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Dysfunction caused by mGluR5 expression or activation is an important mechanism in the development of Parkinson's disease (PD). Early clinical studies on mGluR5 negative allosteric modulators have shown some limitations. It is therefore necessary to find a more specific approach to block mGluR5-mediated neurotoxicity. Here, we determined the role of N-methyl-D-aspartate (NMDA) receptor subunit NR2B in mGluR5-mediated ER stress and DNA damage. In vitro study, rotenone-induced ER stress and DNA damage were accompanied by an increase in mGluR5 expression and overexpressed or activated mGluR5 with agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) induced ER stress and DNA damage, while blocking mGluR5 with antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) alleviated the effect. Furthermore, the damage caused by CHPG was blocked by NMDA receptor antagonist MK-801. Additionally, rotenone or CHPG increased the p-Src and p-NR2B, which was inhibited by MPEP. Blocking p-Src or NR2B with PP2 or CP101,606 alleviated CHPG-induced ER stress and DNA damage. Overactivation of mGluR5 accompanied with the increase of p-Src and p-NR2B in the ER stress and DNA damage was found in rotenone-induced PD rat model. These findings suggest a new mechanism wherein mGluR5 induces ER stress and DNA damage through the NMDA receptor and propose NR2B as the molecular target for therapeutic strategy for PD. [ABSTRACT FROM AUTHOR]

Wheat is an essential food source and is subjected to intense breeding efforts for increased grain yield, but stagnation in grain yield improvements has been reported in many regions. The identification of genetically linked factors impeding further progress in wheat grain yield improvement is therefore urgently required. A comparative meta-analysis of data from 66 publicly available field experiments involving multiple wheat genotypes was performed to identify traits altered in breeding programs, their relationship with grain yield, and their past and current impact on grain yield increases. Wheat grain yield can be increased by increasing either the aboveground biomass (ABM) or the harvest index (HI). However, there was no correlation between these traits since a reduction in plant height can occur with increases in the HI and overall grain yield, but with no reduction in the ABM. The combined data from 32 global datasets revealed a substantial increase in wheat grain yield from 1860 to 2017, accompanied by improvement in HI and yield components. When considering only the genotypes introduced from the 1960s to 2017, there was a linear increase observed in both grain yield and HI until the mid-1980s. However, genetic progress in HI and GY has slowed down since then. Before the mid-1980s, there was a decreasing trend observed in plant height which remained relatively static thereafter. While ABM did not exhibit significant increases during this period. After the mid-1980s, significant improvements have been observed in ABM; however, no obvious increase were observed in other yield components. Since the 1980s, there has been an increase in the aboveground biomass of wheat, while grain weigth and grains per m2 increases trending slowly, and both harvest index and grain yield have almost stagnated. Therefore, increasing grains per m2 and/or grain weight should be the major research direction to further improve the wheat harvest index and grain yield in the future. The systematic study of changes in wheat traits in past breeding efforts for improved grain yields has provided useful indicators for the direction of wheat breeding in the future. • HI kept supporting the increase in wheat yield (per unit area) after 1860. • In 1960s-1980s, dwarfing increased rapidly HI & yield simultaneously. • After 1980s, ABM keeps rising but HI slows down, leading to a yield-increase slowdown. • Increasing grain number & weight should be the future major research directions. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis., Methods: The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed, 2 patients were lost to follow-up at 10 months after surgery, at the final 22 cases were included in the study, including 13 males and 9 females with an average age of (52.00±6.89) years old, were treated with one-stage posterior lesion removal and internal spinal fixation. The operation time, intraoperative bleeding, follow-up time, erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) before and after operation were recorded. The pain visual analogue scale(VAS), Oswestry disability index(ODI), the Japanese Orthopaedic Association(JOA) score for neurofunction, American Spinal Injury Association(ASIA) spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy., Results: All patients were followed up from 12 to 30 months with an average of (17.41±4.45) months. The operation time was 70 to 155 min with an average of (116.59±24.32) min;the intraoperative bleeding volume was 120 to 520 ml with an average of (275.00±97.53) ml. CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than preoperative levels( P <0.05). VAS, JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results( P <0.05). There was no significant difference between ASIA preoperative and 1 week after operation( P >0.05), and a significant difference between preoperative and last follow-up( P <0.05). In the final follow-up, 21 patients had excellent efficacy, 1 patient had fair, and there was no recurrence during the follow-up., Conclusion: One-stage transpedicular lesion removal and internal spinal fixation, with few incisions and short operation time, helps the recovery of neurological function, and the prognosis meets the clinical requirements, which can effectively control Brucella spondylitis.

Objective: To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis., Methods: A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation., Results: ①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased( P <0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation ( P <0.05), but there was no significant difference between the three group( P >0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation ( P <0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation( P <0.05), and the intervertebral heigh was increased compared with that before operation( P <0.05), however, there was no significant difference among three groups at 12 months afrer operation( P >0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation( P >0.05)., Conclusion: The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.