Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Molecular Wiring of Electrocatalytic Nitrate reduction to Ammonia and Water Oxidation by Iron-Coordinated Macroporous Conductive Networks.

Developing stable electrocatalysts with accessible isolated sites is desirable but highly challenging due to metal agglomeration and low surface stability of host materials. Here we report a general approach for synthesis of single-site Fe electrocatalysts by integrating a solvated Fe complex in conductive macroporous organic networks through redox-active coordination linkages. Electrochemical activation of the electrode exposes high-density coordinately unsaturated Fe sites for efficient adsorption and conversion of reaction substrates such as NO3 - and H2O. Using the electrode with isolated active Fe sites, electrocatalytic NO3 - reduction and H2O oxidation can be coupled in a single cell to produce NH3 and O2 at Faradaic efficiencies of 97 % and 100 %, respectively. The electrode exhibits excellent robustness in electrocatalysis for 200 hours with small decrease in catalytic efficiencies. Both the maximized Fe-site efficiency and the microscopic localization effect of the conductive organic matrix contribute to the high catalytic performances, which provides new understandings in tuning the efficiencies of metal catalysts for high-performance electrocatalytic cells.

Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1.

Defects in the prelamin A processing enzyme caused by loss-of-function mutations in the ZMPSTE24 gene are responsible for a spectrum of progeroid disorders characterized by the accumulation of farnesylated prelamin A. Here we report that defective prelamin A processing triggers nuclear RIPK1-dependent signalling that leads to necroptosis and inflammation. We show that accumulated prelamin A recruits RIPK1 to the nucleus to facilitate its activation upon tumour necrosis factor stimulation in ZMPSTE24-deficient cells. Kinase-activated RIPK1 then promotes RIPK3-mediated MLKL activation in the nucleus, leading to nuclear envelope disruption and necroptosis. This signalling relies on prelamin A farnesylation, which anchors prelamin A to nuclear envelope to serve as a nucleation platform for necroptosis. Genetic inactivation of necroptosis ameliorates the progeroid phenotypes in Zmpste24-/- mice. Our findings identify an unconventional nuclear necroptosis pathway resulting from ZMPSTE24 deficiency with pathogenic consequences in progeroid disorder and suggest RIPK1 as a feasible target for prelamin A-associated progeroid disorders.

Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.

TAK1 is a key modulator of both NF-κB signaling and RIPK1. In TNF signaling pathway, activation of TAK1 directly mediates the phosphorylation of IKK complex and RIPK1. In a search for small molecule activators of RIPK1-mediated necroptosis, we found R406/R788, two small molecule analogs that could promote sustained activation of TAK1. Treatment with R406 sensitized cells to TNF-mediated necroptosis and RIPK1-dependent apoptosis by promoting sustained RIPK1 activation. Using click chemistry and multiple biochemical binding assays, we showed that treatment with R406 promotes the activation of TAK1 by directly binding to TAK1, independent of its original target Syk kinase. Treatment with R406 promoted the ubiquitination of TAK1 and the interaction of activated TAK1 with ubiquitinated RIPK1. Finally, we showed that R406/R788 could promote the cancer-killing activities of TRAIL in vitro and in mouse models. Our studies demonstrate the possibility of developing small molecule TAK1 activators to potentiate the effect of TRAIL as anticancer therapies.

ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade.

Despite advances in cancer treatment, immune checkpoint blockade (ICB) only achieves complete response in some patients, illustrating the need to identify resistance mechanisms. Using an ICB-insensitive tumor model, here we discover cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates the expression of Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) in tumors. Arih1 overexpression promotes cytotoxic T cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. ARIH1 mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, which is blocked by the phospho-mimetic mutant T68E/S213D of cGAS protein. Using a high-throughput drug screen, we further identify that ACY738, less cytotoxic than cisplatin, effectively upregulates ARIH1 and activates STING signaling, sensitizing tumors to PD-L1 blockade. Our findings delineate a mechanism that tumors mediate ICB resistance through the loss of ARIH1 and ARIH1-DNA-PKcs-STING signaling and indicate that activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.

SENP1 prevents steatohepatitis by suppressing RIPK1-driven apoptosis and inflammation.

Activation of RIPK1-driven cell death and inflammation play important roles in the progression of nonalcoholic steatohepatitis (NASH). However, the mechanism underlying RIPK1 activation in NASH remains unclear. Here we identified SENP1, a SUMO-specific protease, as a key endogenous inhibitor of RIPK1. SENP1 is progressively reduced in proportion to NASH severity in patients. Hepatocyte-specific SENP1-knockout mice develop spontaneous NASH-related phenotypes in a RIPK1 kinase-dependent manner. We demonstrate that SENP1 deficiency sensitizes cells to RIPK1 kinase-dependent apoptosis by promoting RIPK1 activation following TNFα stimulation. Mechanistically, SENP1 deSUMOylates RIPK1 in TNF-R1 signaling complex (TNF-RSC), keeping RIPK1 in check. Loss of SENP1 leads to SUMOylation of RIPK1, which re-orchestrates TNF-RSC and modulates the ubiquitination patterns and activity of RIPK1. Notably, genetic inhibition of RIPK1 effectively reverses disease progression in hepatocyte-specific SENP1-knockout male mice with high-fat-diet-induced nonalcoholic fatty liver. We propose that deSUMOylation of RIPK1 by SENP1 provides a pathophysiologically relevant cell death-restricting checkpoint that modulates RIPK1 activation in the pathogenesis of nonalcoholic steatohepatitis.

HOIP modulates the stability of GPx4 by linear ubiquitination.

LUBAC-mediated linear ubiquitination plays a pivotal role in regulation of cell death and inflammatory pathways. Genetic deficiency in LUBAC components leads to severe immune dysfunction or embryonic lethality. LUBAC has been extensively studied for its role in mediating TNF signaling. However, Tnfr1 knockout is not able to fully rescue the embryonic lethality of LUBAC deficiency, suggesting that LUBAC may modify additional key cellular substrates in promoting cell survival. GPx4 is an important selenoprotein involved in regulating cellular redox homeostasis in defense against lipid peroxidation-mediated cell death known as ferroptosis. Here we demonstrate that LUBAC deficiency sensitizes to ferroptosis by promoting GPx4 degradation and downstream lipid peroxidation. LUBAC binds and stabilizes GPx4 by modulating its linear ubiquitination both in normal condition and under oxidative stress. Our findings identify GPx4 as a key substrate of LUBAC and a previously unrecognized role of LUBAC-mediated linear ubiquitination in regulating cellular redox status and cell death.

Size selection and placement of pedicle screws using robot-assisted versus fluoroscopy-guided techniques for thoracolumbar fractures: possible implications for the screw loosening rate.

BACKGROUND: There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures. METHODS: A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients' sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery. RESULTS: There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12-18) vs. 21 (16-25), P < 0.001] and a higher "grade A + B" pedicle screw placement rate (96.5% vs. 89.4%, P < 0.05). The mean screw diameter was 6.04 ± 0.55 mm in the RAF group and 5.78 ± 0.50 mm in the FGF group (P < 0.001). The mean screw length was 50.45 ± 4.37 mm in the RAF group and 48.63 ± 3.86 mm in the FGF group (P < 0.001). The correction loss of the KCA and VHR of the RAF group was less than that of the FGT group at the 1-year follow-up [(3.8 ± 1.8° vs. 4.9 ± 4.2°) and (5.5 ± 4.9% vs. 6.4 ± 5.7%)], and screw loosening occurred in 2 out of 34 patients (5.9%) in the RAF group, and 6 out of 36 patients (16.7%) in the FGF group, but there were no significant differences (P > 0.05). CONCLUSION: Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group.

PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote TNFα-mediated cell death.

Activation of TNFR1 by TNFα induces the formation of a membrane-associated, intracellular complex termed complex I. Complex I orchestrates a complex pattern of modifications on key regulators of TNF signaling that collectively determines the cell fate by activating pro-survival or executing cell death programs. However, the regulatory mechanism of complex I in cell-fate decision is not fully understood. Here we identify protein phosphatase-6 (PP6) as a previously unidentified component of complex I. Loss of PP6 protects cells from TNFα-mediated cell death. The role of PP6 in regulating cell death requires its phosphatase activity and regulatory subunits. Further mechanistic studies show that PP6 modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote RIPK1 activation and c-FLIPL degradation. We also show that melanoma-associated PP6 inactivating mutants offer resistance to cell death due to the loss of sensitivity to TNFα. Thus, our study provides a potential mechanism by which melanoma-related PP6 inactivating mutations promote cancer progression.

Deubiquitination and Stabilization of PD-L1 by USP21.

Recent studies have shown that the expression level of PD-L1 in tumor cells positively correlates with tumor metastasis and recurrence rate. The effects of post-translational modifications (PTMs) of PD-L1 are related to immunosuppression. However, the degradation of PD-L1 in cancers has not yet been sufficiently defined. Here, we identified USP21 as a novel deubiquitinase of PD-L1. Overexpression of USP21 significantly increased PD-L1 abundance while its knockdown induced PD-L1 degradation. In vitro deubiquitination assay revealed that USP21-WT, but not USP21-C221A, reduced polyubiquitin chains of PD-L1. These results highlight the role of USP21 in the deubiquitination and stabilization of PD-L1. Furthermore, we show that USP21 is the frequently amplified deubiquitinase in lung cancer, especially in lung squamous cell carcinoma, and its amplification is accompanied by upregulation of PD-L1. This study reveals the mechanism of USP21-mediated PD-L1 degradation, and suggests that USP21 might be a potential target for the treatment of lung cancer.

Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model.

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/ß signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/ß-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aß plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/ß-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

Continuous Low-Dose Apatinib Combined With WBRT Significantly Reduces Peritumoral Edema and Enhances the Efficacy of Symptomatic Multiple Brain Metastases in NSCLC.

BACKGROUND: Symptomatic multiple brain metastases with peritumoral brain edema (PTBE) occur in non-small cell lung cancer patients (NSCLC) who are without driver mutations or are resistant to epidermal growth factor tyrosine kinase (EGFR-TKI) are often associated with an unfavorable prognosis. Whole brain radiation therapy (WBRT) which comes with many complications and unsatisfactory effects, is the only option for the treatment. Previous studies have shown that bevacizumab can reduce the volume of PTBE and improve efficiency of radiotherapy. This study evaluated the effects and safety of apatinib combined with WBRT in NSCLC patients with symptomatic multiple brain metastases and PTBE. METHODS: We performed a retrospective review of 34 patients with symptomatic multiple brain metastases from NSCLC (number >4, and at least 1 measurable brain metastasis lesion with cerebral edema). Intracranial objective response rate (IORR), peritumoral edema and intracranial tumor volumetric measurement, Karnofsky performance status (KPS) and adverse events (AEs) were evaluated. Median intracranial progression-free survival (mIPFS) and median overall survival (mOS) were also analyzed. RESULTS: Thirteen cases received apatinib (125 mg or 250 mg, QD, oral) combined with WBRT and 21 cases received chemotherapy combined with WBRT were inclued. Apatinib combination group can better reduce the volume of intracranial tumors and PTBE and total steroid dosage used. It was associated with a better IORR (84.6% vs 47.6%, P = 0.067), longer mIPFS (6.97 vs 4.77months; P = 0.014). There was no significant difference in mOS(7.70 vs 6.67 months; P = 0.14) between the 2 groups. The most common adverse events of apatinib combination WBRT included grade 1/2 nausea (4/13), fatigue (3/13), hypertension (2/13) and white blood cell decrease (2/13). No grade 3/4 AEs were observed. CONCLUSION: Apatinib plus WBRT is well tolerated and may be a potential choice for relapsed or drug-resistant advanced NSCLC patients with symptomatic multiple brain metastases and PTBE.

Caspase inhibition prolongs inflammation by promoting a signaling complex with activated RIPK1.

Activation of inflammation by lipopolysaccharide (LPS) is an important innate immune response. Here we investigated the contribution of caspases to the LPS-mediated inflammatory response and discovered distinctive temporal roles of RIPK1 in mediating proinflammatory cytokine production when caspases are inhibited. We propose a biphasic model that differentiates the role of RIPK1 in early versus late phase. The early production of proinflammation cytokines stimulated by LPS with caspase inhibition is mediated by the NF-κB pathway that requires the scaffold function of RIPK1 but is kinase independent. Autocrine production of TNFα in the late phase promotes the formation of a novel TNFR1-associated complex with activated RIPK1, FADD, caspase-8, and key mediators of NF-κB signaling. The production of proinflammatory cytokines in the late phase can be blocked by RIPK1 kinase inhibitor Nec-1s. Our study demonstrates a mechanism by which the activation of RIPK1 promotes its own scaffold function to regulate the NF-κB-mediated proinflammatory cytokine production that is negatively regulated by caspases to restrain inflammatory signaling.

ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.

Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.

Ubiquitination of RIPK1 regulates its activation mediated by TNFR1 and TLRs signaling in distinct manners.

RIPK1 is a death-domain (DD) containing kinase involved in regulating apoptosis, necroptosis and inflammation. RIPK1 activation is known to be regulated by its DD-mediated interaction and ubiquitination, though underlying mechanisms remain incompletely understood. Here we show that K627 in human RIPK1-DD and its equivalent K612 in murine RIPK1-DD is a key ubiquitination site that regulates the overall ubiquitination pattern of RIPK1 and its DD-mediated interactions with other DD-containing proteins. K627R/K612R mutation inhibits the activation of RIPK1 and blocks both apoptosis and necroptosis mediated by TNFR1 signaling. However, Ripk1K612R/K612R mutation sensitizes cells to necroptosis and caspase-1 activation in response to TLRs signaling. Ripk1K612R/K612R mice are viable, but develop age-dependent reduction of RIPK1 expression, spontaneous intestinal inflammation and splenomegaly, which can be rescued by antibiotic treatment and partially by Ripk3 deficiency. Furthermore, we show that the interaction of RIPK1 with FADD contributes to suppressing the activation of RIPK3 mediated by TLRs signaling. Our study demonstrates the distinct roles of K612 ubiquitination in mRIPK1/K627 ubiquitination in hRIPK1 in regulating its pro-death kinase activity in response to TNFα and pro-survival activity in response to TLRs signaling.

Reduction of mNAT1/hNAT2 Contributes to Cerebral Endothelial Necroptosis and Aß Accumulation in Alzheimer's Disease.

The contribution and mechanism of cerebrovascular pathology in Alzheimer's disease (AD) pathogenesis are still unclear. Here, we show that venular and capillary cerebral endothelial cells (ECs) are selectively vulnerable to necroptosis in AD. We identify reduced cerebromicrovascular expression of murine N-acetyltransferase 1 (mNat1) in two AD mouse models and hNat2, the human ortholog of mNat1 and a genetic risk factor for type-2 diabetes and insulin resistance, in human AD. mNat1 deficiency in Nat1-/- mice and two AD mouse models promotes blood-brain barrier (BBB) damage and endothelial necroptosis. Decreased mNat1 expression induces lysosomal degradation of A20, an important regulator of necroptosis, and LRP1ß, a key component of LRP1 complex that exports Aß in cerebral ECs. Selective restoration of cerebral EC expression of mNAT1 delivered by adeno-associated virus (AAV) rescues cerebromicrovascular levels of A20 and LRP1ß, inhibits endothelial necroptosis and activation, ameliorates mitochondrial fragmentation, reduces Aß deposits, and improves cognitive function in the AD mouse model.

Correlation between age of onset and gastrointestinal stenosis in hospitalized patients with Crohn's disease.

BACKGROUND: Patients affected by Crohn's disease (CD) are more likely to develop gastrointestinal stenosis and often undergo surgery during the duration of disease. AIM: To identify the risk factors for gastrointestinal stenosis in hospitalized CD patients in China. METHODS: The clinical data of CD patients hospitalized at the Seventh Medical Center, Chinese People's Liberation Army General Hospital from January 2010 to December 2018 were included. Patients with gastrointestinal stenosis were compared to those without gastrointestinal stenosis for clinical variables. The risk factors for gastrointestinal stenosis were identified using univariate and multivariable logistic regression analyses. The treatments for patients with gastrointestinal stenosis were analyzed, and the characteristics of different treatment methods were discussed. RESULTS: The incidence of gastrointestinal stenosis was 59.02% in the 122 hospitalized CD patients. Age of onset of more than 40 years (odds ratio [OR] = 3.072, 95% confidence interval [CI]: 1.298-7.272, P = 0.009) and duration of disease of more than 5 years (OR = 2.101, 95%CI: 1.002-4.406, P = 0.048) were associated with the occurrence of gastrointestinal stenosis. Fifteen (20.83%) patients did not undergo surgery and received internal medicine and nutrition treatment. Surgical treatments were performed in 72.22% (52) of cases. The rate of postoperative complications was 15.38% (8 cases), and during a median follow-up period of 46 mo, 11.54% (6 cases) underwent reoperation. A total of 29.17% (21 cases) were treated with endoscopic therapy, and during a median follow-up period of 32 mo, 76.19% (16 cases) had no surgical event, 23.81% (5 cases) failed to avoid surgical treatments, and no serious postoperative complications occurred after endoscopic therapy. CONCLUSION: Age of onset of more than 40 years and duration of disease of more than 5 years may be strongly correlated with a higher risk of gastrointestinal stenosis in hospitalized CD patients. Endoscopic therapy for gastrointestinal stenosis is relatively safe and effective, and may help to prevent or delay surgery.

Apatinib-induced Grade 3 hand-foot syndrome in advanced lung adenocarcinoma successful treated with thalidomide: A case report.

Hand-foot syndrome (HFS) is a specific cutaneous toxicity caused by a variety of antitumor drugs. The most common drugs include capecitabine, pegylated liposomal doxorubicin and fluorouracil (PLD), tyrosine kinase inhibitor. It is a dose-limiting cutaneous toxicity of these drugs. We reported an advanced lung adenocarcinoma female patient, who developed a Grade 3 HFS after a third-line treatment with apatinib of 250 mg for 10 days, the patient developed intolerable pain with pruritus. Large erythema on the skin of the hand, with local ulceratio, exudation, and desquamation of cutaneous lesions. After treatment with 100 mg of thalidomide every night for 1 week, the patient's HFS was significantly relieved, and the duration of the remission was about 2 months, which not only significantly improved the patient's quality of life, but also maintained the antitumor strength.

Steering CO2 electroreduction toward ethanol production by a surface-bound Ru polypyridyl carbene catalyst on N-doped porous carbon.

Electrochemical reduction of CO2 to multicarbon products is a significant challenge, especially for molecular complexes. We report here CO2 reduction to multicarbon products based on a Ru(II) polypyridyl carbene complex that is immobilized on an N-doped porous carbon (RuPC/NPC) electrode. The catalyst utilizes the synergistic effects of the Ru(II) polypyridyl carbene complex and the NPC interface to steer CO2 reduction toward C2 production at low overpotentials. In 0.5 M KHCO3/CO2 aqueous solutions, Faradaic efficiencies of 31.0 to 38.4% have been obtained for C2 production at -0.87 to -1.07 V (vs. normal hydrogen electrode) with 21.0 to 27.5% for ethanol and 7.1 to 12.5% for acetate. Syngas is also produced with adjustable H2/CO mole ratios of 2.0 to 2.9. The RuPC/NPC electrocatalyst maintains its activity during 3-h CO2-reduction periods.

The volume of 99m Tc sulfur colloid SPET-defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy.

BACKGROUND: The purpose of the current study was to evaluate whether radiation dose-volume metrics to technetium-99m (99m Tc) sulfur colloid single-photon emission tomography (SPET)-defined active bone marrow (ABM) subregions can more accurately predict acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy than conventional dosimetric parameters. METHODS AND MATERIALS: Thirty-nine patients with stage IB2-III cervical cancer who underwent 99m Tc sulfur colloid SPET imaging before treatment with cisplatin-based chemoradiation between January 2017 and March 2018 were analyzed. The total bone marrow (TBM) volume was defined as the external contours of all bones within the vertebral bodies from L4 to the coccyx, the pelvic bones, and the proximal femoral heads. The ABM volume was defined by SPET as the subregion of TBM with a nuclide uptake value greater than or equal to the mean total body nuclide uptake value. Student's t test was used to test for statistical significance between TBM and ABM dose-volume metrics. Receiver operating characteristic (ROC) curves were generated to compare the predictors of grade 3 or higher (grade 3+) hematologic toxicity. RESULTS: The mean ABM-V40 (23.22% ± 7.65%) and ABM-V30 (45.28% ± 9.20%) were significantly lower than the mean TBM-V40 (33.06% ± 6.72%) and TBM-V30 (53.08% ± 7.77%), respectively (t = 5.78, P = .001) (t = 4.13, P = .001). The ABM volume (<387.5 cm3 , AUC = 0.928, P = .001), ABM-V30 (>46.5%, AUC = 0.875, P = .001), and ABM-V40 (>23.5%, AUC = 0.858, P = .001) can predict the occurrence of grade 3+ hematologic toxicity. Among patients with an ABM volume < 387.5 cm3 , 16/19 (84.2%) had grade 3+ hematologic toxicity compared to 3/20 (15%) with an ABM volume > 387.5 cm3 . CONCLUSIONS: The ABM volume (<387.5 cm3 ) may be a better predictor of hematologic toxicity than conventional dose-volume metrics, but this finding needs to be further evaluated.