3D printable elastomers with exceptional strength and toughness.

Three-dimensional (3D) printing has emerged as an attractive manufacturing technique because of its exceptional freedom in accessing geometrically complex customizable products. Its potential for mass manufacturing, however, is hampered by its low manufacturing efficiency (print speed) and insufficient product quality (mechanical properties). Recent progresses in ultra-fast 3D printing of photo-polymers1-5 have alleviated the issue of manufacturing efficiency, but the mechanical performance of typical printed polymers still falls far behind what is achievable with conventional processing techniques. This is because of the printing requirements that restrict the molecular design towards achieving high mechanical performance. Here we report a 3D photo-printable resin chemistry that yields an elastomer with tensile strength of 94.6 MPa and toughness of 310.4 MJ m-3, both of which far exceed that of any 3D printed elastomer6-10. Mechanistically, this is achieved by the dynamic covalent bonds in the printed polymer that allow network topological reconfiguration. This facilitates the formation of hierarchical hydrogen bonds (in particular, amide hydrogen bonds), micro-phase separation and interpenetration architecture, which contribute synergistically to superior mechanical performance. Our work suggests a brighter future for mass manufacturing using 3D printing.

Shape memory polymer with programmable recovery onset.

Stimulus-responsive shape-shifting polymers1-3 have shown unique promise in emerging applications, including soft robotics4-7, medical devices8, aerospace structures9 and flexible electronics10. Their externally triggered shape-shifting behaviour offers on-demand controllability essential for many device applications. Ironically, accessing external triggers (for example, heating or light) under realistic scenarios has become the greatest bottleneck in demanding applications such as implantable medical devices8. Certain shape-shifting polymers rely on naturally present stimuli (for example, human body temperature for implantable devices)8 as triggers. Although they forgo the need for external stimulation, the ability to control recovery onset is also lost. Naturally triggered, yet actively controllable, shape-shifting behaviour is highly desirable but these two attributes are conflicting. Here we achieved this goal with a four-dimensional printable shape memory hydrogel that operates via phase separation, with its shape-shifting kinetics dominated by internal mass diffusion rather than by heat transport used for common shape memory polymers8-11. This hydrogel can undergo shape transformation at natural ambient temperature, critically with a recovery onset delay. This delay is programmable by altering the degree of phase separation during device programming, which offers a unique mechanism for shape-shifting control. Our naturally triggered shape memory polymer with a tunable recovery onset markedly lowers the barrier for device implementation.

Generation for high-dimensional caustics and artificially tailored structured caustic beams.

We theoretically propose and demonstrate topological parabolic umbilic beams (PUBs) with high-dimensional caustic by mapping catastrophe theory into optics. The PUBs are first experimentally observed via dimensionality reduction. Due to the high-dimensionality, such light beams exhibit rich caustic structures characterized by optical singularities where the high-intensity gradient appears. Further, we propose an improved caustic approach to artificially tailored structured beams which exhibit significant intensity gradient and phase gradient. The properties can trap and drive particles to move along the predesigned trajectory, respectively. The advantages for structured caustic beams likely enable new applications in flexible particle manipulation, light-sheet microscopy, and micromachining.

Epidemiological characterization and risk assessment of rabbit haemorrhagic disease virus 2 (RHDV2/b/GI.2) in the world.

A novel variant of rabbit haemorrhagic disease virus, designated RHDV2/b/GI.2, was first discovered in France in 2010. Subsequently, RHDV2 rapidly spread to Africa, North America, Australia, and Asia. RHDV2 outbreaks have resulted in significant economic losses in the global rabbit industry and disrupted the balance of natural ecosystems. Our study investigated the seasonal characteristics of RHDV2 outbreaks using seasonal indices. RHDV2 is prone to causing significant outbreaks within domestic and wild rabbit populations during the spring season and is more likely to induce outbreaks within wild rabbit populations during late autumn in the Southern Hemisphere. Furthermore, based on outbreak data for domestic and wild rabbits and environmental variables, our study established two MaxEnt models to explore the relationship between RHDV2 outbreaks and the environmental factors and conducted outbreak risk predictions for RHDV2 in global domestic and wild rabbit populations. Both models demonstrated good predictive performance, with AUC values of 0.960 and 0.974, respectively. Road density, isothermality, and population density were identified as important variables in the outbreak of RHDV2 in domestic rabbits, while road density, normalized difference vegetation index, and mean annual solar radiation were considered key variables in the outbreak of RHDV2 in wild rabbits. The environmental factors associated with RHDV2 outbreaks identified in our study and the outbreak risk prediction maps generated in our study will aid in the formulation of appropriate RHDV2 control measures to reduce the risk of morbidity in domestic and wild rabbits.

Dual-specificity phosphatase 1 inhibits Singapore grouper iridovirus replication via regulating apoptosis in Epinephelus coioides.

The dual-specificity phosphatase (DUSP) family plays key roles in the maintenance of cellular homeostasis and apoptosis etc. In this study, the DUSP member DUSP1 of Epinephelus coioides was characterized: the length was 2371 bp including 281 bp 5' UTR, 911 bp 3' UTR, and a 1125 bp open reading frame encoding 374 amino acids. E. coioides DUSP1 has two conserved domains, a ROHD and DSPc along with a p38 MAPK phosphorylation site, localized at Ser308. E. coioides DUSP1 mRNA can be detected in all of the tissues examined, and the subcellular localization showed that DUSP1 was mainly distributed in the nucleus. Singapore grouper iridovirus (SGIV) infection could induce the differential expression of E. coioides DUSP1. Overexpression of DUSP1 could inhibit SGIV-induced cytopathic effect (CPE), the expressions of SGIV key genes, and the viral titers. Overexpression of DUSP1 could also regulate SGIV-induced apoptosis, and the expression of apoptosis-related factor caspase 3. The results would be helpful to further study the role of DUSP1 in viral infection.

PHPB ameliorates memory deficits and reduces oxidative injury in Alzheimer's disease mouse model by activating Nrf2 signaling pathway.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

Development of novel treatments for amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes paralysis whose etiology and pathogenesis have not been fully elucidated. Presently it is incurable and rapidly progressive with a survival of 2-5 years from onset, and no treatments could cure it. Therefore, it is urgent to identify which therapeutic target(s) are more promising to develop treatments that could effectively treat ALS. So far, more than 90 novel treatments for ALS patients have been registered on ClinicalTrials.gov, of which 23 are in clinical trials, 12 have been terminated and the rest suspended. This review will systematically summarize the possible targets of these novel treatments under development or failing based on published literature and information released by sponsors, so as to provide basis and support for subsequent drug research and development.

[Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the incidence and risk factors of deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA). METHODS: The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed, including demographic characteristics, concomitant diseases, laboratory examinations (blood routine, biochemistry, coagulation, inflammatory markers, rheumatoid factor, antiphospholipid antibodies and lupus anticoagulant, etc.) and treatment regimens. The patients were compared according to the presence or absence of DVT, and the t test, Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT, followed by Logistic regression analysis to determine risk factors for DVT in patients with RA. RESULTS: The incidence of DVT in the RA patients was 9.6% (31/322); the median age of RA in DVT group was significantly older than that in non-DVT group [64 (54, 71) years vs. 50 (25, 75) years, P < 0.001]; the level of disease activity score using 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) in DVT group was higher than that in non-DVT group [5.2 (4.5, 6.7) vs. 4.5(4.5, 5.0), P < 0.001]; the incidence of hypertension, chronic kidney disease, fracture or surgery history within 3 months, and varicose veins of the lower extremities in DVT group was higher than that in non-DVT group (P < 0.001). The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group (P=0.009, P=0.004), while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group (P < 0.001). The use rate of glucocorticoid in DVT group was higher than that in non-DVT group (P=0.009). Logistic regression analysis showed that the age (OR=1.093, P < 0.001), chronic kidney disease (OR=7.955, P=0.005), fracture or surgery history within 3 months (OR=34.658, P=0.002), DAS28-ESR (OR=1.475, P=0.009), and the use of glucocorticoid (OR=5.916, P=0.003) were independent risk factors for DVT in RA patients. CONCLUSION: The incidence of DVT in hospitalized RA patients was significantly increased, in addition to traditional factors, such as age and chronic kidney disease, increased DAS28-ESR level and the use of glucocorticoid were also independent risk factors for DVT.

Generation of high-dimensional caustic beams via phase holograms using angular spectral representation.

Using angular spectral representation, we demonstrate a generalized approach for generating high-dimensional elliptic umbilic and hyperbolic umbilic caustics by phase holograms. The wavefronts of such umbilic beams are investigated via the diffraction catastrophe theory determined by the potential function, which depends on the state and control parameters. We find that the hyperbolic umbilic beams degenerate into classical Airy beams when the two control parameters are simultaneously equal to zero, and elliptic umbilic beams possess an intriguing autofocusing property. Numerical results demonstrate that such beams exhibit clear umbilics in 3D caustic, which link the two separated parts. The dynamical evolutions verify that they both possess prominent self-healing properties. Moreover, we demonstrate that hyperbolic umbilic beams follow along a curve trajectory during propagation. As the numerical calculation of diffraction integral is relatively complex, we have developed an effective approach for successfully generating such beams by using phase hologram represented by angular spectrum. Our experimental results are in good agreement with the simulations. Such beams with intriguing properties are likely to be applied in emerging fields such as particle manipulation and optical micromachining.

The effects of curcumin on anthropometric and cardiometabolic parameters of patients with metabolic related diseases: a systematic review and dose-effect meta-analysis of randomized controlled trials.

Objective:To perform a meta-analysis of published randomized controlled trials (RCTs) to assess the effects of curcumin supplementation with different formulations on anthropometric and cardiometabolic indices in patients with metabolism-related diseases (MRDs). Methods: Six databases, including PubMed, Embase, Web of Science, China national knowledge internet (CNKI), Wanfang and China Biology Medicine (CBM), were systematically searched to find relevant articles from 2011 to July 2021. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CI). Between-study heterogeneity was assessed using I2. Subgroup analysis was conducted to find possible sources of heterogeneity. Curcumin formulations in this study were divided as low bioavailability, high bioavailability and nanocurcumin. Results: Of the retrieved 1585 articles, 31 were included in the final analysis. Combined effect sizes suggested a significant effect of curcumin supplementation on reduced body weight (BW) (WMD: -0.94 kg, 95% CI: -1.40, -0.47) and body mass index (BMI) (WMD: -0.40 kg/m2, 95% CI: -0.60, -0.19), respectively. The results also showed significant improvements of fasting plasma glucose (FPG) (WMD: -0.50 mg/dL, 95% CI: -0.72, -0.28), glycosylated hemoglobin (Hb1Ac) (WMD: -0.42%, 95% CI: -0.57, -0.26), insulin (INS) (WMD: -1.70 µIU/mL, 95%CI: -2.03, -1.38), homeostasis model assessment-insulin resistance (HOMA-IR) (WMD: -0.71, 95%CI: -1.11, -0.31), high-density lipoprotein cholesterol (HDL-C) (WMD: 1.73 mg/dL, 95%CI: 0.78, 2.68) and high sensitivity C-reactive protein (Hs-CRP) (WMD: -1.11, 95%CI: -2.16, -0.05). Nanocurcumin showed a greater reduction in FPG (WMD: -1.78 mg/dL, 95% CI: -2.49, -1.07), INS (WMD: -1.66 µIU/mL, 95% CI: -3.21, -0.11), TC (WMD: -12.64 mg/dL (95% CI: -23.72, -1.57) and LDL-C (WMD: -8.95 mg/dL, 95% CI: -16.51, -1.38). The dose-effect analysis showed that there were trends of first rising and then falling between the supplemented curcumin dose and BW, BMI, LDL-C, Hb1Ac, which were clearly distinguished at 80 mg/d due to the strong effect of nanocurcumin on outcomes. A slow upward trend between the dose of curcumin supplementation and HDL-C. No relationships between dose and outcomes were found for FPG and insulin, except for nanocurcumin at 80 mg/d. Conclusions: Our study showed some significant beneficial effects of curcumin supplementation on improving BW, BMI, and the levels of FPG, Hb1Ac, HOMA-IR, HDL-C and Hs-CRP in patients with MRDs. Nanocurcumin may have a greater effect on the reduction of FPG, INS, TC and LDL-C than other curcumin formulations. Considering the potential bias and limitations of studies included, further quality studies with larger sample sizes are needed to confirm these results.

Skullcapflavone II, a novel NQO1 inhibitor, alleviates aristolochic acid I-induced liver and kidney injury in mice.

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD = 4.198 µmol/L) and inhibitory activity (IC50 = 2.87 µmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.

Direct start-up of aerobic granular sludge system with dewatered sludge granular particles as inoculant.

Aerobic granular sludge (AGS) is a promising technology for engineering applications in the biological treatment of sewage. New objective is to skip the conventional granulation step to integrate it into a continuous-flow reactor directly. This study proposed a method for integrating spherical pelletizing granular sludge (SPGS) into a new patented aerobic granular sludge bed (AGSB), a continuous up-flow reactor. AGSB system could be startup directly, and after 120 days of operation, the SPGS maintained a relatively intact spherical structure and stability. With an initial high chemical oxygen demand (COD) volume loading of over 2.0 kg/(m3·d), this system achieved the desired effect as the same as a mature AGS system. The final mixed liquid suspended solids, and the ratio of 30 min-5 min sludge volume index (SVI30/SVI5) were 20,000 mg/L, and 0.84, respectively. Although hydraulic elution and filamentous bacteria (FBs) had a slightly negative impact on initial phase pollutant removal, the final removal rates for COD, total nitrogen (TN), ammonia nitrogen (NH4+-H), and total phosphorus (TP) were 90%, 70%, 95%, and 85%, respectively. The presence of specific functional microorganisms promoted the secretion of extracellular polymeric substances (EPS), from 90.65 to 209.78 mg/gVSS. The maturation process of SPGS altered the microbial community structures and reduced the species abundance of microbes in sludge.

Visible-light photocatalytic degradation of water-soluble polyvinyl alcohol in aqueous solution by Cu2O@TiO2: Optimization of conditions, mechanisms and toxicity analysis.

Polyvinyl alcohol (PVA), a water-soluble synthetic polymer, is one of the most prevalent non-native polyvinyl alcohols found in the environment. Due to its inherent invisibility, its potential for causing severe environmental pollution is often underestimated. To achieve efficient degradation of PVA in wastewater, a Cu2O@TiO2 composite was synthesized through the modification of titanium dioxide with cuprous oxide, and its photocatalytic degradation of PVA was investigated. The Cu2O@TiO2 composite, supported by titanium dioxide, facilitated photocarrier separation and demonstrated high photocatalytic efficiency. Under alkaline conditions, the composite exhibited a 98% degradation efficiency for PVA solutions and a 58.7% PVA mineralization efficiency. Radical capture experiments and electron paramagnetic resonance (EPR) analyses revealed that superoxide radicals primarily drive the degradation process within the reaction system. Throughout the degradation process, PVA macromolecules are broken down into smaller molecules, including ethanol, and compounds containing aldehyde, ketone, and carboxylic acid functional groups. Although the intermediate products exhibit reduced toxicity compared to PVA, they still pose certain toxic hazards. Consequently, further research is necessary to minimize the environmental impact of these degradation products.

Enhancer in cancer pathogenesis and treatment.

Enhancers are essential cis-acting regulatory elements that determine cell identity and tumor progression. Enhancer function is dependent on the physical interaction between the enhancer and its target promoter inside its local chromatin environment. Enhancer reprogramming is an important mechanism in cancer pathogenesis and can be driven by both cis and trans factors. Super enhancers are acquired at oncogenes in numerous cancer types and represent potential targets for cancer treatment. BET and CDK inhibitors act through mechanisms of enhancer function and have shown promising results in therapy for various types of cancer. Genome editing is another way to reprogram enhancers in cancer treatment. The relationship between enhancers and cancer has been revised by several authors in the past few years, which mainly focuses on the mechanisms by which enhancers can impact cancer. Here, we emphasize SE's role in cancer pathogenesis and the new therapies involving epigenetic regulators (BETi and CDKi). We suggest that understanding mechanisms of activity would aid clinical success for these anti-cancer agents.

The assembly of a noncanonical LINC complex in Saccharomyces cerevisiae.

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a protein complex across the nuclear envelope and has maintained its general assembly mode throughout evolution. SUN and KASH proteins, which are the major components of LINC complex, interact with each other in the nuclear lumen to transmit forces across the nuclear envelope and have diverse functions. However, research of LINC complex in budding yeast has been limited due to the lack of identification of a canonical KASH protein and a cytoskeleton factor. Here, we review recent findings that addressed these puzzles in budding yeast. We highlight the distinct assembly model of the telomere-associated LINC complex in budding yeast, which could be beneficial for identifying LINC variants in other eukaryotes.

Selecting Candidates for Organ-Preserving Strategies After Neoadjuvant Chemoradiotherapy for Rectal Cancer: Development and Validation of a Model Integrating MRI Radiomics and Pathomics.

BACKGROUND: Histopathologic evaluation after surgery is the gold standard to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). However, it cannot be used to guide organ-preserving strategies due to poor timeliness. PURPOSE: To develop and validate a multiscale model incorporating radiomics and pathomics features for predicting pathological good response (pGR) of down-staging to stage ypT0-1N0 after nCRT. STUDY TYPE: Retrospective. POPULATION: A total of 153 patients (median age, 55 years; 109 men; 107 training group; 46 validation group) with clinicopathologically confirmed LARC. FIELD STRENGTH/SEQUENCE: A 3.0-T; fast spin echo T2 -weighted and single-shot EPI diffusion-weighted images. ASSESSMENT: The differences in clinicoradiological variables between pGR and non-pGR groups were assessed. Pretreatment and posttreatment radiomics signatures, and pathomics signature were constructed. A multiscale pGR prediction model was established. The predictive performance of the model was evaluated and compared to that of the clinicoradiological model. STATISTICAL TESTS: The χ2 test, Fisher's exact test, t-test, the minimum redundancy maximum relevance algorithm, the least absolute shrinkage and selection operator logistic regression algorithm, regression analysis, receiver operating characteristic curve (ROC) analysis, Delong method. P < 0.05 indicated a significant difference. RESULTS: Pretreatment radiomics signature (odds ratio [OR] = 2.53; 95% CI: 1.58-4.66), posttreatment radiomics signature (OR = 9.59; 95% CI: 3.04-41.46), and pathomics signature (OR = 3.14; 95% CI: 1.40-8.31) were independent factors for predicting pGR. The multiscale model presented good predictive performance with areas under the curve (AUC) of 0.93 (95% CI: 0.88-0.98) and 0.90 (95% CI: 0.78-1.00) in the training and validation groups, those were significantly higher than that of the clinicoradiological model with AUCs of 0.69 (95% CI: 0.55-0.82) and 0.68 (95% CI: 0.46-0.91) in both groups. DATA CONCLUSION: A model incorporating radiomics and pathomics features effectively predicted pGR after nCRT in patients with LARC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.

X-Chromosome Inactivation and Related Diseases.

X-chromosome inactivation (XCI) is the form of dosage compensation in mammalian female cells to balance X-linked gene expression levels of the two sexes. Many diseases are related to XCI due to inactivation escape and skewing, and the symptoms and severity of these diseases also largely depend on the status of XCI. They can be divided into 3 types: X-linked diseases, diseases that are affected by XCI escape, and X-chromosome aneuploidy. Here, we review representative diseases in terms of their definition, symptoms, and XCI's role in the pathogenesis of these diseases.

Advances in Interventional Therapies for Painful Diabetic Neuropathy: A Systematic Review.

BACKGROUND: Painful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice. METHODS: We searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN. RESULTS: We identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+). CONCLUSIONS: Moderate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN.

A novel fatty acid metabolism-related signature identifies features of the tumor microenvironment and predicts clinical outcome in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is the most common malignancy of the hematological system, and there are currently a number of studies regarding abnormal alterations in energy metabolism, but fewer reports related to fatty acid metabolism (FAM) in AML. We therefore analyze the association of FAM and AML tumor development to explore targets for clinical prognosis prediction and identify those with potential therapeutic value. METHODS: The identification of AML patients with different fatty acid metabolism characteristics was based on a consensus clustering algorithm. The CIBERSORT algorithm was used to calculate the proportion of infiltrating immune cells. We used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a signature for predicting the prognosis of AML patients. The Genomics of Drug Sensitivity in Cancer database was used to predict the sensitivity of patient samples in high- and low-risk score groups to different chemotherapy drugs. RESULTS: The consensus clustering approach identified three molecular subtypes of FAM that exhibited significant differences in genomic features such as immunity, metabolism, and inflammation, as well as patient prognosis. The risk-score model we constructed accurately predicted patient outcomes, with area under the receiver operating characteristic curve values of 0.870, 0.878, and 0.950 at 1, 3, and 5 years, respectively. The validation cohort also confirmed the prognostic evaluation performance of the risk score. In addition, higher risk scores were associated with stronger fatty acid metabolisms, significantly higher expression levels of immune checkpoints, and significantly increased infiltration of immunosuppressive cells. Immune functions, such as inflammation promotion, para-inflammation, and type I/II interferon responses, were also significantly activated. These results demonstrated that immunotherapy targeting immune checkpoints and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and M2 macrophages, are more suitable for patients with high-risk scores. Finally, the prediction results of chemotherapeutic drugs showed that samples in the high-risk score group had greater treatment sensitivity to four chemotherapy drugs in vitro. CONCLUSIONS: The analysis of the molecular patterns of FAM effectively predicted patient prognosis and revealed various tumor microenvironment (TME) characteristics.

Electrospun nanofibers modified with zeolitic imidazolate framework-8 for electrochemiluminescent determination of terbutaline.

For the first time it is demonstrated that zeolitic imidazolate framework-8 electrospun nanofibers (ZIF-8 NF) could serve as electrochemiluminescence (ECL) accelerator for the facile detection of terbutaline residual. A novel ECL sensor for the determination of terbutaline was fabricated based on ZIF-8 NF. The ZIF-8 NF were successfully prepared according to electrospinning and in-situ growth method. First, chitosan was modified on the surface of the electrode, and then the ZIF-8 NF was modified onto the upper layer of the chitosan. Taking advantages of chitosan and ZIF-8 NF in conductivity and electrocatalysis, the modified electrode presents obvious ECL phenomenon in 0.2 M PBS solution (pH 10.0) containing 0.025 M luminol. After the addition of terbutaline, ECL intensity decreased significantly, and the decreasing value showed a linear relationship with the logarithm of terbutaline concentration. The linear range was from 2.0 × 10-10 to 2.0 × 10-5 M, and the detection limit was 1.41 × 10-11 M (3σ/m). The method had high sensitivity, good stability, and good applicability to actual pork samples.