Genetic evidence strengthens the bidirectional connection between oral health status and psychiatric disorders: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies cannot accurately infer the causal associations between oral health status and psychiatric disorders. METHODS: We conducted univariate and multivariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with eight oral health statuses (periodontitis, DMFS, Nteeth, toothache, loose teeth, painful gums, bleeding gums, and mouth ulcers) and four psychiatric disorders (Schizophrenia, Major Depressive Disorder (MDD), anxiety and stress-related disorder (ASRD), and Bipolar Disorder (BIP)) as instrumental variables. Genetic data were sourced from the Gene-lifestyle interactions in dental endpoints (GLIDE), UK Biobank, Psychiatric Genomics Consortium (PGC), and Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The inverse variance-weighted (IVW) approach, supported by a comprehensive sensitivity analysis, was employed. RESULTS: Genetically predicted mouth ulcers were significantly linked to higher MDD (OR = 2.17, 95 % CI: 1.33--3.54, P< 0.01) and BIP risks (OR = 2.25, 95 % CI: 1.22-4.15, P = 0.01). BIP heightened bleeding gums risk (OR = 1.01, 95 % CI: 1.00-1.01, P < 0.01). These associations were adjusted for smoking status and alcohol consumption. Painful gums were significantly associated with MDD risk (OR = 96.48, 95 % CI: 2.66-3495.28, P = 0.01), while MDD raised periodontitis risk (OR = 2.15, 95 % CI: 1.24-3.75, P = 0.01), both confounded by smoking and alcohol. Relatively small effects between several variables, while others could not withstand correction for multiple tests. LIMITATIONS: The sample size and limitation to European populations limits the study generalizability. CONCLUSIONS: This study provide evidence of possible causal relationships between several oral health conditions and mental illness. Focusing on oral health and valuing mental health are important for each other and overall health.

Axon-like aligned conductive CNT/GelMA hydrogel fibers combined with electrical stimulation for spinal cord injury recovery.

Rehabilitation and regenerative medicine are two promising approaches for spinal cord injury (SCI) recovery, but their combination has been limited. Conductive biomaterials could bridge regenerative scaffolds with electrical stimulation by inducing axon regeneration and supporting physiological electrical signal transmission. Here, we developed aligned conductive hydrogel fibers by incorporating carbon nanotubes (CNTs) into methacrylate acylated gelatin (GelMA) hydrogel via rotating liquid bath electrospinning. The electrospun CNT/GelMA hydrogel fibers mimicked the micro-scale aligned structure, conductivity, and soft mechanical properties of neural axons. For in vitro studies, CNT/GelMA hydrogel fibers supported PC12 cell proliferation and aligned adhesion, which was enhanced by electrical stimulation (ES). Similarly, the combination of aligned CNT/GelMA hydrogel fibers and ES promoted neuronal differentiation and axon-like neurite sprouting in neural stem cells (NSCs). Furthermore, CNT/GelMA hydrogel fibers were transplanted into a T9 transection rat spinal cord injury model for in vivo studies. The results showed that the incorporating CNTs could remain at the injury site with the GelMA fibers biodegraded and improve the conductivity of regenerative tissue. The aligned structure of the hydrogel could induce the neural fibers regeneration, and the ES enhanced the remyelination and axonal regeneration. Behavioral assessments and electrophysiological results suggest that the combination of aligned CNT/GelMA hydrogel fibers and ES could significantly restore motor function in rats. This study demonstrates that conductive aligned CNT/GelMA hydrogel fibers can not only induce neural regeneration as a scaffold but also support ESto promote spinal cord injury recovery. The conductive hydrogel fibers enable merging regenerative medicine and rehabilitation, showing great potential for satisfactory locomotor recovery after SCI.

Recent advances of chitosan as a hemostatic material: Hemostatic mechanism, material design and prospective application.

Uncontrolled hemorrhage arising from surgery or trauma may cause morbidity and even mortality. Therefore, facilitating control of severe bleeding is imperative for health care worldwide. Among diverse hemostatic materials, chitosan (CS) is becoming the most promising material owing to its non-toxic feature, as well as inherently hemostatic performance. However, further enhancing hemostatic property of CS-based materials without compromising more beneficial functions remains a challenge. In this review, representative hemostatic mechanisms of CS-based materials are firstly discussed in detail, mostly including red blood cells (RBCs) aggregation, platelet adherence and aggregation, as well as interaction with plasma proteins. Also, various forms (involving powder/particle, sponge, hydrogel, nanofiber, and other forms) of CS-based hemostatic materials are systematically summarized, mainly focusing on their design and preparation, characteristics, and comparative analysis of various forms. In addition, varied hemostatic applications are described in detail, such as skin wound hemostasis, liver hemostasis, artery hemostasis, and heart hemostasis. Finally, current challenges and future directions of functional design of CS-based hemostatic materials in diverse hemostatic applications are proposed to inspire more intensive researches.

Outdoor light at night and depressive symptoms in male veterans: a multicenter cross-sectional study in China.

Previous studies have indicated depression was associated with environmental exposures, but evidence is limited for the association between outdoor light at night (LAN) and depression. This study aims to examine the association between long-term outdoor LAN exposure and depressive symptoms using data from the Chinese Veteran Clinical Research platform. A total of 6445 male veterans were selected from 277 veteran communities in 18 cities of China during 2009‒2011. Depressive symptoms were evaluated using the Chinese version of the Center for Epidemiological Studies Depression scale. Outdoor LAN was estimated using the Global Radiance Calibrated Nighttime Lights data. The odds ratio and 95% confidence intervals of depressive symptoms at the high level of outdoor LAN exposure against the low level during the 1 years before the investigation was 1.49 (1.15, 1.92) with p-value for trend < 0.01, and those associated with per interquartile range increase in LAN exposure was 1.22 (1.06, 1.40).

Circular RNA hsa_circ_0001846 facilitates the malignant behaviors of pancreatic cancer by sponging miR-204-3p and upregulating KRAS expression.

Pancreatic cancer (PC) is mainly derived from the exocrine pancreatic ductal epithelial cells, and it is strongly aggressive malignant tumor. Due to its insidious onset and the lack of effective diagnostic biomarkers, PC currently remains one of the main causes of cancer-related mortality worldwide. Recent studies have found that hsa_circ_0001846 is involved in the progression of multiple cancers and has the potential to become biomarkers, but its function and mechanism in PC remains unclear. We found by qRT-PCR experiments that hsa_circ_0001846 was upregulated in PC cells and tissues, while circBase, Sanger sequencing, agarose gel electrophoresis and FISH experiments identified the splicing site, ring structure and cellular localization of hsa_circ_0001846. Various functional experiments by using the construction of small interfering RNA targeting hsa_circ_0001846 and overexpression plasmid demonstrated that hsa_circ_0001846 promoted the proliferation, migration and invasion of PC cells. Moreover, the tumor weight and volume of nude mice were significantly reduced after the stable knockdown of hsa_circ_0001846. In the mechanism exploration, RNA pull-down experiments and dual-luciferase experiments helped us to determine that hsa_circ_0001846 regulated the KRAS expression by sponging miR-204-3p in PC, thus playing a pro-cancer role. In this study, the effect of miR-204-3p on PC was also explored for the first time, and we found that knockdown of miR-204-3p reversed the tumor suppressive effect caused by silencing hsa_circ_0001846, and silencing KRAS also rescued the pro-cancer effect caused by overexpression of hsa_circ_0001846. In conclusion, our study revealed the pro-cancer role of hsa_circ_0001846 in PC, and for the first time identified the mechanism that hsa_circ_0001846 regulated KRAS by sponging miR-204-3p to promote PC progression and had the potential to become a cancer biomarker.

The characteristics of audiovisual temporal integration in streaming-bouncing bistable motion perception: considering both implicit and explicit processing perspectives.

This study explored the behavioral and neural activity characteristics of audiovisual temporal integration in motion perception from both implicit and explicit perspectives. The streaming-bouncing bistable paradigm (SB task) was employed to investigate implicit temporal integration, while the corresponding simultaneity judgment task (SJ task) was used to examine explicit temporal integration. The behavioral results revealed a negative correlation between implicit and explicit temporal processing. In the ERP results of both tasks, three neural phases (PD100, ND180, and PD290) in the fronto-central region were identified as reflecting integration effects and the auditory-evoked multisensory N1 component may serve as a primary component responsible for cross-modal temporal processing. However, there were significant differences between the VA ERPs in the SB and SJ tasks and the influence of speed on implicit and explicit integration effects also varied. The aforementioned results, building upon the validation of previous temporal renormalization theory, suggest that implicit and explicit temporal integration operate under distinct processing modes within a shared neural network. This underscores the brain's flexibility and adaptability in cross-modal temporal processing.

Unraveling the Atomic Shuffles of Twinning Nucleation in Hexagonal Close-Packed Rhenium Nanocrystals.

Reining in deformation twinning is crucial for the mechanical properties of hexagonal close-packed (HCP) metals and hinges on an explicit understanding of the twinning nucleation mechanism. Unfortunately, it is often suggested rather than conclusively demonstrated that twinning nucleation can be mediated by pure atomic shuffles. Herein, by utilizing in situ high-resolution transmission electron microscopy, we have dissected the atomic shuffling mechanism during the {101̅2} twinning nucleation in rhenium nanocrystals, which revealed the emergence of an intermediate body-centered tetragonal (BCT) structure. Specifically, the double-layered prismatic planes initially shuffle into single-layered {11̅0}BCT planes; subsequently, adjacent {22̅0}BCT planes shuffle in opposite directions to form the basal planes of the twin embryo. This shuffling mechanism is further corroborated by molecular dynamic simulations. The finding provides direct evidence of shuffle-dominated twinning nucleation with atomic details that may lead to better control of this critical twinning mode in HCP metals.

Quinone-mediated hydrogen anode for non-aqueous reductive electrosynthesis.

Electrochemical synthesis can provide more sustainable routes to industrial chemicals1-3. Electrosynthetic oxidations may often be performed 'reagent-free', generating hydrogen (H2) derived from the substrate as the sole by-product at the counter electrode. Electrosynthetic reductions, however, require an external source of electrons. Sacrificial metal anodes are commonly used for small-scale applications4, but more sustainable options are needed at larger scale. Anodic water oxidation is an especially appealing option1,5,6, but many reductions require anhydrous, air-free reaction conditions. In such cases, H2 represents an ideal alternative, motivating the growing interest in the electrochemical hydrogen oxidation reaction (HOR) under non-aqueous conditions7-12. Here we report a mediated H2 anode that achieves indirect electrochemical oxidation of H2 by pairing thermal catalytic hydrogenation of an anthraquinone mediator with electrochemical oxidation of the anthrahydroquinone. This quinone-mediated H2 anode is used to support nickel-catalysed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption in the pharmaceutical industry13-15. Initial validation of this method in small-scale batch reactions is followed by adaptation to a recirculating flow reactor that enables hectogram-scale synthesis of a pharmaceutical intermediate. The mediated H2 anode technology disclosed here offers a general strategy to support H2-driven electrosynthetic reductions.

Flexible Curcumin-Loaded Zn-MOF Hydrogel for Long-Term Drug Release and Antibacterial Activities.

Management of chronic inflammation and wounds has always been a key issue in the pharmaceutical and healthcare sectors. Curcumin (CCM) is an active ingredient extracted from turmeric rhizomes with antioxidant, anti-inflammatory, and antibacterial activities, thus showing significant effectiveness toward wound healing. However, its shortcomings, such as poor water solubility, poor chemical stability, and fast metabolic rate, limit its bioavailability and long-term use. In this context, hydrogels appear to be a versatile matrix for carrying and stabilizing drugs due to their biomimetic structure, soft porous microarchitecture, and favorable biomechanical properties. The drug loading/releasing efficiencies can also be controlled via using highly crystalline and porous metal-organic frameworks (MOFs). Herein, a flexible hydrogel composed of a sodium alginate (SA) matrix and CCM-loaded MOFs was constructed for long-term drug release and antibacterial activity. The morphology and physicochemical properties of composite hydrogels were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis), Raman spectroscopy, and mechanical property tests. The results showed that the composite hydrogel was highly twistable and bendable to comply with human skin mechanically. The as-prepared hydrogel could capture efficient CCM for slow drug release and effectively kill bacteria. Therefore, such composite hydrogel is expected to provide a new management system for chronic wound dressings.

The association between long-term exposure to outdoor artificial light at night and poor sleep quality among Chinese veterans: A multi-city study.

BACKGROUND: A handful of previous studies have reported the association between exposure to outdoor artificial light at night (ALAN) and sleep problems. However, evidence for such association is limited in low- and middle-income countries. This study aimed to examine the association between outdoor ALAN exposure and sleep quality in veterans across different regions of China. METHODS: Within the network of the Chinese Veteran Clinical Research Platform, we selected 7258 participants from 277 veteran communities in 18 cities across China during December 2009 and December 2011, using a multi-stage stratified cluster sampling strategy. Face-to-face interviews with the participants were conducted by trained investigators. We used the Pittsburgh Sleep Quality Index (PSQI) to assess participants' sleep quality. We defined poor sleep quality as a PSQI global score >7. The 3-year average exposure to outdoor ALAN prior to the baseline interview was calculated using satellite imagery data, according to participants' geolocation information. The association of ALAN exposure with sleep quality was examined using the mixed-effects logistic regression models with natural cubic splines. RESULTS: The exposure-response curve for sleep quality associated with ALAN exposure was nonlinear, with a threshold value of 49.20 nW/cm2/sr for the 3-year average exposure to outdoor ALAN prior to the baseline interview. Higher ALAN exposure above the threshold was associated with increased risk of poor sleep quality. After adjusting for potential confounders, the odds ratios (and 95%CI, 95% confidence intervals) were 1.15 (0.97, 1.36) and 1.45 (1.17, 1.78) at the 75th and 95th percentiles of ALAN against the threshold. The association of ALAN exposure with poor sleep quality was more pronounced in veterans with depression than those without. Higher OR of poor sleep quality at the 75th percentile of ALAN against the threshold was observed in veterans with depression than those without [2.09 (1.16, 3.76) vs. 1.09 (0.92, 1.30)]. CONCLUSIONS: Long-term exposure to outdoor ALAN was associated with higher risk of poor sleep quality in Chinese veterans. Effective outdoor ALAN management may help to reduce the burden of sleep disorders in Chinese veterans.

Additive manufacturing of vascular stents.

With the advancement of additive manufacturing (AM), customized vascular stents can now be fabricated to fit the curvatures and sizes of a narrowed or blocked blood vessel, thereby reducing the possibility of thrombosis and restenosis. More importantly, AM enables the design and fabrication of complex and functional stent unit cells that would otherwise be impossible to realize with conventional manufacturing techniques. Additionally, AM makes fast design iterations possible while also shortening the development time of vascular stents. This has led to the emergence of a new treatment paradigm in which custom and on-demand-fabricated stents will be used for just-in-time treatments. This review is focused on the recent advances in AM vascular stents aimed at meeting the mechanical and biological requirements. First, the biomaterials suitable for AM vascular stents are listed and briefly described. Second, we review the AM technologies that have been so far used to fabricate vascular stents as well as the performances they have achieved. Subsequently, the design criteria for the clinical application of AM vascular stents are discussed considering the currently encountered limitations in materials and AM techniques. Finally, the remaining challenges are highlighted and some future research directions are proposed to realize clinically-viable AM vascular stents. STATEMENT OF SIGNIFICANCE: Vascular stents have been widely used for the treatment of vascular disease. The recent progress in additive manufacturing (AM) has provided unprecedented opportunities for revolutionizing traditional vascular stents. In this manuscript, we review the applications of AM to the design and fabrication of vascular stents. This is an interdisciplinary subject area that has not been previously covered in the published review articles. Our objective is to not only present the state-of-the-art of AM biomaterials and technologies but to also critically assess the limitations and challenges that need to be overcome to speed up the clinical adoption of AM vascular stents with both anatomical superiority and mechanical and biological functionalities that exceed those of the currently available mass-produced devices.

Robust estimation of dementia prevalence from two-phase surveys with non-responders via propensity score stratification.

BACKGROUND: Missing diagnoses are common in cross-sectional studies of dementia, and this missingness is usually related to whether the respondent has dementia or not. Failure to properly address this issue can lead to underestimation of prevalence. To obtain accurate prevalence estimates, we propose different estimation methods within the framework of propensity score stratification (PSS), which can significantly reduce the negative impact of non-response on prevalence estimates. METHODS: To obtain accurate estimates of dementia prevalence, we calculated the propensity score (PS) of each participant to be a non-responder using logistic regression with demographic information, cognitive tests and physical function variables as covariates. We then divided all participants into five equal-sized strata based on their PS. The stratum-specific prevalence of dementia was estimated using simple estimation (SE), regression estimation (RE), and regression estimation with multiple imputation (REMI). These stratum-specific estimates were integrated to obtain an overall estimate of dementia prevalence. RESULTS: The estimated prevalence of dementia using SE, RE, and REMI with PSS was 12.24%, 12.28%, and 12.20%, respectively. These estimates showed higher consistency than the estimates obtained without PSS, which were 11.64%, 12.33%, and 11.98%, respectively. Furthermore, considering only the observed diagnoses, the prevalence in the same group was found to be 9.95%, which is significantly lower than the prevalence estimated by our proposed method. This suggested that prevalence estimates obtained without properly accounting for missing data might underestimate the true prevalence. CONCLUSION: Estimating the prevalence of dementia using the PSS provides a more robust and less biased estimate.

Synthesis of Polycyclic n/5/8 and n/5/5/5 Skeletons Using Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Exocyclic-ene-vinylcyclopropanes and Carbon Monoxide.

A rhodium-catalyzed [5 + 2 + 1] reaction of exocyclic-ene-vinylcyclopropanes (exo-ene-VCPs) and CO has been realized to access challenging tricyclic n/5/8 skeletons (n = 5, 6, 7), some of which are found in natural products. This reaction can be used to build tetracyclic n/5/5/5 skeletons (n = 5, 6), which are also found in natural products. In addition, 0.2 atm CO can be replaced by (CH2O)n as the CO surrogate to achieve the [5 + 2 + 1] reaction with similar efficiency.

RBM4 regulates cellular senescence via miR1244/SERPINE1 axis.

Cellular senescence serves as a powerful tumor suppressing mechanism that inhibits the proliferation of cancer cells bearing oncogenic mutations at the initial stage of cancer development. RNA-binding proteins (RBPs) play important roles in cancer progression and treatment through distinct functions. However, functions and mechanisms of RNA binding proteins in regulating senescence remain elusive. Here we reported that the RNA binding protein RBM4 contributed to cellular senescence. Depletion of RBM4 induced senescence in different types of cells, including multiple cancer cells. Meanwhile, RBM4 ablation inhibited cancer cell progression both in vitro and in vivo. Specifically, knockdown of RBM4 significantly increased the level of SERPINE1, a known promoter of senescence, thereby inducing the senescence of lung cancer cells. Mechanistically, miR-1244 bound to the 3'-UTR of SERPINE1 to suppress its expression, whereas depletion of RBM4 reduced the level of miR-1244 by promoting the degradation of primary miR-1244 transcripts (pri-miR1244), thus increasing the expression of SERPINE1 and inducing subsequent senescence. Moreover, either SERPINE1 inhibitor or miR-1244 mimics attenuated the RBM4 depletion-induced senescence. Altogether, our study revealed a novel mechanism of RBM4 in the regulation of cancer progression through controlling senescence, providing a new avenue for targeting RBM4 in cancer therapeutics.

Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in people with stroke or transient ischaemic attack.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017 and October 2019. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (1 January 2022), the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 12), MEDLINE (1949 to 1 January 2022), Embase (1980 to 1 January 2022), CINAHL (1982 to 1 January 2022), AMED (1985 to 1 January 2022), and 11 Chinese databases (1 January 2022). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous. Recurrent stroke Three studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-certainty evidence). Adverse events Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence intervals and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-certainty evidence). Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-certainty evidence that PPAR-γ agonists led to fewer events (data not meta-analysed). Vascular events Peroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-certainty evidence). Other outcomes One study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life. AUTHORS' CONCLUSIONS: Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.

Surface-Roughness-Induced Plasticity in a Biodegradable Zn Alloy.

Improving plasticity has been an eternal theme of developing metallic materials. It is difficult to increase room-temperature elongation of metallic materials over 100% without sacrificing strength using existing methods. Herein, surface-roughness-induced plasticity (SRIP) is discovered in biodegradable Zn-0.4Mn alloy. Surprisingly, in the good surface range that meets the international standard ISO 6892, reducing surface roughness results in significant increase in plasticity without loss of strength. From unground to 5000# sandpaper ground states, the surface roughness Ra of the alloy decreases from 0.63 to 0.05 µm, while its room temperature elongation increases from 74% to 143%. SRIP is the synergistic result of increased microstructure damage tolerance and decreased surface roughness. It provides a new method for improving plasticity.

Nanomechanical probing of bacterial adhesion to biodegradable Zn alloys.

Bacterial infections on implants cause an inflammatory response and even implant failure. Bacterial adhesion is an initial and critical step during implant infection. The prevention of bacterial adhesion to implant materials has attracted much attention, especially for biodegradable metals. A deep understanding of the mechanisms of bacterial adhesion to biodegradable metals is urgently needed. In this work, a bacterial probe based on atomic force spectroscopy was employed to determine the bacterial adhesion to Zn alloy, which depended on surface charge, roughness, and wettability. Negative surface charges of Zn, Zn-0.5Li, and 316L generated electrostatic repulsion force towards bacteria. The surface roughness of Zn-0.5Li was significantly increased by localized corrosion. Bacterial adhesion forces on Zn, Zn-0.5Li, and 316L were 325.2 pN, 519.1 pN, and 727.7 pN, respectively. The density of attached bacteria (early-stage bacterial adhesion) on these samples exhibited a positive correlation with the bacterial adhesion force. The bacterial adhesion force and adhesion work provide a quantitative determination of the interactions between bacteria and biodegradable alloys. These results provide a deeper understanding of early bacterial adhesion on Zn alloys, which can further guide the antibacterial surface design of biodegradable materials for clinical application.

Chloroplast-inspired Scaffold for Infected Bone Defect Therapy: Towards Stable Photothermal Properties and Self-Defensive Functionality.

Bone implant-associated infections induced by bacteria frequently result in repair failure and threaten the health of patients. Although black phosphorus (BP) material with superior photothermal conversion ability is booming in the treatment of bone disease, the development of BP-based bone scaffolds with excellent photothermal stability and antibacterial properties simultaneously remains a challenge. In nature, chloroplasts cannot only convert light into chemical energy, but also hold a protective and defensive envelope membrane. Inspired by this, a self-defensive bone scaffold with stable photothermal property is developed for infected bone defect therapy. Similar to thylakoid and stroma lamella in chloroplasts, BP is integrated with chitosan and polycaprolactone fiber networks. The mussel-inspired polydopamine multifunctional "envelope membrane" wrapped above not only strengthens the photothermal stability of BP-based scaffolds, but also realizes the in situ anchoring of silver nanoparticles. Bacteria-triggered infection of femur defects in vivo can be commendably inhibited at the early stage via these chloroplast-inspired implants, which then effectively promotes endogenous repair of the defect area under mild hyperthermia induced by near-infrared irradiation. This chloroplast-inspired strategy shows outstanding performance for infected bone defect therapy and provides a reference for the functionality of other biomedical materials.

Circular RNA hsa_circ_0007367 promotes the progression of pancreatic ductal adenocarcinoma by sponging miR-6820-3p and upregulating YAP1 expression.

Circular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.

Long-term exposure to outdoor light at night and mild cognitive impairment: A nationwide study in Chinese veterans.

BACKGROUND: Evidence is limited for the association between outdoor light at night (LAN) and mild cognitive impairment (MCI), a transitional stage between normal aging and dementia and Alzheimer's disease in the elderly. In this study, the association between outdoor LAN and MCI was examined based on a multi-city study among veterans in China. METHODS: A total of 5496 participants from 18 cities across China were investigated during 2009-2011, selected using a multi-stage random sampling method. Participants' cognitive function was firstly assessed using the Mini Mental State Examination and the Montreal Cognitive Assessment in the Chinese version, and then was further confirmed by clinical examination. Participants' exposure to outdoor LAN was estimated using the Global Radiance Calibrated Nighttime Lights Product at a spatial resolution of around 1 km. The mixed-effects logistic regression model was used to examine the association between outdoor LAN and MCI. RESULTS: After controlling for covariates, odds ratio (OR) and 95 % confidence intervals (95%CI) of MCI was 1.44 (95%CI: 1.36, 1.52) associated with per interquartile range (IQR = 21.17 nW/cm2/sr) increase in exposure to outdoor LAN during the 3 years before the investigation, and for categorical variable of LAN, the highest OR was observed for the highest against the lowest quartile of LAN with a monotonically increasing trend (p values for trend <0.001). Furthermore, higher ORs were observed for females, veterans who had less educational attainment, and had no regular social activities. CONCLUSIONS: Our study revealed that exposure to excessive outdoor LAN was associated with higher risk of MCI. Effective measures should be taken to reduce LAN exposure, which may help to prevent MCI.