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Honeycomb‐layered oxides are a class of cathode materials for sodium‐ion batteries with great potential due to their high voltage and high capacity. However, the structural instability and voltage fading during cycling limit their practical application. Herein, it is revealed that Te substitution into Na3Ni2SbO6 induces a new dual‐honeycomb structure, which can elevate the average discharge voltage of the cathode materials from 3.2 to 3.8 V with improved cycle stability and alleviated voltage decay. Synchrotron operando X‐ray diffraction demonstrates that Te substitution can suppress the O3−P3−O1‐phase transition during charge and discharge processes effectively, benefited from the strong TeO covalent bonds. The resulted Na2.2Ni2Sb0.2Te0.8O6 cathode exhibits a high capacity retention of 70.9% after 1000 cycles at 1C, with an elevated operating voltage of ≈3.8 V. Theoretical calculations reveal that the introduced TeO bonds break the symmetric distribution of charge in Ni/Sb honeycomb structure and elevate the operation voltage by increased valence band width. Proper Te substitution can promote the rate and cycle capability of the cathode by suppressing phase transition and decreasing the bandgap. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions The advantages of proton therapy can be further enhanced with online magnetic resonance imaging (MRI) guidance. One of the challenges in the realization of MRI‐guided proton therapy (MRPT) is accurately calculating the radiation dose in the presence of magnetic fields.This study aims to develop an efficient and accurate proton dose calculation algorithm adapted to the presence of magnetic fields.An analytical‐numerical radiation dose calculation algorithm, Proton and Ion Dose Engine (PRIDE), was developed. The algorithm combines the pencil beam algorithm (PBA) with a novel iterative voxel‐based ray‐tracing algorithm. The new ray‐tracing method uses fewer assumptions and ensures broader applicability for proton beam trajectory prediction in magnetic fields, and has been compared to Wolf's method and Schellhammer's method. The accuracy of PRIDE algorithm was validated on three phantoms and two practical plans (one single‐field water plan and one prostate tumor plan) in different magnetic field strengths up to 3.0 T. The validation was performed by comparing the results against the Monte Carlo (MC) simulations, using the global gamma index criteria of 2%/2 mm and 3%/3 mm with a 10% threshold.PRIDE showed good agreement with MC in homogeneous and slab heterogeneous phantom, achieving gamma passing rates (%GPs) above 99% for 2%/2 mm criteria when magnetic field strength is not greater than 1.5 T. Although the agreement decreased for scenarios involving high proton energy (240 MeV) and strong magnetic field (3.0 T), the 2%/2 mm %GPs still remained above 98%. In lateral heterogeneous phantom, the accuracy of PRIDE decreased due to the PBA's limitation. For the two practical plans in different magnetic fields, %GPs exceeded 98% and 99% for 2%/2 mm and 3%/3 mm criteria, respectively.PRIDE can perform efficient and accurate proton dose calculation in magnetic fields up to 3.0 T, and is expected to work as a useful tool for proton dose calculation in MRPT. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Seventeen undescribed lindenane‐related sesquiterpenoid dimers, chlorajaponins A—Q (1—17), and 13 reported analogs (18—30) were isolated from Chloranthus japonicus Sieb. Compound 1 possesses an unprecedented 3/5/7/5/5/6/5/3 fused octacyclic scaffold, featuring a 6(5→4)‐abeo‐lindenane monomer, while 2 exhibits a 3/5/6/6/5/6/5/3 fused octacyclic scaffold. Their structures were determined through a combination of spectroscopic analyses and X‐ray crystallography. Compounds 1, 2, and 18 demonstrated significant inhibitory effects on lipid accumulation and effectively reduced the levels of triglycerides and total cholesterol, as well as the levels of aspartate aminotransferase and alanine aminotransferase in a HepG2 cell model. In addition, compounds 1, 2, and 18 significantly suppressed the protein expression of the fatty acid synthase (FASN) and the sterol regulatory element‐binding protein 1 (SREBP1). Moreover, the anti‐inflammatory assay showed that compounds 19—22 and 25 inhibited the NO production induced by lipopolysaccharide in RAW 264.7 macrophages with IC50 values of 7.89 ± 0.44, 6.25 ± 0.46, 2.98 ± 0.29, 10.77 ± 0.60, and 3.60 ± 0.28 μmol/L. [ABSTRACT FROM AUTHOR]

The association between psoriasis and cardiovascular disease (CVD) has long been discussed and continually refined. However, there is currently a lack of prospective studies on the cardiovascular risk attributed to psoriasis in the United States general population. Representative adult participants were selected from the National Health and Nutrition Examination Survey (NHANES). Risks of cardiovascular symptoms and diseases prevalence were evaluated between participants with and without psoriasis. The hazards for all‐cause mortality and CVD mortality were stratified by psoriasis status. Mediation analysis was then conducted to identify potential mediators between psoriasis and cardiac death. Overall, 19 741 participants were included in the current study, 542 (2.7%) had psoriasis and 19 199 (97.3%) did not have psoriasis. After adjusting for known CVD risk factors, odds for hypertension (OR = 1.37, 95% CI: 1.13–1.66, p = 0.001), hypercholesterolemia (OR = 1.37, 95% CI: 1.13–1.64, p < 0.001) and angina pectoris (OR = 1.74, 95% CI: 1.11–2.60, p = 0.011) were higher in psoriasis patients. Compared with participants without psoriasis, moderate/severe but not mild patients showed significantly higher CVD mortality (HR = 2.55, 95% CI: 1.27–5.15, p = 0.009). This result was supported by subgroup analyses. Mediation analysis further suggested that the direct effect of moderate/severe psoriasis on CVD mortality accounted for 81.4% (65.8%–97.1%). Besides, the indirect effect might derive from disturbance of serum albumin, urea nitrogen and uric acid. Moderate‐to‐severe psoriasis is an independent risk factor for cardiovascular disease, making it necessary to regularly conduct cardiovascular disease‐related examinations for patients with higher severity of psoriasis in clinical settings. [ABSTRACT FROM AUTHOR]

Despite being a convenient clinical substrate for biomonitoring, saliva's widespread utilization has not yet been realized. The non‐Newtonian, heterogenous, and highly viscous nature of saliva complicate the development of automated fluid handling processes that are vital for accurate diagnoses. Furthermore, conventional saliva processing methods are resource and/or time intensive precluding certain testing capabilities, with these challenges aggravated during a pandemic. The conventional approaches may also alter analyte structure, reducing application opportunities in point‐of‐care diagnostics. To overcome these challenges, we introduce the SHEAR saliva collection device that mechanically processes saliva, in a rapid and resource‐efficient way. We demonstrate the device's impact on reducing saliva's viscosity, improving sample's uniformity, and increasing diagnostic performance of a COVID‐19 rapid antigen test. Additionally, a formal user experience study revealed generally positive comments. SHEAR saliva collection device may support realization of the saliva's potential, particularly in large‐scale and/or resource‐limited settings for global and community diagnostics. [ABSTRACT FROM AUTHOR]

Introduction: Although a few research have tried to explore the relationship between problematic smartphone use (PSU) and school engagement, most of them are limited to relatively simple correlation, and the mechanism needs to be further explored. This research focused on the relationship between PSU and school engagement/disengagement, and intended to verify two mediation paths. Methods: We conducted two studies in 2019 at a middle school in China. 289 students (44.6% girls), aged 11–18 (Mage = 13.25, standard deviation [SD] = 1.73), participated in Study 1, a longitudinal cross‐lag analysis intend to verify the relationship between PSU and school engagement/disengagement. Using a separate sample, Study 2 explored the mediating roles of academic procrastination and sleep quality. Four hundred thirty‐two students aged 11–19 (42.1% girls, Mage = 16.11, SD = 1.56) participated in this cross‐sectional study. In both studies, all participants completed self‐report measures in classrooms during regular school hours. Results: In Study 1, the results showed that PSU (T1) could significantly predict school engagement/disengagement (T2), but school engagement/disengagement (T1) could not predict PSU (T2). In Study 2, we found that academic procrastination could mediate the effect of PSU on school engagement, and sleep quality could mediate the effect of PSU on both school engagement and disengagement. Conclusions: Results highlighted that the school engagement/disengagement of adolescents can be influenced by PSU through several different ways, through which we can protect adolescents from the negative effects of PSU. [ABSTRACT FROM AUTHOR]

Introduction: Whether the coronavirus disease‐2019 (COVID‐19) pandemic is associated with a long‐term negative impact on acute stroke care remains uncertain. This study aims to compare the timing of key aspects of stroke codes between patients before and after the COVID‐19 pandemic. Methods: This retrospective cohort study was conducted at an academic hospital in Shanghai, China and included all adult patients with acute ischemic stroke hospitalized via the emergency department (ED) stroke pathway during the 24 months since the COVID‐19 outbreak (COVID‐19: January 1, 2020–December 31, 2021). The comparison cohort included patients with ED stroke pathway visits and hospitalizations during the same period (pre‐COVID‐19: January 1, 2018–December 31, 2019). We compared critical time points of prehospital and intrahospital acute stroke care between patients during the COVID‐19 era and patients during the pre‐COVID‐19 era using t test, χ2, and Mann–Whitney U test where appropriate. Results: A total of 1194 acute ischemic stroke cases were enrolled, including 606 patients in COVID‐19 and 588 patients in pre‐COVID‐19. During the COVID‐19 pandemic, the median onset‐to‐hospital time was about 108 min longer compared with the same period of pre‐COVID‐19 (300 vs 192 min, p = 0.01). Accordingly, the median onset‐to‐needle time was 169 min in COVID‐19 and 113 min in pre‐COVID‐19 (p = 0.0001), and the proportion of patients with onset‐to‐hospital time within 4.5 h was lower (292/606 [48.2%] vs 328/558 [58.8%], p = 0.0003) during the pandemic period. Furthermore, the median door‐to‐inpatient admission and door‐to‐inpatient rehabilitation times increased from 28 to 37 h and from 3 to 4 days (p = 0.014 and 0.0001). Conclusions: During the 24 months of COVID‐19, a prolongation of stroke onset to hospital arrival and to intravenous rt‐PA administration times were noted. Meanwhile, acute stroke patients needed to stay in the ED for a longer time before hospitalization. Educational system support and process optimization should be pursued in order to acquire timely delivery of stroke care during the pandemic. [ABSTRACT FROM AUTHOR]

P53 inactivation occurs in about 50% of human cancers, where p53-driven p21 activity is devoid and p27 becomes essential for the establishment of the G1/S checkpoint upon DNA damage. Here, this work shows that the E2F1-responsive lncRNA LIMp27 selectively represses p27 expression and contributes to proliferation, tumorigenicity, and treatment resistance in p53-defective colon adenocarcinoma (COAD) cells. LIMp27 competes with p27 mRNA for binding to cytoplasmically localized hnRNA0, which otherwise stabilizes p27 mRNA leading to cell cycle arrest at the G0/G1 phase. In response to DNA damage, LIMp27 is upregulated in both wild-type and p53-mutant COAD cells, whereas cytoplasmic hnRNPA0 is only increased in p53-mutant COAD cells due to translocation from the nucleus. Moreover, high LIMp27 expression is associated with poor survival of p53-mutant but not wild-type p53 COAD patients. These results uncover an lncRNA mechanism that promotes p53-defective cancer pathogenesis and suggest that LIMp27 may constitute a target for the treatment of such cancers. [ABSTRACT FROM AUTHOR]

Our objective was to determine effects of feeding lamb's peony byproducts, including stem and leaves (PSL), root (PR), and seeds meal (PSM), on growth, rumen fermentation, slaughter parameters, and meat quality. Sixty‐four lambs (14.0 ± 2.1 kg) were allocated into eight treatments based on BW: no additives (CON), 0.15% aureomycin (CONA), low/high levels of PSL (5%/10% PSL replaced 5%/10% Chinese hay), PR (basal diet with 0.5%/1.0% PR), PSM (5%/10% PSM replaced 5%/10% soybean meal). Growth, digestibility, and rumen fermentation had dose responses whereas slaughter parameters, meat quality, or amino acids indexes were not. Peony byproducts increased DMI (p < 0.001) compared to CON, but higher levels were more advantageous (p = 0.003). However, low levels of peony byproducts decreased the NH3‐N concentration, but increased total volatile fatty acids mole percent more than high levels of that (p < 0.001). All peony byproducts increased dressing percentage (p < 0.05), increased pH and tenderness than CON (p < 0.05). In addition, PSL and PSM improved amino acid profiles of meat compared to CON, and were even better than CONA (p < 0.05). Therefore, peony byproducts not only improved animal growth but also reduced the frequency of antibiotic use in animal feeding. [ABSTRACT FROM AUTHOR]

Emblematic of the ubiquitous wet markets in China, the live‐poultry trade has far‐reaching influences on Chinese people's diet, culinary art, social interactions, and cultural identities. Since the COVID‐19 pandemic began, the live‐poultry trade has also borne the brunt of this public health crisis due to its notorious history of spreading avian flu and its association with the spread of coronavirus. There have been serious consequences—successive open‐ended bans on live poultry trade at urban markets have been announced by several cities, Wuxi, China, included. Based on seven‐week field research on a conventional live‐poultry stall at a major wet market in Wuxi, this article examines the live‐poultry stall's work setting, interactions between live‐poultry vendors and consumers in building and practicing culinary values (including food qualities and cooking mastery), ethical issues around live‐poultry slaughtering, and how the local Wuxi government contrives to rehabilitate the city from an "endemic" business via an epidemic. We argue that there are underlying political agendas relating to cravings for modernity and urbanization behind a seemingly radical hygienic discourse, which tends to proselytize cultural customs and suppress the social functions of public space. The live‐poultry stall thus undergoes intersectional framing as a "culinary oasis" versus a "petri dish," and a "social courtyard" versus a "political theater," in this national anti‐epidemic movement. [ABSTRACT FROM AUTHOR]

To investigate photoactivated disinfection (PAD) to treat acute pseudomembranous stomatitis, an animal model was established. Six‐week‐old male ICR mice were inoculated with Candida albicans under immunosuppression then divided into three groups (15 mice per group). Pseudomembranous area was measured, then mice had 1 mg mL−1 toluidine blue solution spread on the area, left for 1 min (PAD‐1 group) or 2 min (PAD‐2 group), then irradiated with a 750 mW LED red light for 1 min, a control group received no treatment. Fungal load was measured immediately; after 48 h of observation pseudomembranous area and fungal load were measured. The mice were sacrificed and histopathological examination was performed. Before treatment, pseudomembranous area scores were similar (3 to 4 points) in all groups; 48 h after treatment, the treatment groups' scores were lower (1 to 2 points) than the control group (3 to 4 points, P < 0.05). Immediately after treatment and 48 h later, the fungal loads of the treatment groups were lower than the control group (both P < 0.05). Histopathology of the treatment groups improved more than controls. The treatment groups' results were similar. Therefore, this method of PAD, with short treatment time, reduced the fungal load and pseudomembranous area scores in a mouse model of acute pseudomembranous stomatitis and may have clinical potential. [ABSTRACT FROM AUTHOR]

Aluminum adjuvants are currently the most widely used adjuvants for human vaccines. However, concerns about their safety, such as local irritation at the vaccination site and potential neurotoxicity, have been raised over recent years. Herein, the bilayer microneedles are fabricated using commercially available materials and a simple micromolding preparation method in a differential dual‐release manner for sustained antigen release in the outer layer, and fast release of aluminum in the inner layer. The outer layer here replaces aluminum adjuvants to form an antigen depot, and the rapidly released adjuvants of the inner layer can activate dendritic cells, which effectively reduces the amount of aluminum while retaining their effect. The use of ovalbumin in vivo as the model antigen demonstrates that compared with subcutaneous and intramuscular injections, the bilayer microneedles achieve effective humoral immunity and relatively balanced immune response with less aluminum (1/25 of the dose), which may be related to the mechanical adjuvant effect of the microneedles. Mice treated with the bilayer microneedles show little to no aluminum accumulation in different organs, and no local irritation such as granuloma is observed. The superior vaccination safety and strong immunity using bilayer microneedles make it a promising vaccine platform. [ABSTRACT FROM AUTHOR]

Aims: Microglia‐mediated neuroinflammation plays an important role in the pathological process of ischemic stroke, and the effect of imperatorin on post‐stroke neuroinflammation is not fully understood. Methods: Primary microglia were treated with imperatorin for 2 h followed by LPS (100 ng/ml) for 24 h. The expression of inflammatory cytokines was detected by RT‐PCR, ELISA, and Western blot. The activation of MAPK and NF‐κB signaling pathways were analyzed by Western blot. The ischemic insult was determined using a transient middle cerebral artery occlusion (tMCAO) model in C57BL/6J mice. Behavior tests were used to assess the neurological deficits of MCAO mice. TTC staining was applied to measure infract volume. Results: Imperatorin suppressed LPS‐induced activation of microglia and pro‐inflammatory cytokines release and attenuated ischemic injury in MCAO mice. The results of transcriptome sequencing and Western blot revealed that downregulation of MAPK and NF‐κB pathways might contribute to the protective effects of imperatorin. Conclusions: Imperatorin downregulated MAPK and NF‐κB signaling pathways and exerted anti‐inflammatory effects in ischemic stroke, which indicated that imperatorin might be a potential compound for the treatment of stroke. [ABSTRACT FROM AUTHOR]

Aims: Ischemic stroke is a life‐threatening disease with limited therapeutic strategies. Blood‐brain barrier (BBB) disruption is a critical pathological process that contributes to poor outcomes in ischemic stroke. We previously showed that the microglial inhibition of the inflammasome sensor absent in melanoma 2 (AIM2) suppressed the inflammatory response and protected against ischemic stroke. However, whether AIM2 is involved in BBB disruption during cerebral ischemia is unknown. Methods: Middle cerebral artery occlusion (MCAO) and oxygen‐glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice and brain microvascular endothelial cells (HBMECs), respectively. The infarct volume, neurological deficits, and BBB permeability were measured in mice after MCAO. Transendothelial electrical resistance (TEER) and neutrophil adhesion to the HBMEC monolayer were assessed after OGD/R treatment. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Results: AIM2 was shown to be expressed in brain endothelial cells and upregulated after ischemic stroke in the mouse brain. AIM2 deletion reduced the infarct volume, improved neurological and motor functions, and decreased BBB disruption. In vitro, OGD/R significantly increased the protein levels of AIM2 and ICAM‐1 and decreased those of the tight junction (TJ) proteins ZO‐1 and occludin. AIM2 knockdown effectively protected BBB integrity by promoting the expression of TJ proteins and decreasing ICAM‐1 expression and neutrophil adhesion. Mechanistically, AIM2 knockdown reversed the OGD/R‐induced increases in ICAM‐1 expression and STAT3 phosphorylation in brain endothelial cells. Furthermore, treatment with the p‐STAT3 inhibitor AG490 mitigated the effect of AIM2 on BBB breakdown. Conclusion: Our findings indicated that inhibiting AIM2 preserved the BBB integrity after ischemic stroke, at least partially by modulating STAT3 activation and that AIM2 may be a promising therapeutic target for cerebral ischemic stroke. [ABSTRACT FROM AUTHOR]

A new type of plasmonic anti‐counterfeiting labels is designed on the basis of Au@SiO2 core–shell nanoparticles (Au@SiO2 NPs) and electrospun fibers. The fingerprint information of Raman active molecules is amplified by the plasmonic Au nanoparticles, and silica layers endow the stability of encoding information. Electrospun fibers with unordered breathable structure play the role of polymer matrix and own the flexible features. Au@SiO2 NPs are first adsorbed on the surface of poly(methyl methacrylate)/poly(4‐vinylpyridine) (PMMA/P4VP) fibers by noncovalent interactions, and then are decorated in/on the fibers by controlling the temperature. That is, when the temperature is higher than the glass transition temperature (Tg) of polymer matrix, partial Au@SiO2 NPs are embedded in the PMMA/P4VP fibers. The composite fibers based on the Au@SiO2 and PMMA/P4VP fibers are fabricated, and the signals of Raman active molecules are amplified in the Au@SiO2/PMMA/P4VP fibers. The peak positions and intensity of spectra from surface‐enhanced Raman spectroscopy are transferred into plasmonic anti‐counterfeiting labels with different spaces and widths. The anti‐counterfeiting labels are further encrypted into quick response (QR) codes and decrypted by the smartphone. The QR codes are difficult to copy and easy to authenticate, and composite fibers possess superior stability and show potential application in the field of anti‐counterfeiting. [ABSTRACT FROM AUTHOR]

Infrared photodetectors are widely used in the field of remote sensing, communications, biomedical imaging, etc. Most photodetection based on 2D transition‐metal dichalcogenides (TMDs) is limited to the visible (Vis) to near‐infrared (NIR) due to large intrinsic bandgaps (≈1.2–2 eV). Here, a bandgap engineering of HfS2 by a tellurium (Te)‐replacement strategy is obtained via chemical vapor transport method. The bandgap values of HfS2(1−x)Te2x decrease from 1.7 to 0.88 eV with Te composition changing from 0 to 0.095. Few‐layer HfS1.81Te0.19 based field‐effect transistors exhibit a high current on/off ratio of 106 and decent electron mobility of 12.6 cm2 V−1 s−1 at room temperature. The photodetectors show a responsivity of 2 A W−1 with a remarkable photocurrent of ≈3 μA and a fast response speed of 8.8/75 ms at 830 nm simultaneously. Further, the response spectrum of HfS2(1−x)Te2x based photodetectors is broadened from Vis to short‐wavelength infrared (SWIR), covering the free‐space laser communications wavelength and the second NIR region in medicine. Bandgap engineering of 2D TMDs proposed in this work offer a promising route to develop bandgap‐variable 2D materials for infrared photodetection applications. [ABSTRACT FROM AUTHOR]

Smart contact lenses have emerged as novel wearable devices. Due to their multifunctional biosensing capabilities and highly integrated performance, they provide a great platform for the diagnosis of eye diseases and the delivery of drugs. Herein, a brief history of the development of contact lenses is given. Then, the state‐of‐the‐art design and fabrication of smart contact lenses for biomedical applications, including contact lens materials, fabrication technologies, and integration, are presented. Furthermore, biosensors implemented in contact lenses to measure lactic acid, glucose, intraocular pressure, and other key metabolites in tears are highlighted. Applications of smart contact lenses in drug delivery are also described. These unique features make smart contact lenses promising diagnostic and treatment devices. Challenges and future opportunities for further applications of smart contact lenses in biomedicine are also discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oxidized phlorotannin can be used as a protein crosslinking agent to produce high‐quality fish gel products. Phlorotannin can be easily induced to form quinone compounds in an oxidizing environment, while o‐quinone has been proven to be a reactive, electrophilic intermediate that easily reacts with proteins to form rigid molecular crosslinking networks. The objective of this study was to investigate the synergistic effects of ultraviolet A (UVA) irradiation (1 h, 15 W m−2) and various concentrations of Laminaria japonica phlorotannin extracts (PTE) on the gel properties of grass carp myofibrillar protein (MP). RESULTS: UVA treatment and PTE could synergistically improve the MP gel properties more than PTE alone (P < 0.05). At 625 mmol kg−1 MP PTE alone, the gel strength and cooking yield reached 3.10 ± 0.16 g cm and 47.45 ± 0.35%, respectively, while with the same level of PTE plus UVA they became 4.26 ± 0.19 g cm and 53.89 ± 1.54%, respectively. The three‐dimensional network structure of the gel (with PTE + UVA) showed higher connectivity and tightness than that of the control group (no treatment). CONCLUSIONS: The synergistic effects of PTE and UVA could effectively induce crosslinking of grass carp MP, which could lead to an improvement of MP gel quality. These findings would provide a new technical approach to produce high‐quality protein gel products in the fish processing industry. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Assessing programmed death ligand‐1 (PD‐L1) expression in non‐small cell lung cancer (NSCLC), particularly in metastatic cases, remains challenging. In this study, surface plasmon resonance (SPR) analysis and [68Ga]Ga‐DOTA‐WL12 micro‐PET/CT imaging are performed. [68Ga]Ga‐DOTA‐WL12 PET/CT and [18F]FDG PET/CT are performed on a cohort of 20 patients with NSCLC. Semi‐quantitative assessments include SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and target‐to‐background ratio (TBR). DOTA‐WL12 exhibits robust PD‐L1 binding with a KD value of 0.2 nM. Subsequent human studies reveal significant correlations between PD‐L1 expression and the [68Ga]Ga‐DOTA‐WL12 SUVmax in primary and metastatic lesions, surpassing the [18F]FDG results (r = 0.8889, p <0.0001 vs r = 0.0469, p = 0.8127). Notably, [68Ga]Ga‐DOTA‐WL12 imaging discerned SUVmax and TBR differences between PD‐L1 TPS ≤1% and PD‐L1 TPS > 1% groups (p all <0.001). In an NSCLC patient with brain metastases, [68Ga]Ga‐DOTA‐WL12 shows a SUVmean of 0.04 in the brain background, with TBR values of 17 and 23, underscoring its potential for detecting brain metastases. The study provides initial evidence for the clinical utility of [68Ga]Ga‐DOTA‐WL12 PET/CT for lesion detection, immunotherapy selection, and therapeutic efficacy evaluation in PD‐L1‐expressing NSCLC, demonstrating its potential as a valuable tool in NSCLC research and management. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the safety and effectiveness of conservative treatment (CST), internal fixation (IF), and hemiarthroplasty (HA) in treating patients older than 75 years with impacted femoral neck fracture (IFNF). DESIGN A randomized clinical trial to compare clinical outcomes of CST, IF, and HA in IFNF patients older than 75 years with a 1:1:1 ratio. SETTING Nanjing First Hospital, Nanjing Medical University, Nanjing, China. PARTICIPANTS A total of 154 patients with IFNF aged between 75 and 97 years. INTERVENTION Patients with IFNF were allocated to CST, IF, and HA. They all received a 36‐month follow‐up. MEASUREMENTS All patients were evaluated by Harris hip score (HHS) (primary outcome) for hip function, European Quality of Life‐5 Dimensions (EQ‐5D) index scores for health‐related quality of life, and visual analogue scale score for hip pain. Operation duration, blood loss, mortality, union rate, complications, and reoperation were also recorded. Assessors were blind to the type of treatment. RESULTS: The baseline parameters of the three groups were similar. IF group had much lower blood loss than HA group (P <.05), while no significant difference in operative duration was found between the two groups (P >.05). HHS in HA group was significantly higher at 1, 3, and 6 months (P <.05), but no significant difference in HHS was found between CST and IF groups at any of the time points during the overall follow‐up (P >.05). EQ‐5D index score was higher in HA group at each follow‐up within 1 year (P <.05), but the difference was not significant at 2‐ and 3‐year follow‐up (P >.05). There was no significant difference in mortality among the three groups at each follow‐up point (P >.05). The nonunion rate was 11.76% (6/51) in CST group and 9.80% (5/51) in IF group and showed no significant difference (P >.05). CONCLUSION: CST may be a feasible way for IFNF in the older patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04219943. J Am Geriatr Soc 68:2214–2221, 2020. [ABSTRACT FROM AUTHOR]

Autophagy suppresses mitochondrial metabolism to preserve hematopoietic stem cells (HSCs) in mice. However, the mechanism by which autophagy regulates hematopoietic aging, in particular in humans, has largely been unexplored. Here, we demonstrate that reduction of autophagy in both hematopoietic cells and their stem cells is associated with aged hematopoiesis in human population. Mechanistically, autophagy delays hematopoietic aging by activating the downstream expression of Sirt3, a key mitochondrial protein capable of rejuvenating blood. Sirt3 is the most abundant Sirtuin family member in HSC‐enriched population, though it declines as the capacity for autophagy deteriorates with aging. Activation of autophagy upregulates Sirt3 in wild‐type mice, whereas in autophagy‐defective mice, Sirt3 expression is crippled in the entire hematopoietic hierarchy, but forced expression of Sirt3 in HSC‐enriched cells reduces oxidative stress and prevents accelerated hematopoietic aging from autophagy defect. Importantly, the upregulation of Sirt3 by manipulation of autophagy is validated in human HSC‐enriched cells. Thus, our results identify an autophagy‐Sirt3 axis in regulating hematopoietic aging and suggest a possible interventional solution to human blood rejuvenation via activation of the axis. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Previous studies have demonstrated abnormalities in functional connectivity (FC) of AD under the assumption that FC is stationary during scanning. However, studies on the FC dynamics of AD, which may provide more insightful perspectives in understanding the neural mechanisms of AD, remain largely unknown. Methods: Combining the sliding‐window approach and the k‐means algorithm, we identified three reoccurring dynamic FC states from resting‐state fMRI data of 26 AD and 26 healthy controls. The between‐group differences both in FC states and in regional temporal variability were calculated, followed by a correlation analysis of these differences with cognitive performances of AD patients. Results: We identified three reoccurring FC states and found abnormal FC mainly in the frontal and temporal cortices. The temporal properties of FC states were changed in AD as characterized by decreased dwell time in State I and increased dwell time in State II. Besides, we found decreased regional temporal variability mainly in the somatomotor, temporal and parietal regions. Disrupted dynamic FC was significantly correlated with cognitive performances of AD patients. Conclusion: Our findings suggest abnormal dynamic FC in AD patients, which provides novel insights for understanding the pathophysiological mechanisms of AD. [ABSTRACT FROM AUTHOR]

Aims: Homozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy.Methods and Results: Compared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild-type-BPIFB4 exerted no benefit. Interestingly, LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and up-regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 up-regulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor.Conclusions: In mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease. [ABSTRACT FROM AUTHOR]

A highly regio‐ and stereoselective oxyalkenylation of phosphinyl allenes is revealed for the first time. This protocol, merging visible light photoredox and palladium catalysis, provides a direct approach to conjugated tertiary allylic alcohol derivatives with broad functional group tolerance in moderate to excellent yields. Mechanistic studies suggest that, although two possible pathways exist in the transformation, radical oxyalkenylation promoted by visible light photoredox takes over the major pathway. [ABSTRACT FROM AUTHOR]

Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. With a conditional mouse model in which autophagy in the hematopoietic system is disrupted by deletion of the Atg7 gene, we show that incapacitating hematopoietic autophagy causes bone loss and perturbs osteocyte homeostasis. Induction of osteoporosis, either by ovariectomy, which blocks estrogen secretion, or by injection of ferric ammonium citrate to induce iron overload, causes dysfunction in the hematopoietic stem and progenitor cells (HSPCs) similar to that found in autophagy‐defective mice. Transcriptomic analysis of HSPCs suggests promotion of iron activity and inhibition of osteocyte differentiation and calcium metabolism by hematopoietic autophagy defect, while proteomic profiling of bone tissue proteins indicates disturbance of the extracellular matrix pathway that includes collagen family members. Finally, screening for expression of selected genes and an immunohistological assay identifies severe impairments in H vessels in the bone tissue, which results in disconnection of osteocytes from hematopoietic cells in the autophagy‐defective mice. We therefore propose that hematopoietic autophagy is required for the integrity of H vessels that bridge blood and bone cells and that its deterioration leads to osteoporosis. [ABSTRACT FROM AUTHOR]

Over 200 yr of ecosystem succession in northeastern China, conifers have replaced broadleaf trees. Vegetation changes during forest succession may affect soil organic C (SOC) stability, which is associated with altered protection mechanisms. Lignin phenol composition, a predictor of soil organic matter variation, was assessed for macroaggregates, microaggregates, and silt–clay (SC) fractions from successional gradients in five forests aged 19 to 239 yr in the Changbai Mountains nature reserve. The large macroaggregates (4.00–8.00 and 2.00–4.00 mm) comprised 45.17 to 59.87% of bulk dry weight and 40.22 to 60.89% of SOC in the 19‐, 32‐, and 48‐yr‐old pioneer forests. However, we detected increased mass proportions and SOC contents in small macroaggregates (1.00–2.00 and 0.25–1.00 mm) in the mixed broadleaf–Korean pine (Pinus koraiensis Siebold & Zucc.) forest after 122 yr. Lignin in bulk soil and aggregates in the 122‐yr‐old stand had lower acid/aldehyde ratios for the vanillyl and syringyl types than other stands, indicating less lignin decomposition. The highest C (198.20 g kg−1 soil) and lignin concentrations (6.14 mg 100 mg−1 C) were detected in the bulk soil from the 239‐yr‐old stand, where SC fraction occupied 56.18% of the C and 84.17% of the lignin content in bulk soil. Forest succession from broadleaf to a broadleaf–pine mixture shifted SOC sequestration and lignin protection from aggregates to SC fractions, along with the development of plant litter composition, fine‐root biomass and turnover, and microorganism biomass, which prompted effective long‐term SOC accumulation in successional forest communities. [ABSTRACT FROM AUTHOR]

New Findings: •What is the central question of this study?Does miR‐124 affect cell proliferation and apoptosis in acute liver failure (ALF) mice?•What is the main finding and its importance?Inhibiting miR‐124 targets PIM‐3 and thus upregulates its expression, consequently inhibiting liver cell apoptosis and promoting cell proliferation, ultimately preventing the progression of ALF. This highlights a promising competitive new target for ALF treatment. Acute liver failure (ALF) is a complicated syndrome frequently leading to dysfunction and failure of various organs. MicroRNAs (miRNAs) have played crucial roles in the development and progression of human diseases, including ALF. However, the potential role of miR‐124 in ALF still remains elusive. Thus, we investigated the underlying mechanism by which miR‐124 influences ALF in a mouse model of ALF. Initially, ALF mouse models were established using d‐galactosamine and lipopolysaccharide. Then we detected the serum biochemical parameters of liver, and pathological characteristics and ultrastructure of liver tissues. Next, we determined miR‐124 and PIM‐3 expression in liver tissues and cells using RT‐qPCR and western blot analysis. The interaction between miR‐124 and PIM‐3 was identified using the dual luciferase reporter gene assay. Subsequently, expression of miR‐124 and PIM‐3 in liver cells was altered to explore their effects on primary liver cell proliferation, the cell cycle and apoptosis. The results obtained showed that ALF mice exhibited a decreased cholinesterase level with increased levels of alanine aminotransferase, aspartate transaminase and total bilirubin as well as abundant liver cell apoptosis and necrosis. miR‐124 was upregulated while PIM‐3 was downregulated in ALF tissues and cells. Besides, the PIM‐3 gene was a target of miR‐124 and was inhibited by miR‐124. Overexpression of miR‐124 or silencing of PIM‐3 reduced Bcl‐2 expression but elevated tumour necrosis factor α expression, and resulted in a reduction in liver cell proliferation but an increase in cell apoptosis in ALF mice. Altogether, miR‐124 functions as a disease‐promoting miRNA with potential in stimulating ALF by targeting PIM‐3. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the percentage of different programmed cell death‐1 (PD‐1)+ T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD‐1+ T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD‐1+ T cell subsets. These present results revealed that the percentage of circulating PD‐1+ Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non‐small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD‐1+ Tfh cells were also significantly enhanced in patients in the extensive‐stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD‐1+Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD‐1+ Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL‐2 and IFN‐γ derived from PD‐1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD‐1+ T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Both seed length and seed width are important traits for soybean yield. In the present study, 89 Quantitative trait loci (QTLs) of seed length and 65 QTLs of seed width were collected from published papers and our study. QTLs in this study were evaluated by the soymap2, then totally 23 consensus QTLs were located on 17 linkage groups (LGs) through the meta‐analysis. The minimum confidence interval was 0.28 cM and the mean phenotypic variance (R2) was ranged from 5.33% to 23.36%. To optimize these QTLs based on statistic analysis, overview method was further used to narrow down CI, the number of QTLs was narrowed down to 84. Furthermore, 2,750 candidate genes were screened from the consensus QTL intervals by informatics, a total of 37 genes were found to be associated with seed size. All results could lay a foundation for MAS (Molecular Assisted Selection) and gene cloning. [ABSTRACT FROM AUTHOR]

Evidence, demonstrating long noncoding RNAs (lncRNAs) as critical players in cancer, remains to increase. lncRNA SBF2‐AS1 was reported to be involved in several cancers, such as hepatocellular carcinoma. However, the role of SBF2‐AS1 in colorectal cancer (CRC) is unknown. We showed lncRNA SBF2‐AS1 expression was growing in CRC samples, especially in advanced cases. Accordingly, SBF2‐AS1 possesses higher expression in CRC cell lines than in normal cell line. Moreover, SBF2‐AS1 high expression indicated a low survival rate. Functionally, SBF2‐AS1 knockdown suppressed the proliferation, migration, and invasion of CRC cells. In terms of mechanism, SBF2‐AS1 upregulation restrained the activity of miR‐619‐5p and led to overexpression of HDAC3. Importantly, downregulation of miR‐619‐5p or HDAC3 overexpression reversed SBF2‐AS1‐silencing‐caused suppression on proliferation and metastasis. Summarily, our findings elucidated a crucial role of SBF2‐AS1 as a miR‐619‐5p sponge, shedding novel light on lncRNA‐related prognostics. [ABSTRACT FROM AUTHOR]

Hypoxia‐induced excessive pulmonary artery smooth muscle cell (PASMC) proliferation plays an important role in the pathology of pulmonary arterial hypertension (PAH). Berberine (BBR) is reported as an effective antiproliferative properties applied in clinical. However, the effect of BBR on PAH remains unclear. In the present study, we elucidated the protective effects of BBR against abnormal PASMC proliferation and vascular remodeling in chronic hypoxia‐induced hearts. Furthermore, the potential mechanisms of BBR were investigated. For this purpose, C57/BL6 mice were exposed to chronic hypoxia for 4 weeks to mimic severe PAH. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased the right ventricular systolic pressure (RVSP), the right ventricle/left ventricle plus septum RV/(LV + S) weight ratio, and the median width of pulmonary arterioles. BBR attenuated the elevations in RVSP and RV/(LV + S) and mitigated pulmonary vascular structure remodeling. BBR also suppressed the hypoxia‐induced increases in the expression of proliferating cell nuclear antigen (PCNA) and of α‐smooth muscle actin. Furthermore, administration of BBR significantly increased the expression of bone morphogenetic protein type II receptor (BMPR‐II) and its downstream molecules P‐smad1/5 and decreased the expression of transforming growth factor‐β (TGF‐β) and its downstream molecules P‐smad2/3. Moreover, peroxisome proliferator‐activated receptor γ expression was significantly decreased in the hypoxia group, and this decrease was reversed by BBR treatment. Our study demonstrated that the protective effect of BBR against hypoxia‐induced PAH in a mouse model may be achieved through altered BMPR‐II and TGF‐β signaling. [ABSTRACT FROM AUTHOR]

Background: Norepinephrine (NE)‐mediated vasoconstriction plays an important role in pulmonary hypertension associated with left heart disease (PH‐LHD). However, the role of NE‐mediated endothelial cell dysfunction in the pathogenesis of PH‐LHD remains to be elucidated. Methods and Results: An enzyme‐linked immunosorbent assay showed that the NE concentration in the plasma of patients with PH‐LHD was higher and the nitrate–nitrite concentration was lower than those in the control group. NE treatment decreased phospho‐Ser633‐eNOS and β2‐adrenergic receptor (β2‐AR) levels in the membrane of human pulmonary artery endothelial cells (HPAECs) analysed by western blot analysis. Consistently, fluorescence microscopy and flow cytometry showed that nitric oxide (NO) production was also decreased in HPAECs. Coimmunoprecipitation confirmed a direct interaction between β2‐AR and endothelial NO synthase (eNOS). Overexpression of β2‐AR attenuated the decline in phospho‐Ser633‐eNOS and NO production. Additionally, the expression of phospho‐Ser633‐eNOS and β2‐AR was decreased in human pulmonary artery endothelium. Finally, our results indicate that NE stimulated HPAEC proliferation, which was blocked by protein kinase A inhibitor or protein kinase B (PKB–AKT) inhibitor. Conclusions: These data provide a novel mechanism for NE‐decreased endothelium‐derived NO and NE‐induced HPAEC proliferation that leads to PH‐LHD, suggesting a potential therapeutic target for PH‐LHD. These data provide a novel mechanism for norepinephrine (NE)‐decreased endothelium‐derived nitric oxide and NE‐induced human pulmonary artery endothelial cells proliferation that leads to pulmonary hypertension associated with left heart disease (PH‐LHD), suggesting a potential therapeutic target for PH‐LHD. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that exogenous hydrogen sulfide can alleviate the development of diabetic cardiomyopathy (DCM) by inhibiting oxidative stress, inflammation, and apoptosis. However, the underlying mechanism is not fully understood. Nuclear expression and function of the transcription factor Forkhead box protein O (FoxO1) have been associated with cardiovascular diseases, and thus, the importance of FoxO1 in DCM has gained increasing attention. This study was designed to investigate the interactions between hydrogen sulfide (H2S) and nuclear FoxO1 in DCM. Methods: Diabetes was induced in adult male C57BL/6J mice by intraperitoneal injection of streptozotocin and was treated with H2S donor sodium hydrosulfide for 12 weeks. The H9C2 cardiomyoblast cell line and neonatal rat cardiomyocytes (NRCMs) were treated with the slow‐releasing H2S donor GYY4137 before high‐glucose (HG) exposure with or without pretreatment with the Akt inhibitor MK‐2206 2HCl. Changes in FoxO1 protein phosphorylation and subcellular localization were determined in H9C2 cells, NRCMs, and cardiac tissues from normal and diabetic mice. Cardiac structure and function in the diabetic mice were evaluated by echocardiography and histological analysis and compared with those in control animals. Results: The echocardiographic and histopathological data indicated that exogenous H2S improved cardiac function and attenuated cardiac hypertrophy and myocardial fibrosis in diabetic mice. H2S also improved HG‐induced oxidative stress and apoptosis in cardiac tissue and NRCMs. In addition, H2S induced FoxO1 phosphorylation and nuclear exclusion in vitro and in vivo, and this function was not inhibited by MK‐2206 2HCl. Alanine substitution mutation of three sites in FoxO1‐enhanced FoxO1 transcriptional activity, and subsequent treatment with exogenous H2S could not prevent HG‐induced nuclear retention. Conclusions: Our data indicate that H2S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of DCM. Our data indicate that hydrogen sulfide (H2S) is a novel regulator of Forkhead box protein O in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Excessive proliferation, migration, and antiapoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs) underlies the development of pulmonary vascular remodeling. The innervation of the PA is predominantly sympathetic, and increased levels of circulating catecholamines have been detected in pulmonary arterial hypertension (PAH), suggesting that neurotransmitters released by sympathetic overactivation may play an essential role in PAH. However, the responsible mechanism remains unclear. Here, to investigate the effects of norepinephrine (NE) on PASMCs and the related mechanism, we used 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, the proliferating cell nuclear antigen and the cell counting kit‐8 assay to evaluate the proliferation of PASMCs, Boyden chamber migration, and wound‐healing assays to assess migration and western blot analysis to investigate protein expression. We demonstrated that the phosphorylation level of the protein phosphatase 2A (PP2A) catalytic subunit (Y307) was higher in PAH patients and PAH models than in controls, both in vivo and in vitro. In addition, NE induced the proliferation and migration of PASMCs, which was attenuated by berberine (BBR), a Chinese herbal medicine, and/or PP2A overexpression. PP2A inhibition worsened NE‐induced PAH and could not be reversed by BBR. Thus, PP2A is critical in driving PAH, and BBR may alleviate PAH via PP2A signaling pathways, thereby offering a potential therapeutic option for PAH. Our study indicated that protein phosphatase 2A was an essential regulator in pulmonary artery smooth muscle cells (PASMCs) and provided evidence supporting the potential of berberine in inhibiting the migration and proliferation of PASMCs. [ABSTRACT FROM AUTHOR]

ATP‐sensitive potassium channels (KATP) channels are widely distributed in various tissues, including pancreatic beta cells, muscle tissue and brain tissue. KATP channels play an important role in cardioprotection in physiological/pathological situations. KATP channels are inhibited by an increase in the intracellular ATP concentration and are stimulated by an increase in the intracellular MgADP concentration. Activation of KATP channels decreases ischaemia/reperfusion injury, protects cardiomyocytes from heart failure, and reduces the occurrence of arrhythmias. KATP channels are involved in various signalling pathways, and their participation in protective processes is regulated by endogenous signalling molecules, such as nitric oxide and hydrogen sulphide. KATP channels may act as a new drug target to fight against cardiovascular disease in the development of related drugs in the future. This review highlights the potential mechanisms correlated with the protective role of KATP channels and their therapeutic value in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The endothelium glycocalyx layer (ECL), presents on the apical surface of endothelial cells, creates a barrier between circulating blood and the vessel wall. Low shear stress (LSS) may accelerate the degradation of the glycocalyx via hyaluronidase2 (Hyal2) and then alter the cell polarity. Yet the liver kinase B1 (LKB1) signaling pathway plays an important role in regulating cell polarity. However, the relationship between LKB1 and glycocalyx during LSS is not clear. In the current study, we demonstrate that LSS attenuates LKB1 and AMP‐activated protein kinase activation as well as activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47phox) and Hyal2 in the human umbilical vein endothelial cell (HUVEC). Pretreatment with 5‐Aminoimidazole‐4‐carboxamide1‐β‐D‐ribofuranoside (AICAR), or diphenyleneiodonium (DPI chloride) and transfection with LKB1 overexpression vector and p47phox small interfering RNA downregulated LSS‐induced Hyal2 activation. By coimmunoprecipitation, we discovered the existence of p47phox/Hyal2 complex. LSS induced the dissociation of p47phox/Hyal2 complex, which was inhibited by LKB1 overexpression and AICAR. Furthermore, knockdown of Hyal2 performed a positive feedback on LKB1 activity. In addition, we also show that LSS enhanced LKB1 translocation from the cytosol to the nucleus. Taken together, these data indicate that Hyal2 regulates LSS‐induced injury of the glycocalyx via LKB1/AMPK/NADPH oxidase signaling cascades. Our results primarily provided insight into the molecular mechanisms of low shear stress‐induced degradation of glycocalyx and discovered the existence of p47phox/hyaluronidase2 (Hyal2) complex. The finding will likely increase their utility as therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract: A simple and sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of isoquercitrin, kaempferol‐3‐O‐rutinoside and tiliroside in rat plasma. Plasma samples were deproteinized with methanol and separated on a Hypersil Gold C18 column (2.1 × 50 mm, i.d., 3.0 μm) using gradient elution with the mobile phase of water and methanol at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed with negative ion electrospray ionization in selected reaction monitoring mode. All analytes showed good linearity over their investigated concentration ranges (r2 > 0.99). The lower limit of quantification was 1.0 ng/mL for isoquercitrin and 2.0 ng/mL for kaempferol‐3‐O‐rutinoside and tiliroside, respectively. Intra‐ and inter‐day precisions were <8.2% and accuracy ranged from −11.5 to 9.7%. The mean extraction recoveries of analytes and IS from rat plasma were >80.4%. The assay was successfully applied to investigate the pharmacokinetic study of the three ingredients after oral administration of Rubus chingii Hu to rats. [ABSTRACT FROM AUTHOR]

Farrerol is a 2,3-dihydro-flavonoid isolated from rhododendron. In this study, a sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the determination of farrerol in rat plasma. Liquid-liquid extraction by was used for sample preparation. Chromatographic separation was achieved on an Agilent UHPLC XDB-C18 column (2.1 × 100 mm, 1.8 μm) with water and methanol (30:70, v/v) as the mobile phase. An electrospray source was applied and operated in negative ion mode; selection reaction monitoring was used for quantification using target fragment ions m/z 299 → 179 for farrerol and m/z 267 → 252 for internal standard. Calibration plots were linear in the range of 2.88-1440 ng/mL for farrerol in rat plasma. Intra- and inter-day precisions were <11.6%, and the accuracy ranged from −13.9 to 11.9%. The UHPLC-MS/MS method was successfully applied in pharmacokinetics and bioavailability studies of farrerol in rats. [ABSTRACT FROM AUTHOR]

A porous aromatic framework (referred as PAF-39) based on tetrakis(4-(9 H-carbazol-9-yl)phenyl)methane has been designed and synthesized by oxidative coupling polymerization. PAF-39 exhibits high surface area and high heat of adsorption ( Qst) of CO2. Especially, the PAF material was applied for non-enzymatic H2O2 sensing. [ABSTRACT FROM AUTHOR]

Epidemiological studies show that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5-mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let-7 family might play a role in PM-mediated pathological processes. In this study, we investigated the role of let-7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let-7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let-7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let-7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3′-untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let-7a against PM2.5-induced injury. In conclusion, let-7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let-7a/ARG2 axis is a likely therapeutic target for PM2.5-induced airway epithelial injury. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]