A Light-Powered Single-Stranded DNA Molecular Motor with Colour-Selective Single-Step Control.

Top-down control of small motion is possible through top-down controlled molecular motors in replacement of larger actuators like MEMS or NEMS (micro- or nano-electromechanical systems) in the current precision technology. Improving top-down control of molecular motors to every single step is desirable for this purpose, and also for synchronization of motor actions for amplified effects. Here we report a designed single-stranded DNA molecular motor powered by alternated ultraviolet and visible light for processive track-walking, with the two light colours each locking the motor in a full directional step to allow saturated driving but no overstepping. This novel nano-optomechanical driving mechanism pushes the top-down control of molecular motors down to every single step, thus providing a key technical capability to advance the molecular motor-based precision technology and also motor synchronization for amplified effects.

Different effects of intravenous and local anesthesia in patients undergoing ultrasound-guided radiofrequency ablation of thyroid nodules: a prospective cohort study.

PURPOSE: To compare the efficacy and safety of intravenous anesthesia (IV) with local anesthesia (LA) in patients undergoing ultrasound (US)-guided radiofrequency ablation (RFA) of thyroid nodules. METHODS: 50 patients with American Society of Anesthesiologists classification grades I-II undergoing US-guided thyroid RFA were enrolled and randomly (1:1) divided into IV (conscious sedation with Ramsay Sedation Scale [RSS] scores of 2-3 with an anesthesiologist) and LA (subcutaneous anesthesia with lidocaine without an anesthesiologist) groups. Pre-, intra- and post-procedural blood pressure (BP) (SBP0/DBP0, SBP1/DBP1, and SBP2/DBP2), intra- and post-procedural pain (NRS1 and NRS2), ablated area volume, treatment time and adverse events were analyzed and compared. RESULTS: Age, sex, weight, number, nature, volume of nodules, and SBP0/DBP0 showed no difference between both groups. 11 and 0 patients' SBP1/DBP1 were elevated in the LA and IV groups. NRS1 differed between both groups. 6 patients in the LA group had moderate or severe pain, but none in the IV group. No between-group difference in SBP2/DBP2, NRS2, ablation completion rate and ablated volume was noted. The median procedure duration differed from 1109 (176) s in IV group and 723 (227) s in LA groups. There was no increased incidence of adverse events in IV group. CONCLUSIONS: IV with RSS scores of 2-3 maintained intra-procedural BP and relieved intra-procedural pain better, without affecting the ablation efficacy and increasing complications. Despite increased treatment time, IV is a potential option for patients undergoing US-guided RFA of thyroid nodules.

[Biological research of color and quality evaluation in "quality discrimination by character" of Chinese medicine].

In the theories of empirical identification of "arguments on quality" and "five elephants and seven originals", color is regarded as one of the important indicators in the quality evaluation of Chinese medicine. The color of medicinal material including the surface color, the internal color, and the color after processing is caused by the pigment in the cells, which is a characteristic of the "optimal shape". Most pigments have a wide range of pharmacological activities such as anti-oxidation, anti-tumor, anti-atherosclerosis, prevention of coronary heart disease, protection of cardiovascular function, enhancement of immunity, etc. Therefore, the "optimal color" of medicinal materials is unified with the "high quality". This article systematically reviews the research status of "quality discrimination by color", the correlation between L~*, a~*, b~* color space and active ingredients such as alkaloids, flavonoids, terpenes, etc. to explain the "quality discrimination by color" in quantitative characterization. We also summary the research progress on the biosynthesis and regulation of the main pigment components of traditional Chinese medicine, and analyze the biological causes that affect the accumulation of the main pigments. We aim to provide a reference for the theory "quality discrimination by color" in biological knowledge to establish a modern quality control system for Chinese herbal medicines.

The serine/threonine protein kinase of Streptococcus suis serotype 2 affects the ability of the pathogen to penetrate the blood-brain barrier.

Streptococcus suis serotype 2 (SS2) is a zoonotic agent that causes meningitis in humans and pigs. However, the mechanism whereby SS2 crosses the microvasculature endothelium of the brain is not understood. In this study, transposon (TnYLB-1) mutagenesis was used to identify virulence factors potentially associated with invasive ability in pathogenic SS2. A poorly invasive mutant was identified and was found to contain a TnYLB-1 insertion in the serine/threonine kinase (stk) gene. Transwell chambers containing hBMECs were used to model the blood-brain barrier (BBB). We observed that the SS2 wild-type ZY05719 strain crossed the BBB model more readily than the mutant strain. Hence, we speculated that STK is associated with the ability of crossing blood-brain barrier in SS2. In vitro, compared with ZY05719, the ability of the stk-deficient strain (Δstk) to adhere to and invade both hBMECs and bEnd.3 cells, as well as to cross the BBB, was significantly attenuated. Immunocytochemistry using antibodies against claudin-5 in bEnd.3 cells showed that infection by ZY05719 disrupted BBB tight junction proteins to a greater extent than in infection by Δstk. The studies revealed that SS2 initially binds at or near intercellular junctions and crosses the BBB via paracellular traversal. Claudin-5 mRNA levels were indistinguishable in ZY05719- and Δstk-infected cells. This result indicated that the decrease of claudin-5 was maybe induced by protein degradation. Cells infected by ZY05719 exhibited higher ubiquitination levels than cells infected by Δstk. This result indicated that ubiquitination was involved in the degradation of claudin-5. Differential proteomic analysis showed that E3 ubiquitin protein ligase HECTD1 decreased by 1.5-fold in Δstk-infected bEnd.3 cells relative to ZY05719-infected cells. Together, the results suggested that STK may affect the expression of E3 ubiquitin ligase HECTD1 and subsequently increase the degradation of claudin-5, thus enabling SS2 to traverse the BBB.

Extending the time window of mammalian heart regeneration by thymosin beta 4.

Recent studies demonstrated that the heart of 1-day-old neonatal mice could regenerate, with Wt1(+) EPDCs migrating into myocardial regions after partial surgical resection, but this capacity was lost by 7 days of age. By treatment with Tß4 to maintain Wt1 expression and retain the migrating feature of EPDCs in neonatal mice, we explored the possibility of restoring the cardiac regeneration potential of mice. We intraperitoneally injected Tß4 into 1-day-old mice on daily basis and then apical resection was performed on the mice 7 days later. Twenty one days after the resection, morphological analysis revealed that the Tß4-treated mice regenerated the resected ventricular apex, while the mice in PBS control group developed significant fibrosis without apical regeneration. The Tß4-treated mice had significantly better ventricular ejection fraction and fractional shortening than controls. During the process of regeneration, Wt1(+) EPDCs migrated into myocardial region and some of them expressed Islet1 and the markers for mature cardiomyocytes, such as cTnT and SαA. These characteristics of Wt1(+) EPDCs were also seen in the heart regeneration of mice subjected to apical resection 1 day after birth. Tß4 has no essential effect on cell cycle activity as no disruption of actin filaments was observed in Tß4-treated hearts. These results revealed that the cardiac regeneration potential of neonatal mice could be extended to the 7th post-natal day by Tß4 and Wt1(+) EPDCs mobilization might play an important role in the extension.

Different levels of thyroid hormones between impaired fasting glucose and impaired glucose tolerance: free T3 affects the prevalence of impaired fasting glucose and impaired glucose tolerance in opposite ways.

CONTEXT: There is an association between thyroid disorders and diabetes mellitus. OBJECTIVE: To investigate thyroid hormone levels in different glucose metabolic statuses, analyse relationships between thyroid hormone levels and different categories of prediabetes and metabolic parameters within a large euthyroid nondiabetic population. METHODS: A total of 3328 subjects without diabetes or thyroid dysfunction were included in this cross-sectional study. Subjects were divided in to four groups [normal glucose tolerance (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and combined glucose intolerance (CGI)] according to the results of oral glucose tolerance test. Participants were then divided into four groups according to the quartile of free T3 (FT3) in their blood. RESULTS: Subjects with IFG had higher levels of FT3 and ratio of FT3 to FT4 (FT3/FT4), but lower level of free T4 (FT4) than subjects with IGT. FT3/FT4 was negatively associated with postprandial plasma glucose (PPG) [standardized ß (ß) = -0·087; P < 0·001]. The prevalence of IFG and CGI was increased with the level of FT3, while the prevalence of IGT was decreased with the level of FT3 (P for trend: <0·001, 0·003 and <0·001, respectively). FT3 was negatively associated with the risk of IGT (OR = 0·409, 95% CI 0·179-0·935), whereas FT4 was positively associated with the risk of IGT (OR = 1·296, 95% CI 1·004-1·673). CONCLUSIONS: Free thyroid hormone levels were different between subjects with IFG and IGT. FT3 affects the prevalence of IFG and IGT in opposite ways. The difference in thyroid hormone levels may play an important role in the different pathological mechanisms of IFG and IGT.

Advances in the study of autophagy in breast cancer.

Breast cancer is the most prevalent malignant tumor among women, with a high incidence and mortality rate all year round, which seriously affects women's health. Autophagy, a well-conserved cellular process inherent in eukaryotic organisms, plays a pivotal role in degrading damaged proteins and organelles, recycling their breakdown products to aid cells in navigating stress and gradually restoring homeostatic equilibrium. Recent studies have unveiled the intricate connection between autophagy and breast cancer. Autophagy is a double-edged sword in breast cancer, demonstrating a dual role: restraining its onset and progression on one hand, while promoting its metastasis and advancement on the other. It is also because of this interrelationship between the two that regulation of autophagy in the treatment of breast cancer is now an important strategy in clinical treatment. In this article, we systematically survey the recent research findings, elucidating the multifaceted role of autophagy in breast cancer and its underlying mechanisms, with the aim of contributing new references to the clinical management of breast cancer.

Correction: Undenatured type II collagen prevents and treats osteoarthritis and motor function degradation in T2DM patients and db/db mice.

Correction for 'Undenatured type II collagen prevents and treats osteoarthritis and motor function degradation in T2DM patients and db/db mice' by Fan Rui et al., Food Funct., 2021, 12, 4373-4391, https://doi.org/10.1039/D0FO03011B.

Effect of hydrogen intervention on refractory wounds after radiotherapy: A case report.

BACKGROUND: Patients with keloids who receive radiotherapy (RT) after surgery can develop refractory wounds that cannot be healed by the patient's own repair system. Such chronic wounds are uneven and complex due to persistent abscess and ulceration. Without external intervention, they can easily result in local tissue necrosis or, in severe cases, large area tissue resection, amputation, and even death. CASE SUMMARY: This article describes the use of hydrogen to treat a 42-year-old female patient with a chronic wound on her left shoulder. The patient had a skin graft that involved implanting a dilator under the skin of her left shoulder, and then transferring excess skin from her shoulder onto scar tissue on her chest. The skin grafting was followed by two rounds of RT, after which the shoulder wound had difficulty healing. For six months, the patient was treated with 2 h of hydrogen inhalation (HI) therapy per day, in addition to application of sterile gauze on the wound and periodic debridement. We also performed one deep, large, sharp debridement to enlarge the wound area. The wound healed completely within 6 mo of beginning the HI treatment. CONCLUSION: After HI therapy, the patient showed superior progress in reepithelialization and wound repair, with eventual wound closure in 6 mo, in comparison with the previous failures of hyperbaric oxygen and recombinant bovine basic fibroblast growth factor therapies. Our work showed that HI therapy could be a new strategy for wound healing that is cleaner, more convenient, and less expensive than other therapies, as well as easily accessible for further application in clinical wound care.

Undenatured type II collagen prevents and treats osteoarthritis and motor function degradation in T2DM patients and db/db mice.

Osteoarthritis (OA) has been scarcely researched among patients with diabetes mellitus. This study aims to confirm the preventive and therapeutic effects of undenatured type II collagen (UC II) on OA in aging db/db mice and in patients with T2DM. Firstly, aging db/db mice were randomly assigned to three groups: the UC II intervention (UC II) group, old model (OM) group and positive control group. Meanwhile db/m mice and young db/db mice were used as the normal control and young control groups, respectively. Secondly, fifty-five T2DM patients diagnosed with knee OA were randomly assigned to two groups: UC-II and placebo control groups. After a three-month intervention in both mice and T2DM patients, the subjects' gait and physical activities were assessed and the serum biomarkers including inflammatory cytokines, oxidative stress factors and matrix metalloproteinases (MMPs) were measured. Compared with the OM group mice, those in the UC II group showed a significantly greater superiority in terms of motor functions including the movement trajectories area (163.25 ± 20.3 vs. 78.52 ± 20.14 cm2), the tremor index (0.42 vs. 1.23), standing time (left hind: 0.089 ± 0.03 vs. 0.136 ± 0.04 s), swing (right front: 0.12 ± 0.02 vs. 0.216 ± 0.02 s), stride length (right hind: 7.2 ± 0.9 vs. 5.7 ± 1.1 cm), step cycle (right hind: 0.252 ± 0.05 vs. 0.478 ± 0.11 s) and cadence (14.12 ± 2.7 vs. 7.35 ± 4.4 steps per s). In addition, the levels of IL-4, IL-10, CTX- II and TGF-ß in the UC II group were 1.74, 2.23, 1.67 and 1.84 times higher than those in the OM group, respectively, while the levels of MMP-3 and MMP-13 in the UC II group were half those in the OM group. Correspondingly, UC II intervention significantly decreased the scores of pain, stiffness and physical function (p < 0.05), whereas the 6 MWT and total MET distances in the UC II group increased remarkably (p < 0.05). After a three-month period of intervention, the varus angle significantly decreased from 4.6 ± 2.0° to 3.0 ± 1.4° and the knee flexion range obviously increased from 57.9 ± 14.0° to 66.9 ± 10.4°. Importantly, the declining trend in the levels of hs-CRP and MDA and the incremental trend in the SOD level were consistent in the db/db mice and OA patients following UC II administration.

Cisatracurium induces mast cell activation and pseudo-allergic reactions via MRGPRX2.

BACKGROUND: Pseudo-allergic reactions occur when patients receive muscle relaxants during perioperative anesthesia. These reactions may result in a serious threat to the patient's life, particularly to a child's life. Cisatracurium, a relatively new NMBA, has resulted in bronchospasms and cardiovascular collapse. However, the mechanisms underlying the anaphylactoid reactions caused by cisatracurium have not been fully elucidated. METHODS: In the present study, the MRGPRX2-related pseudo-allergic reactions induced by cisatracurium were investigated using hindpaw swelling and extravasation assays in vivo and mast cell degranulation assays. RESULTS: Cisatracurium caused anaphylactoid reactions in wild-type mice. However, cisatracurium did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, mast cell-related G protein-coupled receptor B2-knockout mice did not display an inflammatory response upon treatment with cisatracurium. Cisatracurium induced LAD2 cell degranulation, leading to the dose-dependent release of ß-hexosaminidase, histamine and TNF-α. However, cisatracurium only induced the release of low levels of these mediator LAD2 cells transfected with MRGPRX2 siRNA. Cisatracurium also stimulated intracellular Ca2+ influx in MRGPRX2-HEK293 cells compared with that in NC-HKE293 cells. Interestingly, cytokine release was not observed in LAD2 cells even with high dose of cisatracurium. CONCLUSIONS: Cisatracurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. Therefore, strategies targeting MRGPRX2 might potentially block cisatracurium-induced pseudo-allergic reactions.

Acute toxicity and chemical evaluation of coking wastewater under biological and advanced physicochemical treatment processes.

This study investigated the changes of toxic compounds in coking wastewater with biological treatment (anaerobic reactor, anoxic reactor and aerobic-membrane bioreactor, A1/A2/O-MBR) and advanced physicochemical treatment (Fenton oxidation and activated carbon adsorption) stages. As the biological treatment stages preceding, the inhibition effect of coking wastewater on the luminescence of Vibrio qinghaiensis sp. Nov. Q67 decreased. Toxic units (TU) of coking wastewater were removed by A1/A2/O-MBR treatment process, however approximately 30 % TU remained in the biologically treated effluent. There is a tendency that fewer and fewer residual organic compounds could exert equal acute toxicity during the biological treatment stages. Activated carbon adsorption further removed toxic pollutants of biologically treated effluent but the Fenton effluent increased acute toxicity. The composition of coking wastewater during the treatment was evaluated using the three-dimensional fluorescence spectra, gas chromatography-mass spectrometry (GC-MS). The organic compounds with high polarity were the main cause of acute toxicity in the coking wastewater. Aromatic protein-like matters in the coking wastewater with low biodegradability and high toxicity contributed mostly to the remaining acute toxicity of the biologically treated effluents. Chlorine generated from the oxidation process was responsible for the acute toxicity increase after Fenton oxidation. Therefore, the incorporation of appropriate advanced physicochemical treatment process, e.g., activated carbon adsorption, should be implemented following biological treatment processes to meet the stricter discharge standards and be safer to the environment.

Automatic Reference Color Selection for Adaptive Mathematical Morphology and Application in Image Segmentation.

This paper proposes a novel automatic reference color selection (ARCS) scheme for the adaptive mathematical morphology (MM) method, and is specifically designed for color image segmentation applications. Because of the main advantages of being intuitive and simple, in the past decade, it has contributed to the growing popularity of binary and gray-scale MM processing. However, the MM process typically neglects the details of reference color determination. Applying other ordering methods, which select only black as the reference color for sorting pixels, result in the problem in which the scope of the distance measurement is not optimal. The proposed ARCS scheme is used for determining the ideal reference color for MM and for color image segmentation application. In addition, we use both 1D histogram-based modeling scheme binning from 3D color spaces, such as red-green-blue and hue-saturation-intensity, and 2D color models, such as (H, S), (Cb, Cr), and (I, By). According to the results of the quartile analysis, the threshold determination reacts with less sensitivity to the context variations of the images tested. The experiments focused on color-based image segmentation using the proposed ARCS scheme for color MM processing through a bottom-up scenario. To evaluate the system, four quantitative indices were utilized for an ARCS comparison using advanced segmentation methods in the experiments. The cross validation with different system parameters and a comparison of the morphological gradient operation with different color models are also presented.

Central role for aldose reductase pathway in myocardial ischemic injury.

Aldose reductase (AR), a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications of diabetes. Recently, we demonstrated that aldose reductase is a component of myocardial ischemic injury and that inhibitors of this enzyme protect rat hearts from ischemia-reperfusion injury. To rigorously test the effect of aldose reductase on myocardial ischemia-reperfusion injury, we used transgenic mice broadly overexpressing human aldose reductase (ARTg) driven by the major histocompatibility complex I promoter. Hearts from these ARTg or littermate mice (WT) (n=6 in each group) were isolated, perfused under normoxic conditions, then subjected to 50 min of severe low flow ischemia followed by 60 min of reperfusion. Creatine kinase (CK) release (a marker of ischemic injury) was measured during reperfusion; left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and ATP were measured throughout the protocol. CK release was significantly greater in ARTg mice compared with the WT mice. LVDP recovery was significantly reduced in ARTg mice compared with the WT mice. Furthermore, ATP content was higher in WT mice compared with ARTg mice during ischemia and reperfusion. Infarct size measured by staining techniques and myocardial damage evaluated histologically were also significantly worse in ARTg mice hearts than in controls. Pharmacological inhibition of aldose reductase significantly reduced ischemic injury and improved functional recovery in ARTg mice. These data strongly support key roles for AR in ischemic injury and impairment of functional and metabolic recovery after ischemia. We propose that interventions targeting AR may provide a novel adjunctive approach to protect ischemic myocardium.