Sorting Nexin1 negatively modulates phosphate uptake by facilitating Phosphate Transporter1;1 degradation in Arabidopsis.

High-affinity phosphate (Pi) transporters (PHTs) PHT1;1 and PHT1;4 are necessary for plant root Pi uptake especially under Pi-deficient conditions, but how their protein stability is modulated remains elusive. Here, we identified a Ttransfer DNA insertion mutant of Sorting Nexin1 (SNX1), which had more Pi content and less anthocyanin accumulation than the wild type under deficient Pi. By contrast, the snx1-2 mutant displayed higher sensitivity to exogenous arsenate in terms of seed germination and root elongation, revealing higher Pi uptake rates. Further study showed that SNX1 could co-localize and interact with PHT1;1 and PHT1;4 in vesicles and at the plasma membrane. Genetic analysis showed that increased Pi content in the snx1-2 mutant under low Pi conditions could be extensively compromised by mutating PHT1;1 in the double mutant snx1-2 pht1;1, revealing that SNX1 is epistatic to PHT1;1. In addition, SNX1 negatively controls PHT1;1 protein stability; therefore, PHT1;1 protein abundance in the plasma membrane was increased in the snx1-2 mutant compared with the wild type under either sufficient or deficient Pi. Together, our study (i) identifies SNX1 as a key modulator of the plant response to low Pi and (ii) unravels its role in the modulation of PHT1;1 protein stability, PHT1;1 accumulation at the plasma membrane, and root Pi uptake.

Abscisic acid facilitates phosphate acquisition through the transcription factor ABA INSENSITIVE5 in Arabidopsis.

Low phosphate (LP) in soil is a common nutrient stress that severely restricts agricultural production, but the role, if any, of the major stress phytohormone abscisic acid (ABA) in plant phosphate (Pi) starvation responses remains elusive. Here, we report that LP-induced ABA accumulation promotes Pi uptake in an ABA INSENSITIVE5 (ABI5)-dependent manner in Arabidopsis thaliana. LP significantly activated plant ABA biosynthesis, metabolism, and stress responses, suggesting a role of ABA in the plant response to Pi availability. LP-induced ABA accumulation and expression of two major high-affinity phosphate transporter genes PHOSPHATE TRANSPORTER1;1/1;4 (PHT1;1/1;4) were severely impaired in a mutant lacking BETA-GLUCOSIDASE1 (BG1), which converts conjugated ABA to active ABA, and the mutant had shorter roots and less Pi content than wild-type plants under LP conditions. Moreover, a mutant of ABI5, which encodes a central transcription factor in ABA signaling, also exhibited suppressed root elongation and had reduced Pi content under LP conditions. ABI5 facilitated Pi acquisition by activating the expression of PHT1;1 by directly binding to its promoter, while overexpression of PHT1;1 completely rescued its Pi content under LP conditions. Together, our findings illustrate a molecular mechanism by which ABA positively modulates phosphate acquisition through ABI5 in the Arabidopsis response to phosphate deficiency.

Maize PHYTOMELATONIN RECEPTOR1 functions in plant tolerance to osmotic and drought stress.

Phytomelatonin is a universal signal molecule that regulates plant growth and stress responses; however, only one receptor that can directly bind with and perceive melatonin signaling has been identified so far, namely AtPMTR1/CAND2 in Arabidopsis. Whether other plants contain a similar receptor and, if so, how it functions is still unknown. In this study, we identified a new phytomelatonin receptor in the monocot maize (Zea mays), and investigated its role in plant responses to osmotic and drought stress. Using homology searching, we identified a plasma membrane-localized protein, Zm00001eb214610/ZmPMTR1, with strong binding activity to melatonin as a potential phytomelatonin receptor in maize. Overexpressing ZmPMTR1 in Arabidopsis Col-0 promoted osmotic stress tolerance, and rescued osmotic stress sensitivity of the Arabidopsis cand2-1 mutant. Furthermore, ZmPMTR1 also largely rescued defects in melatonin-induced stomatal closure in the cand2-1 mutant, thereby reducing water loss rate and increasing tolerance to drought stress. In addition, we identified a maize mutant of ZmPMTR1, EMS4-06e2fl, with a point-mutation causing premature termination of protein translation, and found that this mutant had lower leaf temperatures, increased rate of water loss, and enhanced drought stress sensitivity. Thus, we present ZmPMTR1 as the first phytomelatonin receptor to be identified and examined in a monocot plant, and our results indicate that it plays an important function in the response of maize to drought stress.

Clinical correlation between osteoporotic thoracolumbar vertebral compression fractures and lumbar spondylolisthesis.

PURPOSE: This study was to explore the clinical correlation between osteoporosis thoracolumbar vertebral compression fracture (thoracolumbar OVCF) and lumbar spondylolisthesis (LS). METHODS: In total, 208 patients with thoracolumbar OVCF (fracture group) and 250 elderly patients with osteoporosis (non-fracture group) were retrospectively analyzed. The incidence of LS was compared between the two groups. At the same time, 75 cases of elderly patients with osteoporosis were selected, including 25 patients with isthmic spondylolisthesis (IS group), 25 patients with degenerative spondylolisthesis (DS group), and 25 patients without LS (non-LS group). All patients underwent full-length spine anteroposterior and lateral X-ray, and the spinal pelvic imaging parameters were collected for comparison. RESULTS: The incidence of LS in the fracture group (10.1%, 21/208) was significantly higher than that in the non-fracture group (4.8%, 12/250); the difference was statistically significant (χ2 = 4.763, P = 0.029). The incidence of trauma in the fracture group (51.0%, 106/208) was significantly higher than that in the non-fracture group (13.6%, 34/250); the difference was statistically significant (χ2 = 74.673, P = 0.000). The LS (OR = 2.273, 95% CI = 1.030-5.017, P = 0.042) and trauma (OR = 6.622, 95% CI = 4.203-10.432, P = 0.000) were independently associated with thoracolumbar OVCF. There were significant differences in pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), thoracolumbar kyphosis (TLK), and thoracic kyphosis (TK) among the IS, DS, and non-LS groups (P < 0.05). Among them, PI, SS, LL, TLK, and TK of the IS group and the DS group were significantly higher than those of the non-LS group (P < 0.05). CONCLUSIONS: Patients with LS are more likely to suffer from OVCF in the future, and LS is one of the important risk factors for secondary OVCF.

CAND2/PMTR1 Is Required for Melatonin-Conferred Osmotic Stress Tolerance in Arabidopsis.

Osmotic stress severely inhibits plant growth and development, causing huge loss of crop quality and quantity worldwide. Melatonin is an important signaling molecule that generally confers plant increased tolerance to various environmental stresses, however, whether and how melatonin participates in plant osmotic stress response remain elusive. Here, we report that melatonin enhances plant osmotic stress tolerance through increasing ROS-scavenging ability, and melatonin receptor CAND2 plays a key role in melatonin-mediated plant response to osmotic stress. Upon osmotic stress treatment, the expression of melatonin biosynthetic genes including SNAT1, COMT1, and ASMT1 and the accumulation of melatonin are increased in the wild-type plants. The snat1 mutant is defective in osmotic stress-induced melatonin accumulation and thus sensitive to osmotic stress, while exogenous melatonin enhances the tolerance of the wild-type plant and rescues the sensitivity of the snat1 mutant to osmotic stress by upregulating the expression and activity of catalase and superoxide dismutase to repress H2O2 accumulation. Further study showed that the melatonin receptor mutant cand2 exhibits reduced osmotic stress tolerance with increased ROS accumulation, but exogenous melatonin cannot revert its osmotic stress phenotype. Together, our study reveals that CADN2 functions necessarily in melatonin-conferred osmotic stress tolerance by activating ROS-scavenging ability in Arabidopsis.

WDR5a functions in cadmium-inhibited root meristem growth by regulating nitric oxide accumulation in Arabidopsis.

MAIN CONCLUSION: Cadmium stress induces WDR5a expression to promote NO accumulation to repress root meristem growth via suppressing auxin transport and synthesis in Arabidopsis. Nitric oxide (NO) synthase (NOS)-like activity plays a vital role in toxic cadmium (Cd)-induced NO production and inhibition of root meristem growth, while factor(s) regulating NOS-like activity and root meristem growth in plant response to Cd has not been identified yet. Here, we report that WD40 repeat 5a (WDR5a) functions in Cd-induced NOS-like activity, NO accumulation and root meristem growth suppression. We found that wdr5a-1 mutant root has increased root meristem growth with lower NOS-like activity and NO accumulation than wild type upon Cd exposure, and exogenous NO donors sodium nitroprusside or nitrosoglutathione can restore its reduced Cd sensitivity. In addition, Cd activates WDR5a expression in roots, and overexpressing WDR5a results in increased NO accumulation and suppressed root meristem growth similar to Cd-stressed wild-type roots, while scavenging NO or inhibiting NOS-like activity significantly reverts these effects of Cd. Furthermore, WDR5a acts in Cd-repressed auxin accumulation through reducing the levels of auxin efflux carriers PIN1/3/7 and biosynthetic enzyme TAA1, and reduced sensitivity of wdr5a-1 root meristem to Cd can be partially reverted by inhibiting TAA1 activity pharmaceutically or mutating TAA1 genetically. This study identified WDR5a as a key factor modulating NO accumulation and root meristem growth in plant response to Cd.

Dyadobacter flavalbus sp. nov., isolated from lake sediment.

A novel bacterial strain, designated NS28T, was isolated from interfacial sediment sampled at Taihu Lake, PR China. Cells were rod-shaped, Gram-negative, aerobic and non-motile on Reasoner's 2A medium. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NS28T was most closely related to species from the genus Dyadobacter, with 98.4 and 96.0 % 16S rRNA gene sequence similarity to its closest phylogenetic neighbours Dyadobacter sediminis CGMCC 1.12895T and Dyadobacter luticola CCTCC AB 2017091T, respectively. MK-7 was the only cellular menaquinone. The major fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 and C16 : 1ω5c. The major polar lipids were phosphatidylethanolamine, one phospholipid, one aminolipid, one lipid and two unidentified lipids. Genomic analysis of strain NS28T indicated that the total genome size was 6 477 094 bp with a G+C content of 44.8 mol%, 5380 protein-coding genes, 79 contigs and an N50 length of 299584 bp. On the basis of the genomic DNA sequence, the average nucleotide identity values were 90.5 and 74.1 % with D. sediminis CGMCC 1.12895T and D. luticola CCTCC AB 2017091T, respectively. Digital DNA-DNA hybridization results of strain NS28T with D. sediminis CGMCC 1.12895T and D. luticola CCTCC AB 2017091T were 40.9 and 18.6 %, respectively. Based on the phenotypic, chemotaxonomic, phylogenetic and genome sequence data presented here, it is proposed that strain NS28T represents a novel species of the genus Dyadobacter for which the name Dyadobacter flavalbus is proposed . The type strain is NS28T (=NBRC 113854T=MCCC 1K03764T).

Agrococcus sediminis sp. nov., an actinobacterium isolated from lake sediment.

A novel strain, designated NS18T, was isolated from sediment sampled at Taihu Lake, PR China. Cells of the isolate were spherical, aerobic, non-motile, Gram-stain-positive and non-endospore-forming. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain NS18T clustered in a clade of the genus Agrococcus. Its closest phylogenetic neighbour was Agrococcus lahaulensis DSM 17612T with 98.2 % 16S rRNA gene sequence similarity. The complete genome of NS18T was 2 736 037 bp and its genomic DNA G+C content was 72.8 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain NS18T and A. lahaulensis DSM 17612T based on their whole genomes were 85.1 and 28.7 %, respectively. The major fatty acids were anteiso-C17 : 0 and anteiso-C15 : 0. The predominant menaquinones were MK11 and MK12. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol and two unidentified lipids. The components of the peptidoglycan were Ala, Gly, Asp, Thr and DAB. The whole-cell sugars contained rhamnose, ribose, xylose and glucose. According to the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain NS18T (=NBRC 113859T=MCCC 1K03759T) represents a novel species, for which the name Agrococcus sediminis sp. nov is proposed.

Rufibacter hautae sp. nov., a red-pigmented bacterium from freshwater lake sediment, and proposal of Rufibacter quisquiliarum as a latter heterotypic synonym of Rufibacter ruber.

A taxonomic identification using a polyphasic approach was performed on strain NBS58-1T, which was isolated from the interfacial sediment of Taihu Lake in China. Strain NBS58-1T was Gram-stain-negative, aerobic, non-spore-forming and catalase-positive. Phylogenetic analyses based on 16S rRNA gene and three housekeeping genes (rpoB, gyrB and dnaK) sequences supported the position that strain NBS58-1T should be classified within the genus Rufibacter. The 16S rRNA gene sequence of strain NBS58-1T possessed the highest similarity to Rufibacter sediminis H-1T (96.60 %), followed by Rufibacter glacialis MDT1-10-3T (96.17 %). And the ANI value between strain NBS58-1T and R. glacialis MDT1-10-3T was 79.3 %. The respiratory quinone was menaquinone 7 (MK-7). The major cellular fatty acids comprised iso-C15 : 0 and summed feature 3. Phosphatidylethanolamine, two unidentified phospholipids and four unidentified lipids were the main polar lipids. The genomic DNA G+C content was 51.3 mol%. Based on phenotypic features and phylogenetic position, a novel species with the name Rufibacter hautae sp. nov. is proposed. The type strain is NBS58-1T=(KACC 21309T=MCCC 1K04037T). We also proposed Rufibacter quisquiliarum as a latter heterotypic synonym of Rufibacter ruber.

Gemmobacter caeruleus sp. nov., a novel species originating from lake sediment.

An aerobic, Gram-stain-negative, non-spore-forming and rod-shaped bacterial strain, designated N8T, was isolated from the interfacial sediment of Taihu Lake in PR China. The strain formed white to blue colonies on R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain N8T represented a member of the genus Gemmobacter and was most closely related to Gemmobacter aquaticus A1-9T (97.97 %). The average nucleotide identity and digital DNA-DNAhybridization values between strain N8T and G. aquaticus A1-9T based on their whole genomes were 78.8 and 21.7 %, respectively. Q-10 was the main predominant ubiquinone. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 0 and C16 : 0. The G+C content of the genomic DNA was 66.1 mol%. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, two unidentified glycolipids and two unidentified lipids. Based on its physiological, biochemical and chemotaxonomic characteristics, strain N8T represents a novel species of the genus Gemmobacter, for which the name Gemmobacter caeruleus sp. nov. is proposed. The type strain is N8T=(KACC 21307T=MCCC 1K04036T).

Predictors of surgical outcome in cervical spondylotic myelopathy: focusing on the quantitative signal intensity.

PURPOSE: The association between intramedullary increased signal intensity (ISI) on T2-weighted magnetic resonance imaging and surgical outcome in cervical spondylotic myelopathy (CSM) remains controversial. The purpose of this study is to assess the impact of quantitative signal change ratio (SCR) on the surgical outcome for CSM. METHODS: The prospective study included 108 consecutive patients who underwent surgical treatment for CSM. The Japanese Orthopaedic Association (JOA) score and recovery rate were used to evaluate clinical outcomes. JOA recovery rate less than 50% was defined as a poor clinical result. The SCR was defined as the signal intensity at the level of ISI or severely compressed cord (in cases with no ISI) divided by the signal intensity at the C7-T1 disc level. Age, sex, body mass index, duration of symptoms, surgical technique, preoperative JOA score, levels of compression, preoperative SCR, preoperative C2-7 angle, preoperative C2-7 range of motion were assessed. RESULTS: Forty patients (37.0%) had a recovery rate of less than 50%. Multivariate logistic regression analysis revealed that a higher preoperative SCR and a longer duration of symptoms were significant risk factors for a poor clinical outcome. Receiver operating characteristic (ROC) curve analysis showed that the optimal preoperative SCR cutoff value as a predictor of poor clinical result was 1.46. The area under the ROC curve of preoperative SCR for predicting a poor surgical outcome was 0.844. CONCLUSIONS: Preoperative SCR significantly reflected the surgical outcome in patients with CSM. Patients with SCR greater than or equal to 1.46 can experience poor recovery after surgery.

Relationship between developmental canal stenosis and surgical results of anterior decompression and fusion in patients with cervical spondylotic myelopathy.

BACKGROUND: Anterior cervical decompression and fusion (ACDF) has long been the preferred treatment for cervical spondylotic myelopathy (CSM). However, few studies have focused on surgical results of CSM in patients with developmental canal stenosis (DCS). The purpose of this study was to investigate DCS as a comorbidity in patients with CSM and the correlation between surgical results and DCS. METHODS: From January 1995 to December 2005, 122 patients treated with ACDF for CSM were enrolled in this retrospective study. Pavlov's ratio was used to evaluate cervical spinal canal size, with a value of < 0.82 at least one level indicating DCS. Patients were divided into two groups: those with DCS preoperatively (DCS group, n = 50 [41.0 %]) and those without DCS (non-DCS group, n = 72). Clinical data and radiological parameters were compared between groups. RESULTS: There were no significant differences in preoperative and 2-year follow-up Japanese Orthopedic Association scores between groups. Both groups achieved satisfactory fusion rates (DCS, 92.0 %; non-DCS, 93.0 %). Adjacent-segment degeneration (ASD) was detected in 66.0 % of patients in the DCS group and in 43.0 % of patients in the non-DCS group (p = 0.01). However, there was no significant difference in the incidence of ASD requiring surgery between groups (p = 0.20). DISCUSSION: DCS is a common comorbidity in patients with CSM. The findings of this study have added knowledge on the correlation between DCS and ASD after anterior fusion surgery. CONCLUSIONS: DCS did not affect neurologic improvement postoperatively at short-term follow-up. Although DCS increased the incidence of ASD after anterior fusion, it did not predict ASD requiring surgery. Therefore, patients with DCS must receive close follow-up.

Superlubricity of two-dimensional fluorographene/MoS2 heterostructure: a first-principles study.

The atomic-scale friction of the fluorographene (FG)/MoS2 heterostructure is investigated using first-principles calculations. Due to the intrinsic lattice mismatch and formation of periodic Moiré patterns, the potential energy surface of the FG/MoS2 heterostructure is ultrasmooth and the interlayer shear strength is reduced by nearly two orders of magnitude, compared with both FG/FG and MoS2/MoS2 bilayers, entering the superlubricity regime. The size dependency of superlubricity is revealed as being based on the relationship between the emergence of Moiré patterns and the lattice mismatch ratio for heterostructures.

Comparison of vertebroplasty and kyphoplasty in the treatment of osteoporotic vertebral compression fractures with intravertebral clefts.

BACKGROUND: Few studies have compared the surgical outcomes of vertebroplasty (VP) and kyphoplasty (KP) in the treatment of osteoporotic vertebral compression fractures (VCFs) with intravertebral clefts. METHODS: A retrospective study was conducted to review patients with a single-level osteoporotic VCF treated by VP or KP. Intravertebral clefts were assessed by preoperative computed tomography (CT) and magnetic resonance scans. All enrolled patients were followed up for 12 months. Clinical outcomes, radiological findings and complications were evaluated. RESULTS: A total of 53 patients were available for data analysis. Most of the fractures (75.5 %) occurred in the region of the thoracolumbar junction (T10-L2). Twenty-four patients received VP and 29 patients received KP. Patients in both group had significant pain relief after surgery (P < 0.01). Compared with VP group, there was a significant lower visual analogue scale (VAS) score in KP group at the 6- (P = 0.04) and 12-month follow-up (P = 0.02), but the decreased values of VAS score had no significant correlation with the magnitude of deformity correction. Restoration of vertebral body height and reduction in kyphotic angle were achieved in both groups, and the magnitude of correction was more significant in KP group (P < 0.01). Cement leakage rate in VP group (66.7 %) was higher than that in KP group (20.7 %), and there was a significant difference (P < 0.01). CONCLUSIONS: Intravertebral clefts occur primarily at the thoracolumbar junction and can be detected easily by CT and magnetic resonance imaging scans. Both VP and KP are effective in the treatment of clefts, but patients in KP group tend to have a better pain relief at the medium and long-term follow-up. However, the better pain relief effect of KP cannot be attributed to the higher magnitude of deformity correction.

The Relationship Between Endplate Defect Scores and Lumbar Sagittal Translation Stability in Lumbar Spondylolisthesis Patients.

BACKGROUND: Lumbar instability and endplate defects are commonly seen in patients with spondylolisthesis. However, little is known about associations between segmental stability and endplate defects. The present study explored associations between stability-related radiographic parameters and endplate defect scores and assessed whether endplate defect scores can predict lumbar stability in lumbar spondylolisthesis. METHODS: Neutral, flexion, and extension radiographs of 159 patients with monosegmental lumbar spondylolisthesis were analyzed. Radiographic parameters included average intervertebral disc height (IDH), slip distance, sagittal translation (ST) and sagittal angulation (SA). Correlation analysis and linear regression analysis were used to explore associations between endplate defect scores and radiographic parameters. Logistic regression analysis was used to assess associations between endplate defect scores and ST stability. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the value of the endplate defect score in predicting ST stability. RESULTS: A total of 11.9% of patients had ST ≥ 4 mm, and 30% of patients had SA ≥ 10°. Endplate defect scores were negatively correlated with ST and IDH and positively correlated with slip distance in isthmic spondylolisthesis but not in degenerative spondylolisthesis. In multiple regression analysis, endplate defect scores were significantly associated with ST, slip distance, IDH, and disc degeneration. ST instability was associated with endplate defect scores in isthmic spondylolisthesis (OR=0.460, P = 0.010). The AUCs for using the endplate defect score to evaluate ST stability in overall patients and isthmic spondylolisthesis patients were 0.672 and 0.774, respectively. The optimal threshold of the endplate defect score constructed by the Youden index was 7.5 for predicting ST stability. CONCLUSIONS: Endplate defect scores increase with a reduction in IDH, progression of slippage and a decrease in ST in isthmic spondylolisthesis but not in degenerative spondylolisthesis. ST instability was associated with endplate defect scores in isthmic spondylolisthesis, and endplate defect scores could be used to reflect lumbar stability at the slippage segment.

Causal associations between modifiable risk factors and intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common degenerative condition, which is thought to be a major cause of lower back pain (LBP). However, the etiology and pathophysiology of IVDD are not yet completely clear. PURPOSE: To examine potential causal effects of modifiable risk factors on IVDD. STUDY DESIGN: Bidirectional Mendelian randomization (MR) study. PATIENT SAMPLE: Genome-wide association studies (GWAS) with sample sizes between 54,358 and 766,345 participants. OUTCOME MEASURES: Outcomes included (1) modifiable risk factors associated with IVDD use in the forward MR; and (2) modifiable risk factors that were determined to have a causal association with IVDD in the reverse MR, including smoking, alcohol intake, standing height, education level, household income, sleeplessness, hypertension, hip osteoarthritis, HDL, triglycerides, apolipoprotein A-I, type 2 diabetes, fasting glucose, HbA1c, BMI and obesity trait. METHODS: We obtained genetic variants associated with 33 exposure factors from genome-wide association studies. Summary statistics for IVDD were obtained from the FinnGen consortium. The risk factors of IVDD were analyzed by inverse variance weighting method, MR-Egger method, weighted median method, MR-PRESSO method and multivariate MR Method. Reverse Mendelian randomization analysis was performed on risk factors found to be caustically associated with IVDD in the forward Mendelian randomization analysis. The heterogeneity of instrumental variables was quantified using Cochran's Q statistic. RESULTS: Genetic predisposition to smoking (OR=1.221, 95% CI: 1.068-1.396), alcohol intake (OR=1.208, 95% CI: 1.056-1.328) and standing height (OR=1.149, 95% CI: 1.072-1.231) were associated with increased risk of IVDD. In addition, education level (OR=0.573, 95%CI: 0.502-0.654)and household income (OR=0.614, 95%CI: 0.445-0.847) had a protective effect on IVDD. Sleeplessness (OR=1.799, 95%CI: 1.162-2.783), hypertension (OR=2.113, 95%CI: 1.132-3.944) and type 2 diabetes (OR=1.069, 95%CI: 1.024-1.115) are three important risk factors causally associated with the IVDD. In addition, we demonstrated that increased levels of triglycerides (OR=1.080, 95%CI:1.013-1.151), fasting glucose (OR=1.189, 95%CI:1.007-1.405), and HbA1c (OR=1.308, 95%CI:1.017-1.683) could significantly increase the odds of IVDD. Hip osteoarthritis, HDL, apolipoprotein A-I, BMI and obesity trait factors showed bidirectional causal associations with IVDD, therefore we considered the causal associations between these risk factors and IVDD to be uncertain. CONCLUSIONS: This MR study provides evidence of complex causal associations between modifiable risk factors and IVDD. It is noteworthy that metabolic disturbances appear to have a more significant effect on IVDD than biomechanical alterations, as individuals with type 2 diabetes, elevated triglycerides, fasting glucose, and elevated HbA1c are at higher risk for IVDD, and the causal association of obesity-related characteristics with IVDD incidence is unclear. These findings provide new insights into potential therapeutic and prevention strategies. Further research is needed to clarify the mechanisms of these risk factors on IVDD.

Efficacy and Safety of High-Viscosity Bone Cement in Percutaneous Vertebroplasty for Kummell's Disease.

Background: To analyze and evaluate the clinical outcomes of using high-viscosity bone cement compared to low-viscosity bone cement in percutaneous vertebroplasty (PVP) for treatment of Kummell's disease. Methods: From July 2017 to July 2019, 68 Kummell's disease patients who underwent PVP were chosen and separated into 2 groups: H group (n = 34), were treated with high-viscosity bone cement and L group (n = 34), treated with low-viscosity bone cement during treatment. The operation time, number of fluoroscopy tests done, and amount of bone cement perfusion were recorded for both groups. Clinical outcomes were compared, by measuring their Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Kyphosis Cobb's angle, vertebral height compression rate, and other complications. Results: High-viscosity group showed less operation time and reduced number of fluoroscopy tests than the low-viscosity group (P < 0.05). When compared to preoperative period, both groups' VAS and ODI scores were significantly reduced at 1 day and 1 year postoperatively (P < 0.05). The vertebral height compression rate and Cobb's angle were significantly lower (P < 0.05) in both groups after surgery compared with those before surgery (P < 0.05). The cement leakage rate in group H was 26.5%, which was significantly lower than that in group L, which was 61.8% (P < 0.05). Conclusions: High-viscosity and low-viscosity bone cement in PVP have similar clinical efficacy in reducing pain in patients during the treatment, but in contrast, high-viscosity bone cement shortens the operative time, reduces number of fluoroscopy views and vertebral cement leakage and improves surgical safety.

Effect of shape and severity of vertebral fractures on the outcomes of kyphoplasty.

UNLABELLED: The aim of this retrospective study was to evaluate the effect of shape and severity of osteoporotic vertebral fractures on the clinical and surgical outcomes of kyphoplasty. Ninety-four patients with single level vertebral fractures were enrolled. Fractures were divided into two types according to the shape of the fractured vertebrae: wedge type (n = 54) or biconcave type (n = 40). All fractures were further classified into 3 grades (grade 1-3) according to their severity. The Visual Analog Score for back pain improved significantly in the "wedge" and in the "biconcave" group: there was no significant difference between groups. Wedge type fractures had a significantly greater correction of anterior vertebral height and kyphotic angle than biconcave type fractures (p < 0.01). Biconcave type fractures had a significantly greater correction of the middle vertebral height (p < 0.01), but had a higher risk of intradiscal cement leakage (p = 0.03). Rates of cement leakage in grade 1, grade 2, and grade 3 fractures were 12.8%, 25.8%, and 50.0%, respectively : there was a gradually higher risk of cement leakage as the severity of compression increased (p < 0.01). CONCLUSION: assessing the shape and severity of fractured osteoporotic vertebrae gives an idea of the potential correction of body height and kyphosis, and of the risk of cement leakage.

Identification of mitochondria-related key gene and association with immune cells infiltration in intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration and its inflammatory microenvironment can result in discogenic pain, which has been shown to stem from the nucleus pulposus (NP). Increasing evidence suggests that mitochondrial related genes are strictly connected to cell functionality and, importantly, it can regulate cell immune activity in response to damaged associated signals. Therefore, identification of mitochondria related genes might offer new diagnostic markers and therapeutic targets for IVD degeneration. In this study, we identified key genes involved in NP tissue immune cell infiltration during IVD degeneration by bioinformatic analysis. The key modules were screened by weighted gene co-expression network analysis (WCGNA). Characteristic genes were identified by random forest analysis. Then gene set enrichment analysis (GSEA) was used to explore the signaling pathways associated with the signature genes. Subsequently, CIBERSORT was used to classify the infiltration of immune cells. Function of the hub gene was confirmed by PCR, Western blotting and ELISA. Finally, we identified MFN2 as a crucial molecule in the process of NP cell pyroptosis and NLRP3 inflammasome activation. We speculate that the increased MFN2 expression in NP tissue along with the infiltration of CD8+ T cells, NK cell and neutrophils play important roles in the pathogenesis of IVD degeneration.

[mRNA expression of lipogenic genes in mouse mammary gland in different lactation stages].

To investigate the expression pattern of lipogenic genes in mammary gland of mouse in different lactation stages, the relative mRNA abundance and expression of 20 genes involved in milk fat synthesis and secretion of lactating mammary tissues were assessed using real-time PCR. Results revealed the significant upregulation of mRNA expression for both high abundant genes (abundance > 5%), such as LPL, ACACA, SCD, XDH, BTN, and ADFP and moderate abundant genes (5% > abundance > 1%), such as CD36, FASN, AGPAT6, and DGAT in lactation stages compared to pregnancy (P < 0.05). The mRNA expression of lipogenic enzyme genes for ACACA, SCD, FASN, AGPAT6, and DGAT exhibited lower expression lever in early (6 d) and late (18 d) lactation stages but higher expression level at middle stage (12 d), demonstrating a low-high-low pattern. Besides, the mRNA levels of some gene regulators were also measured. The mRNA expression of SREBF gene increased gradually along with the lactation, which showed a 10-fold elevation at middle stage (12 d). The expression pattern of SREBF gene was the same as lipogenic enzyme genes, suggesting that SREBF may play an important role in the regulation of lipogenic enzyme genes in the lactating mammary gland.