ( P<0.001), and M-A type was the most common. Conclusion: Vertebral artery injury is more common in pedicle stenosis and/or high-riding vertebral artery and/or IAVA M-A type. Preoperative head and neck CT angiography examination has clinical guiding significance.

Percutaneous endoscopic interlaminar discectomy via inner border of inferior pedicle approach for downmigrated disc herniation: a retrospective study.

OBJECTIVE: To evaluate the efficacy and feasibility of percutaneous endoscopic interlaminar discectomy (PEID) via the inner border of the inferior pedicle approach for downmigrated disc herniation. METHODS: Seventeen patients who had downmigrated disc herniation were included in this study from May 2020 to February 2021. After PEID via the inner border of the inferior pedicle approach, a retrospective study was conducted on all patients. Radiologic findings were investigated, and based on the level of migration seen on preoperative magnetic resonance imaging (MRI), participants were divided into two types (high-grade and low-grade migrations). Preoperative, 1st post-operative day, 3rd post-operative month, and the final follow-up visual analogue scale (VAS) assessments for back and leg pain and preoperative, 3rd post-operative month, and the final follow-up Oswestry disability index (ODI) evaluations were performed. The clinical effects at the final follow-up were assessed by the modified MacNab criterion. RESULTS: All patients successfully completed surgery. There were 10 males and 7 females in the group. These patients were 42 years old on average (range, 25-68 years). Four and 13 patients had downmigrated disc herniation with high-grade and low-grade, respectively, on MRI. The mean follow-up duration was 10.47 ± 1.84 months (range, 8-14 months). The mean VAS score for back and leg improved from 5.18 ± 0.81 preoperatively to 1.35 ± 0.49 at the final follow-up (P < 0.05) and 6.94 ± 0.66 preoperatively to 1.47 ± 0.51 at the final follow-up (P < 0.05), respectively. The mean ODI score improved from 48.00 ± 3.64 preoperatively to 18.71 ± 1.31 at the final follow-up (P < 0.05). According to the modified MacNab criterion, 15 patients (88.2%) obtained excellent, while the rest 2 patients (11.8%) reported good outcomes. CONCLUSION: PEID via the inner border of the inferior pedicle approach could be a good alternative option for the treatment of downmigrated disc herniation.

Fast, Sensitive, and Highly Selective Room-Temperature Hydrogen Sensing of Defect-Rich Orthorhombic Nb2O5-x Nanobelts with an Abnormal p-Type Sensor Response.

The research and development of low-power-consumption and room-temperature hydrogen sensors are of great significance for the safe application of hydrogen energy. Herein, orthorhombic Nb2O5-x nanobelts are prepared through a combined procedure of hydrothermal, ion exchange, and annealing treatment in Ar. The topological transformation process results in the formation of abundant surface defects including chemical defects such as Nb4+, oxygen vacancies, and disordered microregions, which lead to the abnormal p-type conducting and hydrogen sensing behavior. Moreover, the orthorhombic Nb2O5-x nanobelts exhibit fast and sensitive room-temperature hydrogen sensing performance, which shows greater advancement than the monoclinic, tetragonal, and hexagonal Nb2O5 one-dimensional (1D) nanostructures. The response time and lowest limit of detection of the as-fabricated room-temperature sensor decrease to 28 s and 3.5 ppm, respectively. The sensor also exhibits a highly selective hydrogen response against CO, CH4, ethanol, H2S, and NH3. The hydrogen response of the Nb2O5-x nanobelts can be attributed to the redox reaction between hydrogen and preadsorbed oxygens. The defective surface structure and the prolonged dimension of the nanobelts give rise to the highly reactive surface and the suppression of the negative nanojunction effect, which greatly improves the sensing performance. The orthorhombic lattice structure can also promote gas adsorption and diffusion behavior due to its specific catalytic and pathway effect. The results of this work can be helpful for the rational design and defect engineering of the Nb2O5-based 1D nanostructures for room-temperature hydrogen sensing applications.