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During the chemical manufacturing control processing of new paclitaxel formulations, a photodegradation impurity called C3-C11 bridge-bond isomer appeared. Our work describes the synthesis, isolation, purification, and structural characterization methods using four spectroscopies: FT-IR, UV, NMR (1H and 13 C), and LC-MS. In addition, we discovered that the C3-C11 bridge-bond isomer can promote A549 cells pyroptosis, and increase pyroptosis-related proteins, including cleaved-caspase 3, cleaved-PARP, GSDME-N, and lactate dehydrogenase, thus making it anti-tumor effects. The study offered data suggesting that the C3-C11 bridge bond isomer may be used as an anti-tumour drug in the future.

Silicosis is an occupational lung disease caused by inhaling silica dust. The disease is characterized by early lung inflammation and late irreversible pulmonary fibrosis. Here we report the effect of Baicalin, a main flavonoid compound from the roots of Chinese herbal medicine Huang Qin on silicosis in a rat model. Results showed Baicalin (50 or 100 mg/kg/day) can mitigate the silica-induced lung inflammation and reduce the harm of alveolar structure and the blue region of collagen fibers in rat lung at 28 days after administration. At the same time, Baicalin also diminished the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in lung tissues. The protein expression of collagen I (Col-1), α-smooth muscle actin (α-SMA) and vimentin were down-regulated while E-cadherin (E-cad) was increased in Baicalin-treated rats. In addition, the Toll Like Receptor 4 (TLR4)/ nuclear factor kappaB (NF-κB) pathway was enabled at 28 days after silica infusion, and the treatment of Baicalin diminished the expression of TLR4 and NF-κB in the lungs of rat with silicosis. These results suggested that Baicalin inhibited the pulmonary inflammatory and fibrosis in a rat model of silicosis, which could be attributed to inhibition of the TLR4/NF-κB pathway.

A practical Rh(iii)-catalyzed, redox-neutral C–H alkenylation of benzamides with gem-difluorohomoallylic silyl ethers enables the synthesis of 2-(3,3-difluoro-4-(silyloxy)but-1-en-1-yl)benzamides with a broad substrate scope and high regioselectivity.

For a long time, wind speed profile measurement has been the primary task of weather forecasting. Therefore, the detection of atmospheric wind speed is extremely important for studying the changes in atmospheric motion. In order to solve the problems of insufficient data collection, low resolution, and low accuracy in atmospheric wind field detection, this paper introduces the relevant theories of wind speed detection, completes the optical design of the system according to the research objectives, and determines the selection of optical devices. At the same time, a Doppler wind lidar system based on a quadrichannel Mach–Zehnder interferometer is designed and built to carry out ground-based observation experiments, collect echo signal data, and inverse the atmospheric radial wind speed. Furthermore, the wind measurement error is analyzed. Firstly, the paper introduces the basic principle of the wind measurement system, i.e., using the Doppler effect of light, and then analyzes the frequency discrimination device of the system in detail, and obtains the theoretical calculation method of atmospheric wind speed inversion. At the same time, the relevant datasets of wind measurement system are analyzed, including backscattering ratio, aerosol, and molecular extinction coefficient, and the emission mechanism of the large pulse laser is also studied in detail, which provides a theoretical basis for the model construction of Doppler lidar and the research on the enhancement of pulsed laser emission energy. Secondly, according to the research index of wind measurement, a Doppler wind measurement lidar system based on a quadrichannel Mach–Zehnder interferometer is designed, including the design of ab external light path transceiver system, internal light path interferometer, software and hardware, and algorithm. The calibration of the quadrichannel Mach–Zehnder interferometer is completed, with its maximum interference contrast reaching 0.869. Through the self-developed optical transceiver system and data acquisition system, the echo signal of lidar is received and detected. Lastly, the data of echo signals collected by the interferometer are analyzed, the radial atmospheric wind speed profile is inversed, and the signal-to-noise ratio and wind speed measurement error of the system are evaluated. The experimental results show that the maximum signal-to-noise ratio (SNR) of the system can reach 1433 when the emission pulse energy of the large pulse laser is adjusted to 255 mJ, and the farthest wind speed detection distance is about 8 km. The high-precision wind speed detection range can reach 2 km, the actual wind measurement errors in this range are all within 1.593 m/s, and the minimum error is only 0.418 m/s. In addition, the backscattering coefficient and extinction coefficient of atmospheric molecules and aerosols in the range of 8 km and the atmospheric temperature in the range of 10 km are also measured. The measurement accuracy of the aerosol extinction coefficient is ±0.001 m−1, and the measurement error of atmospheric temperature within 10 km is within 2 K, achieving the expected goals.

Keratin (KRT), a natural fibrous structural protein, can be classified into two categories: "soft" cytosolic KRT that is primarily found in the epithelia tissues (e.g., skin, the inner lining of digestive tract) and "hard" KRT that is mainly found in the protective tissues (e.g., hair, horn). The latter is the predominant form of KRT widely used in biomedical research. The oxidized form of extracted KRT is exclusively denoted as keratose (KOS) while the reduced form of KRT is termed as kerateine (KRTN). KOS can be processed into various forms (e.g., hydrogel, films, fibers, and coatings) for different biomedical applications. KRT/KOS offers numerous advantages over other types of biomaterials, such as bioactivity, biocompatibility, degradability, immune/inflammatory privileges, mechanical resilience, chemical manipulability, and easy accessibility. As a result, KRT/KOS has attracted considerable attention and led to a large number of publications associated with this biomaterial over the past few decades; however, most (if not all) of the published review articles focus on KRT regarding its molecular structure, biochemical/biophysical properties, bioactivity, biocompatibility, drug/cell delivery, and in vivo transplantation, as well as its applications in biotechnical products and medical devices. Current progress that is directly associated with KOS applications in tissue regeneration and drug delivery appears an important topic that merits a commentary. To this end, the present review aims to summarize the current progress of KOS-associated biomedical applications, especially focusing on the in vitro and in vivo effects of KOS hydrogel on cultured cells and tissue regeneration following skin injury, skeletal muscle loss, peripheral nerve injury, and cardiac infarction.

An efficient, one-pot approach has been established for synthesizing a wide range of 3-amino-[1,2,4]-triazolo pyridines and related heterocycles from the electrochemically induced desulfurative cyclization of 2-hydrazinopyridines with isothiocyanates. The protocol allows for the formation of C-N bonds under simple conditions without transition metals or external oxidants. The practicability of this strategy is demonstrated by its broad substrate scope, good functional group compatibility, and gram-scale synthesis. The late-stage modification of 3-amino-[1,2,4]-triazolo pyridines enables us to obtain several molecules with potent anticancer activity.

To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens.This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P 0.05.There was no significant difference in the distribution of pathogens between Groups II and Groups III (P0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria.In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.

This study investigated the seismic performance of an innovative semi-precast concrete sandwich shear wall (SCSSW) system. The system consists of two precast reinforced concrete (RC) wythes, a core cast-in-place RC wythe, a core thermal insulation layer, the fiber reinforced polymer connectors and the steel trusses. A total of three RC shear wall specimens were fabricated and tested under in-plane cyclic load. They consists of one conventional cast-in-place RC shear wall, one structural wythe of SCSSW (i.e., the assemble of a precast and a cast-in-place RC wythe), and one typical SCSSW. The failure mode, hysteretic curve, ductility and energy dissipation of the three specimens were studied and compared. Furthermore, numerical simulation based on multi-layer shell element was conducted to reproduce the test, and parametric analysis was conducted to facilitate a better understanding on the SCSSW. It was concluded that the SCSSW presented a ductile failure behavior; the seismic performance of the SCSSW including hysteretic curves, skeleton curves, stiffness degradation and the energy dissipation was similar to that of the cast-in-place RC shear wall, while the ductility of the SCSSW was slightly lower; and the facade precast RC wythe contributed few effect on the seismic performance of the SCSSW.

There will be generated some adverse conditions in the process of acquculture farming with the continuous improvement of the intensive degree of modern aquaculture, such as crowding stress, hypoxia, and malnutrition, which will easily lead to oxidative stress. Se is an effective antioxidant, participating and playing an important role in the antioxidant defense system of fish. This paper reviews the physiological functions of selenoproteins in resisting oxidative stress in aquatic animals, the mechanisms of different forms of Se in anti-oxidative stress in aquatic animals and the harmful effects of lower and higher levels of Se in aquaculture. To summarize the application and research progress of Se in oxidative stress in aquatic animals and provide scientific references for its application in anti-oxidative stress in aquaculture.

Background Emergence delirium (ED) is a postoperative cognitive dysfunction that not only causes distress to patients and their families in the early post-anesthesia period, but also has long-term adverse effects in children. There are assumptions that non-delirium sedatives reduce adverse outcomes in children admitted to PACU( Post anesthesia care unit )1. Main purpose to verify whether dexmedetomidine can reduce the occurrence of PACU ED in children. To compare the effects of different administration methods of dexmedetomidine on reducing ED. And exploring whether giving dexmedetomidine at different times during the perioperative period affects the incidence of ED. Research type A systematic review and meta-analysis of randomized controlled trials. Data acquisition We searched WOS, WHO Trials, Cochrane Library, Clinical Trials.gov and PubMed for all published studies from the establishment of the library up to 23 Oct.2022. Eligibility criteria If the subjects were actively given dexmedetomidine before entering the PACU, and the occurrence of ED was used as the outcome measure, and the sample mean / median age was no more than 18 years old, they were included in the study. Studies examining the use of dexmedetomidine after surgery were excluded. Results A data analysis from seven studies involving 512 patients showed that prophylactic use of dexmedetomidine reduced the incidence of ED in children(risk ratio[RR] 0.40 ; 95% confidence interval [CI] 0.30–0.55 ; P P = 0.002.), intranasal injection of dexmedetomidine (n = 162, [RR] 0.29, 95%[CI] 0.16–0.52, P P = 0.05.), dexmedetomidine given before and during surgery (n = 162, [RR] 0.29, 95%[CI] 0.16–0.52, P P = 0.02) has a better effect on reducing the incidence of ED. In addition, prophylactic application of dexmedetomidine can reduce the occurrence of PONV (postoperative nausea and vomiting): 7 studies: n = 512 patients; [RR] 0.24; 95%[CI] 0.12–0.49; P = 0.0001. The occurrence of bradycardia was not statistically significant (2 studies: n = 157; [RR] 3.24; 95%[CI] 0.52–20.40; P = 0.21). Otherwise, because there was only one case of hypotension, we did not perform a meta-analysis. Prophylactic application of dexmedetomidine reduced PACU stay time after extubation (n = 446; mean difference [MD] -1.57; 95%[CI] -3.07 to -0.07, P = 0.04). However, sensitivity analysis of PACU stay time after extubation was not statistically significant and stable (n = 296; [MD] -0.55; 95%[CI] -1.30-0.19, P = 0.15) Conclusion Prophylactic use of dexmedetomidine can reduce the occurrence of ED in children and the adverse events no significant increase. In pediatric surgery, the anesthesiologist should consider the use of dexmedetomidine. In the future, we hope to confirm our findings through multi-center trials and clarify and explain the mechanism behind the reduction of ED with dexmedetomidine. TRIAL REGISTRATION PROSPERO: CRD42022371840.

Supplementary Table S3

Purpose:Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC).Experimental Design: The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and in vitro bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.Results:Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosa-associated organs. Tumor-derived MAIT cells displayed a typical CCR7−CD45RA−CD45RO+CD95+ effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretion and cytolysis effector function like NFKB1 and STAT5B and by upregulating genes like IL8, CXCL12, and HAVCR2 (TIM-3). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.Conclusions:HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.See related commentary by Carbone, p. 3199

Objective: This study aimed to investigate the effect of preoperative current smoking on chronic postsurgical pain in patients who underwent thoracic surgery. Methods: A total of 5,395 patients aged over 18 years old who underwent thoracic surgery from January 2016 to March 2020 in Henan Provincial People’s Hospital were enrolled. Patients were divided into two groups: the smoking group (SG group) and the nonsmoking group (NSG group). Propensity score matching was utilized to eliminate the influence of confounding factors, and a multivariable logistic regression model was established to determine the effect of preoperative current smoking on chronic postsurgical pain. The dose-response relationship between the smoking index (SI) and chronic postsurgical pain at rest was analyzed using a restricted cubic spline curve. Results: In a matched cohort of 1028 patients, the incidence of chronic pain at rest was 13.2% in the smoking group and 19.0% in the nonsmoking group (P = 0.011). Three different models were used to verify the stability of the model between preoperative current smoking and chronic postsurgical pain. A regression model was established to determine the influence of different smoking indexes (SIs) on chronic postsurgical pain. The incidence of chronic pain at rest was lower in patients with SI ≥400 before thoracic surgery than in patients whose SI was less than 400. Conclusions: A relationship between the preoperative current smoking index and chronic postsurgical pain at rest was observed. The incidence of chronic postsurgical pain at rest was lower in patients whose SI was greater than 400.

HMOs (human milk oligosaccharides) are the third most important nutrient in breast milk. As complex glycans, HMOs play an important role in regulating neonatal intestinal immunity, resisting viral and bacterial infections, displaying anti-inflammatory characteristics, and promoting brain development. Although there have been some previous reports of HMOs, a detailed literature review summarizing the structure-activity relationships and dose-dependent effects of HMOs is lacking. Hence, after introducing the structures and synthetic pathways of HMOs, this review summarizes and categorizes identified structure-function relationships of HMOs. Differential mechanisms of different structural HMOs utilization by microorganisms are summarized. This review also emphasizes the recent advances in the interactions between different health benefits and the variance of dosage effect based on in vitro cell tests, animal experiments, and human intervention studies. The potential relationships between the chemical structure, the dosage selection, and the physiological properties of HMOs as functional foods are vital for further understanding of HMOs and their future applications.

We present a hybrid quantum system composed of a magnetic vortex and a nanomechanical resonator. We show that the gyrotropic mode of the vortex can coherently couple to the quantized mechanical motion of the resonator through magnetic interaction. Benefiting from the topologically protected properties and the low damping of vortices, as well as the excellent coherent features of nanomechanical resonators, the proposed system can achieve strong coupling and even the ultrastrong coupling regime by choosing appropriate parameters. In combination with other quantum systems, such as a nitrogen-vacancy (NV) center, coherent state transfer between the vortex excitation and the spin can be realized. This setup provides a potential platform for quantum information processing and investigations into the ultrastrong coupling regimes and macroscopic quantum physics., To appear in PR Applied, 12 pages, 9 figures

With the advantages of high energy density, long cycle life and high stability, lithium-ion batteries have been used in a large number of fields such as electric vehicles and grid scale energy storage. To ensure the safe and reliable operation of battery systems, it is important to make an accurate and rapid estimation of the state of health (SOH) of Li-ion cells. A Li-ion cell is a complex nonlinear dynamic system. The SOH of a Li-ion can not be measured directly in actual working conditions; it can only be estimated indirectly by external characteristic parameters that reflects the extent of cell aging. It is difficult to ensure the reliability of method based on a single aging feature or model. Therefore, this paper proposes a multi-feature SOH estimation method that combines data-driven XGBoost and a Kalman filter. Firstly, a principal component analysis algorithm to reconstruct multiple battery aging features based on data is used, and an XGBoost online estimation model incorporating multiple features based on the reconstructed feature data is constructed. Finally, the joint optimal estimation of SOH of Li-ion cells by introducing a time-domain Kalman filter based on the real-time correction of the XGBoost model is achieved in this method. The results show that the method improves the accuracy and robustness of the estimation model and achieves a high-precision joint estimation of SOH for Li-ion cells.

A versatile approach towards 2-hydroxy-2-substituted indol-3-ones via a copper-catalyzed radical cyclization of 2-arylethynylanilines in the presence of O2 has been developed. The products can be transformed to 3-hydroxy-3-substituted indol-2-ones.

Additional file 1: Supplementary Table 1. Timeconsumption (seconds) of AI and experienced interpreter.

Objective. In this study, we aimed to explore the efficacy of the autologous platelet-rich plasma (PRP) interventional circulatory perfusion combined with radiofrequency ablation and thermocoagulation (RFAT) in the treatment of discogenic low back pain (DLBP). Methods. From January 2020 to November 2022, 158 patients of the Second Affiliated Hospital of Nanchang University were selected as the study subjects, and 24 patients met the exclusion criteria. The 134 patients who met the inclusion criteria were divided into 65 patients in the control group (3 patients lost to follow-up) and 69 patients in the observation group (5 patients lost to follow-up), so 126 patients were actually completed the study, including 62 patients in the control group and 64 patients in the observation group. The control group responsible disc received RFAT, and an interventional circulatory perfusion was performed; the observation group received RFAT, and an interventional circulatory perfusion was performed, and then autologous PRP 2 ml was injected. Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were performed before and 4 and 8 weeks after treatment, and the efficacy was evaluated at 4 and 8 weeks after treatment. The changes of lumbar disc MRI before and after treatment were observed. Results. The differences in the Visual Analog Scale (VAS) scores and the Oswestry Disability Index (ODI) between the observation group and the control group before the treatment were not statistically significant (P>0.05 in both). However, four weeks and eight weeks after the treatment, the VAS scores and the ODIs were significantly lower in both groups than those before the treatment (P

Precisely controlling the selectivity of nanocatalysts has always been a hot topic in heterogeneous catalysis but remains difficult owing to their complex and inhomogeneous catalytic sites. Herein, an effective strategy to regulate the chemoselectivity of Pd nanocatalysts for selective hydrogenation reactions by inserting single-atom Zn into Pd nanoparticles is reported. Taking advantage of the tannic acid coating-confinement strategy, small-sized Pd nanoparticles with inserted single-atom Zn are obtained on the O-doped carbon-coated alumina. Compared with the pure Pd nanocatalyst, the Pd nanocatalyst with single-atom Zn insertion exhibits prominent selectivity for the hydrogenation of p-iodonitrobenzene to afford the hydrodeiodination product instead of nitro hydrogenation ones. Further computational studies reveal that the single-atom Zn on Pd nanoparticles strengthens the adsorption of the nitro group to avoid its reduction and increases the d-band center of Pd atoms to facilitate the reduction of the iodo group, which leads to enhanced selectivity. This work provides new guidelines to tune the selectivity of nanocatalysts with guest single-atom sites.

The immersion weakening effect of natural soil has always been a difficult problem encountered in geotechnical engineering practice. The bond dissolution is a common cause of soil strength deterioration, which is not yet fully understood. In this study, a thermodynamic-based constitutive model of structural soils based on the α model is first established, considering the bond strength by modifying the yield surface size and gradually reducing the bond strength with the development of plastic strain. Furthermore, by taking the meso-mechanisms of bond dissolution into account, the evolution rule of the free energy during the bond dissolution process is derived based on a homogenization approach, and a thermodynamic-based constitutive model of structural soil with bond dissolution is thereafter developed. By comparing with the results of one-dimensional compression tests and conventional triaxial tests, the model is verified to be capable of reflecting the gradual destructuration process of soil while loading. The comparison with triaxial test results of completely decomposed granite after different immersion durations and parametric studies show that based on the cross-scale energy equivalence, the model can well reflect the strength deterioration characteristics of completely decomposed granite with bond dissolution mechanisms at the mesoscale fully considered.

An efficient, sustainable and straightforward method is reported for the synthesis of a series of α,α-difluoromethyl carbinols via K2CO3-triggered Friedel–Crafts reaction of electron-rich arenes using the stable and easily affordable 2,2-difluorovinyl arylsulfonate.

A versatile hydroxy-directed aldehyde C–H activation/annulation of salicylaldehydes with fluorovinyl tosylates enables the synthesis of diverse 2,3-non-substituted and 2-fluoroalkoxy-substituted chromones via Cp*Ir(iii) or Cp*Rh(iii) catalysis.

Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which are rich in many vegetables, fruits, nuts, dairy products, and meats. An increasing number of clinical studies have demonstrated a strong relationship between elevated plasma TMAO levels and adverse cardiovascular events. It is commonly agreed that TMAO acts as an independent risk factor and a prognostic index for patients with cardiovascular disease. Although most animal (mainly rodent) data support the clinical findings, the mechanisms by which TMAO modulates the cardiovascular system are still not well understood. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for diagnosis and treatment of patients with cardiovascular disease.

This paper considers the time difference of arrival (TDOA) and frequency difference of arrival (FDOA) estimation problem for joint localization using unmanned aerial vehicles (UAVs), involving range migration (RM) and Doppler ambiguity within observation interval. A robust estimation method based on interpolation and resampling is proposed. Specifically, the interpolation artificially increases the pulse repetition frequency (PRF). After that, the resampling eliminates the coupling between range frequency and slow time. Finally, a coherent integration step based on inverse discrete Fourier transform (IDFT) is used to achieve parameter estimation and suppress the grating lobes caused by interpolation. The proposed method could be efficiently implemented by fast Fourier transform (FFT), inverse FFT (IFFT) and non-uniform FFT (NUFFT) without parameter searching procedures. Numerical experiments indicate that the proposed method has nearly optimal anti-noise performance but much lower computational complexity than the maximum likelihood estimator, which makes it more competitive in practical applications.

The detection of microRNA (miRNA) in human serum has great significance for cancer prevention. Herein, a novel self-powered biosensing platform is developed, which effectively integrates an enzymatic biofuel cell (EBFC)-based self-powered biosensor with a matching capacitor for miRNA detection. A catalytic hairpin assembly and hybrid chain reaction are used to improve the analytical performance of EBFC. Furthermore, the matching capacitor is selected as an auxiliary signal amplifying device, and graphdiyne is applied as substrate material for EBFC. The results confirm that the developed method obviously increases the output current of EBFC, and the sensitivity can reach 2.75 μA/pM, which is 786% of pure EBFC. MiRNA can be detected in an expanded linear range of 0.1-100000 fM with a detection limit of 0.034 fM (S/N = 3). It can offer a selective and sensitive platform for nucleotide sequence detection with great potential in clinical diagnostics.

Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.

Current medicinal treatments for diseases comprise largely of two categories: small molecular (chemical) (e.g., aspirin) and larger molecular (peptides/proteins, e.g., insulin) drugs. Whilst both types of therapeutics can effectively treat different diseases, ranging from well-understood (in view of pathogenesis and treatment) examples (e.g., flu), to less-understood chronic diseases (e.g., diabetes), classical small molecule drugs often possess significant side-effects (a major cause of drug withdrawal from market) due to their low- or non-specific targeting. By contrast, therapeutic peptides, which comprise short sequences from naturally occurring peptides/proteins, commonly demonstrate high target specificity, well-characterized modes-of-action, and low or non-toxicity in vivo. Unfortunately, due to their small size, linear permutation, and lack of tertiary structure, peptidic drugs are easily subject to rapid degradation or loss in vivo through chemical and physical routines, thus resulting in a short half-life and reduced therapeutic efficacy, a major drawback that can reduce therapeutic efficiency. However, recent studies demonstrate that the short half-life of peptidic drugs can be significantly extended by various means, including use of enantiomeric or non-natural amino acids (AAs) (e.g., L-AAs replacement with D-AAs), chemical conjugation [e.g., with polyethylene glycol], and encapsulation (e.g., in exosomes). In this context, we provide an overview of the major in vivo degradation forms of small therapeutic peptides in the plasma and anti-degradation strategies. We also update on the progress of small peptide therapeutics that are either currently in clinical trials or are being successfully used in clinical therapies for patients with non-infectious diseases, such as diabetes, multiple sclerosis, and cancer. Accepted version

This multicenter prospective, randomized controlled clinical trial compared the clinical performance of supraglottic airway device (SAD) BlockBusterA total of 651 adult patients scheduled for elective surgery in 13 hospitals were randomly allocated into BlockBuster group (n = 351) or Supreme group (n = 300). The primary outcome was oropharyngeal leak pressure (OLP). Duration and ease of insertion, fiberscopic view of positioning, airway manipulations, and complications were also assessed.The OLP was significantly higher in BlockBuster group compared with Supreme group (29.9 ± 4.2 cmHBoth SAD BlockBusterThe trial is registered at www.chictr.org.cn (ChiCTR-ONC-16009105).