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Purpose: To analyze cardiorespiratory fitness (CRF) levels using the gold-standard, laboratory-based cardiopulmonary exercise test (CPET) in community-dwelling older adults (N = 145) with amnestic mild cognitive impairment (aMCI), specifically CPET feasibility, CRF prediction, and CRF status in comparison to published sedentary, cognitively normal, age- and sex-adjusted normative data. Method: Peak oxygen consumption (VO[sub.2Peak] [mL/kg/min]) was assessed by CPET, which was categorized as submaximal, near-maximal, or maximal tests. VO[sub.2Max] predicted was compared to VO[sub.2Max] measured to assess its utility. Data were analyzed with t tests. Results: Participants' mean age was 73.77 years (SD = 5.74 years), with 51.7% males, 91.7% Caucasian, 68.3% married, and 16.9 years (SD = 2.88 years) of education. Mean VO[sub.2Peak] measured was 17.07 (SD = 4.92) for the total sample (18.29 [SD = 4.64] for males, 15.78 [SD = 4.91] for females). Sixteen (11.03%) CPETs were submaximal, 53 (36.55%) were near-maximal, and 76 (52.41%) were maximal. Mean VO[sub.2Max] predicted was 28.59 (SD = 21.94) for the total sample (29.36 [SD = 22.3] for males, 27.76 [SD = 21.68] for females) and was significantly higher than VO[sub.2Max] measured (p < 0.0001). Among participants with maximal CPETs, VO[sub.2Peak] measured was significantly lower than sedentary normative data (p < 0.0001). Conclusion: CPET was feasible for older adults with aMCI. VO[sub.2Max] predicted overly inflates CRF estimates. Low levels of CRF in older adults with aMCI suggest aerobic exercise as an important intervention. [Journal of Gerontological Nursing, 50(9), 31–36.], Understanding the role cardiorespiratory fitness (CRF) plays in Alzheimer's disease is a critical, understudied area of research. CRF is a physiological measure of habitual physical activity and exercise and has [...]

Objective: To assess how age-friendly deprescribing trials are regarding intervention design and outcome assessment. Reduced use of potentially inappropriate medications (PIMs) can be addressed by deprescribing--a systematic process of discontinuing and/or reducing the use of PIMs. The 4Ms--'Medication', 'Mentation', 'Mobility', and 'What Matters Most' to the person--can be used to guide assessment of age-friendliness of deprescribing trials. Data Source: Published literature. Study Design: Scoping review. Data Extraction Methods: The literature was identified using keywords related to deprescribing and polypharmacy in PubMed, EMBASE, Web of Science, ProQuest, CINAHL, and Cochrane and snowballing. Study characteristics were extracted and evaluated for consideration of 4Ms. Principal Findings: Thirty-seven of the 564 trials identified met the review eligibility criteria. Intervention design: 'Medication' was considered in the intervention design of all trials; 'Mentation' was considered in eight trials; 'Mobility' (n = 2) and 'What Matters Most' (n = 6) were less often considered in the design of intervention. Most trials targeted providers without specifying how matters important to older adults and their families were aligned with deprescribing decisions. Outcome assessment: 'Medication' was the most commonly assessed outcome (n = 33), followed by 'Mobility' (n = 13) and 'Mentation' (n = 10) outcomes, with no study examining 'What Matters Most' outcomes. Conclusions: 'Mentation' and 'Mobility', and 'What Matters Most' have been considered to varying degrees in deprescribing trials, limiting the potential of deprescribing evidence to contribute to improved clinical practice in building an age-friendly health care system. KEYWORDS age-friendly health systems, deprescribing, empirical typology, polypharmacy, review What is known on this topic * The 4Ms--'Medication', 'Mentation', 'Mobility', and 'What Matters Most'--are the guiding principles in the Age Friendly Health Initiative for providing high-quality patient-centered care for older adults. * More than one third of older adults use potentially unnecessary or inappropriate medications that can increase their risk of falls, hospitalizations, and death. * Deprescribing--reducing or stopping the potentially unnecessary or inappropriate medications for improved patient safety--is an essential component in age-friendly care and should incorporate the 4Ms. What this study adds * Varying consideration of the 4Ms of age-friendly care has been observed in the intervention design and outcome assessment of existing deprescribing trials. * Clear consideration of 'Medication' was noted in deprescribing trials, as expected. * 'Mentation' and 'Mobility', and 'What Matters Most' have been considered to varying degrees in deprescribing trials, limiting the potential of deprescribing evidence to contribute to improved clinical practice in building an age-friendly health care system., 1 | INTRODUCTION Age-friendly care--care that systematically considers the complex and interrelated needs of each patient in making health care decisions--is recognized as key in providing high-quality geriatric care. (1) [...]

Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated.

Although metal halide–based X-ray scintillators have obtained significant development with adjustable radioluminescent spectral range, the red light–emitting scintillator has been sparsely reported and remains a great challenge until now. To remedy this research blank, we investigated the scintillating property of red light–emissive one-dimensional (1D) organic manganese halide of (MBIZ)(MnCl3H2O)·H2O (MBIZ = 2-methyl-1H-benzoimidazolium) with a high PLQY of 71% under UV light excitation. Remarkably, this manganese halide single crystal exhibits a compelling X-ray scintillating property in the red light spectral range with a light yield of 19 600 photons MeV–1and detection limit of 0.204 μGy/s, which is significantly better than the standard dosage for X-ray diagnostics. Furthermore, this manganese halide also exhibits excellent radiation resistance ability toward long-term continuous irradiation of high-dose X-ray with stable radiophotoluminescence intensity. Benefiting from the abovementioned combined merits, (MBIZ)(MnCl3H2O)·H2O demonstrates high-performance X-ray imaging with an outstanding spatial resolution of 11.1 lpmm–1. As far as we know, this is an infrequent red-emissive X-ray scintillator in metal halide materials, which highlights a successful structural design concept to explore new manganese halides as more desirable scintillators and expand the application field in medical diagnosis.

Although organic–inorganic hybrid Mn2+halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C–H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4[BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor β-SiAlON:Eu2+and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2–units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron–phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

Triterpenoid saponins, synthesized via the mevalonic acid (MVA) pathway in the cytoplasm, provide protection against pathogens and pests in plants and health benefits for humans. However, the mechanisms by which triterpenoid saponins are transported between cellular compartments remain uncharacterized. Here, we characterize a tonoplast localized multidrug and toxic compound extrusion transporter, GmMATE100 (encoded by Glyma.18G143700), from soybean (Glycine maxL.). GmMATE100is co-expressed with soyasaponin biosynthetic genes, and its expression was induced by MeJA treatment, which also led to soyasaponin accumulation in soybean roots. GmMATE100 efficiently transports multiple type-B soyasaponins as well as type-A soyasaponins with low affinity from the cytosol to the vacuole in a yeast system. The GmMATE100loss-of-function mutant showed a significant decrease in type-A and type-B soyasaponin contents in soybean roots. This study not only characterized the first soybean triterpenoid saponin transporter but also provided new knowledge for the rational engineering of soyasaponin content and composition in soybean plants to modulate their levels within crop environments.

Despite significant advancements in surgical instruments and operation skills, short- and long-term outcomes following anterior cruciate ligament reconstruction (ACLR) remain unsatisfactory, as many patients fail to return to their pre-injury level of sports. Inadequate ACL rehabilitation is the primary cause of poor outcomes. Nurses have become a crucial element in the rehabilitation process. Although there is no consensus regarding the optimal post-operative rehabilitation protocols, restoring muscle strength and neuromuscular control are consistently the primary goals. This literature review presents nurse-assisted rehabilitation protocols aiming at improving muscle strength and neuromuscular control. The review discusses postoperative rehabilitation, including home-based and supervised rehabilitation, open and closed kinetic chain exercises, eccentric and concentric training, blood flow restriction training, and plyometric training. Each training protocol has its benefits and drawbacks, and should be used cautiously in specific stages of rehabilitation. Neuromuscular training, such as neuromuscular electrical stimulation, neuromuscular control exercises, and vibration therapy, is considered crucial in rehabilitation.

Al–10Bi–7Zn and Al–10Bi–7Zn–1.5X (X: Cu, Fe, Ni, in wt.%) composite powders were designed and prepared through phase diagram calculation and gas atomization method. The effects of Cu, Fe, and Ni on the hydrolysis of Al–Bi–Zn-base composite powders for hydrogen production were investigated respectively. The composition and morphology of powders were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) with energy disperse spectroscopy (EDS) analyses. Hydrolysis performance test results indicate that the additions of Cu, Fe, or Ni can modify the hydrogen production rate and enhance oxidation resistance in Al–10Bi–7Zn ternary alloy composite powder. In the quaternary composite powder system, Al–10Bi–7Zn–1.5Ni (wt.%) exhibits the best performance with the hydrogen generation yield of 75.3% (954.1 mL/g) within 500 min when reacting with distilled water at 60 °C and maintains a hydrogen yield of 57.9% (733.7 mL/g) within 1500 min after being stored (30 °C, relative humidity of 60%) for 7 d. In addition, the mechanism investigation suggested that the additions of Cu, Fe, or Ni in Al–Bi–Zn-base composite powders can stabilize the Al matrix to retain the high activity of powders resulting from inhibiting the cracking of composite powders in the air.

• Electronic structure of HTiNbO 5 was regulated by Ti 3 C 2 MXene loading. • 2D/2D MX/RTS Schottky junction was prepared for TCH photodegradation. • The synergistic effect of Ti 3 C 2 MXene boosted photodegradation activity. • Coexisting ions on TCH photodegradation were investigated. • TCH photodegradation mechanism over MX/RTS was proposed. Developing high-efficiency photocatalysts for tetracycline hydrochloride (TCH) degradation is of great significance to ecosystems and human beings. In this work, a two-step process of exfoliation and re-stacking was performed to prepare re-stacked HTiNbO 5 nanosheets (R-HTNS) and then coupled with Ti 3 C 2 MXene to construct Ti 3 C 2 MXene/R-HTNS (MX/RTS) with a 2D/2D Schottky heterojunction. These 2D/2D heterostructures between Ti 3 C 2 MXene and R-HTNS can produce an internal electric field and provide maximum interface area for efficient charge transfer across the intimate interface. The photocatalytic performance of samples was evaluated by TCH degradation under simulated sunlight. The MX/RTS composites, with an optimal sample of 3-MX/RTS, show enhanced photocatalytic activity for TCH degradation compared with R-HTNS. The characterization results reveal that the introduction of Ti 3 C 2 MXene can significantly increase specific surface area for providing more reactive sites and broaden the light absorption region. Besides, the incident light energy is absorbed by the Ti 3 C 2 MXene component in MX/RTS composites to generate photothermal energy (heat), which facilitates the charge carrier separation and surface reaction kinetics. Thus, the enhanced TCH photodegradation activity for MX/RTS composites is due to the introduction of Ti 3 C 2 MXene, which possesses the synergistic effect of the increased specific surface area, improved light-harvesting capacity, 2D/2D Schottky heterojunction, and photothermal energy effect. Additionally, the TCH photodegradation behavior is deliberated with a detailed discussion on various coexisting ions. During TCH photodegradation, the active radical species are determined for 3-MX/RTS. According to the characterization results, the possible TCH photodegradation pathway and mechanism over 3-MX/RTS are explored. This work may offer a novel insight for constructing MXene-based heterostructured photocatalysts with high efficiency. Ti 3 C 2 MXene/HTiNbO 5 nanosheets Schottky heterojunctions exhibited the high efficiency for solar TCH photodegradation due to the synergistic effect of the increased specific surface area, improved light harvesting capacity, 2D/2D Schottky heterojunction and photothermal energy effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Accidental pharyngeal fishbone ingestion is a common complaint in ear, nose, and throat clinics. Approximately two-thirds of the accidentally ingested fishbones can be removed using tongue depressors and indirect laryngoscopy. However, the remaining third is challenging to identify and remove using these methods. These difficult fishbones require identification and removal via more advanced approaches. Video-guided laryngoscope is used to deal with difficult fishbones in our center. This study aimed to explore the risk factors for difficult fishbones.Methods: A prospective study was performed at a teaching hospital on 2080 patients. Univariate and multivariate analyses were performed to identify the risk factors.Results: The common fishbone locations were the tonsils (39.8%; defined as STEP-I), tongue base (37.1%), vallecula (13.3%; STEP-II), and hypopharynx (9.8%; STEP-III). With increasing STEP level, the ratio of difficult fishbones correspondingly increased (Z = 13.919, P< .001), and the proportions were 21.1%, 41.9%, and 70% in STEP-I, II, and III, respectively. In particular, fishbones in STEP-III (vs STEP-I) had a higher risk of difficult fishbones (odds ratio [OR]: 11.573, 95% CI: 7.987-16.769). Complaints of neck pain (yes vs no), foreign body sensation (yes vs no), and shorter length of fishbones always had a lower risk of difficult fishbones (OR: 0.455, 95% CI: 0.367-0.564; OR: 0.284, 95% CI: 0.191-0.422; OR: 0.727, 95% CI: 0.622-0.85). Missing teeth (yes vs no), swallowing behavior after fishbone ingestion (yes vs no), and male patients (vs female) had a higher risk of difficult fishbones (OR: 1.9, 95% CI: 1.47-2.456; OR: 1.631, 95% CI: 1.293-2.059; OR: 1.278, 95% CI: 1.047-1.56).Conclusions: Neck pain, foreign body sensation, fishbone length, patient age and sex, tooth status, and swallowing behavior after fishbone ingestion are independent risk factors for difficult fishbones.

A novel Al−10Nb−3Ce−2.5B inoculant was prepared, and its effect on microstructures, damping and tensile mechanical properties of Zn−Al eutectoid (ZA22) alloy was systematically studied. It was found that the inoculant had an effective refining effect on the α-phase in the ZA22 alloy (α-phase could be refined to 16 μm), and the morphology of the α-phase could also change from coarse dendrite to small petal. Orientation relationships (ORs) between the α-phase and the CeB6and NbB2particles in the inoculant were established by the edge−edge matching model (E2EM), and based on the E2EM, the refining mechanism of the inoculant on the ZA22 alloy was revealed. Compared with the uninoculated ZA22 alloy, the high temperature damping of the inoculated ZA22 alloy, especially the damping peak arising from the reverse eutectoid transformation, was significantly improved. Moreover, the room temperature tensile mechanical properties of the inoculated ZA22 alloy were also significantly improved. The tensile strength and elongation of the ZA22 alloy with the best refining effect were 18.56% and 119.04% higher than those of the unrefined ZA22 alloy, respectively. Correlated mechanisms were discussed.

Graphical abstract:

Chronic itch is a maladaptive and debilitating symptom in patients with allergic contact dermatitis (ACD), adversely affecting their quality of life. There is a lack of effective treatments for ACD-associated uncontrollable itch. In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensisGeorgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD. The ACD mice were intraperitoneally injected with BE (5, 30, and 60 mg·kg−1·d−1) for 7 days during the DCP challenge phase. The results showed that DCP-treated mice exhibited severe spontaneous scratching behaviors that was reduced after BE injections in a dose-dependent manner accompanied by inhibition of spinal astrocyte activation. We observed that the spinal astrocytic STAT3–LCN2 cascade plays a crucial role in controlling the activation of astrocytes in chronic itch. Intrathecal injection of the STAT3 inhibitor AG490 or Lcn2siRNA significantly reduced scratching behavior and astrocyte activation in ACD mice. Moreover, BE markedly attenuated the increased phosphorylation of STAT3 (p-STAT3) and LCN2 expression in the spinal cords of ACD mice and in lipopolysaccharide-stimulated primary spinal astrocytes. Altogether, BE relieved chronic itch by suppressing the spinal astrocytic STAT3–LCN2 cascade. These findings provide a potential avenue for the management of chronic itch.

Introduction: Chronic post-surgical pain (CPSP) remains a prevalent issue following video-assisted thoracic surgery (VATS), despite advancements in surgical techniques. Various regional anesthesia techniques, including thoracic paravertebral block (PVB), intercostal nerve block (ICNB), serratus anterior plane block (SAPB), erector spinae plane block (ESPB), and thoracic epidural anesthesia (TEA), have been employed in VATS procedures to mitigate this issue. This study aims to compare the efficacy of these analgesia methods in reducing the incidence of CPSP in VATS patients through a network meta-analysis. Methods: A systematic search was conducted in PubMed, the Cochrane Library, and EMBASE for randomized controlled trials (RCTs) comparing the incidence of CPSP associated with PVB, ICNB, SAPB, ESPB, and TEA. The occurrence of CPSP was evaluated at both 2–3 months and 6 months post-surgery. Results: Six RCTs, involving 652 patients, were included in the analysis of CPSP incidence at 2–3 months, while seven RCTs, involving 715 patients, were included for 6 months analysis. PVB, ICNB, or TEA reduced CPSP incidence compared with control group (without regional anesthesia techniques) at both 2–3 months and 6 months post-surgery. However, SAPB was found less effective in reducing CPSP incidence at 2–3 months post-VATS compared to PVB, ICNB, or TEA. Conclusions: PVB, ICNB, and TEA exhibit significant effects on reducing CPSP incidence following VATS. Conversely, SAPB is not recommended for reducing CPSP incidence post-VATS. Nonetheless, considering the limitation of a small sample size in this network meta-analysis, additional RCTs are necessary to validate these conclusions and enhance the management of CPSP after VATS.

Age at menarche (AAM) is a sign of puberty of females. It is a heritable trait associated with various adult diseases. However, the genetic mechanism that determines AAM and links it to disease risk is poorly understood. Aiming to uncover the genetic basis for AAM, we conducted a joint association study in up to 438,089 women from 3 genome-wide association studies of European and East Asian ancestries. A series of bioinformatical analyses and causal inference were then followed to explore in-depth annotations at the associated loci and infer the causal relationship between AAM and other complex traits/diseases. This largest meta-analysis identified a total of 21 novel AAM associated loci at the genome wide significance level (P< 5.0  × 10−8), 4 of which were European ancestry-specific loci. Functional annotations prioritized 33 candidate genes at newly identified loci. Significant genetic correlations were observed between AAM and 67 complex traits. Further causal inference demonstrated the effects of AAM on 13 traits, including forced vital capacity (FVC), high blood pressure, age at first live birth, etc, indicating that earlier AAM causes lower FVC, worse lung function, hypertension and earlier age at first (last) live birth. Enrichment analysis identified 5 enriched tissues, including the hypothalamus middle, hypothalamo hypophyseal system, neurosecretory systems, hypothalamus and retina. Our findings may provide useful insights that elucidate the mechanisms determining AAM and the genetic interplay between AAM and some traits of women.

Acrylamide (AA), a probable human carcinogen, is a widely-used industrial chemical but is also present in tobacco smoke and carbohydrate-rich foods processed at high temperatures. AA is metabolized to glycidamide (GA) to cause the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct induced by GA, was recently detected in urine of smokers and non-smokers. In this study, we assessed the variability of AA exposure and biomarkers of AA exposure in urine samples repeatedly collected from AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine samples were collected from the exposed group in parallel with personal sampling for eight consecutive days and from the control group on day 1 of the study. Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) were analyzed using on-line solid phase extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry methods. We found that N7-GAG levels in urine were significantly higher in exposed workers than in controls and that N7-GAG level correlated positively with AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly remain the more preferred biomarkers of AA exposure and that N7-GAG levels could be elevated by occupational exposures to AA and serve as a biomarker of AA-induced genotoxicity for epidemiological studies.

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP–seq and RNA–seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2–SP1–SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2–SP1–SAT1 axis.

The ability to survive starvation is an integral part of bacterial fitness and determines composition, turnover and biodiversity in microbial ecosystems. Starving bacteria enter a state known as plasmolysis in which their cytoplasm contracts from the cell wall. Plasmolysis is often thought to be a pathological, passive condition, arising automatically from the lack of ATP. Here we show that contrary to this notion, maintaining plasmolysis is an active, ATP-consuming state that is essential for starvation survival. We show that ion homeostasis to maintain plasmolysis consumes the largest part of the energy budget of starving cells and directly determines death rates in starvation. Our mathematical model accurately predicts death rates for various starvation conditions and perturbations. This enabled the development of an optimized starvation medium that would be ideally suited for preserving and transplanting natural microbial communities by maintaining viability but preventing outgrowth of a subset of the species.

Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling, whereas effective pharmacological treatments targeting cardiac inflammation remain unclear. Lipoprotein-associated phospholipase A2 (Lp-PLA2) contributes to vascular inflammation-related diseases by mediating macrophage migration and activation. Darapladib, the most advanced Lp-PLA2 inhibitor, has been evaluated in phase III trials in atherosclerosis patients. However, the role of darapladib in inhibiting hypertensive cardiac fibrosis remains unknown. Using a murine angiotensin II (Ang II) infusion-induced hypertension model, we found that Pla2g7(the gene of Lp-PLA2) was the only upregulated PLA2 gene detected in hypertensive cardiac tissue, and it was primarily localized in heart-infiltrating macrophages. As expected, darapladib significantly prevented Ang II-induced cardiac fibrosis, ventricular hypertrophy, and cardiac dysfunction, with potent abatement of macrophage infiltration and inflammatory response. RNA sequencing revealed that darapladib strongly downregulated the expression of genes and signaling pathways related to inflammation, extracellular matrix, and proliferation. Moreover, darapladib substantially reduced the Ang II infusion-induced expression of nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) and interleukin (IL)-1β and markedly attenuated caspase-1 activation in cardiac tissues. Furthermore, darapladib ameliorated Ang II-stimulated macrophage migration and IL-1β secretion in macrophages by blocking NLRP3 inflammasome activation. Darapladib also effectively blocked macrophage-mediated transformation of fibroblasts into myofibroblasts by inhibiting the activation of the NLRP3 inflammasome in macrophages. Overall, our study identifies a novel anti-inflammatory and anti-cardiac fibrosis role of darapladib in Lp-PLA2 inhibition, elucidating the protective effects of suppressing NLRP3 inflammasome activation. Lp-PLA2 inhibition by darapladib represents a novel therapeutic strategy for hypertensive cardiac damage treatment.

The electrochemical synthesis of 5-aminocoumaran derivatives from easily oxidizable aminophenols and readily available olefins is described. The reaction efficiently produces 5-aminocoumarans in high yield under mild and environmentally friendly conditions without the necessity of catalysts, additives, oxidizing agents, or sacrificial reagents. Hydrogen as the sole byproduct of the reaction makes the method clean, highly atom-efficient, and step-economical.

Determining the optimal structures and clarifying the corresponding hierarchical evolution of transition metal clusters are of fundamental importance for their applications. The global optimization of clusters containing a large number of atoms, however, is a vastly challenging task encountered in many fields of physics and chemistry. In this work, a high-efficiency self-adaptive differential evolution with neighborhood search (SaNSDE) algorithm, which introduced an optimized cross-operation and an improved Basin Hopping module, was employed to search the lowest-energy structures of CoN, PtN, and FeN(N= 3–200) clusters. The performance of the SaNSDE algorithm was first evaluated by comparing our results with the parallel results collected in the Cambridge Cluster Database (CCD). Subsequently, different analytical methods were introduced to investigate the structural and energetic properties of these clusters systematically, and special attention was paid to elucidating the structural evolution with cluster size by exploring their overall shape, atomic arrangement, structural similarity, and growth pattern. By comparison with those results listed in the CCD, 13 lower-energy structures of FeNclusters were discovered. Moreover, our results reveal that the clusters of three metals had different magic numbers with superior stable structures, most of which possessed high symmetry. The structural evolution of Co, Pt, and Fe clusters could be, respectively, considered as predominantly closed-shell icosahedral, Marks decahedral, and disordered icosahedral-ring growth. Further, the formation of shell structures was discovered, and the clusters with hcp-, fcc-, and bcc-like configurations were ascertained. Nevertheless, the growth of the clusters was not simply atom-to-atom piling up on a given cluster despite gradual saturation of the coordination number toward its bulk limit. Our work identifies the general growth trends for such a wide region of cluster sizes, which would be unbearably expensive in first-principles calculations, and advances the development of global optimization algorithms for the structural prediction of clusters.

In this present study, AA 7072/7075/7072 composite sheets with different finish rolling temperatures (210–350 °C) were prepared by the muti-pass hot finish rolling process. Effects of final rolling temperature on microstructure and properties of AA 7072/7075/7072 composite sheets were investigated after aging (AA 7075-T6 composite) via optical microscopy (OM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and transmission electron microscope (TEM). It was found that bendability of AA 7075-T6 composite alloy is highly dependent on finish rolling temperature. The results show that when increasing the finish rolling temperature, the tensile properties of 7075 hot rolled (7075-F) decreases, while tensile properties of 7075 annealed (7075-O) composites sheets increase. With excessive finish rolling temperature (280 °C and above), grain is not uniform along the thickness direction and texture was dominated by Goss texture. Bending test results show that break occurred for AA7075-T6 composite sheet when the finish rolling temperature was 280 °C and above. Texture and inhomogeneous coarse grain propagate formation of crack and degenerate bendability of the alloy.

MYC is an oncogenic transcription factor with a novel role in enhancing global transcription when overexpressed. However, how MYC promotes global transcription remains controversial. Here, we used a series of MYC mutants to dissect the molecular basis for MYC-driven global transcription. We found that MYC mutants deficient in DNA binding or known transcriptional activation activities can still promote global transcription and enhance serine 2 phosphorylation (Ser2P) of the RNA polymerase (Pol) II C-terminal domain (CTD), a hallmark of active elongating RNA Pol II. Two distinct regions within MYC can promote global transcription and Ser2P of Pol II CTD. The ability of various MYC mutants to promote global transcription and Ser2P correlates with their ability to suppress CDK9 SUMOylation and enhance positive transcription elongation factor b (P-TEFb) complex formation. We showed that MYC suppresses CDK9 SUMOylation by inhibiting the interaction between CDK9 and SUMO enzymes including UBC9 and PIAS1. Furthermore, MYC’s activity in enhancing global transcription positively contributes to its activity in promoting cell proliferation and transformation. Together, our study demonstrates that MYC promotes global transcription, at least in part, by promoting the formation of the active P-TEFb complex via a sequence-specific DNA-binding activity-independent manner.

Suprachiasmatic nucleus (SCN) in mammals functions as the master circadian pacemaker that coordinates temporal organization of physiological processes with the environmental light/dark cycles. But the causative links between SCN and cardiovascular diseases, specifically the reparative responses after myocardial infarction (MI), remain largely unknown. In this study we disrupted mouse SCN function to investigate the role of SCN in cardiac dysfunction post-MI. Bilateral ablation of the SCN (SCNx) was generated in mice by electrical lesion; myocardial infarction was induced via ligation of the mid-left anterior descending artery (LAD); cardiac function was assessed using echocardiography. We showed that SCN ablation significantly alleviated MI-induced cardiac dysfunction and cardiac fibrosis, and promoted angiogenesis. RNA sequencing revealed differentially expressed genes in the heart of SCNx mice from D0 to D3 post-MI, which were functionally associated with the inflammatory response and cytokine-cytokine receptor interaction. Notably, the expression levels of insulin-like growth factor 2 (Igf2) in the heart and serum IGF2 concentration were significantly elevated in SCNx mice on D3 post-MI. Stimulation of murine peritoneal macrophages in vitro with serum isolated from SCNx mice on D3 post-MI accelerated the transition of anti-inflammatory macrophages, while antibody-mediated neutralization of IGF2 receptor blocked the macrophage transition toward the anti-inflammatory phenotype in vitro as well as the corresponding cardioprotective effects observed in SCNx mice post-MI. In addition, disruption of mouse SCN function by exposure to a desynchronizing condition (constant light) caused similar protective effects accompanied by elevated IGF2 expression on D3 post-MI. Finally, mice deficient in the circadian core clock genes (Ckm-cre; Bmal1f/fmice or Per1/2double knockout) did not lead to increased serum IGF2 concentration and showed no protective roles in post-MI, suggesting that the cardioprotective effect observed in this study was mediated particularly by the SCN itself, but not by self-sustained molecular clock. Together, we demonstrate that inhibition of SCN function promotes Igf2expression, which leads to macrophage transition and improves cardiac repair post-MI.

The 14.6‐inch 202‐ppi rollable micro LED display was fabricated on flexible LTPS TFT backplanes. The tiny micro LEDs, those size are less than 30 um, were bonded on backplanes by flip‐chip soldering technologies. More than 11 million micro LEDs were transferred to achieve brightness of >1000 nits, contrast ratio of >1,000,000:1 and resolution of 2560xRGBx1440. We investigated the structure and mechanism to achieve the rollable capability for micro LED displays.

In 2021, an outbreak of an infectious disease characterized by torticollis, cataracts, and neurological disorders caused massive mortality in farmed American bullfrogs Rana catesbeianain Hubei province, China. We identified the causal agent in this outbreak, characterized its pathogenicity, and screened candidate antimicrobial agents for future disease control. Bacterium was isolated from the diseased American bullfrogs and identified based on biochemical tests, sequence analyses (16S ribosomal RNA; DNA gyrase subunit B), and experimental challenge. Furthermore, antibiotic sensitivity of the isolated strain was detected with Kirby–Bauer paper diffusion method, and the antibacterial activity of 60 traditional Chinese herbal extracts against the isolated strain was evaluated by agar disc diffusion and broth dilution assays. We identified Elizabathkingia miricolastrain FB210601 as the causative agent of this disease. The isolated E. miricolastrain FB210601 exhibited extensive antibiotic resistance to all tested quinolones, β‐lactam antibiotics, and aminoglycosides. Eight herbal extracts exhibited excellent antimicrobial activity against E. miricolaFB210601, especially Caesalpinia sappanand Rhus chinensis, with minimal inhibitory concentrations less than 0.2 mg/mL. Additionally, the combined effects of two‐component herbal mixtures containing C. sappanor R. chinensiswere greater than those of the individual extracts. Our results provide a reference for understanding the pathogenesis of Elizabethkingiainfection in frogs. Furthermore, this study will aid in the application of herbal extracts for protection against infections caused by multidrug‐resistant Elizabathkingiain the future. Impact statementThis work studies the Elizabathkingia miricolaisolated from diseased American bullfrogs in China, including bacterial identification, its sensitivity to different antibiotics and Chinese herbal extracts, which provides a scientific reference for understanding the pathogenesis of Elizabethkingiain frogs as well as for disease control and prevention. This work studies the Elizabathkingia miricolaisolated from diseased American bullfrogs in China, including bacterial identification, its sensitivity to different antibiotics and Chinese herbal extracts, which provides a scientific reference for understanding the pathogenesis of Elizabethkingiain frogs as well as for disease control and prevention.

In the last two decades, the Yangtze Estuary has undergone significant changes under the influence of reduced sediment inflow and estuary engineering. This study investigates the influence of floods and typhoons on sediment concentration and the morphological evolution of shoals and channels in the Yangtze Estuary. The analysis is conducted through the utilization of topographic data measured pre- and post-flood events and observations of hydro-sedimentary changes during typhoons. By using a generalized estuary mathematical model, this study examines the interplay between varying tidal ranges, tidal divisions, runoff volumes, and regulation projects on the erosion and deposition of shoals and channels in bifurcated estuaries. The results show that due to the implementation of river and waterway regulation projects, the impact of the 2020 flood on the main channel and shoal was significantly less than that of the 1998 flood. The swing amplitude of the South Branch main channel decreased. However, local river sections such as the Southern Waterway of Baimao Shoal exhibited erosion. During typhoons, sediment concentration in the 20 cm above the bottom increased significantly and was closely related to wave processes, with a weakened correlation to tidal dynamics. After typhoons, high shoals in South Passage above 0 m were silted up, while the terrain on one side of the tail of Jiuduan Shoal in the downstream deep-water area was generally scoured due to strong wave action. The generalized mathematical model of the bifurcated estuary revealed that M2 tidal component contributed most to the erosion and deposition evolution of estuary shoals and channels, with floods exhibiting characteristics of sedimentation on shoals and erosion on channels. With the implementation of a branch rectification project, branch resistance increased, diversion decreased, and the riverbed changed from pre-project erosion to post-project sedimentation, with an increase in erosion in non-project branches.

Purpose: This study aims to investigate the growth-promoting and stress-resistant effects of Cronobactersp. Y501 on maize under drought conditions. Methods: Morphological and phylogenetic analyses were performed to identify bacterial strain Y501. Contents of chlorophyll and malondialdehyde (MDA), the activity of antioxidant enzymes, and phytohormone levels were detected by standard procedures to investigate the effects of Y501 on maize under water deficit conditions. Real-time PCR was conducted to analyze gene expression variations related to hormone regulation and signaling transduction in maize with Y501 inoculation. Results: A plant growth-promoting rhizobacterium (PGPR) strain, Y501, was isolated and identified as Cronobactersp.. Inoculation with Y501 optimized the growth attributes of maize, including biomass, plant height, and root viability under a drought environment. Application of Y501 led to a remarkable recovery in chlorophyll -a (19.23% increase compared to the control) and -b contents (36.12% increase compared to the control), decrease in MDA accumulation (44.07% decrease compared to the control), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities (17.86%, 10.28%, and 27.35% decrease, respectively, compared to the control) under drought conditions, which showed that Y501 was responsible for the improved capacity of photosynthetic efficiency and osmotic adjustment in maize. Further investigations have validated that Y501 inhibited abscisic acid (ABA) signaling under drought conditions and had the ability for indole-3-acetic acid (IAA) biosynthesis in a tryptophan-dependent manner. Moreover, Y501 inoculation could regulate the expression of auxin transporters in maize under drought conditions for effectively utilizing exogenous IAA produced by Y501 to promote plant growth. Conclusions: The present study has demonstrated the phytostimulation effects of Cronobactersp. Y501 on maize plants responding to drought stress, which made the identified Y501 a potential bio-inoculant in arid areas.

The influence of low-frequency electromagnetic casting (LFEC) and Sc addition as variables on the microstructure, properties, and deformation behavior of 7A36 aluminum alloy has been systematically examined. The results have predicted that the LFEC could make the grains of the as-cast alloy finer by electromagnetic stirring and forced convection. By the addition of Sc, the average diameters of the equiaxed grains have been reduced and the intensity of the fiber texture has become weakened. The fine and continuous η′ precipitates on the grain boundaries (GBs) instead of the coarse large-sized discontinuous η′ precipitates, which results in a more uniform distribution of plastic deformation and which is beneficial for improving plasticity. By adding Sc and applying LFEC, the large size η′ internal grain precipitated phase decreased slightly. The fine nano-sized Al3(Sc, Zr) phase particles were dispersed in the matrix. As the dislocation movement had to travel less distance, that's why this process consumed less energy. These features also reduced the strain difference within the grain and near the grain boundary, which result in the increase of EL. The excellent mechanical properties of 7A36 aluminum as extruded plates were obtained when it was aged at 120 °C for 8 h by Sc micro-alloying and applying LFEC. The yield strength (YS) and ultimate tensile strength (UTS) remained at 738.3 MPa and 767.0 MPa, respectively, while the elongation (EL) to failure 6.5% is increased by 160% than the value of direct chill casting.

ABSTRACT Underground concrete structures usually suffer from carbonic acid water corrosion, thus evaluation and prediction of the carbonic acid water corrosion are very important for cement-based materials. Portland cement pastes [...]

ABSTRACTCompetition is a core element in systems of government purchase of services. Using government procurement data collected from three cities (Zhuhai, Zhongshan, and Foshan) from 2011 to 2018, this study develops a rigorous competition measurement index to interpret the quality of bidding entities. We find most procurement projects in social services to contain policy-driven and market-driven competition. Significant differences are observed in competition among cities due to purchase scale, geographical location, and government protectionism. Moreover, competition gradually decreases over time. The paper also presents implications for China’s welfare governance.

An altered proteome in lymph nodes often suggests abnormal signaling pathways that may be associated with diverse lymphatic disorders. Current clinical biomarkers for histological classification of lymphomas have encountered many discrepancies, particularly for borderline cases. Therefore, we launched a comprehensive proteomic study aimed to establish a proteomic landscape of patients with various lymphatic disorders and identify proteomic variations associated with different disease subgroups. In this study, 109 fresh-frozen lymph node tissues from patients with various lymphatic disorders (with a focus on Non-Hodgkin’s Lymphoma) were analyzed by data-independent acquisition mass spectrometry. A quantitative proteomic landscape was comprehensively characterized, leading to the identification of featured protein profiles for each subgroup. Potential correlations between clinical outcomes and expression profiles of signature proteins were also probed. Two representative signature proteins, phospholipid-binding proteins Annexin A6 (ANXA6) and Phospholipase C Gamma 2 (PLCG2), were successfully validated via immunohistochemistry. We also evaluated the capability of acquired proteomic signatures to segregate multiple lymphatic abnormalities and identified several core signature proteins, such as Sialic Acid Binding Ig Like Lectin 1 (SIGLEC1) and GTPase of immunity-associated protein 5 (GIMAP5). In summary, the established lympho-specific data resource provides a comprehensive map of protein expression in lymph nodes during multiple disease states, thus extending the existing human tissue proteome atlas. Our findings will be of great value in exploring protein expression and regulation underlying lymphatic malignancies, while also providing novel protein candidates to classify various lymphomas for more precise medical practice.

Recognizing that the interrelationships between chronic conditions that complicate rheumatoid arthritis (RA) are poorly understood, we aimed to identify patterns of multimorbidity and to define their prevalence in RA through machine learning. We constructed RA and age‐ and sex‐matched (1:1) non‐RA cohorts within a large commercial insurance database (MarketScan) and the Veterans Health Administration (VHA). Chronic conditions (n = 44) were identified from diagnosis codes from outpatient and inpatient encounters. Exploratory factor analysis was performed separately in both databases, stratified by RA diagnosis and sex, to identify multimorbidity patterns. The association of RA with different multimorbidity patterns was determined using conditional logistic regression. We studied 226,850 patients in MarketScan (76% female) and 120,780 patients in the VHA (89% male). The primary multimorbidity patterns identified were characterized by the presence of cardiopulmonary, cardiometabolic, and mental health and chronic pain disorders. Multimorbidity patterns were similar between RA and non‐RA patients, female and male patients, and patients in MarketScan and the VHA. RA patients had higher odds of each multimorbidity pattern (odds ratios [ORs] 1.17–2.96), with mental health and chronic pain disorders being the multimorbidity pattern most strongly associated with RA (ORs 2.07–2.96). Cardiopulmonary, cardiometabolic, and mental health and chronic pain disorders represent predominant multimorbidity patterns, each of which is overrepresented in RA. The identification of multimorbidity patterns occurring more frequently in RA is an important first step in progressing toward a holistic approach to RA management and warrants assessment of their clinical and predictive utility.

[C14H23N3S1], monoclinic, P21/c(no. 14), a= 15.1642(8) Å, b= 6.9215(3) Å, c= 15.2182(7) Å, β= 112.675(2)°, V= 1473.83(12) Å3, Z= 4, Rgt(F) = 0.0453, wRref(F2) = 0.1240, T = 296(2) K.

C26H22N6O7Co, triclinic, P1‾$P\overline{1}$ (no. 2), a= 9.0033(4) Å, b= 10.1338(5) Å, c= 15.5122(8) Å, α= 96.164(4)°, β= 100.835(4)∘$100.835{(4)}^{\circ }$ , γ= 113.867(5)∘$113.867{(5)}^{\circ }$ , V= 1244.20(11) Å3, Z= 2, Rgt(F) = 0.0473, wRref(F2) = 0.1023, T = 293(2) K.

ABSTRACT Due to the high compressive strength and durability properties of ultra high strength concrete, prestressed ultra high strength concrete beam was used extensively in bridge engineering, but it possessed [...]

Given the abundant reserves of seawater and the scarcity of freshwater, real seawater electrolysis is a more economically appealing technology for hydrogen production relative to orthodox freshwater electrolysis. However, this technology is greatly precluded by the undesirable chlorine oxidation reaction and severe chloride corrosion at the anode, further restricting the catalytic efficiency of overall seawater splitting. Herein, a feasible strategy by engineering multifunctional collaborative catalytic interfaces is reported to develop porous metal nitride/phosphide heterostructure arrays anchoring on conductive Ni2P surfaces with affluent iron sites. Collaborative catalytic interfaces among iron phosphide, bimetallic nitride, and porous Ni2P supports play a positive role in improving water adsorption/dissociation and hydrogen adsorption behaviors of active Fe sites evidenced by theoretical calculations for hydrogen evolution reactions, and enhancing oxygenated species adsorption and nitrate-rich passivating layers resistant to chloride corrosion for oxygen evolution reaction, thus cooperatively propelling high-performance bifunctional seawater splitting. The resultant material Fe2P/Ni1.5Co1.5N/Ni2P performs excellently as a self-standing bifunctional catalyst for alkaline seawater splitting. It requires extremely low cell voltages of 1.624 and 1.742 V to afford current densities of 100 and 500 mA/cm2in 1 M KOH seawater electrolytes, respectively, along with superior long-term stability, outperforming nearly all the ever-reported non-noble bifunctional electrocatalysts and benchmark Pt/IrO2coupled electrodes for freshwater/seawater electrolysis. This work presents an effective strategy for greatly enhancing the catalytic efficiency of non-noble catalysts toward green hydrogen production from seawater electrolysis.

ABSTRACTThe AISC 341–16 (2016) has loading protocols for beam-to-column moment connections and buckling-restrained braces, but it does not have a loading protocol for columns. Because a first-story column base is expected to form a plastic hinge in a building, a loading protocol for first-story columns in a dual system that comprises moment-resisting frames and buckling-restrained braced frames under varied axial force and lateral drift is required. Moreover, the symmetric cyclic loading protocols of AISC 341 do not include the effect of near-fault earthquakes, which is common in Taiwan. Therefore, the effect of near-fault earthquakes on first-story columns must be considered during the development of a loading protocol for dual systems. In the present study, four dual systems (representing 3-story, 7-story, 15-story, and 25-story frames) are subjected to 11 near-fault earthquake motions, used for developing near-fault loading protocols of first-story columns for the lateral drift and axial load responses.

This study was designed to examine demographics of University of Nebraska Medical Center College of Dentistry graduates over a recent 10‐year period and factors related to their choice of rural or urban practice. Findings were compared to similar previous studies to analyze trends. Using data from the annual Health Professions Tracking Service 2019 Dentistry Profile survey, we examined the demographic information of 169 graduates from 2009 to 2018 practicing in Nebraska at the end of 2018. We analyzed factors such as rural or urban high school graduation, gender, and other background information to explore associations with their 2018 practice location (urban vs. rural) using chi‐square tests and logistic regression. This study found that some demographic variables were associated with future practice location. Specifically, a higher proportion of graduates of rural high schools chose to work in a rural location (60%) relative to those who graduated from an urban high school (18%) (p< 0.0001). A higher proportion of men (50%) selected rural practice compared to women (33%) (p= 0.02). Only 17 graduates who attended high school outside of Nebraska stayed to practice in Nebraska, and there was a lower proportion of these graduates working in rural locations (18%) relative to in‐state high school graduates (45%) (p= 0.03). We found significant positive associations between dentists who chose rural practice and demographic factors such as being rural high school graduates, male, and in‐state predental residents. Our findings differ from descriptive results of similar previous studies.

Splitting water into hydrogen by electrolysis using renewable electricity is one of the promising routes for green hydrogen production. The key dilemma for this electrochemical route is the extremely high overpotentials required for oxygen evolution reaction at the anode. Innovative strategies are desirable to fabricate inexpensive metal-based multifunctional catalysts with robust catalytic performance and large-current durability for electrochemical hydrogen production in freshwater or urea-containing water. Here we report the rational design and synthesis of hydrangea-like CoP/Ni3FeN heterostructure arrays as excellent multifunctional electrocatalysts for both alkaline water and urea electrolysis. This catalyst presents superb trifunctional catalytic activities and outstanding large-current durability in basic media, requiring ultralow potentials of −0.160, 1.538 and 1.419 V to facilitate hydrogen, oxygen evolution and urea oxidation reactions (HER, OER and UOR) at an extremely large current density of 1000 mA cm−2, respectively. Remarkably, the as-constructed two-electrode cells using this electrocatalyst as both the cathode and anode demand extremely low cell voltages of 1.577 and 1.668 V to deliver 500 mA cm−2stably for urea and water electrolysis, respectively, suggesting its superb activity and outstanding stability for trifunctional catalysis. OperandoRaman spectroscopic studies in combination with density functional theory calculations validate that the CoP/Ni3FeN hybrid can greatly facilitate the formation of active metal (oxy)hydroxide species for both OER and UOR, and also reduce the adsorption energy barriers of *H2O and *H intermediates for HER. This work provides an effective pathway for developing multifunctional catalysts for electrochemical hydrogen production at low voltages whenever fresh or urea-containing water is available.