Tomatidine activates autophagy to improve lung injury and inflammation in sepsis by inhibiting NF-κB and MAPK pathways.

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity. Autophagy is involved in the pathophysiological process of sepsis-induced ALI, including inflammation, which indicates that regulating autophagy may be beneficial for this disease. Tomatidine, a natural compound abundant in unripe tomatoes, has been reported to have anti-inflammatory, anti-tumorigenic, and lipid-lowering effects. However, the biological functions and mechanisms of tomatidine in sepsis-induced ALI remain unknown. The principal objective of this study was to investigate the effect of tomatidine on sepsis-induced ALI. Cecal ligation and puncture (CLP) was used to induce septic lung injury in mice, and 10 mg/kg tomatidine was intraperitoneally injected into mice 2 h after the operation. The results of hematoxylin and eosin staining and assessment of lung edema and total protein levels in bronchoalveolar lavage fluid (BALF) demonstrated that tomatidine alleviated CLP-induced severe lung injuries such as hemorrhage, infiltration of inflammatory cells, and interstitial and alveolar edema in mice. Additionally, the levels of proinflammatory cytokines in BALF and lung tissues were measured by enzyme-linked immunosorbent assay (ELISA), and the results showed that tomatidine inhibited CLP-induced inflammatory damage to lungs. Moreover, the results of western blotting showed that tomatidine promoted autophagy during CLP-induced ALI. Mechanistically, immunofluorescence staining and western blotting were used to measure the protein levels of TLR4, phosphorylated NF-κB, phosphorylated IκBα, and phosphorylated MAPKs, showing that tomatidine inactivated NF-κB and MAPK signaling in lung tissues of CLP-induced ALI mice. In conclusion, tomatidine exerts protective effects against sepsis-induced severe damage to the lungs by inhibiting inflammation and activating autophagy in CLP-treated mice through inactivating the NF-κB and MAPK pathways, which may be an effective candidate for treating septic ALI.

Fine-tuning rice heading date through multiplex editing of the regulatory regions of key genes by CRISPR-Cas9.

Heading date (or flowering time) is a key agronomic trait that affects seasonal and regional adaption of rice cultivars. An unoptimized heading date can either not achieve a high yield or has a high risk of encountering abiotic stresses. There is a strong demand on the mild to moderate adjusting the heading date in breeding practice. Genome editing is a promising method which allows more precise and faster changing the heading date of rice. However, direct knock out of major genes involved in regulating heading date will not always achieve a new germplasm with expected heading date. It is still challenging to quantitatively adjust the heading date of elite cultivars with best adaption for broader region. In this study, we used a CRISPR-Cas9 based genome editing strategy called high-efficiency multiplex promoter-targeting (HMP) to generate novel alleles at cis-regulatory regions of three major heading date genes: Hd1, Ghd7 and DTH8. We achieved a series of germplasm with quantitative variations of heading date by editing promoter regions and adjusting the expression levels of these genes. We performed field trials to screen for the best adapted lines for different regions. We successfully expanded an elite cultivar Ningjing8 (NJ8) to a higher latitude region by selecting a line with a mild early heading phenotype that escaped from cold stress and achieved high yield potential. Our study demonstrates that HMP is a powerful tool for quantitatively regulating rice heading date and expanding elite cultivars to broader regions.

Performance of fibroblast activating protein inhibitor PET imaging for pancreatic neoplasms assessment: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment. PURPOSE: This article is dedicated to comparing the diagnostic efficacy of FAPI PET and [18F]fluorodeoxyglucose (FDG) PET in the evaluation of primary tumors, lymph nodes, and distant metastases in pancreatic cancer. METHODS: In this review, we conducted a systematic search of studies published in PubMed and Web of Science databases up to September 18, 2023. All included studies used radionuclide labeled FAPI and FDG as PET diagnostic tracers to evaluate their applicability in patients with pancreatic cancer. RESULTS: The FAPI PET imaging group showed significantly higher sensitivity in the detection of primary lesions (1.000, [95% CI: 0.999-1.000]), lymph node metastases (0.624 [95% CI: 0.391-0.834]) and distant metastatic (0.965 [95% CI: 0.804-1.000]) in pancreatic cancer compared to the FDG PET imaging group (0.889 [95% CI: 0.788-0.966], 0.373 [95% CI: 0.163-0.606] and 0.889 [95% CI: 0.689-0.999], respectively). Furthermore, the maximum standardized uptake value (SUVmax) in FAPI PET imaging is significantly higher than that in FDG imaging for primary lesions (mean difference (MD) = 7.51, 95% CI: 5.34-9.67). CONCLUSION: Compared with [18F]FDG PET/CT, FAPI PET imaging showed higher sensitivity, SUVmax. This method can be effectively utilized for the evaluation of pancreatic cancer. CLINICAL RELEVANCE STATEMENT: Fibroblast activating protein inhibitor PET may be a better alternative to [18F]FDG in evaluating primary pancreatic cancer, lymph node metastases, and distant metastases. KEY POINTS: Fibroblast activating protein inhibitor (FAPI) PET is compared with FDG PET for evaluating pancreatic cancer. Multiple radiolabeled FAPI variants have shown promising results in the diagnosis of pancreatic cancer. FAPI PET imaging effectively helps clinicians diagnose and stage pancreatic cancer.

Polarity is destiny.

The GTPase Cdc42 specifies polarity in various biological processes. Kesavan et al. (2009) now demonstrate that Cdc42 also regulates epithelial cell polarity in the developing mouse pancreas, where it is required for tubule formation and maintenance. Furthermore, the polarization of epithelial tissue influences the differentiation of pancreatic progenitor cells, linking cell polarity to cell specification.

Biomechanical changes of oblique lumbar interbody fusion with different fixation techniques in degenerative spondylolisthesis lumbar spine: a finite element analysis.

OBJECTIVE: There is a dearth of comprehensive research on the stability of the spinal biomechanical structure when combining Oblique Lumbar Interbody Fusion (OLIF) with internal fixation methods. Hence, we have devised this experiment to meticulously examine and analyze the biomechanical changes that arise from combining OLIF surgery with different internal fixation techniques in patients diagnosed with degenerative lumbar spondylolisthesis. METHODS: Seven validated finite element models were reconstructed based on computed tomography scan images of the L3-L5 segment. These models included the intact model, a stand-alone (S-A) OLIF model, a lateral screw rod (LSR) OLIF model, a bilateral pedicle screw (BPS) OLIF model, an unilateral pedicle screw (UPS) OLIF model, a bilateral CBT (BCBT) OLIF model, and an unilateral CBT(UCBT) OLIF model. The range of motion (ROM), as well as stress levels in the cage, L4 lower endplate, L5 upper endplate, and fixation constructs were assessed across these different model configurations. RESULTS: S-A model had the highest average ROM of six motion modes, followed by LSR, UPS, UCBT, BPS and BCBT. The BCBT model had a relatively lower cage stress than the others. The maximum peak von Mises stress of the fixation constructs was found in the LSR model. The maximum peak von Mises stress of L4 lower endplate was found in the S-A model. The peak von Mises stress on the L4 lower endplate of the rest surgical models showed no significant difference. The maximum peak von Mises stress of the L5 upper endplate was found in the S-A model. The minimum peak von Mises stress of the L5 upper endplate was found in the BCBT model. No significant difference was found for the peak von Mises stress of the L5 upper endplate among LSR, BPS, UPS and UCBT models. CONCLUSION: Among the six different fixation techniques, BCBT exhibited superior biomechanical stability and minimal stress on the cage-endplate interface. It was followed by BPS, UCBT, UPS, and LSR in terms of effectiveness. Conversely, S-A OLIF demonstrated the least stability and resulted in increased stress on both the cage and endplates. Combining OLIF with BCBT fixation technique enhanced biomechanical stability compared to BPS and presented as a less invasive alternative treatment for patients with degenerative lumbar spondylolisthesis.

Tauroursodeoxycholic acid combined with selenium accelerates bone regeneration in ovariectomized rats.

More recently, increased studies have revealed that antioxidants can cure osteoporosis by inhibiting oxidative stress. Tauroursodeoxycholic acid (TUDCA) and Selenium (Se) have been confirmed to possess potent anti-oxidative effects and accelerate bone regeneration. In addition, very little is currently known about the effects of a combination with Se and TUDCA on bone defects in osteoporotic states. We, therefore, aimed to assess the protective effect of combination with Se and TUDCA on bone regeneration and investigate the effect and underlying mechanisms. When MC3T3-E1 was cultured in the presence of H2H2, Se, TUDCA and Se/TUDCA therapy could increase the matrix mineralization and promote expression of anti-oxidative stress markers in MC3T3-E1, while reducing intracellular reactive oxygen species (ROS) and mitochondrial ROS levels. Meanwhile, silent information regulator type 1 (SIRT1) was upregulated in response to Se, TUDCA and Se/TUDCA exposures in H2H2 treated-MC3T3-E1. In the OVX rat model, Se, TUDCA and Se/TUDCA showed a clear positive effect against impaired bone repair in osteoporosis. The results above demonstrate that Se/TUDCA exhibits superior efficacy in both cellular and animal experiments, as compared to Se and TUDCA. In conclusion, combination with Se and TUDCA stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.

The additional role of [68Ga]Ga-FAPI-04 PET/CT in patients with unknown primary lesion with a negative or equivocal [18F]FDG.

PURPOSE: [18F]FDG PET/CT to detect unknown primary lesions is essential for clinical management but still has limitations. [68Ga]Ga-FAPI is a tumor-stromal imaging agent that provides a promising alternative to [18F]FDG for the assessment of malignancies. We aimed to investigate whether [68Ga]Ga-FAPI PET/CT has an additional role in identifying unknown primary lesions with negative or equivocal [18F] FDG PET/CT results. METHODS: This single-center prospective clinical study was conducted between March 2020 and March 2022 at Southwest Medical University Hospital. Patients underwent [18F]FDG PET/CT for the identification of unknown primary lesions. They underwent repeat [68Ga]Ga-FAPI PET/CT when [18F]FDG PET/CT results were negative or equivocal. Histopathological examination, surgery, or clinical follow-up (at least 3 months) for FAPI-positive lesions. The diagnostic efficacy of [68Ga]Ga-FAPI in identifying unknown primary lesions was evaluated. RESULTS: A total of 44 participants (median age, 57 ± 12 [SD]; 22 [50%] men) were evaluated. Thirteen of the 44 patients had equivocal [18F]FDG PET/CT findings, while the diagnosis was clear on [68Ga]Ga-FAPI PET/CT. [68Ga]Ga-FAPI PET/CT also revealed primary lesions in additional 17 patients with negative [18F]FDG PET/CT findings. In fourteen of 44 patients, no primary lesion was detected by either tracer. On this basis, we analyzed 94 lymph node metastatic lesions. The mean SUVmax of lymph node metastases on [68Ga] Ga-FAPI PET/CT and [18F]FDG PET/CT were 9.2 ± 5.1, 7.9 ± 4.8 (p = 0.03) and the mean TBR were 9.1 ± 5.2, 4.9 ± 3.1 (p < 0.01), respectively. CONCLUSION: [68Ga]Ga-FAPI PET/CT showed great potential for identifying unknown primary lesions and has the potential to improve the detection rate of unknown primary lesions with negative or equivocal for [18F]FDG findings. TRIAL REGISTRATION: ClinicalTrial.gov. Identifier: ChiCTR2100044131.

Interface Engineering a High Content of Co3+ Sites on Co3O4 Nanoparticles to Boost Acidic Oxygen Evolution.

Non-noble metal oxides have emerged as potential candidate electrocatalysts for acidic oxygen evolution reactions (OERs) due to their earth abundance; however, improving their catalytic activity and stability simultaneously in strong acidic electrolytes is still a major challenge. In this work, we report Co3O4@carbon core-shell nanoparticles on 2D graphite sheets (Co3O4@C-GS) as mixed-dimensional hybrid electrocatalysts for acidic OER. The obtained Co3O4@C-GS catalyst exhibits a low overpotential of 350 mV and maintains stability for 20 h at a current density of 10 mA cm-2 in H2SO4 (pH = 1) electrolyte. X-ray photoelectron and X-ray absorption spectroscopies illustrate that the higher content of Co3+ sites boosts acidic OER. Operando Raman spectroscopy reveals that the catalytic stability of Co3O4@C nanoparticles during the acidic OER is enhanced by the introduction of graphite sheets. This interface engineering of non-noble metal sites with high valence states provides an efficient approach to boost the catalytic activity and enhance the stability of noble-metal-free electrocatalysts for acidic OER.

Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches in lamellipodia.

The dendritic actin network generated by the Arp2/3 complex in lamellipodia underlies formation of protrusions, directional sensing, and migration. While the generation of this network is well studied, the mechanisms regulating network disassembly are poorly understood. We report that Coronin 1B disassembles Arp2/3-containing actin filament branches by inducing Arp2/3 dissociation. This activity is antagonized by Cortactin, a filament branch stabilizer. Consistent with this biochemical competition, depletion of both proteins partially rescues defects in lamellipodial dynamics observed upon depletion of either protein alone. Coronin 1B targets actin branches in a manner that is mutually exclusive with the Arp2/3 complex and alters the branch angle. We conclude that Coronin 1B replaces the Arp2/3 complex at actin filament branches as the dendritic network matures and drives the turnover of branched actin networks.

Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy.

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.

Clinical application of spinal robot in cervical spine surgery: safety and accuracy of posterior pedicle screw placement in comparison with conventional freehand methods.

The novel robot-assisted (RA) technique has been utilized increasingly to improve the accuracy of cervical pedicle screw placement. Although the clinical application of the RA technique has been investigated in several case series and comparative studies, the superiority and safety of RA over conventional freehand (FH) methods remain controversial. Meanwhile, the intra-pedicular accuracy of the two methods has not been compared for patients with cervical traumatic conditions. This study aimed to compare the rate and risk factors of intra-pedicular accuracy of RA versus the conventional FH approach for posterior pedicle screw placement in cervical traumatic diseases. A total of 52 patients with cervical traumatic diseases who received cervical screw placement using RA (26 patients) and FH (26 patients) techniques were retrospectively included. The primary outcome was the intra-pedicular accuracy of cervical pedicle screw placement according to the Gertzbin-Robbins scale. Secondary outcome parameters included surgical time, intraoperative blood loss, postoperative drainage, postoperative hospital stay, and complications. Moreover, the risk factors that possibly affected intra-pedicular accuracy were assessed using univariate analyses. Out of 52 screws inserted using the RA method, 43 screws (82.7%) were classified as grade A, with the remaining 7 (13.5%) and 2 (3.8%) screws classified as grades B and C. In the FH cohort, 60.8% of the 79 screws were graded A, with the remaining screws graded B (21, 26.6%), C (8, 10.1%), and D (2, 2.5%). The RA technique showed a significantly higher rate of optimal intra-pedicular accuracy than the FH method (P = 0.008), but there was no significant difference between the two groups in terms of clinically acceptable accuracy (P = 0.161). Besides, the RA technique showed remarkably longer surgery time, less postoperative drainage, shorter postoperative hospital stay, and equivalent intraoperative blood loss and complications than the FH technique. Furthermore, the univariate analyses showed that severe obliquity of the lateral atlantoaxial joint in the coronal plane (P = 0.003) and shorter width of the lateral mass at the inferior margin of the posterior arch (P = 0.014) were risk factors related to the inaccuracy of C1 screw placement. The diagnosis of HRVA (P < 0.001), severe obliquity of the lateral atlantoaxial joint in the coronal plane (P < 0.001), short pedicle width (P < 0.001), and short pedicle height (P < 0.001) were risk factors related to the inaccuracy of C2 screw placement. RA cervical pedicle screw placement was associated with a higher rate of optimal intra-pedicular accuracy to the FH technique for patients with cervical traumatic conditions. The severe obliquity of the lateral atlantoaxial joint in the coronal plane independently contributed to high rates of the inaccuracy of C1 and C2 screw placements. RA pedicle screw placement is safe and useful for cervical traumatic surgery.

Characteristics and evaluation of C1 posterior arch variation for transpedicular screw placement between patients with and without basilar invagination.

BACKGROUND: C1 transpedicular screw (C1TS) placement provided satisfactory pullout resistance and 3D stability, but its application might be limited in patients with basilar invagination (BI) due to the high incidences of the atlas anomaly and vertebral artery (VA) variation. However, no study has explored the classifications of C1 posterior arch variations and investigated their indications and ideal insertion trajectories for C1TS in BI. PURPOSE: To investigate the bony and surrounding arterial characteristics of the atlas, classify posterior arch variations, identify indications for C1TS, evaluate ideal insertion trajectories for C1TS in BI patients without atlas occipitalization (AO), and compare them with those without BI and AO as control. METHODS: A total of 130 non-AO patients with and without BI (52 patients and 78 patients, respectively) from two medical centers were included at a 1:1.5 ratio. The posterior arch variations were assessed using a modified C1 morphological classification. Comparisons regarding the bony and surrounding arterial characteristics, morphological classification distributions, and ideal insertion trajectories between BI and control groups were performed. The subgroup analyses based on different morphological classifications were also conducted. In addition, the factors possibly affecting the insertion parameters were investigated using multiple linear regression analyses. RESULTS: The BI group was associated with significantly smaller lateral mass height and width, sagittal length of posterior arch, pedicle height, vertical height of posterior arch, and distance between VA and VA groove (VAG) than control group. Four types of posterior arch variations with indications for different screw placement techniques were classified; Classifications I and II were suitable for C1TS. The BI cohort showed a significantly lower rate of Classification I than the control cohort. In the BI group, the subgroup of Classification I had significantly larger distance between the insertion point (IP) and inferior aspect of the posterior arch. In addition, it had the narrowest width along ideal screw trajectory, but a significantly more lateral ideal mediolateral angle than the subgroup of Classification II. Multiple linear regression indicated that the cephalad angle was significantly associated with the diagnosis of BI (B = 3.708, P < 0.001) and sagittal diameter of C1 (B = 3.417, P = 0.027); the ideal mediolateral angle was significantly associated with BMI (B = 0.264, P = 0.031), sagittal diameter of C1 (B = - 4.559, P = 0.002), and pedicle height (B = - 2.317, P < 0.001); the distance between the IP and inferior aspects of posterior arch was significantly associated with age (B = - 0.002, P = 0.035), BMI (B = - 0.007, P = 0.028), sagittal length of posterior arch (B = - 0.187, P = 0.032), pedicle height (B = - 0.392, P < 0.001), and middle and lower parts of posterior arch (B = 0.862, P < 0.001). CONCLUSION: The incidence of posterior arch variation in BI patients without AO was remarkably higher than that in control patients. The insertion parameters of posterior screws were different between the morphological classification types in BI and control groups. The distance between VA V3 segments and VAG in BI cohort was substantially smaller than that in control cohort. Preoperative individual 3D computed tomography (CT), CT angiography and intraoperative navigation are recommended for BI patients receiving posterior screw placement.

Posterior osteosynthesis with a new self-designed lateral mass screw-plate system for unstable atlas burst fractures.

BACKGROUND: In the treatment of unstable atlas fractures using the combined anterior-posterior approach or the posterior monoaxial screw-rod system, factors such as severe trauma or complex surgical procedures still need to be improved despite the favourable reduction effect. This research described and evaluated a new technique for the treatment of unstable atlas fracture using a self-designed lateral mass screw-plate system. METHODS: A total of 10 patients with unstable atlas fractures using this new screw-plate system from January 2019 to December 2021 were retrospectively reviewed. All patients underwent posterior open reduction and internal fixation (ORIF) with a self-designed screw-plate system. The medical records and radiographs before and after surgery were noted. Preoperative and postoperative CT scans were used to determine the type of fracture and evaluate the reduction of fracture. RESULTS: All 10 patients were successfully operated with this new system, with an average follow-up of 16.7 ± 9.6 months. A total of 10 plates were placed, and all 20 screws were inserted into the atlas lateral masses. The mean operating time was 108.7 ± 20.1 min and the average estimated blood loss was 98.0 ± 41.3 ml. The lateral mass displacement (LMD) averaged 7.1 ± 1.9 mm before surgery and almost achieved satisfactory reduction after surgery. All the fractures achieved bony healing without reduction loss or implant failure. No complications (vertebral artery injury, neurologic deficit, or wound infection) occurred in these 10 patients. At the final follow-up, the anterior atlantodens interval (AADI) was 2.3 ± 0.8 mm and the visual analog scale (VAS) was 0.6 ± 0.7 on average. All patients preserved almost full range of motion of the upper cervical spine and achieved a good clinical outcome at the last follow-up. CONCLUSIONS: Posterior osteosynthesis with this new screw-plate system can provide a new therapeutic strategy for unstable atlas fractures with simple and almost satisfactory reduction.

Medium and long-term radiographic and clinical outcomes of Dynesys dynamic stabilization versus instrumented fusion for degenerative lumbar spine diseases.

BACKGROUND: Dynesys stabilization (DS) is utilized to preserve mobility at the instrumental segments and prevent adjacent segment pathology in clinical practice. However, the advantages of DS method in medium and long-term follow-up remain controversial. OBJECTIVE: To compare the radiographic and clinical outcomes between DS and instrumented fusion in the treatment of degenerative lumbar spine disease with or without grade I spondylolisthesis with a minimum follow-up period of 2 years. METHODS: We conducted a comprehensive search of PubMed, EMBASE, Cochrane, and Web of Science databases, Chinese National Knowledge Databases, and Wanfang Database for potentially eligible articles. Clinical outcomes were assessed in terms of VAS and ODI scores, screw loosening and breakage, and surgical revision. Radiographic outcomes were assessed in terms of postoperative range of movement (ROM) and disc heigh. Moreover, adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) were evaluated. RESULTS: Seventeen studies with 1296 patients were included in the meta-analysis. The DS group was associated with significantly lower postoperative VAS scores for low-back and leg pain, and lower rate of surgical revision than the fusion group. Moreover, the Dynesys group showed significantly less ASDeg than the fusion group but showed no significant advantage over the fusion group in terms of preventing ASDis. Additionally, the ROM at the stabilized segments of the fusion group decreased significantly and that at the adjacent segments increased significantly compared with those of the DS group. CONCLUSION: DS showed comparable clinical outcomes and provided benefits in preserving the motion at the stabilized segments, thus limiting the hypermobility at the adjacent segments and preventing ASDeg compared with the fusion method in degenerative disease with or without grade I spondylolisthesis.

Operando Direct Observation of Stable Water-Oxidation Intermediates on Ca2-xIrO4 Nanocrystals for Efficient Acidic Oxygen Evolution.

We report Ca2-xIrO4 nanocrystals exhibit record stability of 300 h continuous operation and high iridium mass activity (248 A gIr-1 at 1.5 VRHE) that is about 62 times that of benchmark IrO2. Lattice-resolution images and surface-sensitive spectroscopies demonstrate the Ir-rich surface layer (evolved from one-dimensional connected edge-sharing [IrO6] octahedrons) with high relative content of Ir5+ sites, which is responsible for the high activity and long-term stability. Combining operando infrared spectroscopy with X-ray absorption spectroscopy, we report the first direct observation of key intermediates absorbing at 946 cm-1 (Ir6+═O site) and absorbing at 870 cm-1 (Ir6+OO- site) on iridium-based oxides electrocatalysts, and further discover the Ir6+═O and Ir6+OO- intermediates are stable even just from 1.3 VRHE. Density functional theory calculations indicate the catalytic activity of Ca2IrO4 is enhanced remarkably after surface Ca leaching, and suggest IrOO- and Ir═O intermediates can be stabilized on positive charged active sites of Ir-rich surface layer.

Novel insights into NOD-like receptors in renal diseases.

Nucleotide-binding oligomerization domain-like receptors (NLRs), including NLRAs, NLRBs (also known as NAIPs), NLRCs, and NLRPs, are a major subfamily of pattern recognition receptors (PRRs). Owing to a recent surge in research, NLRs have gained considerable attention due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, which is a central phenomenon in the pathogenesis of multiple diseases, including renal diseases. NLRs are expressed in different renal tissues during pathological conditions, which suggest that these receptors play roles in acute kidney injury, obstructive nephropathy, diabetic nephropathy, IgA nephropathy, lupus nephritis, crystal nephropathy, uric acid nephropathy, and renal cell carcinoma, among others. This review summarises recent progress on the functions of NLRs and their mechanisms in the pathophysiological processes of different types of renal diseases to help us better understand the role of NLRs in the kidney and provide a theoretical basis for NLR-targeted therapy for renal diseases.

Characteristics of ST11 KPC-2-producing carbapenem-resistant hypervirulent Klebsiella pneumoniae causing nosocomial infection in a Chinese hospital.

BACKGROUND: The purpose of our study is to analyze the microbiological and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) that causes nosocomial infection. METHODS: We collected the carbapenem-resistant K. pneumoniae (CRKP) strains that caused nosocomial infection in a hospital in China and collected the relevant clinical data. We characterized these strains for their antimicrobial and virulence-associated phenotype and genotype and analyzed the clonal relatedness. We screened hypervirulent strains and compared them with non-hypervirulent strains. RESULTS: We retrospectively analyzed 62 CRKP strains that caused nosocomial infection in a tertiary hospital within 1 year, of which 41 (41/62, 66.1%) CRKP were considered as CR-hvKP. All CR-hvKP strains were multi-drug resistance (MDR) and the vast majority of isolates (39/41, 95.1%) were ST11 KPC-2-producing strains. Two hypermucoviscous isolates and 4 capsular types were found in 41 CR-hvKP. Twenty-nine isolates (29/41, 70.7%) showed hypervirulence in Galleria mellonella infection model. PFGE showed that ST11-KL47 CR-hvKP and ST11-KL64 CR-hvKP exhibited a high degree of clonality, while non-hypervirulent strains were not significant. CR-hvKP had higher positive rates of blaKPC-2 and blaCTX-M-65 and higher levofloxacin resistance (p < 0.001, p = 0.005 and p = 0.046, respectively) when compared to the non-hypervirulent strains. There was no significant difference between the two groups in terms of in-hospital mortality (7/41, 17.1% vs 5/21, 23.8%, p = 0.743). CONCLUSION: Our research finds that ST11 KPC-2-producing CR-hvKP is the main type of CRKP that caused nosocomial infection, and clonal spread has occurred. We provide more information about CR-hvKP in health care.

A new classification and strategies for endovascular treatment of celiac artery aneurysms.

BACKGROUND: Endovascular treatment is being increasingly used for celiac artery aneurysms (CAAs), but systematic endovascular treatment strategies have not been defined yet. This study intended to investigate the strategies of endovascular management of CAAs according to a single-center experience. METHODS: Anatomically, CAAs were classified into two types: Type I CAAs located in the main trunk of celiac artery. Type II CAAs located on the branches of the celiac artery. Type I and Type II CAAs can be further divided into two different subtypes according to fusiform (a) or saccular or (b) morphology: type Ia, type Ib, type IIa, and type IIb. Patient demographics, clinical manifestations, aneurysm characteristics, endovascular intervention procedures, and perioperative and follow-up outcomes were reviewed and analyzed. RESULTS: Between August 2012 and August 2020, 18 consecutive patients (12 men; mean age, 56.8 ± 14.5 years) with CAAs were identified and treated with endovascular procedures. There were seven patients with type Ia, three patients with type Ib, four patients with type IIa, and four patients with type IIb CAAs. One patient died of hemorrhagic shock due to a ruptured aneurysm. Technical success was achieved in 16 patients (88.9%). The mean follow-up period was 51.7 ± 19.4 months. No hepatic or intestinal ischemia or death developed perioperatively or during the follow-up period. No aneurysmal expansion was detected on CTA surveillance, except for one patient who was diagnosed with an endoleak during the follow-up and received reintervention. CONCLUSIONS: The endovascular strategy based on the novel classification of CAAs was safe and effective, with a favorable mid-term clinical outcome.

Rates and risk factors of intrapedicular accuracy and cranial facet joint violation among robot-assisted, fluoroscopy-guided percutaneous, and freehand techniques in pedicle screw fixation of thoracolumbar fractures: a comparative cohort study.

BACKGROUND: Robot-assisted (RA) technique has been increasingly applied in clinical practice, providing promising outcomes of inserting accuracy and cranial facet joint protection. However, studies comparing this novel method with other assisted methods are rare, and the controversy of the superiority between the insertion techniques remains. Thus, we compare the rates and risk factors of intrapedicular accuracy and cranial facet joint violation (FJV) of RA, fluoroscopy-guided percutaneous (FP), and freehand (FH) techniques in the treatment of thoracolumbar fractures. METHODS: A total of 74 patients with thoracolumbar fractures requiring pedicle screw instruments were retrospectively included and divided into RA, FP, and FH groups from June 2016 to May 2020. The primary outcomes were the intrapedicular accuracy and cranial FJV. The factors that affected the intrapedicular accuracy and cranial FJV were assessed using multivariate analyses. RESULTS: The optimal intrapedicular accuracy of pedicle screw placement (Grade A) in the RA, FP, and FH groups was 94.3%, 78.2%, and 88.7%, respectively. This finding indicates no significant differences of RA over FH technique (P = 0.062) and FP technique (P = 0.025), but significantly higher accuracies of RA over FP (P < 0.001). In addition, the rates of proximal FJV in RA, FP, and FH groups were 13.9%, 30.8%, and 22.7%, respectively. RA had a significantly greater proportion of intact facet joints than the FP (P = 0.002). However, FP and FH (P = 0.157), as well as RA and FH (P = 0.035) showed significantly similar outcomes with respect to the proximal FJV. The logistic regression analysis showed that FP technique (OR = 3.056) was independently associated with insertion accuracy. Meanwhile, the age (OR = 0.974), pedicle angle (OR = 0.921), moderate facet joint osteoarthritis (OR = 5.584), and severe facet joint osteoarthritis (OR = 11.956) were independently associated with cranial FJV. CONCLUSION: RA technique showed a higher rate of intrapedicular accuracy and a lower rate of cranial FJV than FP technique, and similar outcomes to FH technique in terms of intrapedicular accuracy and cranial FJV. RA technique might be a safe method for pedicle screw placement in thoracolumbar surgery. LEVEL OF EVIDENCE: 3.

Predictors of accurate intrapedicular screw placement in single-level lumbar (L4-5) fusion: robot-assisted pedicle screw, traditional pedicle screw, and cortical bone trajectory screw insertion.

BACKGROUND: The superiorities in proximal facet joint protection of robot-assisted (RA) pedicle screw placement and screw implantation via the cortical bone trajectory (CBT) have rarely been compared. Moreover, findings on the screw accuracy of both techniques are inconsistent. Therefore, we analyzed the screw accuracy and incidence of facet joint violation (FJV) of RA and CBT screw insertion in the same study and compared them with those of conventional pedicle screw (PS) insertion. The possible factors affecting screw accuracy and FJV were also analyzed. METHODS: A total of 166 patients with lumbar degenerative diseases requiring posterior L4-5 fusion were retrospectively included and divided into the RA, PS, and CBT groups from March 2019 to December 2021. The grades of intrapedicular accuracy and superior FJV were evaluated according to the Gertzbin-Robbins scale and the Babu scale based on postoperative CT. Univariable and multivariable analyses were conducted to assess the possible risk factors associated with intrapedicular accuracy and superior FJV. RESULTS: The rates of optimal screw insertion in the RA, PS, and CBT groups were 87.3%, 81.3%, and 76.5%, respectively. The difference between the RA and CBT groups was statistically significant (P = 0.004). Superior FJVs occurred in 28.2% of screws in RA, 45.0% in PS, and 21.6% in CBT. The RA and CBT groups had fewer superior FJVs than the PS group (P = 0.008 and P < 0.001, respectively), and no significant difference was observed between the RA and CBT groups (P = 0.267). Multivariable analysis revealed that the CBT technique was an independent risk factor for intrapedicular accuracy. Furthermore, older age, the conventional PS technique and a smaller facet angle were independently associated with the incidence of superior FJVs. CONCLUSIONS: The RA and CBT techniques were associated with fewer proximal FJVs than the PS technique. The RA technique showed a higher rate of intrapedicular accuracy than the CBT technique. The CBT technique was independently associated with screw inaccuracy. Older age, conventional PS technique and coronal orientation of the facet join were independent risk factors for superior FJV.