An integrated cofactor and co-substrate recycling pathway for the biosynthesis of 1,5-pentanediol.

BACKGROUND: 1,5-pentanediol (1,5-PDO) is a linear diol with an odd number of methylene groups, which is an important raw material for polyurethane production. In recent years, the chemical methods have been predominantly employed for synthesizing 1,5-PDO. However, with the increasing emphasis on environmentally friendly production, it has been a growing interest in the biosynthesis of 1,5-PDO. Due to the limited availability of only three reported feasible biosynthesis pathways, we developed a new biosynthetic pathway to form a cell factory in Escherichia coli to produce 1,5-PDO. RESULTS: In this study, we reported an artificial pathway for the synthesis of 1,5-PDO from lysine with an integrated cofactor and co-substrate recycling and also evaluated its feasibility in E.coli. To get through the pathway, we first screened aminotransferases originated from different organisms to identify the enzyme that could successfully transfer two amines from cadaverine, and thus GabT from E. coli was characterized. It was then cascaded with lysine decarboxylase and alcohol dehydrogenase from E. coli to achieve the whole-cell production of 1,5-PDO from lysine. To improve the whole-cell activity for 1,5-PDO production, we employed a protein scaffold of EutM for GabT assembly and glutamate dehydrogenase was also validated for the recycling of NADPH and α-ketoglutaric acid (α-KG). After optimizing the cultivation and bioconversion conditions, the titer of 1,5-PDO reached 4.03 mM. CONCLUSION: We established a novel pathway for 1,5-PDO production through two consecutive transamination reaction from cadaverine, and also integrated cofactor and co-substrate recycling system, which provided an alternative option for the biosynthesis of 1,5-PDO.

Groundwater chemical evolution characteristics and human health risk assessment in Shicheng County, Jiangxi Province.

Groundwater plays a pivotal role in the water resources of Shicheng County; however, the issue of excessive fluoride content in groundwater and its associated health risks often goes unnoticed. Groundwater assumes a crucial role in the hydrological dynamics of Shicheng County; nevertheless, the matter concerning elevated levels of fluoride within groundwater and its accompanying health hazards frequently evades attention. The hydrogeochemical analysis, obscure comprehensive water quality assessment based on cloud model, and probabilistic human health risk assessment using Monte Carlo simulation were conducted on 34 collected water samples. The findings indicate that the predominant groundwater hydrochemical types are SO4·Cl-Na and HCO3-Na. The processes of rock weathering and cation exchange play crucial roles in influencing water chemistry. Groundwater samples generally exhibit elevated concentrations of F-, surpassing the drinking water standard, primarily attributed to mineral dissolution. The concentrations of F- in more than 52.94% and 23.53% of the groundwater samples exceeded the acceptable non-carcinogenic risk limits for children and adults, respectively. Considering the inherent uncertainty in model parameters, it is anticipated that both children and adults will have a probability exceeding 49.36% and 30.50%, respectively, of being exposed to elevated levels of F ions in groundwater. The utilization of stochastic simulations, in contrast to deterministic methods, enables a more precise depiction of health risks. The outcomes derived from this investigation possess the potential to assist policymakers in formulating strategies aimed at ensuring the provision of secure domestic water supplies.

Association of Serum Unsaturated Fatty Acid Patterns with the Risk of Diabetic Nephropathy.

Introduction: Unsaturated fatty acids play an essential role in the progression of diabetic nephropathy (DN). However, previous studies were mainly focused on the role of individual unsaturated fatty acid. The serum unsaturated fatty acid patterns (FAPs) in patients with DN remain to be determined. Methods: A total of 135 patients with DN (DN group) and 322 patients with type II diabetes without nephropathy (non-DN group) were included in this study. Clinical data, serum levels of unsaturated fatty acids, and other laboratory indicators were collected. Multivariate logistic regression was applied to identify risk factors for serum unsaturated fatty acid level in both groups. Serum unsaturated fatty acids were subjected to factor analysis to identify distinct FAPs. Multivariable logistic regression was employed to assess the risk of DN associated with different serum FAPs. Results: After adjusting for confounders, three types of unsaturated fatty acid including C20:5 (eicosapentaenoic acid [EPA]), C22:6 (docosahexaenoic acid [DHA]), and C22:5 n-3 (docosapentaenoic acid n-3) were significantly associated with DN in the population. The odds ratios (ORs) (95% confidence interval [CI]) of DN were 0.583 (0.374, 0.908), 0.826 (0.716, 0.954), and 0.513 (0.298, 0.883), respectively. Factor analysis revealed five major FAPs, among which FAP2 (enriched with EPA and DHA) exhibited a significant inverse association with DN. In the multivariate-adjusted model, the OR (95% CI) was 0.678 (0.493, 0.933). Additionally, a combination of DHA and EPA enriched in FAP2 further decreased extracellular matrix production induced by transforming growth factor beta 1 in podocytes and tubular cells. Conclusions: Our findings suggest that FAP2 which is enriched with DHA and EPA is associated with a reduced risk of DN. This highlights the potential of targeting FAP2 for the patients with DN.

Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.

Versatile design for temporal shape control of high-power nanosecond pulsed fiber laser amplifier.

This research proposed a novel pulse-shaping design for directly shaping distorted pulses after the amplification. Based on the principle of the design we made a pulse shaper. With this pulse shaper, we successfully manipulate the pulse's leading edge and width to achieve an 'M'-shaped waveform in an amplification system. Comparative experiments were conducted within this system to compare the output with and without the integration of the pulse shaper. The results show a significant suppression of the nonlinear effect upon adding the pulse shaper. This flexible and effective pulse shaper can be easily integrated into a high-power all-fiber system, supplying the capability to realize the desired output waveform and enhance the spectral quality.

Neutrophil to albumin ratio: a biomarker in non-alcoholic fatty liver disease and with liver fibrosis.

Objective: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and its potential to progress to liver fibrosis, it is crucial to identify the presence of NAFLD in patients to guide their subsequent management. However, the current availability of non-invasive biomarkers for NAFLD remains limited. Therefore, further investigation is needed to identify and develop non-invasive biomarkers for NAFLD. Methods: A retrospective analysis was conducted on 11,883 patients admitted to the Healthcare Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2016 to December 2019 and divided into NAFLD and non-NAFLD groups. Anthropometric and laboratory examination data were collected. The correlations between variables and NAFLD were evaluated using the student's t-test or Mann-Whitney U test and binary logistic regression analysis. The predictive ability of these variables for NAFLD was assessed using the areas under the curves (AUCs) of receiver operating characteristics. Results: Among the included patients, 3,872 (32.58%) were diagnosed with NAFLD, with 386 (9.97%) individuals having liver fibrosis. Patients with NAFLD exhibited a higher proportion of males, elevated body mass index (BMI), and increased likelihood of hypertension, diabetes mellitus, and atherosclerosis. Logistic regression analysis identified the neutrophil to albumin ratio (NAR) as the most promising novel inflammation biomarkers, with the highest AUC value of 0.701, a cut-off value of 0.797, sensitivity of 69.40%, and specificity of 66.00% in identifying the risk of NAFLD. Moreover, NAR demonstrated superior predictive value in identifying NAFLD patients at risk of liver fibrosis, with an AUC value of 0.795, sensitivity of 71.30%, and specificity of 73.60% when NAR reached 1.285. Conclusion: These findings highlight that the novel inflammatory biomarker, NAR, is a convenient and easily accessible non-invasive predictor for NAFLD and NAFLD with liver fibrosis.

Low-cost dual-energy CBCT by spectral filtration of a dual focal spot X-ray source.

Dual-energy cone beam computed tomography (DE-CBCT) has been shown to provide more information and improve performance compared to a conventional single energy spectrum CBCT. Here we report a low-cost DE-CBCT by spectral filtration of a carbon nanotube x-ray source array. The x-ray photons from two focal spots were filtered respectively by a low and a high energy filter. Projection images were collected by alternatively activating the two beams while the source array and detector rotated around the object, and were processed by a one-step materials decomposition and reconstruction method. The performance of the DE-CBCT scanner was evaluated by imaging a water-equivalent plastic phantom with inserts containing known densities of calcium or iodine and an anthropomorphic head phantom with dental implants. A mean energy separation of 15.5 keV was achieved at acceptable dose rates and imaging time. Accurate materials quantification was obtained by materials decomposition. Metal artifacts were reduced in the virtual monoenergetic images synthesized at high energies. The results demonstrated the feasibility of high quality DE-CBCT imaging by spectral filtration without using either an energy sensitive detector or rapid high voltage switching.

Altered plasma levels and tissue expression of fibroblast activation protein alpha in giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium and large-sized arteries accompanied by remodeling of the vessel wall. Fibroblast activation protein alpha (FAP) is a serine protease which promotes both inflammation and fibrosis. Here we investigated the plasma levels and vascular expression of FAP in GCA. METHODS: Plasma FAP levels were measured with ELISA in treatment-naive GCA (n=60) and polymyalgia rheumatica (PMR, n=63) patients (compared to age- and sex-matched healthy controls (HC), n=42) and during follow-up, including treatment free remission (TFR). Inflamed temporal artery biopsies (TAB) of GCA patients (n=9), non-inflamed TAB (n=14), aorta samples from GCA- (n=9) and atherosclerosis-related aneurysm (n=11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts(CD90), macrophages(CD68/CD206/FRß), vascular smooth muscle cells(desmin), myofibroblasts(αSMA), interleukin(IL)-6 and matrix metalloproteinase(MMP)-9. RESULTS: Baseline plasma FAP levels were significantly lower in GCA compared to PMR patients and HC, and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months upon remission in GCA, and gradually increased to the level of HC in TFR. FAP expression was increased in inflamed TAB and aorta of GCA patients compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Part of the FAP+ fibroblasts expressed IL-6 and MMP-9. CONCLUSION: FAP expression in GCA is clearly modulated both in plasma and in vessels. FAP may be involved in the inflammatory and remodeling processes in GCA and have utility as target for imaging and therapeutic intervention.

CuCl2/FeCl3 Bimetallic Photocatalyst for Sustainable Ethylene Production from Ethanol via Recoverable Redox Cycles.

Photocatalytic conversions of ethanol to valuable chemicals are significant organic synthesis reactions. Herein, we developed a CuCl2/FeCl3 bimetallic photocatalyst for sustainable dehydration of ethanol to ethylene by recoverable redox cycles. The selectivity of ethylene was 98.3% for CuCl2/FeCl3, which is much higher than that of CuCl2 (34.5%) and FeCl3 (86.5%). Due to the ligand-to-metal charge transfer (LMCT) process involved in generating the liquid products, the CuCl2/FeCl3 catalyst will be reduced to CuCl/FeCl2. Oxygen (O2) is required for the recovery of CuCl2/FeCl3 to avoid exhaustion. The soluble Fe3+/Fe2+ redox species deliver catalyst regeneration properties more efficiently than single metal couples, making a series of redox reactions (Cu2+/Cu+, Fe3+/Fe2+, and O2/ethanol couples) recyclable with synergistic effects. A flow reactor was designed to facilitate the continuous production of ethylene. The understanding of bimetallic synergism and consecutive reactions promotes the industrial application process of photocatalytic organic reactions.

Microplastics change soil properties, plant performance, and bacterial communities in salt-affected soils.

Microplastics (MPs) are emerging contaminants found globally. However, their effects on soil-plant systems in salt-affected habitats remain unknown. Here, we examined the effects of polyethylene (PE) and polylactic acid (PLA) on soil properties, maize performance, and bacterial communities in soils with different salinity levels. Overall, MPs decreased soil electrical conductivity and increased NH4+-N and NO3--N contents. Adding NaCl alone had promoting and inhibitive effects on plant growth in a concentration-dependent manner. Overall, the addition of 0.2% PLA increased shoot biomass, while 2% PLA decreased it. Salinity increased Na content and decreased K/Na ratio in plant tissues (particularly roots), which were further modified by MPs. NaCl and MPs singly and jointly regulated the expression of functional genes related to salt tolerance in leaves, including ZMSOS1, ZMHKT1, and ZMHAK1. Exposure to NaCl alone had a slight effect on soil bacterial α-diversity, but in most cases, MPs increased ACE, Chao1, and Shannon indexes. Both MPs and NaCl altered bacterial community composition, although the specific effects varied depending on the type and concentration of MPs and the salinity level. Overall, PLA had more pronounced effects on soil-plant systems compared to PE. These findings bridge knowledge gaps in the risks of MPs in salt-affected habitats.

Bruceantinol works as a CDK2/4/6 inhibitor to inhibit the growth of breast cancer cells.

Bruceantinol (BOL), isolated from the dried fruit of the Brucea javanica (L.) Merr., exhibits cytotoxic effects on breast cancer cells. However, the underlying mechanism remains to be fully addressed. In this paper, the MCF-7 and MDA-MB-231 human breast cancer cell lines were used as experimental models to uncover how BOL inhibits breast cancer cell growth. The effects of BOL on cell growth, proliferation, the cell cycle, and apoptosis were investigated using the MTT assays, EdU incorporation assays, and flow cytometry, respectively. Bioinformatics techniques were applied to predict the key targets of BOL in breast cancer. Subsequent validation of these targets and the anti-breast cancer mechanism of BOL was conducted through Western blotting, RT-PCR, siRNA transfection, and molecular docking analysis. The results demonstrated that BOL dose- and time-dependently reduced the growth of both cell lines, impeded cell proliferation, disrupted the cell cycle, and induced necrosis in MCF-7 cells and apoptosis in MDA-MB-231 cells. Furthermore, CDK2/4/6 were identified as BOL targets, and their knockdown reduced cell sensitivity to BOL. BOL was found to potentially bind with CDK2/4/6 to facilitate protein degradation through the proteasome pathway. Additionally, BOL activated ERK in MDA-MB-231 cells, and this activation was required for BOL's functions in these cells. Collectively, BOL may act as an inhibitor of CDK2/4/6 to exert anti-breast cancer effects. Its effects on cell growth and CDK2/4/6 expression may also depend on ERK activation in HRs-HER2- breast cancer cells. These results suggest the potential of using BOL for treating breast cancer.

Characterization of winged helix domain fusion endonucleases as N6-methyladenine-dependent type IV restriction systems.

Winged helix (wH) domains, also termed winged helix-turn-helix (wHTH) domains, are widespread in all kingdoms of life and have diverse roles. In the context of DNA binding and DNA modification sensing, some eukaryotic wH domains are known as sensors of non-methylated CpG. In contrast, the prokaryotic wH domains in DpnI and HhiV4I act as sensors of adenine methylation in the 6mApT (N6-methyladenine, 6mA, or N6mA) context. DNA-binding modes and interactions with the probed dinucleotide are vastly different in the two cases. Here, we show that the role of the wH domain as a sensor of adenine methylation is widespread in prokaryotes. We present previously uncharacterized examples of PD-(D/E)XK-wH (FcyTI, Psp4BI), PUA-wH-HNH (HtuIII), wH-GIY-YIG (Ahi29725I, Apa233I), and PLD-wH (Aba4572I, CbaI) fusion endonucleases that sense adenine methylation in the Dam+ Gm6ATC sequence contexts. Representatives of the wH domain endonuclease fusion families with the exception of the PLD-wH family could be purified, and an in vitro preference for adenine methylation in the Dam context could be demonstrated. Like most other modification-dependent restriction endonucleases (MDREs, also called type IV restriction systems), the new fusion endonucleases except those in the PD-(D/E)XK-wH family cleave close to but outside the recognition sequence. Taken together, our data illustrate the widespread combinatorial use of prokaryotic wH domains as adenine methylation readers. Other potential 6mA sensors in modified DNA are also discussed.

Engineering RuBisCO-based shunt for improved cadaverine production in Escherichia coli.

The process of biological fermentation is often accompanied by the release of CO2, resulting in low yield and environmental pollution. Refixing CO2 to the product synthesis pathway is an attractive approach to improve the product yield. Cadaverine is an important diamine used for the synthesis of bio-based polyurethane or polyamide. Here, aiming to increase its final production, a RuBisCO-based shunt consisting of the ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and phosphoribulate kinase (PRK) was expressed in cadaverine-producing E. coli. This shunt was calculated capable of increasing the maximum theoretical cadaverine yield based on flux model analysis. When a functional RuBisCO-based shunt was established and optimized in E. coli, the cadaverine production and yield of the final engineered strain reached the highest level, which were 84.1 g/L and 0.37 g/g Glucose, respectively. Thus, the design of in situ CO2 fixation provides a green and efficient industrial production process.

Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents.

Existing pharmacodynamic (PD) mathematical models for drug combinations discriminate antagonistic, additive, multiplicative, and synergistic effects, but fail to consider how concentration-dependent drug interaction effects may vary across an entire dose-response matrix. We developed a two-way pharmacodynamic (TWPD) model to capture the PD of two-drug combinations. TWPD captures interactions between upstream and downstream drugs that act on different stages of viral replication, by quantifying upstream drug efficacy and concentration-dependent effects on downstream drug pharmacodynamic parameters. We applied TWPD to previously published in vitro drug matrixes for repurposed potential anti-Ebola and anti-SARS-CoV-2 drug pairs. Depending on the drug pairing, the model recapitulated combined efficacies as or more accurately than existing models and can be used to infer efficacy at untested drug concentrations. TWPD fits the data slightly better in one direction for all drug pairs, meaning that we can tentatively infer the upstream drug. Based on its high accuracy, TWPD could be used in concert with PK models to estimate the therapeutic effects of drug pairs in vivo.

Prognostic value of measurement of myocardial extracellular volume using dual-energy CT in heart failure with preserved ejection fraction.

Diffuse myocardial fibrosis is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Dual-energy CT (DECT) can noninvasively assess myocardial fibrosis by quantification of extracellular volume (ECV) fraction. This study evaluated the association between ECV measured by DECT and clinical outcomes in patients with HFpEF. 125 hospitalized HFpEF patients were enrolled in this retrospective cohort study. ECV was measured using DECT with late iodine enhancement. The composite endpoint was defined as HFpEF hospitalization and all-cause mortality during the follow-up. During the median follow-up of 10.4 months, 34 patients (27.20%) experienced the composite outcomes, including 5 deaths; and 29 HFpEF hospitalizations. The higher DECT-ECV group had higher rates of composite outcomes than the low ECV group (log-rank X2 = 6.818, P = 0.033). In multivariate Cox regression analysis, the ECV (HR 1.17, 95% CI 1.06-1.30, P = 0.001) and NT-pro BNP (HR 2.83, 95% CI 1.16-6.88, P = 0.022) were independent risk factors for the adverse outcomes. Myocardial ECV measured using DECT was an independent risk factor for adverse outcomes in patients with HFpEF.

rs2736098, a synonymous polymorphism, is associated with carcinogenesis and cell count in multiple tissue types by regulating TERT expression.

rs2736098 is a synonymous polymorphism in TERT (telomerase reverse transcriptase), an enzyme involved in tumor onset of multiple tissues, and should play no roles in carcinogenesis. However, a search in cancer somatic mutation database indicated that the mutation frequency at rs2736098 is much higher than the average one for TERT. Moreover, there are significant H3K4me1 and H3K27Ac signals, two universal histone modifications for active enhancers, surrounding rs2736098. Therefore, we hypothesized that rs2736098 might be within an enhancer region, regulate TERT expression and influence cancer risk. Through luciferase assay, it was verified that the enhancer activity of rs2736098C allele is significantly higher than that of T in multiple tissues. Transfection of plasmids containing TERT coding region with two different alleles indicated that rs2736098C allele can induce a significantly higher TERT expression than T. By chromatin immunoprecipitation, it was observed that the fragment spanning rs2736098 can interact with USF1 (upstream transcription factor 1). The two alleles of rs2736098 present evidently different binding affinity with nuclear proteins. Database and literature search indicated that rs2736098 is significantly associated with carcinogenesis in multiple tissues and count of multiple cell types. All these facts indicated that rs2736098 is also an oncogenic polymorphism and plays important role in cell proliferation.

Topological Characteristics of the Pore Network in the Tight Sandstone Using Persistent Homology.

Tight sandstone reservoirs have become important areas for unconventional reservoir development, and their pore network is a key feature for identifying tight sandstone, which affects fluid migration path and reservoir development efficiency. However, the connectivity characteristics of the pore network at different scales have remained unclear owing to the numerous pores and uneven pore shape. Here, using pore size distributions from many hundreds of tight sandstone samples and subsequent topological data analysis, we construct the topological structure of the pore network in the Yanchang Formation tight sandstone of the Ordos Basin in China and visualize the topological characteristics of the pore network with distances. We show that there are three connected groups within the pore structure of the tight sandstone. The topology of the pore network resides on a trident ring manifold, suggesting that the pore network in the tight sandstone encompasses three obvious dominant connection paths. One prominent bar on the H0 dimension in the barcode indicates a two-point connection from nanoscale to microscale in the pore network. Three prominent bars with varying durations on the H1 dimension indicate the presence of three separate multipoint connections within a limited extent in the pore network. Connectivity of combined pores is good and controlled by the topological structure of the pore network. This demonstration of pore connections on a trident ring manifold provides a population-level visualization of the pore network in the tight sandstone.

Comparison of the Clinical Efficacy and Bone Cement Distribution Difference Between Kummell's Disease and Osteoporotic Vertebral Compression Fracture After Percutaneous Kyphoplasty.

BACKGROUND: Kummell's disease (KD) and osteoporotic vertebral compression fracture (OVCF) are commonly found in patients with osteoporosis. Several studies have been conducted on bone cement distribution in OVCF or KD; a comparison between the 2 diseases is rarely reported. OBJECTIVES: To compare the clinical efficacy and bone cement distribution difference between KD and OVCFs after percutaneous kyphoplasty (PKP). STUDY DESIGN: This was a retrospective, nonrandomized controlled study. SETTING: Department of Orthopedics from an affiliated hospital. METHODS: From January 2018 to December 2020, 61 patients who underwent PKP surgery for single KD or OVCF and met the inclusion criteria were retrospectively reviewed. All patients were assigned to 2 groups: the KD group and the OVCF group. Clinical and radiologic characteristics, including the bone cement volume, leakage, bone cement dispersion scale, anterior vertebral height (AVH), median vertebral height (MVH), posterior vertebral height (PVH), Cobb angle and Visual Analog Scale (VAS) were analyzed and compared using Mimics three-dimensional (3D) reconstruction images and 3D reconstruction computed tomography, preoperatively, postoperatively, and 2 years after the operation, respectively. The correlations between the bone cement dispersion scale and the VH improvement rate (VHIR), VH change rate (VHCR), VAS improvement rate (VASIR), and follow-up VAS improvement rate (f-VASIR) were also evaluated. RESULTS: The mean follow-up time was 24.0 months. Postoperative VH, Cobb angle, vertebra volume, and VAS score were significantly improved in the 2 groups (P < 0.05). There was no statistical difference in postoperative parameters between the 2 groups. While a strong positive correlation between VHIR and bone cement dispersion scale was observed in the OVCF group (P < 0.01), no significant correlation between VHIR and bone cement dispersion scale was found in the KD group. There was no correlation between VASIR and bone cement dispersion scale in both groups. Compared with postoperation, VH was lower in both groups in later follow-up, and the difference between the 2 groups was statistically significant (P < 0.05). VH, VAS, f-VASIR, and VHCR had a worse manifestation in the KD group than in the OVCF group. However, no significant correlation was found between VHCR, f-VASIR, and bone cement dispersion scale in the 2 groups. LIMITATIONS: This study was limited by the non-randomized design, small sample size, and lack of a comprehensive follow-up period. CONCLUSIONS: Although there was no significant difference in the bone cement distribution and early clinical efficacy between KD and OVCF patients under the same surgical plan and surgeon, OVCF patients exhibited better long-term radiologic and clinical outcomes.

A carbon nanotube x-ray source array designed for a new multisource cone beam computed tomography scanner.

Cone beam computed tomography (CBCT) is known to suffer from strong scatter and cone beam artifacts. The purpose of this study is to develop and characterize a rapidly scanning carbon nanotube (CNT) field emission x-ray source array to enable a multisource CBCT (ms-CBCT) image acquisition scheme which has been demonstrated to overcome these limitations. A CNT x-ray source array with eight evenly spaced focal spots was designed and fabricated for a medium field of view ms-CBCT for maxillofacial imaging. An external multisource collimator was used to confine the radiation from each focal spot to a narrow cone angle. For ms-CBCT imaging, the array was placed in the axial direction and rapidly scanned while rotating continuously around the object with a flat panel detector. The x-ray beam profile, temporal and spatial resolutions, energy and dose rate were characterized and evaluated for maxillofacial imaging. The CNT x-ray source array achieved a consistent focal spot size of 1.10 ± 0.04 mm × 0.84 ± 0.03 mm and individual beam cone angle of 2.4°±0.08 after collimation. The x-ray beams were rapidly switched with a rising and damping times of 0.21 ms and 0.19 ms, respectively. Under the designed operating condition of 110 kVp and 15 mA, a dose rate of 8245µGy s-1was obtained at the detector surface with the inherent Al filtration and 2312µGy s-1with an additional 0.3 mm Cu filter. There was negligible change of the x-ray dose rate over many operating cycles. A ms-CBCT scan of an adult head phantom was completed in 14.4 s total exposure time for the imaging dose in the range of that of a clinical CBCT scanner. A spatially distributed CNT x-ray source array was designed and fabricated. It has enabled a new multisource CBCT to overcome some of the main inherent limitations of the conventional CBCT.

Compound Z526 alleviates chemotherapy-induced cachectic muscle loss by ameliorating oxidative stress-driven protein metabolic imbalance and apoptosis.

Chemotherapy is one of the primary and indispensable intervention against cancers though it is always accompanied by severe side effects especially cachexia. Cachexia is a fatal metabolic disorder syndrome, mainly characterized by muscle loss. Oxidative stress is the key factor that trigger cachectic muscle loss by inducing imbalance in protein metabolism and apoptosis. Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo. Furthermore, Z526 also could ameliorate C2C12 myotube atrophy induced by the combination of chemotherapeutic agents with conditioned medium of various tumor cells in vitro as well as mice muscle atrophy of C26 tumor-bearing mice treated with oxaliplatin. The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers.