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Graph self-supervised learning is an effective technique for learning common knowledge from unlabeled graph data through pretext tasks. To capture the interrelationships between nodes and their essential roles globally, existing methods use clustering labels as self-supervised signals. However, in some cases, these methods may introduce noise, leading to over-fitting of the model and a reduction in performance. To address these issues, a novel framework for Graph Self-Supervised Curriculum Learning based on clustering label smoothing called GSSCL has been proposed. GSSCL clusters knowledge in an easy-to-difficult manner, reducing the heavy dependence on the reliability of clustering and improving the generalizability of the model. Moreover, the Silhouette Coefficient is employed to evaluate the clustering confident scores for all nodes. Some nodes are selected based on high confident scores to perform self-supervised learning. To account for the possibility of complex heterophilous information in graphs (e.g., noisy links), clustering pseudo-label smoothing is performed on K-nearest neighbor graphs built upon the similarities between node features instead of the original graph structures. The obtained multi-scale knowledge is then applied to curriculum learning. Finally, comprehensive experiments conducted across diverse public graph benchmarks demonstrate the superior performance of the proposed framework. It exhibits comparable results to state-of-the-art methods across semi-supervised node classification and clustering tasks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The flavonoid contents of different bamboo-leaf extracts and their relationships to antioxidant activity were investigated in this study by preparing nine samples using two commercially available bamboo-leaf extract products and seven bamboo-leaf extracts such as Phyllostachys edulis . A high performance liquid chromatography (HPLC) method was established to determine seven flavonoid components (orientin, isoorientin, vitexin, isovitexin, tricin, luteolin and luteoloside) in these samples, which were separated using a SymmetryShield TM RP8 column (250 mm×4.6 mm, 5 μm) under gradient-elution conditions using acetonitrile as mobile phase A and 0.5% (v/v) acetic acid aqueous solution as mobile phase B. The antioxidant activities of the samples were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging assays, with half inhibitory concentration (IC 50 ) as an indicator and the butylated hydroxytoluene (BHT) and tert -butylhydroquinone (TBHQ) antioxidants as positive controls. Pearson correlation was then used to analyze the relationship between flavonoid content and antioxidant activity. The HPLC method was found to be accurate and reliable for determining the flavonoid contents of the bamboo-leaf extracts. The seven flavonoids were well separated, and good linear relationships were exhibited (correlation coefficients ( R 2 )≥0.9990). Furthermore, the contents of the seven flavonoids in the bamboo-leaf extracts ranged from 14.97 to 183.94 mg/g, with the highest content of 183.94 mg/g recorded for Phyllostachys edulis . The bamboo species exhibited significantly different flavonoid contents, with Phyllostachys edulis showing the highest orientin, isoorientin, and vitexin levels of 38.45, 101.30, and 9.42 mg/g, respectively. Moreover, the bamboo-leaf extracts exhibited IC 50 values of 78.23-179.41 mg/L for DPPH-radical-scavenging, while values of 203.48-1250.81 mg/L were recorded for hydroxyl radicals. The Phyllostachys edulis leaf extract exhibited the strongest antioxidant activity, with the lowest IC 50 values of 78.23 and 203.48 mg/L for DPPH and hydroxyl, respectively; it showed greatly significant for the further development and application of Phyllostachys edulis . Finally, the relationships between flavonoid content and the DPPH- and hydroxyl-radical-scavenging activities (based on the IC 50 values) were correlated, which revealed that the orientin and isoorientin contents are closely related to the antioxidant activities of the bamboo-leaf extracts. Consequently, the orientin and isoorientin contents can be used as indicators for evaluating the antioxidant activities of bamboo-leaf extracts.

Bamboo leaf extract (BLE) is a pale brown powder extracted from bamboo leaves, and it is listed in the Chinese Standard GB-2760 as a legal and safe food additive. The present study aims to identify and characterize the major flavonoids in BLE. The identification of major flavonoids was carried out using ultra performance liquid chromatography combined with electrospray ionization quadruple time-of-flight tandem mass spectrometry (HPLC/ESI-QTOF-MS/MS). A total of 31 flavonoid compounds were identified and tentatively characterized base on reference standards and MS dissociation mechanisms. HPLC/ESI-QTOF-MS can serve as an important analytical platform to identification structure of bamboo leaf flavonoids (BLF).

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27 S15/78/82A ) and Hsp27 S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27 S15A and Hsp27 S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2A pro ) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27 S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27 S82A . However, Hsp27 S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.

Background: Environment and genes both contribute to schizophrenia. However, the impact of different natural environments surrounding residential addresses on schizophrenia in urban settings remains unknown. This study aimed to investigate the association of urbanisation, measured by residential environments, with late-onset schizophrenia and explore whether genetic risk for schizophrenia modified the associations., Methods: We examined the associations between residential environments and late-onset schizophrenia and its interaction with genetic risk factors in UK Biobank, followed from 2006 to 2010 (baseline) to Dec 2021. Residential environments, including greenspace, domestic garden, blue space, and total natural environment, were evaluated using land use coverage percentage. The polygenic risk score (PRS) of schizophrenia was derived using a Bayesian approach and adjusted it against ancestry. Cox proportional hazard regression model was used to assess the associations between per interquartile (IQR) increase of each type of residential environments and late-onset schizophrenia. Interactive effects of PRS and residential environments on late-onset schizophrenia were assessed on both additive and multiplicative scales., Results: A total of 393,680 participants were included in the analysis, with 844 cases of late-onset schizophrenia being observed after 12.8 years of follow-up. Within 300 m buffer surrounding the residential addresses, per interquartile increase in greenspace (31.5 %) and total natural environment (34.4 %) were both associated with an 11 % (HR = 0.89, 95 % CI 0.80, 0.99) lower risk of late-onset schizophrenia. Domestic garden and blue space did not show significant protective effects on late-onset schizophrenia. A strong dose-response relationship between schizophrenia PRS and schizophrenia was found, while no additive or multiplicative interaction effects were present between residential environments and PRS on late-onset schizophrenia., Conclusion: Residential greenspace and total natural environment may protect against late-onset schizophrenia in older people regardless of genetic risk. These findings shed light on the prevention of schizophrenia and urban planning to optimise ecosystem benefits linked to schizophrenia., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Five new glycosides, namely methyl 3-methoxybenzoate-4,5-di- O - β -D-glucopyranoside (1) , (1a S ,3a S ,3 R )-3-(4'- O - β -D-glucopyranosyl-3'-methoxyphenyl)-5,6-dioxa-bicyclo[3.3.0]octane-1-one (2) , quinolin-4(1 H )-one-3- O - β -D-glucopyranoside (3) , 3-methoxy-propiophenone 4- O -(6'- β -D-xylopyranosyl)- β -D-glucopyranoside (4) , methyl 3-methoxybenzoate 4- O -(6'- β -D-xylopyranosyl)- β -D-glucopyranoside (5) , and one known compound, bambulignan B (6) were isolated from the culms of Phyllostachys nigra var . henonis . Their structures were determined using spectroscopic analysis. All compounds were evaluated for their DPPH radical scavenging activity. Compound 6 exhibited antioxidant activity with IC 50 value of 59.5 μM (positive control, L-ascorbic acid, IC 50 = 12.4 μM; 2,6-ditertbutyl-4-methyl phenol, IC 50 = 11.8 μM).

In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM., (© 2024. The Author(s).)

Background: In 2017 and 2021, the National Medical Products Administration (NMPA) announced to revise the drug label of fluoroquinolones. We aimed to evaluate the association of fluoroquinolone prescribing with the NMPA announcements of label changes., Research Design and Methods: Monthly prevalence of fluoroquinolone prescriptions for uncomplicated urinary tract infections (uUTI), acute exacerbation of chronic bronchitis (AECB), and acute sinusitis (AS) between 2016 and 2022 was calculated, and interrupted time series analysis was applied to assess the impacts of NMPA label changes on fluoroquinolone use., Results: Prevalence of fluoroquinolone prescriptions decreased by 2.39% (95% CI, -4.72% to -0.07%) for uUTI but increased by 3.02% (95% CI, 1.71% to 4.34%) for AS immediately after the 2017 label change. Moreover, after the 2021 label change, fluoroquinolone use decreased shortly in all the three indications. However, a significant increasing trend was observed in fluoroquinolone use for AECB episodes, and fluoroquinolons were used for 61.4% of treated uUTI, 31.6% of treated AECB, and 5.42% of treated AS at the end of 2022, respectively., Conclusions: The label changes issued by the NMPA had no substantial impacts on fluoroquinolone prescribing in the study region in China. Fluoroquinolone prescribing was still highly prevalent for uUTI and AECB and thus requiring further antimicrobial stewardship.

Ionogels have grabbed significant interest in various applications, from sensors and actuators to wearable electronics and energy storage devices. However, current ionogels suffer from low strength and poor ionic conductivity, limiting their performance in practical applications. Here, inspired by the mechanical reinforcement of natural biomacromolecules through noncovalent aggregates, a strategy is proposed to construct nanofibril-based ionogels through complex coacervation-induced assembly. Cellulose nanofibrils (CNFs) can bundle together with poly(ionic liquid) (PIL) to form a superstrong nanofibrous network, in which the ionic liquid (IL) can be retained to form ionogels with high liquid inclusion and ionic conductivity. The strength of the CNF-PIL-IL ionogels can be tuned by the IL content over a wide range of up to 78 MPa. The optical transparency, high strength, and hygroscopicity enabled them to be promising candidates in moist-electricity generation and applications such as energy harvesting windows and wearable power generators. In addition, the ionogels are degradable and the ionogel-based generators can be recycled through dehydration. Our strategy suggests perspectives for the fabrication of high-strength and multifunctional ionogels for sustainable applications.

The utilization of natural products in food preservation represents a promising strategy for the dual benefits of controlling foodborne pathogens and enhancing the nutritional properties of foods. Among the phytonutrients, flavonoids have been shown to exert antibacterial effects by disrupting bacterial cell membrane functionality; however, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of quercetin on the cell membrane permeability of Staphylococcus aureus ATCC 27217. A combined metabolomic and transcriptomic approach was adopted to examine the regulatory mechanism of quercetin with respect to the fatty acid composition and associated genes. Kinetic analysis and molecular docking simulations were conducted to assess quercetin's inhibition of β-ketoacyl-acyl carrier protein reductase (FabG), a potential target in the bacterial fatty acid biosynthesis pathway. Metabolomic and transcriptomic results showed that quercetin increased the ratio of unsaturated to saturated fatty acids and the levels of membrane phospholipids. The bacteria reacted to quercetin-induced stress by attempting to enhance fatty acid biosynthesis; however, quercetin directly inhibited FabG activity, thereby disrupting bacterial fatty acid biosynthesis. These findings provide new insights into the mechanism of quercetin's effects on bacterial cell membranes and suggest potential applications for quercetin in bacterial inhibition.

Background: TikTok is emerging as a vital platform for health information dissemination. Despite myopia being a global public health issue, the high-quality myopia information shared by health educators often fails to go viral. It is imperative to analyze the factors influencing video quality and popularity, especially from diverse perspectives of researchers, health educators, and audiences., Methods: TikTok myopia-related videos were retrieved using TikTok's default comprehensive search (DCS) and most liked search (MLS) strategies. Venn diagrams were employed to illustrate the relationships and commonalities between the two strategies across four sample sizes (top 200, 150, 100, and 50). Video metadata, including details such as creator information, production properties, upload time, video duration, and viewer engagement, were collected. Video quality was assessed using the DISCERN tool. Video content covering six aspects of myopia were evaluated. The impact of search strategies, video sample sizes, production properties, and myopia content on video quality and audience engagement was analyzed through single-factor or multi-factor analysis., Results: DCS and MLS retrieval strategies, as well as varying sample sizes, resulted in differences in audience engagement for myopia videos (P < 0.039), while The DISCERN quality scores remained comparable (P > 0.221). Videos published by healthcare professionals (HCPs) and non-profit organizations (NPOs) were associated with high-quality (P ≤ 0.014) but comparatively lower popularity (P < 0.033). Videos that reported contents of risk factors, management, and outcomes showed high popularity (P < 0.018), while longer video duration (> 60s) exhibited the opposite trend (P < 0.032). Content on myopia evaluation (P ≤ 0.001) and management (P ≤ 0.022) and video duration were positively correlated with higher DISCERN quality., Conclusion: Videos created by HCPs and NPOs deserve greater attention. Rather than pursuing entertaining effects, professional educators should emphasize producing concise, and high-quality myopia content that readily resonates with the audience and has the potential to go viral on the platform., (© 2024. The Author(s).)

The electrospinning technology has set off a tide and given rise to the attention of a widespread range of research territories, benefiting from the enhancement of nanofibers which made a spurt of progress. Nanofibers, continuously produced via electrospinning technology, have greater specific surface area and higher porosity and play a non-substitutable key role in many fields. Combined with the degradability and compatibility of the natural structure characteristics of polysaccharides, electrospun polysaccharide nanofiber membranes gradually infiltrate into the life field to help filter air contamination particles and water pollutants, treat wounds, keep food fresh, monitor electronic equipment, etc., thus improving the life quality. Compared with the evaluation of polysaccharide-based nanofiber membranes in a specific field, this paper comprehensively summarized the existing electrospinning technology and focused on the latest research progress about the application of polysaccharide-based nanofiber in different fields, represented by starch, chitosan, and cellulose. Finally, the benefits and defects of electrospun are discussed in brief, and the prospects for broadening the application of polysaccharide nanofiber membranes are presented for the glorious expectation dedicated to the progress of the eras., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Double-network hydrogels based on calcium alginate are extensively exploited. Unfortunately, their low strength and unstable constitution to open environments limit their application potential. Herein, a new type of double-network organohydrogel (OHG) is proposed. By solvent exchange, a stable physical network is established based on dimethyl sulfoxide (DMSO)-alginate in the presence of a polyacrylamide network. The DMSO content endows tunable mechanical properties, with a maximum tensile strength of ≈1.7 MPa. Importantly, the OHG shows much better environmental stability compared to the conventional double-network hydrogels. Due to the reversible association of hydrogen bonds, the OHG possesses some unique properties, including free-shapeability, shape-memory, and self-adhesion, that offers several promising ways to utilize alginate-based gels for wide applications., (© 2024 Wiley‐VCH GmbH.)

Bioinspired artificial skins integrated with reliable human-machine interfaces and stretchable electronic systems have attracted considerable attention. However, the current design faces difficulties in simultaneously achieving satisfactory skin-like mechanical compliance and self-powered multimodal sensing. Here, this work reports a microphase-separated bicontinuous ionogel which possesses skin-like mechanical properties and mimics the multimodal sensing ability of biological skin by ion-driven stimuli-electricity conversion. The ionogel exhibits excellent elasticity and ionic conductivity, high toughness, and ultrastretchability, as well as a Young's modulus similar to that of human skin. Leveraging the ion-polymer interactions enabled selective ion transport, the ionogel can output pulsing or continuous electrical signals in response to diverse stimuli such as strain, touch pressure, and temperature sensitively, demonstrating a unique self-powered multimodal sensing. Furthermore, the ionogel-based I-skin can concurrently sense different stimuli and decouple the variations of the stimuli from the voltage signals with the assistance of a machine-learning model. The ease of fabrication, wide tunability, self-powered multimodal sensing, and the excellent environmental tolerance of the ionogels demonstrate a new strategy in the development of next-generation soft smart mechano-transduction devices., (© 2023 Wiley‐VCH GmbH.)

Droplet manipulation with high efficiency, high flexibility, and programmability, is essential for various applications in biomedical sciences and engineering. Bioinspired liquid-infused slippery surfaces (LIS), with exceptional interfacial properties, have led to expanding research for droplet manipulation. In this review, an overview of actuation principles is presented to illustrate how materials or systems can be designed for droplet manipulation on LIS. Recent progress on new manipulation methods on LIS is also summarized and their prospective applications in anti-biofouling and pathogen control, biosensing, and the development of digital microfluidics are presented. Finally, an outlook is made on the key challenges and opportunities for droplet manipulation on LIS., (© 2023 Wiley‐VCH GmbH.)

Objective: This study aimed to investigate the effect of residential exposure to green space on the incident osteoporosis and further explore the modification effect of genetic susceptibility., Methods: Participants from the UK Biobank were followed from 2006 to 2010 (baseline) to December 31st, 2022. Using land use coverage, we evaluated exposure to residential surrounding green space, natural environment, and domestic gardens. We used the Cox regression to examine the association between the residential environment and incident osteoporosis. The interactive effects between polygenic risk score (PRS) of osteoporosis and residential environments on incident osteoporosis were investigated., Results: This study included 292,662 participants. Over a median follow-up period of 13.65 years, we documented 9177 incidents of osteoporosis. Per interquartile (IQR) increase in greenness and natural environment at a 300 m buffer was associated with a 4% lower risk of incident osteoporosis [HR = 0.96 (95% CI: 0.93, 0.99)] and [HR = 0.96 (95% CI: 0.93, 0.98)], respectively. We did not identify any interactive effects between genetic risk and residential environment on incident osteoporosis., Conclusions: This study found that public greenness and natural environments could reduce the risk of incident osteoporosis regardless of genetic predisposition. Developing sustainable and publicly accessible natural environments might benefit populations' bone health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With the growing maritime economy, ensuring the quality of communication for maritime users has become imperative. The maritime communication system based on nearshore base stations enhances the communication rate of maritime users through dynamic resource allocation. A virtual queue-based deep reinforcement learning beam allocation scheme is proposed in this paper, aiming to maximize the communication rate. More particularly, to reduce the complexity of resource management, we employ a grid-based method to discretize the maritime environment. For the combinatorial optimization problem of grid and beam allocation under unknown channel state information, we model it as a sequential decision process of resource allocation. The nearshore base station is modeled as a learning agent, continuously interacting with the environment to optimize beam allocation schemes using deep reinforcement learning techniques. Furthermore, we guarantee that grids with poor channel state information can be serviced through the virtual queue method. Finally, the simulation results provided show that our proposed beam allocation scheme is beneficial in terms of increasing the communication rate.

Background: Dry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients' quality of life. The association between air pollution and the risk of dry eye disease remains uncertain., Methods: Data on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution., Results: Among the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 μg/m 3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 μm (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 μm (PM2.5) showed a significant association with DED outpatient visits in males and the 19-59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season., Conclusion: The noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xia, Yang, Sun, Huang, Huang, Zhang and Yao.)

Non-invasive droplet manipulation with no physical damage to the sample is important for the practical value of manipulation tools in multidisciplinary applications from biochemical analysis and diagnostics to cell engineering. It is a challenge to achieve this for most existing photothermal, electric stimuli, and magnetic field-based technologies. Herein, we present a droplet handling toolbox, the ferrofluid transporter, for non-invasive droplet manipulation in an oil environment. It involves the transport of droplets with high robustness and efficiency owing to low interfacial friction. This capability caters to various scenarios including droplets with varying components and solid cargo. Moreover, we fabricated a droplet array by transporter positioning and achieved droplet gating and sorting for complex manipulation in the droplet array. Benefiting from the ease of scale-up and high biocompatibility, the transporter-based droplet array can serve as a digital microfluidic platform for on-chip droplet-based bioanalysis, cell spheroid culture, and downstream drug screening tests.

Waxgels are known for their unique ability to generate sacrificial wax layers during anti-icing. To address the severe slow regrowth of the wax layer, here, carbon black is incorporated in the waxgel network to endow photothermal function. The rate of the regrowth of the wax layer is raised by >6 times under natural light conditions. Meanwhile, the photothermal waxgel showed improved anti-icing performances in terms of delayed ice formation and lower ice adhesion strength.

Recently, there is much interest in droplet condensation on soft or liquid or liquidlike substrates. Droplets can deform soft and liquid interfaces resulting in a wealth of phenomena not observed on hard, solid surfaces (e.g., increased nucleation, interdroplet attraction). Here, we describe a unique collective motion of condensate water droplets that emerges spontaneously when a solid substrate is covered with a thin oil film. Droplets move first in a serpentine, self-avoiding fashion before transitioning to circular motions. We show that this self-propulsion (with speeds in the 0.1-1  mm s^{-1} range) is fueled by the interfacial energy release upon merging with newly condensed but much smaller droplets. The resultant collective motion spans multiple length scales from submillimeter to several centimeters, with potentially important heat-transfer and water-harvesting applications.

Pterostilbene (PTE), a natural stilbene found in blueberries and several varieties of grapes, has several pharmacological activities, including anti-inflammatory and antioxidative activities. However, its role in abdominal aortic aneurysm (AAA), which is a severe inflammatory vascular disease, remains incompletely understood. In this study, we investigated the protective effects of natural stilbene PTE on AAA formation and the underlying mechanism. Two AAA mouse models (Ang II-induced model and PPE-induced model) were used to examine the effect of PTE on AAA formation. We showed that PTE administration attenuated AAA formation in mice. Furthermore, we found that PTE significantly inhibited inflammatory responses in mouse aortas, as PTE suppressed macrophage pyroptosis and prevented macrophage infiltration in aortas, resulting in reduced expression of pro-inflammatory cytokines in aortas. We also observed similar results in LPS + ATP-treated Raw 264.7 cells (a macrophage cell line) and primary peritoneal macrophages in vitro . We showed that pretreatment with PTE restrained inflammatory responses in macrophages by inhibiting macrophage pyroptosis. Mechanistically, miR-146a-5p and TRAF6 interventions in vivo and in vitro were used to investigate the role of the miR-146a-5p/TRAF6 axis in the beneficial effect of PTE on macrophage pyroptosis and AAA. We found that PTE inhibited macrophage pyroptosis by miR-146a-5p-mediated suppression of downstream TRAF6 expression. Moreover, miR-146a-5p knockout or TRAF6 overexpression abrogated the protective effect of PTE on macrophage pyroptosis and AAA formation. These findings suggest that miR-146a-5p/TRAF6 axis activation by PTE protects against macrophage pyroptosis and AAA formation. PTE might be a promising agent for preventing inflammatory vascular diseases, including AAA.

Objectives: The global prevalence of osteoporosis is rising, yet it is unclear whether people with osteoporosis have a higher risk of depression than those without osteoporosis., Study Design: A cross-sectional study., Methods: We used nationally representative data from the US National Health and Nutrition Examination Survey (NHANES) in 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2020. The diagnosis of osteoporosis was based on the bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a score ≥5 as depressive symptoms and a score ≥10 as probable depression. We used logistic regression models to evaluate the association between osteoporosis and depressive symptoms and probable depression., Results: We included 11,603 adults (aged 50 years and older, 52.3% male) and observed 5.2% of them had osteoporosis. 31.9% of these osteoporotic people had depressive symptoms, and 10.0% had probable depression. Compared to participants without osteoporosis, those with osteoporosis were 1.73 times more likely to experience depressive symptoms (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.20-2.50) and 1.91 times more likely to experience probable depression (OR = 1.91, 95% CI 1.02-3.59), after adjusting for sex, age, race/ethnicity, education, marital status, family income, body mass index, smoking, physical activity, and alcohol abuse. Moderate-to-vigorous activities mediated the associations between osteoporosis and depression and depressive symptoms., Conclusions: Osteoporosis is an independent risk factor for depression. This study highlights the need to evaluate the mental well-being of patients with osteoporosis in clinical and primary health care., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show that the cAMP-binding protein EPAC1 is a central regulator of adaptive BAT growth. In vivo, selective pharmacological activation of EPAC1 increases BAT mass and browning of white fat, leading to higher energy expenditure and reduced diet-induced obesity. Mechanistically, EPAC1 coordinates a network of regulators for proliferation specifically in thermogenic adipocytes, but not in white adipocytes. We pinpoint the effects of EPAC1 to PDGFRα-positive preadipocytes, and the loss of EPAC1 in these cells impedes BAT growth and worsens diet-induced obesity. Importantly, EPAC1 activation enhances the proliferation and differentiation of human brown adipocytes and human brown fat organoids. Notably, a coding variant of RAPGEF3 (encoding EPAC1) that is positively correlated with body mass index abolishes noradrenaline-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and energy expenditure to combat metabolic diseases., (© 2024. The Author(s).)

Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient's sputum and in cloacal smear samples from domesticated pigeons belonging to the patient's neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.

The rapid-developing soft robots and wearable devices require flexible conductive materials to maintain electric functions over a large range of deformations. Considerable efforts are made to develop stretchable conductive materials; little attention is paid to the frequent failures of integrated circuits caused by the interface mismatch of soft substrates and rigid silicon-based microelectronics. Here, we present a stretchable solder with good weldability that can strongly bond with electronic components, benefiting from the hierarchical assemblies of liquid metal particles, small-molecule modulators, and non-covalently crosslinked polymer matrix. Our self-solder shows high conductivity (>2×10 5   S  m -1 ), extreme stretchability (~1000%, and >600% with chip-integrated), and high toughness (~20 MJ m -3 ). Additionally, the dynamic interactions within our solder's surface and interior enable a range of unique features, including ease of integration, component substitution, and circuit recyclability. With all these features, we demonstrated an application as thermoforming technology for three-dimensional (3D) conformable electronics, showing potential in reducing the complexity of microchip interfacing, as well as scalable fabrication of chip-integrated stretchable circuits and 3D electronics., (© 2023. The Author(s).)

The patch-based delivery system has been a promising therapeutic approach for treating various vascular diseases. However, conventional methods face several challenges, including labor-intensive and time-consuming processes associated with patch fabrication or factor incorporation, inadequate physical properties, and uncontrolled release of factors. These limitations restrict the potential applications in clinical settings. To overcome these issues, we propose a novel core-shell-shaped droplet patch system called an angiogenic patch (AP). Our system offers several distinct advantages over conventional patches. It enables a rapid and straightforward fabrication process utilizing only two biodegradable ingredients [alginate and ε-poly(l-lysine)], ensuring minimal toxicity. Moreover, the AP exhibits excellent physical integrity to match and withstand physiological mechanics and allows for customizable patch dimensions tailored to individual patients' pathological conditions. Notably, the AP enables facile loading of angiogenic cytokines during patch fabrication, allowing sustained release at a controlled rate through tunable network cross-linking. Subsequently, the AP, delivering a precisely formulated cocktail of angiogenic cytokines (VEGF, bFGF, EGF, and IGF), demonstrated significant effects on endothelial cell functions (migration and tubule formation) and survival under pathological conditions simulating ischemic injury. Likewise, in in vivo experiments using a mouse model of hindlimb ischemia, the AP encapsulating the angiogenic cocktail effectively restored blood flow following an ischemic insult, promoting muscle regeneration and preventing limb loss. With its simplicity and rapid processability, user-friendly applicability, physical tunability, and the ability to efficiently load and control the delivery of angiogenic factors, the AP holds great promise as a therapeutic means for treating patients with ischemic diseases.

Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom-up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre-vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self-organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein-1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter-scale beige adipose micro-tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Supramolecular organogel coatings that can disinfect the deposited microbial pathogens are emerging as an effective vehicle to prevent pathogen transmission. However, the development of anti-pathogen supramolecular adhesives with mechanical robustness and controlled oil inclusion is technically challenging. Here, we report supramolecular adhesives with mechanical integrity and robust interfacial adhesion over a wide range of biogenic antimicrobial oil. Bifunctional monomers are synthesized and assembled into linear polymers with semicrystalline stackings through hierarchical hydrogen bonds, where incorporated bioactive oil could regulate the semicrystalline stackings into nanosized crystalline domains through intermolecular hydrogen bonds. The abundant bonding motifs provided by the supramolecular cross-linked networks could accommodate oil molecules with high inclusion capability and provide more interfacial binding sites with high adhesion strength, and the nanosized crystalline domains could stabilize the organogel network and compensate for the interactions with oil molecules to enhance structural and mechanical stability. In addition, rapid healing, robust adhesion, and antimicrobial and antiviral properties of the resultant organogel coatings are demonstrated. This study paves the way for the development of high-performance antimicrobial supramolecular adhesives with controlled oil inclusion, showing potential applications in soft robotics, tissue engineering, and biomedical devices.

A strain of Lactobacillus plantarum CQPC02 (LP-CQPC02) isolated from naturally fermented kimchi was utilized in this investigation. In order to construct an animal model of lupus nephritis, pristane was used. We then used a kit to identify markers in mouse blood and tissues and a quantitative polymerase chain reaction (qPCR) to measure the expression of genes associated to nuclear factor kappa-B (NF-κB) in mouse kidney tissue. According to the results of the experiments, oral administration of LP-CQPC02 LP-CQPC02 may lessen the lupus nephritis-related rise in urine protein as well as the cytokine levels that were rising in the serum and renal tissues, including IL-6, IL-12, tumor necrosis factor alpha, and interferon. Additionally, in mice with nephritis, LP-CQPC02 can lower serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raise total protein (TP) and albumin (ALB) levels. In mice with nephritis, LP-CQPC02 can also reduce the positive rate of double-stranded deoxyribonucleic acid (dsDNA). Pathological sections were examined, and it was shown that LP-CQPC02 can lessen tissue damage such incomplete glomerular morphology and inflammatory infiltration brought on by nephritis. In the kidneys of mice with lupus nephritis, LP-CQPC02 can upregulate the expression of inhibitor of NF-κB (IκB-α), downregulate the expression of NF-κB, transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Lactobacillus plantarum CQPC02 has been confirmed to have an intervention effect on nephritis in mice and has the potential as a probiotic., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Objective: During the COVID-19 pandemic, nurses, especially if females and working in intensive care units or emergencies unit, were much more at risk than other health-workers categories to develop malaise and acute stress symptoms. This study aimed to examine the nurses' post-traumatic growth and associated influencing factors during the COVID-19 pandemic., Methods: A cross-sectional study using an online survey was conducted at Henan Provincial People's Hospital to gather data from nurses. A set of questionnaires was used to measure the participants' professional identity, organizational support, psychological resilience and post-traumatic growth. Univariate, correlation, and multiple linear regression analyses were used to determine significant factors influencing post-traumatic growth. A theoretical framework based on the Bayesian network was constructed to understand post-traumatic growth and its associated factors comprehensively., Results: In total, 1,512 nurses participated in the study, and a moderate-to-high level of post-traumatic growth was reported. After screening, the identified variables, including psychological counseling, average daily working hours, average daily sleep duration, professional identity, organizational support, and psychological resilience, were selected to build a Bayesian network model. The results of Bayesian network showed that professional identity and psychological resilience positively affected post-traumatic growth directly, which was particularly pronounced in low- and high-scoring groups. While organizational support positively affected post-traumatic growth indirectly., Conclusion: Although this study identified a moderate-to-high level of nurses' post-traumatic growth, proactive measures to improve psychological resilience fostered by professional identity and organizational support should be prioritized by hospitals and nursing managers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yao, Wang, Yang and Zhang.)

Directional liquid transport along one-dimensional structures finds vast applications in fog harvest, liquid separation, sensing, chemical synthesis, and numerous other scenarios. Dynamically, the liquid transport speed is boosted by the driving force and retarded by the hysteresis from the liquid/substrate interface. A capillary force-relied lubricant film or a covalently attached polymer brush on the surface could increase liquid mobility temporarily by reducing the interfacial hysteresis. However, the easy depletion of the lubricant film and the stringent restriction of the substrate severely hamper droplet's directional transport in a long run. Herein, we report a feasible and durable hysteresis reduction design with the polymer-brush stabilized lubricating surface (PBSLS). The PBSLS is achieved through incorporating liquid-like polydimethylsiloxane brushes ( b -PDMS) and the liquid PDMS oligomer ( o -PDMS). The covalent attached b -PDMS "locks" the lubricant oil o -PDMS to the cone surface via strong intermolecular van der Waals force in between. The PBSLS on the cone surface can be sustained under constant shearing force from liquid transport for at least 6 h. A cone with such PBSLS shows increased ability of droplet transport and enhanced fog collection performance in the long run. This design supplies an effective way toward regulating macro-level interfacial performance through surface design on the molecular level.

Objectives: To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. Methods: We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases. Results: From March 2020 to September 2022, the increased mortality (measured by excess risks) for Clostridium difficile colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4-2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for C. difficile colitis. Conclusion: The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Han, Shi, Li, Qi, Wang, Gu, Wu, Zhao, Cao, Xu, Deng, Yao and Ran.)

Background: Cisplatin is a widely used anti-tumor agent but its use is frequently limited by nephrotoxicity. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel which is generally viewed as a sensor of oxidative stress, and increasing evidence supports its link with autophagy, a critical process for organelle homeostasis. Methods: Cisplatin-induced cell injury and mitochondrial damage were both assessed in WT and Trpm2- knockout mice and primary cells. RNA sequencing, immunofluorescence staining, immunoblotting and flowcytometry were applied to interpret the mechanism of TRPM2 in cisplatin nephrotoxicity. Results: Knockout of TRPM2 exacerbates renal dysfunction, tubular injury and cell apoptosis in a model of acute kidney injury (AKI) induced by treatment with cisplatin. Cisplatin-caused tubular mitochondrial damage is aggravated in TRPM2-deficient mice and cells and, conversely, alleviated by treatment with Mito-TEMPO, a mitochondrial ROS scavenger. TRPM2 deficiency hinders cisplatin-induced autophagy via blockage of Ca 2+ influx and subsequent up-regulation of AKT-mTOR signaling. Consistently, cisplatin-induced tubular mitochondrial damage, cell apoptosis and renal dysfunction in TRPM2-deficient mice are mitigated by treatment with a mTOR inhibitor. Conclusion: Our results suggest that the TRPM2 channel plays a protective role in cisplatin-induced AKI via modulating the Ca 2+ -AKT-mTOR signaling pathway and autophagy, providing novel insights into the pathogenesis of kidney injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Postoperative cognitive dysfunction (POCD) is a clinically frequent postoperative complication in the elderly, which is mainly manifested by the occurrence of cognitive dysfunction after anesthetized surgery in patients. To explore the involvement of C/EBPα in microglial polarization in sevoflurane anesthesia induced cognitive impairment in aged rats., Methods: Sprague-Dawley (SD) rats were anesthetized by inhalation of 3% sevoflurane for 6 h to establish the POCD model. The histopathological structure of hippocampus was observed by hematoxylin and eosin (HE) staining. Associative learning and memory function and spatial learning and memory function were assessed by conditioned fear test and water maze test. The concentrations of inflammatory factors in the hippocampus were measured by ELISA. The levels of microglial activation marker (Iba1) and microglial M1 (CD86) and M2 (CD206) polarization markers were determined by immunofluorescence staining and RT-qPCR, respectively. The transcriptional regulation of HDAC1 by C/EBPα was confirmed by dual luciferase reporter assay and ChIP assay., Results: Sevoflurane-induced pathomorphological damage in the hippocampal tissue of aged rats, accompanied by elevated expression of C/EBPα. Silencing of C/EBPα alleviated hippocampal histopathological injury, inhibited M1 microglial activation and the expression of M1 marker CD86, enhanced the expression of M2 marker CD206. C/EBPα transcriptionally activated HDAC1. Knockdown of C/EBPα downregulated the expression of HDAC1 and STAT3 phosphorylated proteins, which inhibited the pro-inflammatory factors (IL-6 and TNF-α) and accelerated anti-inflammatory factors (IL-10 and TGF-β) secretion. In addition, silencing of C/EBPα caused rats to have a delayed freezing time in contextual conditioned fear, a shorter escape latency, and an increased number of platform crossings., Conclusion: Inhibition of C/EBPα promotes the M2 polarization of microglia and reduces the production of pro-inflammatory cytokines to alleviate the cognitive dysfunction of sevoflurane-induced elderly rats by HDAC1/STAT3 pathway., Competing Interests: The authors declare there are no competing interests., (©2023 Xu et al.)

Background: Granulosa cell (GC) proliferation and apoptosis are critical events of the ovum energy supply, which lead to follicular growth retardation or atresia, and various ovulatory obstacles, eventually resulting in the development of ovarian disorders such as polycystic ovarian syndrome (PCOS). Apoptosis and dysregulated miRNA expression in GCs are manifestations of PCOS. miR-4433a-3p has been reported to be involved in apoptosis. However, there is no study reporting the roles of miR-4433a-3p in GC apoptosis and PCOS progression., Methods: miR-4433a-3p and peroxisome proliferator-activated receptor alpha (PPAR-α) levels in GCs of PCOS patients or in tissues of a PCOS rat model were examined by quantitative polymerase chain reaction and immunohistochemistry. Bioinformatics analyses and luciferase assays were used to examine the association between miR-4433a-3p and PPAR-α, as well as PPAR-α and immune cell infiltration, in PCOS patients., Results: miR-4433a-3p expression in GCs of PCOS patients was increased. miR-4433a-3p overexpression inhibited the growth of the human granulosa-like tumor cell line (KGN) and promoted apoptosis, while co-treatment with PPAR-α and miR-4433a-3p mimic rescued miR-4433a-3p-induced apoptosis. PPAR-α was a direct target of miR-4433a-3p and its expression was decreased in PCOS patients. PPAR-α expression was also positively correlated with the infiltration of activated CD4 + T cells, eosinophils, B cells, gamma delta T cells, macrophages, and mast cells, but negatively correlated with the infiltration of activated CD8 + T cells, CD56 + bright natural killer cells, immature dendritic cells, monocytes, plasmacytoid dendritic cells, neutrophils, and type 1 T helper cells in PCOS patients., Conclusion: The miR-4433a-3p/PPAR-α/immune cell infiltration axis may function as a novel cascade to alter GC apoptosis in PCOS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The brick-and-mortar architecture of nacre shells brings radiant structural colors, high toughness, and strength, inspiring numerous designs for structural and optical materials. However, constructing structural color is not always easy, especially among soft materials where aligning components against random and dynamically active environments is generally difficult. Here, we propose a composite organohydrogel capable of visualizing multiple levels of stress, featuring broad tunable mechanical properties, dynamic mechanochromism, deep low working temperatures, and anti-drying attributes. In the composite gels, the intercalation between α-zirconium phosphate (α-ZrP) nanoplates and poly-(diacetone acrylamide- co -acrylamide) is induced by shear-orientation-assisted self-assembly followed by solvent replacement. The highly tailorable (from ∼780 nm to ∼445 nm) range of colors was achieved by regulating the concentration of α-ZrP and glycerol inside the matrix. With the help from glycerol, the composite gels exhibited long-term stability (7 d) in the arid condition and remarkable low-temperature tolerance (-80 °C). The extraordinary mechanical property (compressive strength up to 119 MPa) of composite gels is achieved by the assembled α-ZrP plates with a small aspect ratio, high negative charge repulsion, and abundant hydrogen bonding sites. As a result, the mechanochromic sensor based on the composite gel enjoys a wide range of stress detection (0-1862 KPa). This study provides a new strategy for constructing high strength structural-colored gels, opening up opportunities for sensitive yet strong mechanochromic sensors in extreme environments.

Vaccination is an effective measure to prevent infectious diseases. Protective immunity is induced when the immune system is exposed to a vaccine formulation with appropriate immunogenicity. However, traditional injection vaccination is always accompanied by fear and severe pain. As an emerging vaccine delivery tool, microneedles overcome the problems associated with routine needle vaccination, which can effectively deliver vaccines rich in antigen-presenting cells (APCs) to the epidermis and dermis painlessly, inducing a strong immune response. In addition, microneedles have the advantages of avoiding cold chain storage and have the flexibility of self-operation, which can solve the logistics and delivery obstacles of vaccines, covering the vaccination of the special population more easily and conveniently. Examples include people in rural areas with restricted vaccine storage facilities and medical professionals, elderly and disabled people with limited mobility, infants and young children afraid of pain. Currently, in the late stage of fighting against COVID-19, the main task is to increase the coverage of vaccines, especially for special populations. To address this challenge, microneedle-based vaccines have great potential to increase global vaccination rates and save many lives. This review describes the current progress of microneedles as a vaccine delivery system and its prospects in achieving mass vaccination against SARS-CoV-2.

Background: Although the COVID-19 pandemic has persisted for more than two years with the evident excess mortality from diabetes, few studies have investigated its temporal patterns. This study aims to estimate the excess deaths from diabetes in the United States (US) during the COVID-19 pandemic and evaluate the excess deaths by spatiotemporal pattern, age groups, sex, and race/ethnicity., Methods: Diabetes as one of multiple causes of death or an underlying cause of death were both considered into analyses. The Poisson log-linear regression model was used to estimate weekly expected counts of deaths during the pandemic with adjustments for long-term trend and seasonality. Excess deaths were measured by the difference between observed and expected death counts, including weekly average excess deaths, excess death rate, and excess risk. We calculated the excess estimates by pandemic wave, US state, and demographic characteristic., Results: From March 2020 to March 2022, deaths that diabetes as one of multiple causes of death and an underlying cause of death were about 47.6 % and 18.4 % higher than the expected. The excess deaths of diabetes had evident temporal patterns with two large percentage increases observed during March 2020, to June 2020, and June 2021 to November 2021. The regional heterogeneity and underlying age and racial/ethnic disparities of the excess deaths were also clearly observed., Conclusions: This study highlighted the increased risks of diabetes mortality, heterogeneous spatiotemporal patterns, and associated demographic disparities during the pandemic. Practical actions are warranted to monitor disease progression, and lessen health disparities in patients with diabetes during the COVID-19 pandemic., Competing Interests: Conflict of interests All authors declare that they have no conflict of interest or financial conflicts to disclose. The funding agencies have no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Human induced pluripotent stem cells (hiPSCs) have the potential to be differentiated into any cell type, making them a relevant tool for therapeutic purposes such as cell-based therapies. In particular, they show great promise for obesity treatment as they represent an unlimited source of brown/beige adipose progenitors (hiPSC-BAPs). However, the low brown/beige adipocyte differentiation potential in 2D cultures represents a strong limitation for clinical use. In adipose tissue, besides its cell cycle regulator functions, the cyclin-dependent kinase inhibitor 2A ( CDKN2A ) locus modulates the commitment of stem cells to the brown-like type fate, mature adipocyte energy metabolism and the browning of adipose tissue. Here, using a new method of hiPSC-BAPs 3D culture, via the formation of an organoid-like structure, we silenced CDKN2A expression during hiPSC-BAP adipogenic differentiation and observed that knocking down CDKN2A potentiates adipogenesis, oxidative metabolism and the browning process, resulting in brown-like adipocytes by promoting UCP1 expression and beiging markers. Our results suggest that modulating CDKN2A levels could be relevant for hiPSC-BAPs cell-based therapies.

On-skin electronic sensors are demanded for healthcare monitoring such as the continuous recording of biopotential and motion signals from patients. However, the mechanical mismatches and poor interface adhesion at the skin/sensor interfaces always cause high interfacial impedance and artifacts, frequent interfacial failure, and unexpected depletion of the device, which significantly limit the performance of the sensors. We here develop an on-skin sensor based on a conductive pressure-sensitive tape, which is assembled from supramolecular dual-cross-linked hydrogel composites. Both covalent and noncovalent cross-links in the hydrogel networks could harvest high flexibility, pressure-sensitive adhesion, and high interfacial toughness altogether, enabling a convenient "Press-N-Go" application of the sensor on human skin without additional pre/post-treatment on the skin or the senor. The high conformability and low resistivity of the tape can sustainably lower the interfacial impedance and thus improve signal quality in various measurement conditions. Our design provides a feasible path to develop interface-toughened on-skin electronics, which is desired in dynamic human-machine interfaces.

Background: Many important clinical decisions require causal knowledge (CK) to take action. Although many causal knowledge bases for medicine have been constructed, a comprehensive evaluation based on real-world data and methods for handling potential knowledge noise are still lacking., Objective: The objectives of our study are threefold: (1) propose a framework for the construction of a large-scale and high-quality causal knowledge graph (CKG); (2) design the methods for knowledge noise reduction to improve the quality of the CKG; (3) evaluate the knowledge completeness and accuracy of the CKG using real-world data., Material and Methods: We extracted causal triples from three knowledge sources (SemMedDB, UpToDate and Churchill's Pocketbook of Differential Diagnosis) based on rule methods and language models, performed ontological encoding, and then designed semantic modeling between electronic health record (EHR) data and the CKG to complete knowledge instantiation. We proposed two graph pruning strategies (co-occurrence ratio and causality ratio) to reduce the potential noise introduced by SemMedDB. Finally, the evaluation was carried out by taking the diagnostic decision support (DDS) of diabetic nephropathy (DN) as a real-world case. The data originated from a Chinese hospital EHR system from October 2010 to October 2020. The knowledge completeness and accuracy of the CKG were evaluated based on three state-of-the-art embedding methods (R-GCN, MHGRN and MedPath), the annotated clinical text and the expert review, respectively., Results: This graph included 153,289 concepts and 1,719,968 causal triples. A total of 1427 inpatient data were used for evaluation. Better results were achieved by combining three knowledge sources than using only SemMedDB (three models: area under the receiver operating characteristic curve (AUC): p < 0.01, F1: p < 0.01), and the graph covered 93.9 % of the causal relations between diseases and diagnostic evidence recorded in clinical text. Causal relations played a vital role in all relations related to disease progression for DDS of DN (three models: AUC: p > 0.05, F1: p > 0.05), and after pruning, the knowledge accuracy of the CKG was significantly improved (three models: AUC: p < 0.01, F1: p < 0.01; expert review: average accuracy: + 5.5 %)., Conclusions: The results demonstrated that our proposed CKG could completely and accurately capture the abstract CK under the concrete EHR data, and the pruning strategies could improve the knowledge accuracy of our CKG. The CKG has the potential to be applied to the DDS of diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The self-healing property based on metal-ligand physical coordination is particularly interesting in bio-hydrogel science due to its allowance for multiple local healing events to process. As the most abundant renewable green resource in nature, Gleditsia sinensis galactomannan has great potential as a starting material for functional materials. In this study, the biocompatible Gleditsia sinensis galactomannan and cellulose were firstly chemically modified and then taken as the main constituent for constructing the metal-ligand coordination through an enzyme-regulated strategy. The hydrogel could quickly gelatinize in the surrounding environment, corresponding to the violent exothermic phenomenon, and exhibit extraordinary self-healing behavior. The molecular dynamics simulation of the hydrogel confirmed the more stable coordinated configuration from Fe(III)-chelates than Fe(II)-chelates. The morphology, mechanical property, antibacterial, and cytotoxicity of the prepared hydrogel were also studied. Our results indicated that galactomannan hydrogel based on the metal-ligand networks could balance the kinetic stability and intrinsic healability through the enzyme-induced route, which provide a new perspective in the field of biomaterial applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Newborn neurons from the subventricular zone (SVZ) are essential to functional recovery following ischemic stroke. However, the number of newly generated neurons after stroke is far from enough to support a potent recovery. Adiponectin could increase neurogenesis in the dentate gyrus of hippocampus in neurodegenerative diseases. However, the effect of adiponectin on the neurogenesis from SVZ and the functional recovery after ischemic stroke was unknown, and the underlying mechanism was not specified either. The middle cerebral artery occlusion model of mice was adopted and adiponectin was administrated once a day from day 3 to 7 of reperfusion. The levels of BDNF and p-STAT3 were detected by western blotting on day 7 of reperfusion. The virus-encoded BDNF shRNA with GFAP promoter and a STAT3 inhibitor Stattic were used, respectively. Neurogenesis was evidenced by the expression of doublecortin and 5-bromo-2'-deoxyuridine (BrdU) labelling and brain atrophy was revealed by Nissl staining on day 28 of reperfusion. Neurological functional recovery was assessed by the adhesive removal test and the forepaw grip strength. We found that adiponectin increased both the doublecortin-positive cells and NeuN/BrdU double-positive cells around the injured area on day 28 of reperfusion, along with the improved long-term neurological recovery. Mechanistically, adiponectin increased the protein levels of p-STAT3 and BDNF in astrocytes on day 7 of reperfusion, while silencing BDNF diminished the adiponectin-induced neurogenesis and functional recovery. Moreover, inhibition of STAT3 not only prevented the increase of BDNF but also the improved neurogenesis and functional recovery after stroke. In conclusion, adiponectin enhances neurogenesis and functional recovery after ischemic stroke via STAT3/BDNF pathway in astrocytes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Based on fracture mechanics theory, a finite element method was used to determine the stress intensity factors of the inclined crack on the inner surface of the pipe under axial compression load and external pressure. The effects of different influencing factors on the stress intensity factor along the crack front considering crack closure were systematically explored, which were different to those under internal pressure. The effects of high aspect ratio on K II , the crack inclination asymmetry caused by curvature and the effects of the friction coefficient on the stress intensity factors of the pipe with an inclined inner surface crack under axial compression load and external pressure were explored in this paper. To be fit for defect assessment, the solutions for stress intensity factors K II and K III were derived, and new correction factors f θ and f μ were proposed in the empirical solutions to accommodate the crack inclination asymmetry and the friction coefficient, respectively.

Purpose: To assess the association between sarcopenia and the risk of early biliary infection (EBI) after percutaneous transhepatic biliary stent (PTBS) placement in patients with inoperable biliary tract cancer (BTC)., Patients and Methods: In this single center, retrospective observational study, patients diagnosed with inoperable BTC undergoing PTBS placement between January 2013 and July 2021 were enrolled. Preoperative sarcopenia was defined based on skeletal muscle mass measured by computed tomography images on the level of third lumbar vertebra within one month before PTBS placement. Patients were divided into two groups in accordance with the status of sarcopenia. Univariate and further multivariate logistic analyses were performed to determine predictors for EBI. Stratified and interactive analyses were conducted to investigate the stability of results. Further receiver operating characteristic curve was performed to determine the predictive value of sarcopenia on EBI after PTBS placement., Results: Totally, 134 patients were included in this retrospective study, with 45 (33.6%) patients characterized as sarcopenia. The incidence rate of EBI was 26.9% (36/134). Multivariate analyses demonstrated that sarcopenia [Odds ratio (OR), 2.75; 95%CI: 1.11-6.77; P =0.028], obstruction length (OR, 1.04; 95%CI: 1.00-1.08; P =0.030) and diabetes (OR, 2.46; 95%CI: 1.01-5.96; P =0.047) were significant predictors of EBI. There were no significant interactions in different subgroups ( P for interaction > 0.05). Moreover, the areas under the curves (AUC) revealed that the combined index containing sarcopenia, obstruction length, and diabetes showed the better predictive value (AUC= 0.723) than either one alone., Conclusion: Sarcopenia increased the risk of EBI in patients with inoperable BTC after PTBS placement. Preoperative assessment of sarcopenia may aid in risk stratification. Patients with sarcopenia should be given intensive monitoring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Lu, Wang, Feng, Yao and Guo.)

Background: The pathological phenotype of perineural invasion (PNI) in squamous cell carcinoma (ESCC) is prevalent but highly heterogeneous., Methods: Postoperative specimens from all patients with ESCC at Shaanxi Provincial People's Hospital were evaluated for PNI using haematoxylin and eosin (H&E) staining and S100 immunohistochemistry (IHC). We determined the correlation between PNI status and clinical outcomes., Results: Among 349 ESCC cases, PNI was identified in 127 patients (36.3%), and four subtypes of PNI were identified in our study. Correlation analysis confirmed that PNI was related to tumour invasion depth (pT stage) and lymph node status (pN stage) (P < 0.05). Multivariate analysis showed that PNI (P = 0.001) was an independent factor affecting disease-free survival (DFS) in ESCC, and a similar result was found for overall survival (OS) (P = 0.017). Further analysis revealed that PNI status was a prognostic factor of DFS (P < 0.001) and OS (P = 0.003) exclusively in pN-negative patients. We also found that patients with the PNI-a subtype had better DFS (P = 0.002) and OS (P = 0.002) than patients with the other three subtypes (PNI-b, c, d)., Conclusion: The pathological phenotypes of PNI are diverse, and the identification of PNI subtypes has important clinical guiding value., (© 2022. The Author(s).)