Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches.

Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KITW-SH/W-SH) mice to construct a model of Modic changes and found that the severity of Modic changes in KITW-SH/W-SH mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes.

Mitigating air pollution benefits multiple sustainable development goals in China.

Achieving the United nations 2030 Sustainable Development Goals (SDGs) remains a significant challenge, necessitating urgent and prioritized strategies. Among the various challenges, air pollution continues to pose one of the most substantial threats to the SDGs due to its widespread adverse effects on human health and ecosystems. However, the connections between air pollution and the SDGs have often been overlooked. This study reveals that out of the 169 SDG targets, 71 are adversely impacted by air pollution, while only 6 show potential positive effects. In China, two major atmospheric nitrogen pollutants, ammonia and nitrogen oxides, resulted in an economic loss of 400 billion United States Dollar (USD) in 2020, which could be reduced by 33% and 34% by 2030, respectively. It would enhance the progress towards SDGs in China by 14%, directly contributing to the achievement of SDGs 1 to 6 and 11 to 15. This improvement is estimated to yield overall benefits totaling 119 billion USD, exceeded the total implementation cost of 82 billion USD with ammonia as the preferential mitigation target. This study underscores the importance of robust scientific evidence in integrated policies aimed at aligning improvements in environmental quality with the priorities of sustainable development.

FATP2 regulates Osteoclastogenesis by increasing lipid metabolism and ROS production.

Lipid metabolism plays a crucial role in maintaining bone homeostasis, particularly in osteoclasts (OCs) formation. Here, we found the expression level of FATP2, a transporter for long-chain and very-long-chain fatty acids, was significantly upregulated during OC differentiation and in the bone marrow of mice fed a high-fat diet (HFD). Notably, the use of FATP2 siRNA or a specific inhibitor (Lipofermata) resulted in significant inhibition of OC differentiation while only slightly affecting osteoblasts (OBs). In pathological models of bone loss induced by LPS or OVX, in vivo treatment with Lipofermata was able to rescue the loss of bone mass by inhibiting OC differentiation. RNA sequencing (RNA-seq) revealed that Lipofermata reduced fatty acid ß-oxidation and inhibited energy metabolism, while regulating reactive oxygen species (ROS) metabolism to decrease ROS production, ultimately inhibiting OC differentiation. Treatment with Lipofermata, either in vivo or in vitro, effectively rescued the overactivation of OCs, indicating that FATP2 regulated OC differentiation by modulating fatty acid uptake and energy metabolism. These findings suggested that targeting FATP2 may represent a promising therapeutic approach for pathological osteoporosis.

The inhibition of osteoclastogenesis by Lipofermata, a FATP2 inhibitor, was achieved through the reprogramming of energy metabolism and regulation of ROS levels. In both pathological bone loss and HFD-induced osteoporosis models, the expression levels of FATP2 were significantly upregulated and Lipofermata demonstrated potential therapeutic effects in the pathological bone loss model.

Induction of cervical disc degeneration and discogenic pain by low concentration Propionibacterium acnes infection: an in vivo animal study.

BACKGROUND: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. METHODS: Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. RESULTS: IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. CONCLUSION: P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.

The role of prevertebral soft tissue swelling in dysphagia after anterior cervical corpectomy fusion: change trends and risk factors.

OBJECTIVES: This study aimed to analyze the change trends of prevertebral soft tissue swelling (PSTS) for anterior cervical corpectomy fusion(ACCF) and to evaluate the risk factors of PSTS for postoperative dysphagia. METHODS: There were 309 patients with degenerative cervical diseases who were treated with ACCF from November 2015 and September 2019 in our hospital. According to the symptom of swallowing function after ACCF, those were divided into the dysphagia group and the normal-swallowing function group. Cervical computed tomography(CT) was analyzed, and radiological evaluation of the prevertebral soft tissue was measured between the antero-inferior corner of each vertebral body and the air shadow of the airway through CT mid-sagittal slice images before operation and after operation(one week, one month, eight months and twelve months). RESULTS: The incidence of dysphagia after ACCF was 41.1%. 120 of 127(94.5%) patients had dysphagia disappeared at the 8 months after ACCF, and all disappeared at the 12 months. In both groups, PSTS would be biggest at 1 week postoperatively comparing to the preoperative, and then get smaller from 1 week to 12 months postoperatively (p < 0.05). After 12 months of operation, the PSTS of all cervical spinal levels would get equal to the preoperative size in the normal-swallowing function group, while the PSTS in dysphagia group would get equal only in C5-7 levels. The PSTS of preoperative C6 level and postoperative C2 level were more closely related to the present of postoperative dysphagia (OR: 9.403, 95%CI: 2.344-37.719, OR: 3.187, 95%CI: 1.78-5.705). It was more important to predict postoperative dysphagia using the value of PSTS at preoperative C6 level and postoperative C2 level, with the cutoff threshold for the PSTS of preoperative C6 level ≦1.51 cm and postoperative C2 level ≦1.3915 cm, which could get sensitivity & specificity 66.929% and 61.54%, 77.17% and 64.29%, respectively. CONCLUSION: Our study showed that the increasing of the PSTS after ACCF should be considered as a risk factor of dysphagia after surgery. With the recovery of PSTS over time, the incidence of postoperative dysphagia decreases. The PSTS of preoperative C6 level and and postoperative C2 level should play an important part in predicting the risk of postoperative dysphagia.

A Dual-Targeted Metal-Organic Framework Based Nanoplatform for the Treatment of Rheumatoid Arthritis by Restoring the Macrophage Niche.

Inflammatory infiltration and bone destruction are important pathological features of rheumatoid arthritis (RA), which originate from the disturbed niche of macrophages. Here, we identified a niche-disrupting process in RA: due to overactivation of complement, the barrier function of VSIg4+ lining macrophages is disrupted and mediates inflammatory infiltration within the joint, thereby activating excessive osteoclastogenesis and bone resorption. However, complement antagonists have poor biological applications due to superphysiologic dose requirements and inadequate effects on bone resorption. Therefore, we developed a dual-targeted therapeutic nanoplatform based on the MOF framework to achieve bone-targeted delivery of the complement inhibitor CRIg-CD59 and pH-responsive sustained release. The surface-mineralized zoledronic acid (ZA) of ZIF8@CRIg-CD59@HA@ZA targets the skeletal acidic microenvironment in RA, and the sustained release of CRIg-CD59 can recognize and prevent the complement membrane attack complex (MAC) from forming on the surface of healthy cells. Importantly, ZA can inhibit osteoclast-mediated bone resorption, and CRIg-CD59 can promote the repair of the VSIg4+ lining macrophage barrier to achieve sequential niche remodeling. This combination therapy is expected to treat RA by reversing the core pathological process, circumventing the pitfalls of traditional therapy.

Mechanism of antibiotic resistance development in an activated sludge system under tetracycline pressure.

The mechanism of antibiotic resistance (AR) development in an activated sludge system under tetracycline (TC) pressure was discussed and analyzed. According to the variation of macro-factors, including TC, COD, TN, TP, NH3-N, pH, heavy metals, and reactor settings, the tet genes respond accordingly. Consequently, the enrichment sites of tet genes form an invisible AR selection zone, where AR microorganisms thrive, gather, reproduce, and spread. The efflux pump genes tetA and tetB prefer anaerobic environment, while ribosome protective protein genes tetM, tetO, tetQ, tetT, and tetW were more concentrated in aerobic situations. As a corresponding micro-effect, different types of tet genes selected the corresponding dominant bacteria such as Thauera and Arthrobacter, suggesting the intrinsic relationship between tet genes and potential hosts. In summary, the macro-response and micro-effect of tet genes constitute an interactive mechanism with tet genes as the core, which is the crucial cause for the continuous development of AR. This study provides an executable strategy to control the development of AR in actual wastewater treatment plants from the perspective of macro-factors and micro-effects.

Disc degeneration is easily occurred at the same and adjacent cephalad level in cervical spine when Modic changes are present.

OBJECTIVE: This research aimed to evaluate the influence of Modic changes (MCs) on disc degeneration at the same and adjacent cephalad levels in the cervical spine. METHODS: This research retrospectively reviewed 1036 patients with neck pain, upper limb pain, or numbness who were treated at our out-patient clinic and underwent cervical MRI and cervical anteroposterior/lateral radiography from Jan, 2016 to Jan, 2021. MCs and disc degeneration parameters at same and nearby cephalad levels of MCs were evaluated. Discs were divided into the MCs, adjacent, and control groups, and the association between MCs and disc degeneration at the same and adjacent cephalad levels was investigated. RESULTS: Of the 1036 patients whose MRI scans were reviewed, 986 met the inclusion criteria (503 women and 483 men; average age, 62.8 years; scope of 35-79 years). The prevalence of MCs in the cervical spine was 13.0% (128/986). Type I, II, III changes were observed in 38 (29.69%), 82 (64.06%), and 8 (6.25%) patients, respectively. MCs were most frequently identified at the C5-6 (59/986; 5.98%) and C6-7 (38/986; 3.85%) levels. Disc with MCs showed worse outcomes with regard to disc degeneration grade, anterior osteophyte formation than the adjacent and control groups (p < 0.05), whereas they were more severe in the adjacent group compared to normal group. CONCLUSION: Our findings indicate that MCs increased disc degeneration at the same and nearby cephalad levels in cervical spine, and the severity of degeneration at the same segment was more serious than that at the cephalad level.

Alteration of the migration trajectory of antibiotic resistance genes by microplastics in a leachate activated sludge system.

The environmental behavior of emerging contaminants of microplastics (MPs), antibiotics and antibiotic resistance genes (ARGs) in the leachate activated sludge system has been monitored and analyzed comprehensively. The results suggested that MPs could effectively alter the migration trajectory of tetracycline resistance genes (tet genes) in the leachate activated sludge system under intermittent and continuous influent conditions. After adding MPs, the total average abundance of tet genes in leachate increased from 0.74 ± 0.07 to 0.78 ± 0.07 (log10tet genes/log10 16S rRNA) and that in sludge increased from 0.65 ± 0.08 to 0.70 ± 0.06 (log10tet genes/log10 16S rRNA). Except for tetA, the abundance of tetB, tetO, tetM and tetQ on MPs increased with increasing TC concentration under both aerobic and anaerobic conditions. MPs not only significantly affect the abundance level and migration trajectory of ARGs in the leachate activated sludge system, but also remarkably improve the level of heavy metals in the ambient environment, indirectly promoting the selective effect of antibiotic-resistant bacteria (ARB) and promoting the development of antibiotic resistance (AR). In addition, MPs changed their physicochemical properties and released hazardous substances with aging to force tet genes to migrate from the leachate activated sludge system to the MPs, making AR more difficult to eliminate and persisted in wastewater treatment plants. Meanwhile, microorganisms played a driving role, making MPs serve as a niche for ARGs and ARB colonization. The co-occurrence network analysis indicated the specific distribution pattern of tet genes and microorganisms in different media, and the potential host was speculated. This study improves the understanding of the environmental behavior of emerging contaminants in leachate activated sludge system and lays a theoretical for protecting the ecological environment.

Corrigendum: Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

[This corrects the article DOI: 10.3389/fsurg.2022.1063354.].

The role of esophageal area for dysphagia after anterior cervical corpectomy fusion: Change trends and risk factors.

The objective of this study is to assess the change trends of perioperative esophageal area for anterior cervical corpectomy fusion (ACCF) and to analyze the risk factors of the area for postoperative dysphagia. We retrospectively analyzed 309 patients who underwent ACCF due to degenerative cervical diseases between November 2015 and September 2019 at our hospital. Patients were divided into 2 groups named the dysphagia group and the normal swallowing function group, according to the swallowing function after ACCF. The esophageal area was measured at T1 level using computed tomography axial plane images before and after surgery (1 week, 1 month, 8 months, and 12 months), in order to assess the change trends of esophageal area perioperatively and analyze risk factors of the area for dysphagia after ACCF. The area was highest at 1 week after surgery and would be decreased over time in both groups, which was recovered to the preoperative levels in 12 months after surgery. The incidence of dysphagia after ACCF was 41.1%. In the dysphagia group, 127 patients (mean age 59.299 years) had dysphagia after ACCF. In the normal-swallowing function group, 182 patients (mean age 59.8352 years) had normal swallowing function after ACCF. The preoperative esophageal area was larger in the dysphagia group than in the normal-swallowing function group. Preoperative esophageal area was correlated with postoperative dysphagia (odds ratio: 1.3457, 95% confidence interval: 1.106-1.637). When the esophageal area at preoperation was above 3.388 cm2, the risk of postoperative dysphagia was higher. The esophageal area was the biggest at 1 week postoperatively, significantly decreased over time and would be recovered to the normal size at 12 months after surgery. Preoperative esophageal area should be considered when evaluating the risk factor for dysphagia after ACCF.

Driving forces of nitrogen use efficiency in Chinese croplands on county scale.

Nitrogen use efficiency (NUE, defined as the fraction of N input harvested as product) is an important indicator to understand nitrogen use and losses in croplands as an element of determining sustainable food production. China, as the country with the largest amount of nitrogen fertilizer use globally, research into NUE consistently finds it to be much lower than that in developed countries. Understanding the driving forces of the underlying causes of this low NUE is thus crucial to improve nitrogen use and reduce losses in China. Here we applied the CHANS model to estimate cropland NUE for over 2800 counties in China for the year 2017. Results showed that in most counties NUE ranged between 20% and 40%, while an NUE >50% was mainly found in Northeastern China, likely as a result of large-scale, modern agriculture operations. The source of N input and crop types significantly affected NUE in our assessment. Nitrogen deposition, straw recycling, and biological nitrogen fixation (BNF) could improve NUE, while chemical nitrogen fertilizer and manure inputs reduce NUE. Grain crops have a much higher NUE compared to vegetables, which are often over-fertilized. Moreover, NUE in Southern China is strongly influenced by natural factors such as temperature and precipitation. Specifically, NUE in the Yangtze River Delta (eastern coastal region of China) is associated with socio-economic factors including GDP and the degree of urbanization, while in North-central China, NUE is mainly determined by nitrogen input sources. These examples illustrate that approaches aiming at improving NUE need to be location-specific with consideration of multiple natural and socioeconomic factors.

Anterior cervical transpedicular screw fixation system in subaxial cervical spine: A finite element comparative study.

Multilevel cervical corpectomy has raised the concern among surgeons that reconstruction with the anterior cervical screw plate system (ACSPS) alone may fail eventually. As an alternative, the anterior cervical transpedicular screw (ACTPS) has been adopted in clinical practice. We used the finite element analysis to investigate whether ACTPS is a more reasonable choice, in comparison with ACSPS, after a 2-level corpectomy in the subaxial cervical spine. These 2 types of implantation models with the applied 75 N axial pressure and 1 N • m pure moment of the couple were evaluated. Compared with the intact model, the range of motion (ROM) at the operative segments (C4-C7) decreased by 97.5% in flexion-extension, 91.3% in axial rotation, and 99.3% in lateral bending in the ACTPS model, whereas it decreased by 95.1%, 73.4%, 96.9% in the ACSPS model respectively. The ROM at the adjacent segment (C3/4) in the ACTPS model decreased in all motions, while that of the ACSPS model increased in axial rotation and flexion-extension compared with the intact model. Compared to the ACSPS model, whose stress concentrated on the interface between the screws and the titanium plate, the stress of the ACTPS model was well-distributed. There was also a significant difference between the maximum stress value of the 2 models. ACTPS and ACSPS are biomechanically favorable. The stability in reducing ROM of ACTPS may be better and the risk of failure for internal fixator is relatively low compared with ACSPS fixation except for under lateral bending in reconstruction the stability of the subaxial cervical spine after 2-level corpectomy.

Vertical distribution of antibiotics and antibiotic resistance genes in a representative municipal solid waste landfill, China.

The vertical distribution of sulfonamides (SAs), tetracyclines (TCs), macrolides (MLs), and their related antibiotic resistance genes (ARGs) were comprehensively investigated and characterized in a representative municipal solid waste (MSW) landfill in China. The total concentrations of target antibiotics in the MSW landfill were SAs > TCs > MLs. The abundances of mexF (10.78 ± 0.65 log10copies/g) and sul genes (9.15 ± 0.54 log10copies/g) were relatively high, while the tet genes (7.19 ± 0.77 log10copies/g) were the lowest. Both the abundance of antibiotics and genes fluctuated with landfill depth, and the ARGs of the same antibiotics were consistent with depth change. Intl1 and sul genes (sul1, sul2) were tightly connected, and a close relationship also existed between tet genes (tetM, tetQ) and MLs resistance genes (ermB, mefA). High-throughput sequencing showed the dominant genera were Sporosarcina (38%) and Thiobacillus (17%) at sampling points A and C, while the microbial community varied with depth increase at point B were Brevundimonas (20%), Sporosarcina (20%), Pseudomonas (24%), Lysobacter (28%), and Thioalkalimicrobium (14%), respectively. Network analysis further visualized the relationship among antibiotics, genes, and microbial communities and the results indicated the non-random connection among them and the possible host of the target gene. Even at 12.0 m below the landfill surface, the pollution of antibiotics resistance was still serious, which posed difficulties for subsequent landfill remediation and pollution control.

DNMT3a promotes osteoblast differentiation and alleviates osteoporosis via the PPARγ/SCD1/GLUT1 axis.

Background: This study was designed to elucidate the role of DNMT3a and PPARγ functions in postmenopausal osteoporosis. Materials & methods: Mice were ovariectomized to establish an in vivo osteoporosis model and MC3T3-E1-14 osteoblasts were induced to differentiate. Gain- or loss-of-function approaches were used to manipulate the expression of PPARγ, DNMT3a and SCD1, followed by an evaluation of their role in postmenopausal osteoporosis both in vivo and in vitro. Results: DNMT3a induced methylation of the PPARγ promoter region, consequently stimulating osteoblast differentiation. PPARγ elevated SCD1, which decreased GLUT1 and inhibited osteoblast differentiation. Inhibition of PPARγ reduced SCD1 while increasing GLUT1 expression, thus alleviating postmenopausal osteoporosis in mice. Conclusion: DNMT3a promotes osteoblast differentiation and prevents postmenopausal osteoporosis by regulating the PPARγ/SCD1/GLUT1 axis.

Different responses of cervical intervertebral disc caused by low and high virulence bacterial infection: a comparative study in rats.

The aims of this study were to investigate the outcomes of low- and high-virulence bacterial cervical intervertebral discs (IVDs) infection and its association with cervical IVDs degeneration in rats. A total of 75 clean grade male rats were used to establish the corresponding animal models of low and high virulent bacterial cervical disc infection via an anterior cervical approach, with injection of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) with a 29 G needle to cervical IVDs. Specimens were collected for evaluation of Blood routine (Blood-RT), histological staining, and gene expression assays after a magnetic resonance imaging (MRI) scan. There were no statistical differences in all groups in white blood cells (WBC) at 2 and 6 weeks postoperatively (P = 0.136). The highest percentage of neutrophils was found in the S. epidermidis group at 2 weeks postoperatively (P = 0.043). MRI and histology showed that at 6 weeks postoperatively, the puncture group and P. acnes group had similar disc degeneration. In the S. epidermidis group, the disc and subchondral bone structure had been destroyed and bony fusion had occurred after the discitis. The upregulation of pro-inflammatory factor expression had the strongest effect of S. epidermidis on the early stage, while the upregulation in the puncture and P. acnes groups was more persistent. P. acnes infection of the cervical IVDs can lead to degenerative changes, whereas S. epidermidis infection leads to the manifestation of septic discitis. The correlation between P. acnes infection and cervical IVDs degeneration found in clinical studies was confirmed.

The panorama of antibiotics and the related antibiotic resistance genes (ARGs) in landfill leachate.

Landfill leachate is an important source and sink of antibiotics and antibiotic resistance genes (ARGs), which poses a potential threat to human health and ecological environment. Ten antibiotics and 8 ARGs in leachates collected from Zhejiang Province, China, were systematically investigated. The effects of multiple factors were considered: leachate age, season when the leachate was sampled (dry or rainy), heavy metal concentrations, and leachate quality parameters. Leachate age was crucial to the profile of the detectable antibiotics and ARGs. The total concentration of antibiotics were in the order of macrolides > sulfonamides > tetracyclines and they decreased significantly with leachate age. Similarly, fewer ARGs were harbored in aged leachate; the order of abundance of the ARGs was mexF (11.92 ± 0.22 log10 gene copies/L) > sul2 > Intl1 > sul1 > ermB > mefA > tetM > tetQ (9.57 ± 1.32 log10 gene copies/L). The extreme abundances (i.e., the maxima and minima) of ARGs relating to the same class of antibiotic were always surprisingly similar and appeared in leachate of the same age. Seasonal variation greatly affected the concentrations of antibiotics in the leachate-the concentration difference between the dry and rainy seasons could reach two orders of magnitude. Heavy metal concentrations and leachate quality parameters also had important effects on the distribution of antibiotics and ARGs. Overall, the profile of antibiotics and ARGs in leachates was influenced by numerous factors, and the pollution of antibiotics and ARGs may be reduced and controlled by adjusting the environmental factors.

[Establishment of finite element model of anterior cervical transpedicular system for reconstruction of cervical stability after subtotal resection of two segments of lower cervical spine].

OBJECTIVE: To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C3-C7) in order to provide a finite element modeling method for anterior cervical reconstruction. METHODS: The CT data of the cervical segment (C1-T1) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C3-C7) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C5 and C6 vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3 in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups. RESULTS: There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C3-C7) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C3,4 segment was increased slightly. CONCLUSION: The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.

Discovery of seneciobipyrrolidine derivatives for the amelioration of glucose homeostasis disorders through 4E-BP1/Akt/AMPK signaling activation.

Modulating the glucose transport in skeletal muscle is a promising strategy for ameliorating glucose homeostasis disorders. However, the complicated mechanisms of glucose transport make it difficult to find compounds therapeutically relevant molecular mechanisms of action, while phenotypic screening is thought to be an alternative approach to mimic the cell state of interest. Here, we report (±)-seneciobipyrrolidine (1a) is first found to enhance glucose uptake in L6 myotubes through phenotype-based screening. Further SAR investigation led to the identfication of compound A27 (EC50 = 2.7 µM). Proteomiic analysis discloses the unique function mechanism of A27 through upregulating the level of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), subsequently enhancing the Akt and AMPK phosphorylation, thereby promoting the glucose uptake. Chronic oral administration of A27 significantly lowers blood glucose and improves glucose tolerance in db/db mice. This work is new research on seneciobipyrrolidine derivatives, providing a promising avenue for ameliorating glucose homeostasis.

Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

Objective: To compare the differences in the correction effect for lumbosacral lordosis and clinical outcomes between OLIF with/without posterior pedicle screw fixation (PSF) and MIS-TLIF through a retrospective cohort study. Method: There were 98 consecutive patients originally enrolled for the study, but 15 patients were excluded due to intraoperative endplate injury or osteotomy performed for severe spinal deformity. Thus, 83 patients included in this study (36 males and 47 females, mean age 65.8 years) underwent single to three-segment OLIF (including OLIF + PSF and OLIF Standalone) or MIS-TLIF surgery from 2016 to 2018. The operation time, bleeding and blood transfusion, fusion rate, complication, pre-and postoperative visual analogue scale (VAS), Oswestry Disability Index (ODI) were evaluated. In addition, radiological parameters including lumbosacral lordosis (LL), fused segment lordosis (FSL), anterior disc height (ADH) and posterior disc height (PDH) were measured. The clinical outcomes, LL, FSL, ADH and PDH restored and were compared between the OLIF group, OLIF subgroups and MIS-TLIF group. Results: The average operation time and intraoperative bleeding were significantly less in the OLIF group than in the MIS-TLIF group (163 ± 68 vs. 233 ± 79 min, 116 ± 148 vs. 434 ± 201 ml, P < 0.001). There was no statistically significant difference between the OLIF group and the MIS-TLIF group in VAS and ODI improvements, fusion rate, complication, LL and FSL correction (P > 0.05). The ADH and PDH increases in the OLIF group were more than that in MIS-TLIF group (P < 0.001). The correction of LL was significantly more in the OLIF + PSF group than in the MIS-TLIF group (9.9 ± 11.1 vs. 4.2 ± 6.1deg, P = 0.034). Conclusion: OLIF and MIS-TLIF are both safe and effective procedures, capable of restoring lumbosacral lordosis and disc height partly. Combined with PSF, OLIF can achieve a better correction effect of lumbosacral lordosis than MIS-TLIF.