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Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p

Abstract Background Ischemic stroke (IS) is known for its high morbidity, disability and mortality rates, and studies designed to explore its pathophysiological mechanisms and identify novel therapeutic strategies are urgently needed. We aimed to probe the effects of the deubiquitinase OTUD3-IRP2-p53/PTGS2 pathway on cerebral ischemia‒reperfusion (I/R) injury and hippocampal neuron ferroptosis. Methods A cerebral I/R mouse model was established. Furthermore, lentiviral vectors that overexpressed OTUD3 and knocked down IRP2 were constructed, and a series of assays were performed to probe the OTUD3/IRP2/p53/PTGS2 mechanism. An oxygen‒glucose deprivation and reoxygenation (OGD/R) model of mouse hippocampal neurons was constructed. Then, OTUD3 and IRP2 were knocked down and overexpressed, and p53 was overexpressed to explore the mechanism of the OTUD3/IRP2/p53/PTGS2 pathway. Results OTUD3 and IRP2 were expressed at low levels in cerebral I/R models. OTUD3 promoted IRP2 expression to protect damaged hippocampal neurons. Moreover, IRP2 affected ferroptosis in hippocampal neurons. In addition, IRP2 inhibited p53. After IRP2 and p53 were overexpressed, IRP2 regulated the p53/PTGS2 pathway and affected ferroptosis in hippocampal neurons. In vivo, after overexpressing OTUD3 and knocking down IRP2, we found that overexpression of OTUD3 promoted IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway. Conclusions The deubiquitinase OTUD3 stabilized IRP2 expression to reduce hippocampal neuron ferroptosis via the p53/PTGS2 pathway to subsequently ameliorate cerebral I/R injury.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a common but frequently unrecognized complication of obesity and type 2 diabetes. The association between these conditions is multifaceted and involves complex interactions between metabolic, inflammatory, and genetic factors. Here we assess the underlying structural and molecular processes focusing on the immunological phase of MASH in the nonobese inflammation and fibrosis (NIF) mouse model and compare it to the human disease as well as other murine models. Histopathology together with synchrotron-radiation-based x-ray micro-computed tomography (SRµCT) was used to investigate structural changes within the hepatic sinusoids network in the NIF mouse in comparison to patients with different severities of MASH. A time-course, bulk RNA-sequencing analysis of liver tissue from NIF mice was performed to identify the dynamics of key processes associated with the pathogenesis. Transcriptomics profiling of the NIF mouse revealed a gradual transition from an initially reactive inflammatory response to a regenerative, pro-fibrotic inflammatory response suggesting new avenues for treatment strategies that focus on immunological targets. Despite the lack of metabolic stress induced liver phenotype, a large similarity between the NIF mouse and the immunological phase of human MASH was detected. The translational value was further supported by the comparative analyses with MASH patients and additional animal models. Finally, the impact of diets known to induce metabolic stress, was explored in the NIF mouse. An obesogenic diet was found to induce key physiological, metabolic, and histologic changes akin to those observed in human MASH.

Abstract Background The Medium and Long-Term Plan for the Prevention and Treatment of Chronic Diseases (2017–2025) in China has highlighted the importance of reducing fat, sodium, and sugar in foods. However, front-of-pack labeling, which enables consumers to assess the health levels of prepackaged foods, is lacking in China. In response to the Zhejiang Provincial Health Commission’s request, we sought to develop a method for efficiently evaluating the health level of prepackaged foods. Methods Through a comprehensive literature review, we established a systematic framework: the Prepackaged Foods Healthiness Ranking Index (PHRI). We determined specific threshold values and grading criteria and conducted two rounds of Delphi survey to refine the index. Using a measurement dataset, we aimed to determine the optimal limit values for assessing the health level of prepackaged foods in real-world settings. Results After two rounds of Delphi surveys, the PHRI underwent multiple revisions until consensus among experts was reached. The final decision regarding the upper limit values set 30% Nutrient Reference Values as the limit for solid foods and 15% Nutrient Reference Values for liquid foods. The calculation of PHRI values was successfully implemented with the dataset, in accord with current nutrition awareness and real-world conditions. Conclusions The PHRI provides a valuable tool for assessing the healthiness of prepackaged foods. This front-of-pack labeling system provides a convenient method for evaluating the nutritional quality of prepackaged foods. Ultimately, the PHRI has the potential to contribute to advancements in health policy, practice, and education in China.

Abstract Background Although clinical substance use disorder (SUD) care is multidisciplinary there are few opportunities to collaborate for quality improvement or systems change. In Oregon, the Project ECHO (Extension for Community Healthcare Outcomes) model was adapted to create a novel multidisciplinary SUD Leadership ECHO. The objective of this study was to understand the unique effects of the adapted ECHO model, determine if the SUD Leadership ECHO could promote systems change, and identify elements that enabled participant-leaders to make changes. Methods Four focus groups were conducted between August and September of 2022 with a purposive sample of participants from the second cohort of the Oregon ECHO Network’s SUD Leadership ECHO that ran January to June 2022. Focus group domains addressed the benefits of the adapted ECHO model, whether and why participants were able to make systems change following participation in the ECHO, and recommendations for improvement. Thematic analysis developed emergent themes. Results 16 of the 53 ECHO participants participated in the focus groups. We found that the SUD Leadership ECHO built a multi-disciplinary community of practice among leaders and reduced isolation and burnout. Three participants reported making organizational changes following participation in the ECHO. Those who successfully made changes heard best practices and how other organizations approached problems. Barriers to initiating practice and policy changes included lack of formal leadership authority, time constraints, and higher-level systemic issues. Participants desired for future iterations of the ECHO more focused presentations on a singular topic, and asked for a greater focus on solutions, advocacy, and next steps. Conclusions The adapted ECHO model was well received by focus group participants, with mixed reports on whether participation equipped them to initiate organizational or policy changes. Our findings suggest that the SUD Leadership ECHO model, with fine-tuning, is a promising avenue to support SUD leaders in promoting systems change and reducing isolation among SUD leaders.

As concerns about personal health continue to escalate, there is an urgent need to innovate the development and production of photopolymeric 3D printing thermoset materials with inherent antibacterial properties and high elongation, paving the way for significant advances in 3D printing technology. In this work, two acrylate compounds (CMA and CAMA)with inherent antibacterial properties were synthesized using renewable monomers derived from citronellol and cinnamyl alcohol. The chemical structures of the two acrylate compounds were verified via Fourier transform infrared spectroscopy(FT-IR) and 1H NMR. The addition of these compounds to the photopolymeric 3D printing resin system can facilitate the production of 3D printed thermoset materials with inherent antibacterial properties. The mechanical and antibacterial properties of photopolymeric 3D printing thermosets were assessed utilizing tensile tests and oscillation methods. The results show that the addition of CMA and CAMA can significantly improve the fracture elongation and antibacterial performance of photopolymeric 3D printing thermosets. The improved systems exhibited the highest antibacterial rate (94.2 % and 98.9 %, respectively), and fracture productivities (47 % and 50 %, respectively). These results highlight the significant impact of integrating CMA and CAMA to enhance the toughness and antibacterial effects of photopolymeric 3D printing systems.

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

A novel type of tailless FBG smart bolt with good performance is developed. Owe to the innovative design of an integrated FBG sensor comprising a strain measured FBG and a temperature-compensated FBG, the tailless FBG smart bolt serves the purpose of torque monitoring or bolt looseness monitoring. We use a theoretical approach to establish the linear correlation between the applied torque and the central wavelength of the tailless FBG smart bolt. Additionally, a newly designed M24 bolt with a nominal strength has been integrated as a crucial component of the tailless FBG smart bolt. To enable the experimental study, the tailless FBG smart bolt is newly designed, fabricated and tested. The experimental results show a strong linear correlation between the applied torque and the central wavelength of the tailless FBG smart bolt, showing good agreement with the theory.

Abstract Bridging molecular information to ecosystem-level processes would provide the capacity to understand system vulnerability and, potentially, a means for assessing ecosystem health. Here, we present an integrated dataset containing environmental and metagenomic information from plant-associated microbial communities, plant transcriptomics, plant and soil metabolomics, and soil chemistry and activity characterization measurements derived from the model tree species Populus trichocarpa. Soil, rhizosphere, root endosphere, and leaf samples were collected from 27 different P. trichocarpa genotypes grown in two different environments leading to an integrated dataset of 318 metagenomes, 98 plant transcriptomes, and 314 metabolomic profiles that are supported by diverse soil measurements. This expansive dataset will provide insights into causal linkages that relate genomic features and molecular level events to system-level properties and their environmental influences.

Alfred Hitchcock, film director and “Master of Suspense,” observed that terror is not driven by a negative event, but “only in the anticipation of it.” This observation is not restricted to the movies: Anxiety builds when we anticipate uncertain negative events, and heightened reactivity during uncertain threat anticipation is a transdiagnostic marker of anxiety (Grupe & Nitschke, 2013; Holley & Fox, 2022; Hur et al., 2020; Krain et al., 2008; Simmons et al., 2008; Yassa et al., 2012). Here, we manipulate the temporal dynamics of an uncertain threat to demonstrate how the evolving expectation of threat can lead people to forgo rewards and experience fear/anxiety. Specifically, we show that increased “hazard rate,” which can build during periods of uncertainty, promotes a tendency to avoid threatening contexts while increasing fear/anxiety. These results provide insight into why the anticipation of temporally uncertain threats elicits fear/anxiety, and reframe the underlying causes of related psychopathology.

In this contribution to the proceedings of the 182nd Nobel Symposium, I reflect on the concept of “discovery” as it is used by physicists and astronomers. In particular, I comment on how the scientific community distinguishes discoveries from propositions that are supported only by lesser forms of evidence, emphasizing the social nature of this process and remarking on the subjective factors that go into making such judgments. I advocate for an approach that is intentionally Bayesian in nature, in which individuals are encouraged to evaluate and publicly state their priors and to update them systematically. I close by applying these practices to the case example of the Galactic Center Gamma-Ray Excess.

Profoundly autistic man Tito Mukhopadhyay has been presented as the perfection of the perfection of autism treatment. A cure for autism has of course never been devised. And no one even knows what kind of treatment could even possibly cure autism, because no one knows what the neurological mechanism of autism is. However, I demonstrate that Tito’s communication therapist engaged in multifaceted communicative deception with him during the 2003 – 2017 extensive nationally televised presentations of the therapists’ communicative method. The therapist is Soma Mukhopadhyay, who also is Tito’s mother. It was not known that she was using a speech encryption method, nor other methods of deception. However, from the outset there was suspicion among a vast array of scientists, clinicians, etc., that she was, somehow, responsible for Tito’s written communications. However, despite that they analyzed Soma’s presentations with Tito, and published journal-articles on the “absence of evidence” that Tito, himself, was communicating, they were not able to auditorily observe the speech encryption, nor visually observe and auditorily observe the other methods of deception. That is, they were not able to observe “proof of deception”. “Absence of evidence” and “proof of deception” are of course different. In 2008, a team of scientists who studied Soma and Tito for over 1 year, including the renowned Michael Merzenich, and in 2011 the renowned Oliver Sacks, concluded that there is an abundance of evidence that Tito himself is able to communicate via writing. However, I demonstrate that there is an abundance of proof of deception, and that Sacks, Merzenich, etc., were not able to observe the speech encryption and other methods of deception. (This article consists of revisions and a correction of my 2021 article).

Humification plays a significant role in converting phenolic pollutants and forming heterogeneous polymers, but few studies have been performed to investigate exolaccase-started humification (ESH). Herein, the influences of lignin precursors (LPs) on exolaccase-induced bisphenol A (BPA) removal and humification were explored. In particular, the architectural features and botanical effects of the formed humification products were also tested. ESH was extremely beneficial in boosting BPA removal in the presence of LPs. Compared with LP-free (58.49%), 100% of BPA was eliminated after the reaction with ESH for 72 h. Such a process was controlled by an exolaccase-caused random assembly of radicals, which generated a large number of hydrophobic polymers through nonspecific covalent binding of C–C and/or C–O. These humified polymers were extremely stable at pH 2.0–10.0 and −20 °C to 80 °C and displayed unique functions, i.e., scavenged 2,2-diphenyl-1-picrylhydrazyl/2,2′-azino-bis3-ethylbenzothiazoline-6-sulphonic acid radicals and exerted antioxidant capacities. More importantly, the functional polymers could act as auxin analogs to increase the germination index (>100%), plant biomass, and salt tolerance of radish seedlings. Our findings disclosed that ESH could not only be optimized to mitigate the ecological risks of phenolic pollutants and sequester organic carbon in environmental bioremediation, but the resulting abundant auxin analogs also contributed to agricultural productivity.

Objective: The effects of Coronavirus disease 2019 (COVID-19) infection and altered processes of care on nonelective coronary artery bypass grafting (CABG) outcomes remain unknown. We hypothesized that patients with COVID-19 infection would have longer hospital lengths of stay and greater mortality compared with COVID-negative patients, but that these outcomes would not differ between COVID-negative and pre-COVID controls. Methods: The National COVID Cohort Collaborative 2020-2022 was queried for adult patients undergoing CABG. Patients were divided into COVID-negative, COVID-active, and COVID-convalescent groups. Pre-COVID control patients were drawn from the National Surgical Quality Improvement Program database. Adjusted analysis of the 3 COVID groups was performed via generalized linear models. Results: A total of 17,293 patients underwent nonelective CABG, including 16,252 COVID-negative, 127 COVID-active, 367 COVID-convalescent, and 2254 pre-COVID patients. Compared to pre-COVID patients, COVID-negative patients had no difference in mortality, whereas COVID-active patients experienced increased mortality. Mortality and pneumonia were higher in COVID-active patients compared to COVID-negative and COVID-convalescent patients. Adjusted analysis demonstrated that COVID-active patients had higher in-hospital mortality, 30- and 90-day mortality, and pneumonia compared to COVID-negative patients. COVID-convalescent patients had a shorter length of stay but a higher rate of renal impairment. Conclusions: Traditional care processes were altered during the COVID-19 pandemic. Our data show that nonelective CABG in patients with active COVID-19 is associated with significantly increased rates of mortality and pneumonia. The equivalent mortality in COVID-negative and pre-COVID patients suggests that pandemic-associated changes in processes of care did not impact CABG outcomes. Additional research into optimal timing of CABG after COVID infection is warranted.

Abstract Introduction Fifteen to 25% of patients with colorectal cancer have combined liver metastases at the time of diagnosis, whereas an additional 15 to 25% will develop liver metastases after curative resection of primary colorectal cancer, with the vast majority (80–90%) of liver metastases unresponsive to curative resection at first. Colorectal cancer liver metastasis is also the leading cause of death in patients with colorectal cancer. In recent years, several studies have demonstrated that intestinal flora, especially Fusobacterium nucleatum, plays a crucial role in the development of colorectal cancer liver metastasis, so we hypothesized that long-term metronidazole use could effectively reduce the incidence of postoperative liver metastasis in colorectal cancer patients. Methods/design This study is a prospective, single-centre, randomized, double-blind controlled study in which 300 patients will be randomly assigned to the test group or the control group in a 1:1 allocation ratio. The aim of this trial is to demonstrate that long-term oral antibiotics can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer. Ethics and dissemination Ethics approval was obtained from the Ethics Committee at the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20210229). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Trial registration Chinese Clinical Trial Registry ChiCTR2100046201. Registered on July 05, 2021.

Summary: Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome hyperactivation contributes to many human chronic inflammatory diseases, and understanding how NLRP3 inflammasome is regulated can provide strategies to treat inflammatory diseases. Here, we demonstrate that NLRP3 Cys126 is palmitoylated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7), which is critical for NLRP3-mediated inflammasome activation. Perturbing NLRP3 Cys126 palmitoylation by ZDHHC7 knockout, pharmacological inhibition, or modification site mutation diminishes NLRP3 activation in macrophages. Furthermore, Cys126 palmitoylation is vital for inflammasome activation in vivo. Mechanistically, ZDHHC7-mediated NLRP3 Cys126 palmitoylation promotes resting NLRP3 localizing on the trans-Golgi network (TGN) and activated NLRP3 on the dispersed TGN, which is indispensable for recruitment and oligomerization of the adaptor ASC (apoptosis-associated speck-like protein containing a CARD). The activation of NLRP3 by ZDHHC7 is different from the termination effect mediated by ZDHHC12, highlighting versatile regulatory roles of S-palmitoylation. Our study identifies an important regulatory mechanism of NLRP3 activation that suggests targeting ZDHHC7 or the NLRP3 Cys126 residue as a potential therapeutic strategy to treat NLRP3-related human disorders.

Objectives To evaluate the effectiveness of COVID-19 vaccinations (initial and booster) during pre-Delta, Delta and Omicron dominant periods among pregnant people via (1) COVID-19 incident and severe infections among pregnant people who were vaccinated versus unvaccinated and (2) post-COVID-19 vaccination breakthrough infections and severe infections among vaccinated females who were pregnant versus non-pregnant.Design Retrospective cohort study using nationally sampled electronic health records data from the National COVID Cohort Collaborative, 10 December 2020 –7 June 2022.Participants Cohort 1 included pregnant people (15–55 years) and cohort 2 included vaccinated females of reproductive age (15–55 years).Exposures (1) COVID-19 vaccination and (2) pregnancy.Main outcome measures Adjusted HRs (aHRs) for COVID-19 incident or breakthrough infections and severe infections (ie, COVID-19 infections with related hospitalisations).Results In cohort 1, 301 107 pregnant people were included. Compared with unvaccinated pregnant people, the aHRs for pregnant people with initial vaccinations during pregnancy of incident COVID-19 were 0.77 (95% CI 0.62 to 0.96) and 0.88 (95% CI 0.73 to 1.07) and aHRs of severe COVID-19 infections were 0.65 (95% CI 0.47 to 0.90) and 0.79 (95% CI 0.51 to 1.21) during the Delta and Omicron periods, respectively. Compared with pregnant people with full initial vaccinations, the aHR of incident COVID-19 for pregnant people with booster vaccinations was 0.64 (95% CI 0.58 to 0.71) during the Omicron period. In cohort 2, 934 337 vaccinated people were included. Compared with vaccinated non-pregnant females, the aHRs of severe COVID-19 infections for people with initial vaccinations during pregnancy was 2.71 (95% CI 1.31 to 5.60) during the Omicron periods.Conclusions Pregnant people with initial and booster vaccinations during pregnancy had a lower risk of incident and severe COVID-19 infections compared with unvaccinated pregnant people across the pandemic stages. However, vaccinated pregnant people still had a higher risk of severe infections compared with non-pregnant females.

Regulatory T cells (Tregs) residing in visceral adipose tissue (VAT) play a pivotal role in regulating tissue inflammation and metabolic dysfunction associated with obesity. However, the specific phenotypic and functional characteristics of Tregs in obese VAT, as well as the regulatory mechanisms shaping them, remain elusive. This study demonstrates that obesity selectively reduces Tregs in VAT, characterized by restrained proliferation, heightened PD-1 expression, and diminished ST2 expression. Additionally, obese VAT displays distinctive maturation of dendritic cells (DCs), marked by elevated expressions of MHC-II, CD86, and PD-L1, which are inversely correlated with VAT Tregs. In an in vitro co-culture experiment, only obese VAT DCs, not macrophages or DCs from subcutaneous adipose tissue (SAT) and spleen, result in decreased Treg differentiation and proliferation. Furthermore, Tregs differentiated by obese VAT DCs exhibit distinct characteristics resembling those of Tregs in obese VAT, such as reduced ST2 and IL-10 expression. Mechanistically, obesity lowers IL-33 production in VAT DCs, contributing to the diminished Treg differentiation. These findings collectively underscore the critical role of VAT DCs in modulating Treg generation and shaping Treg phenotype and function during obesity, potentially contributing to the regulation of VAT Treg populations.

Background: The role of continuous wound infusion catheters as part of a multimodal analgesia strategy after Caesarean delivery is unclear. We introduced continuous wound infusion catheters to our multimodal analgesia regimen to evaluate the impact on analgesic outcomes after Caesarean delivery. Methods: After institutional review board (IRB) approval, a 4-month practice change was instituted as a quality improvement initiative. In addition to multimodal analgesia, continuous wound infusion catheters for up to 3 days were offered on alternate weeks for all women undergoing Caesarean deliveries. The primary outcome was postoperative in-hospital opioid consumption. Secondary outcomes were static and dynamic pain scores at 24 and 72 h, time until first analgesic request, opioid-related side-effects, length of stay, satisfaction (0–100%), and continuous wound infusion catheter-related complications. Results: All women scheduled for Caesarean delivery (n=139) in the 4-month period were included in the analysis, with 70 women receiving continuous wound infusion catheters, and 69 in the control group. Opioid consumption (continuous wound infusion catheter group 11.3 [7.5–61.9] mg morphine equivalents vs control group 30.0 [11.3–48.8] mg morphine equivalents), pain scores (except 24 h resting pain scores which were higher in the control group 2 [1–3] vs 1.5 [0–3] in the continous wound infusion catheters group; P=0.05), side-effects, length of stay, and complications were similar between groups. Satisfaction scores at 24 h were higher with continuous wound infusion catheters (100% [91–100%] vs 90% [86–100%]; P=0.003) with no differences at 72 h. One patient demonstrated symptoms of systemic local anaesthetic toxicity which resolved without significant harm. Conclusions: The addition of continuous wound infusion catheters to a multimodal analgesia regimen for post-Caesarean delivery pain management demonstrated minimal clinically significant analgesic benefits. Future studies are needed to explore the use of continuous wound infusion catheters in populations that may benefit most from this intervention.

Abstract Background Long non-coding RNAs play an important role in the development of colorectal cancer (CRC), while many CRC-related lncRNAs have not yet been identified. Methods The relationship between the expression of LINC00955 (Long Intergenic Non-protein Coding RNA 955) and the prognosis of colorectal cancer patients was analyzed using the sequencing results of the TCGA database. LINC00955 expression levels were measured using qRT-PCR. The anti-proliferative activity of LINC00955 was evaluated using CRC cell lines in vitro and xenograft models in nude mice in vivo. The interaction of TRIM25-Sp1-DNMT3B-PHIP-CDK2 was analyzed by western blotting, protein degradation experiment, luciferase, RNA-IP, RNA pull-down assays and immunohistochemically analysis. The biological roles of LINC00955, tripartite motif containing 25 (TRIM25), Sp1 transcription factor (Sp1), DNA methyltransferase 3 beta (DNMT3B), pleckstrin homology domain interacting protein (PHIP), cyclin dependent kinase 2 (CDK2) in colorectal cancer cells were analyzed using ATP assays, Soft agar experiments and EdU assays. Results The present study showed that LINC00955 is downregulated in CRC tissues, and such downregulation is associated with poor prognosis of CRC patients. We found that LINC00955 can inhibit CRC cell growth both in vitro and in vivo. Evaluation of its mechanism of action showed that LINC00955 acts as a scaffold molecule that directly promotes the binding of TRIM25 to Sp1, and promotes ubiquitination and degradation of Sp1, thereby attenuating transcription and expression of DNMT3B. DNMT3B inhibition results in hypomethylation of the PHIP promoter, in turn increasing PHIP transcription and promoting ubiquitination and degradation of CDK2, ultimately leading to G0/G1 growth arrest and inhibition of CRC cell growth. Conclusions These findings indicate that downregulation of LINC00955 in CRC cells promotes tumor growth through the TRIM25/Sp1/DNMT3B/PHIP/CDK2 regulatory axis, suggesting that LINC00955 may be a potential target for the therapy of CRC.

The aerodynamic effects of wing corrugation on insect flight have received widespread attention. However, there has hardly been any specific focus on dynamic changes to corrugation angle in the models. The flexible vein joints containing resilin in the wings of dragonflies and damselflies enable the longitudinal veins to rotate and thereby change the corrugation angles throughout flapping cycles. Therefore, a two-dimensional corrugated airfoil with time-varying corrugation angles is proposed and the aerodynamic performance is evaluated in terms of aerodynamic force, power and efficiency. The results indicate that the airfoil with time-varying corrugations outperforms the rigid one in terms of enhancing thrust and reducing power consumption. The aerodynamic performance of time-varying corrugated airfoils is optimal when the angle varies in a specific range, and an excessively large angle variation may have negative effects. In addition, excessive height or a negative leading edge of the corrugation can lead to a reduction in the thrust. A design concept for the 2D airfoil with time-varying corrugations is provided and the findings are of significance for enhancing the aerodynamic performance of biomimetic flexible flapping-wing vehicles.

Lexical bundles (LBs) are crucial in L2 oral proficiency, yet their complexity in terms of length is under-researched. This study therefore examines the relationship between longer and shorter LBs and oral proficiency among 150 L2 learners of varying proficiency levels at a UK university. Through the analysis of oral presentation data (scores ranging from intermediate to advanced) and employing a combined text-internal and text-external approach (two- to five-word bundles), this study advances an innovative text-internal LB refinement procedure, thus isolating the unique contribution of LB length. Robust regression, dominance analysis, and random forest statistical techniques reveal the predictive power of bigram mutual information (MI) and longer three-to-five-word sequences on higher proficiency scores. Our results show that learners using higher MI score bigrams tend to perform better in their presentations, with a strong positive impact on scores (b = 14.38, 95% CI [8.01, 20.76], t = 4.42; dominance weight = 58.63%). Additionally, the use of longer three-to-five-word phrases also contributes to better performance, though to a lesser extent (dominance weight = 18.80%). These findings highlight the pedagogical potential of a nuanced approach to the strategic deployment of LBs, particularly bigram MI, to foster oral proficiency. Suggestions for future LB proficiency research are discussed in relation to L2 speech production models.

Abstract Background To manage injuries effectively, players, head coaches, and medical personnel need to have excellent knowledge, attitudes, and behaviours in relation to the identification of risk factors for injuries, the implementation of injury prevention initiatives, as well as the implementation of effective injury management strategies. Understanding the injury context, whereby specific personal, environmental, and societal factors can influence the implementation of injury prevention initiatives and injury management strategies is critical to player welfare. To date, no qualitative research investigating the context of injuries, has been undertaken in elite-level women’s football. The aim of our study was to explore the knowledge, attitudes, and behaviours of players, head coaches, and medical personnel in the Irish Women’s National League (WNL) to injury prevention and injury management. Methods We used qualitative research methods to explore the knowledge, attitudes, and behaviours of players, head coaches, and medical personnel in the Irish WNL to injury prevention and injury management. Semi-structured interviews were undertaken with 17 players, 8 medical personnel, and 7 head coaches in the Irish WNL. The data were analysed using thematic analysis. Our study is located within an interpretivist, constructivist research paradigm. Results The participants had incomplete knowledge of common injuries in elite-level football, and many held beliefs about risk factors for injuries, such as menstrual cycle stage, which lacked evidence to support them. Jumping and landing exercises were commonly used to reduce the risk of injuries but evidence-based injury prevention exercises and programmes such as the Nordic hamstring curl, Copenhagen adduction exercise, and the FIFA 11+ were rarely mentioned. Overall, there was dissatisfaction amongst players with their medical care and strength and conditioning (S & C) support, with resultant inadequate communication between players, head coaches, and medical personnel. Conclusion Poor quality and availability of medical care and S & C support were considered to be a major obstacle in the effective implementation of injury risk reduction strategies and successful return-to-sport practices. More original research is required in elite-level women’s football to explore injury risk factors, injury prevention initiatives, and contextual return-to-sport strategies, so that players, head coaches, and medical personnel can use evidence that is both up-to-date and specific to their environment.

Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to reduced endothelium-derived relaxing factor nitric oxide (NO) generation, causing and accelerating CMD. Endoplasmic reticulum stress (ER stress) has been shown to reduce NO production in umbilical vein endothelial cells. Oxidized low-density lipoprotein (ox-LDL) damages endothelial cell function. However, the relationship between ox-LDL and coronary microcirculation has yet to be assessed. Short-chain fatty acid (SCFA), a fermentation product of the gut microbiome, could improve endothelial-dependent vasodilation in human adipose arterioles, but the effect of SCFA on coronary microcirculation is unclear. In this study, we found ox-LDL stimulated expression of ER chaperone GRP78. Further, we activated downstream PERK/eIF2a, IRE1/JNK, and ATF6 signaling pathways, decreasing eNOS phosphorylation and NO production in human cardiac microvascular endothelial. Furthermore, SCFA-propionate can inhibit ox-LDL-induced eNOS phosphorylation reduction and raise NO production; the mechanism is related to the inhibition of ER stress and downstream signaling pathways PERK/eIF2a, IRE1/JNK, and ATF6. In summary, we demonstrate that ox-LDL induced CMD by activating ER stress, propionate can effectively counteract the adverse effects of ox-LDL and protect coronary microcirculation function via inhibiting ER stress.

In today's dynamic and competitive business landscape, innovation is paramount for companies striving to maintain a competitive edge. Among various innovation strategies, corporate green innovation has gained prominence as an efficient means of achieving sustainable growth. In response to the pressing need for sustainable development, this study investigates the bidirectional cointegration link between green innovation and overall corporate innovation in a panel dataset of Chinese-listed enterprises.As China emphasizes principles like "greening" and "innovation" for twenty-first-century development, this research aligns with the nation's goal of fostering sustainable industry growth through "green innovation". It employs panel cointegration tests, including the Westerlund test, dynamic panel ordinary least square (DOLS), and the panel vector error correction model (VECM), using data from Chinese A-listed firms spanning from 2008 to 2020. The study reveals a robust long-term, bidirectional relationship between corporate innovation and green innovation. Notably, it demonstrates that green innovation causally impacts corporate innovation in both the short and long term. This research also conducts subsample analysis, ensuring the robustness of the main findings across both non-polluted and polluted industries. These findings provide valuable insights into how corporate innovation factors influence corporate green innovation. Consequently, they offer valuable insights for policymakers and organizations, aiding in the formulation of policies that promote environmentally friendly innovation while elevating corporate innovation standards.

The impact of outbreak response immunization (ORI) can be estimated by comparing observed outcomes to modelled counterfactual scenarios without ORI, but the most appropriate metrics depend on stakeholder needs and data availability. This study developed a framework for using mathematical models to assess the impact of ORI for vaccine-preventable diseases. Framework development involved (1) the assessment of impact metrics based on stakeholder interviews and literature reviews determining data availability and capacity to capture as model outcomes; (2) mapping investment in ORI elements to model parameters to define scenarios; (3) developing a system for engaging stakeholders and formulating model questions, performing analyses, and interpreting results; and (4) example applications for different settings and pathogens. The metrics identified as most useful were health impacts, economic impacts, and the risk of severe outbreaks. Scenario categories included investment in the response scale, response speed, and vaccine targeting. The framework defines four phases: (1) problem framing and data sourcing (identification of stakeholder needs, metrics, and scenarios); (2) model choice; (3) model implementation; and (4) interpretation and communication. The use of the framework is demonstrated by application to two outbreaks, measles in Papua New Guinea and Ebola in the Democratic Republic of the Congo. The framework is a systematic way to engage with stakeholders and ensure that an analysis is fit for purpose, makes the best use of available data, and uses suitable modelling methodology.

Rumexpatientia L. ×Rumextianshanicus A. Los (RRL), known as “protein grass” in China, was recognized as a new food ingredient in 2021. However, the cultivation and product development of RRL are still at an early stage, and no peptide research has been reported. In this study, two novel antioxidant peptides, LKPPF and LPFRP, were purified and identified from RRL and applied to H2O2-induced HepG2 cells to investigate their antioxidant properties. It was shown that 121 peptides were identified by ultrafiltration, gel filtration chromatography, and LC-MS/MS, while computer simulation and molecular docking indicated that LKPPF and LPFRP may have strong antioxidant properties. Both peptides were not cytotoxic to HepG2 cells at low concentrations and promoted cell growth, which effectively reduced the production of intracellular ROS and MDA, and increased cell viability and the enzymatic activities of SOD, GSH-Px, and CAT. Therefore, LKPPF and LPFRP, two peptides, possess strong antioxidant activity, which provides a theoretical basis for their potential as food additives or functional food supplements, but still need to be further investigated through animal models as well as cellular pathways.

Primary colorectal squamous cell carcinoma (CSCC) is a rare pathological subtype. Currently, clinical data with regards to its prognosis and treatment is limited, and there is no optimal treatment method. The case presented involves a proficient mismatch repair (pMMR) and microsatellite-stable (MSS) Colorectal cancer (CRC) patient with squamous cell carcinoma (SCC) located transversely in the colon. Based on the imaging assessment, the tumor infiltration depth is classified as T4. After receiving 4 cycles of neoadjuvant treatment with oxaliplatin and capecitabine (XELOX), the patients were evaluated for partial response (PR) in 2 cycles and stable disease (SD) in 4 cycles. The patient underwent a right hemicolectomy and received postoperative paclitaxel/cisplatin (TC) adjuvant chemotherapy. After 23 months, a systemic examination revealed abdominal metastasis. A needle biopsy was conducted on the detected abdominal metastases, with the resulting pathology indicating the presence of metastatic SCC. The individual exhibited expression of programmed cell death ligand 1 (PD-L1) and a mutation in the TP53 gene. Considering the patient’s disease recurrence based on medical history, a treatment plan was formulated. This involved Sintilimab plus Cetuximab and the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen. The patient received four cycles of treatment with an efficacy evaluation of SD- and seven cycles of treatment with an efficacy evaluation of SD+, which resulted in a progression-free survival (PFS) duration of 7 months. This case study presents the conventional XELOX chemotherapy protocol, which has shown limited effectiveness, and highlights the favorable results achieved by implementing the TC adjuvant chemotherapy regimen in individuals diagnosed with primary colonic SCC. Furthermore, combining immune checkpoint blockade (ICB) with other therapies for patients with advanced disease is anticipated to provide an extended duration of survival.

Bamboo is one of the fastest-growing plants commonly used in food, fibre, paper, biofuel, ornamental and medicinal industries. Natural hybridization in bamboo is rare due to its long vegetative period followed by gregarious flowering and death of the entire population. In the current study, a new bamboo species, Bambusa changningensis, shows intermediate characteristics of Dendrocalamus farinosus and B. rigida morphologically, but it is unknown whether B. changningensis is a natural hybrid. Moreover, B. changningensis has been identified as a superior variety of Sichuan Province with high pulping yield, fibre length and width. Therefore, we analyzed the morphological characteristics, DNA markers, DNA barcoding and chloroplast genomes to identify the hybrid origin of B. changningensis and possible maternal parent. We have developed the transcriptomic data for B. changningensis and mined the SSR loci. The putative parental lines and hybrid were screened for 64 SSR makers and identified that SSR14, SSR28, SSR31 and SSR34 markers showed both alleles of the parental species in B. changningensis, proving heterozygosity. Sequencing nuclear gene GBSSI partial regions and phylogenetic analysis also confirm the hybrid nature of B. changningensis. Further, we have generated the complete chloroplast genome sequence (139505 bp) of B. changningensis. By analyzing the cp genomes of both parents and B. changningensis, we identified that B. rigida might be the female parent. In conclusion, our study identified that B. changningensis is a natural hybrid, providing evidence for bamboo’s natural hybridization. This is the first report on confirming a natural bamboo hybrid and its parents through SSR and chloroplast genome sequence.

The use of solvent-free approach to manufacture antibacterial epoxy coatings with high renewable carbon content is of important for environmental sustainability and the diversity of antibacterial materials. Herein, an epoxy monomer with inherent antibacterial properties, eugenol-modified epoxidized soybean oil (EUESO) with totally natural carbon was synthesized from renewable epoxidized soybean oil (ESO) and eugenol via one-step solvent-free method. Then, EUESO was cured with DGEBA and 4, 4′-diaminodicyclohexylmethane (HDDM) to construct mechanically robust and anti-release antibacterial epoxy coatings. The influence of the weight ratio of EUESO on epoxy coating and comprehensive performance was systematically studied. According to DSC, TGA and bending test on the thermal and mechanical properties of the cured resins, all cured resins demonstrated high thermodynamic properties and high Tg. Meanwhile, in the dynamic shake test, all cured resins demonstrated a certain degree of killing effect on Escherichia coli (E. coli), with a maximum killing rate of 93.8% as the concentration of EUESO increased.

This study uses multivariate statistics including cluster analysis (CA) and principal component analysis (PCA) to evaluate the variability and key indicators causing changes in soil quality in Tram Chim National Park, Dong Thap province, Vietnam. Soil samples were collected in the dry season at the habitats of Ischaemum rugosum (CM), Panicum repens (CO), Nelumbo nucifera (LS), Eleocharis dulcis (NO), Oryza rufipogon (LM), Rice field (RL), Melaleuca cajuputi (T) in two layers A (0-20 cm) and layer B (20-40 cm). The parameters of pH, total nitrogen (TN), total phosphorus (TP), total acidity (TA), organic matter (OM), total iron (Fe) and exchanged aluminum (Al3+) were used to assess soil quality. The results showed that soil pH was low in both A and B layers. Fe and Al were both high, and the concentrations of these metals in layer A were higher than those in layer B. The OM content was medium level while TN and TP levels were very low. Most of the soil quality indicators tended to decrease with the depth (except for TA). The results of CA analysis showed that there was almost no major change in soil quality between the two soil layers; however, the soil quality in rice field habitat was different with other habitats. The cause may be due to human impact in adding fertilizers/pesticides during farming practices. The PCA results showed at least five influencing factors, explaining 99.7% and 99.9% of soil quality variation in A and B layers. The parameters of Al3+, TA, OM, and TP had the main influence on soil quality of layer A. Meanwhile, indicators of pH, Al3+, TA, TN, Fet had influence on soil quality of layer B. These indicators need to be future surveyed to assess the evolution of soil quality in the study area.

Abstract Introduction Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. Methods The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3–4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm). Results LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p

Abstract Whale entanglements with fishing gear, exacerbated by changing environmental conditions, pose significant risk to whale populations. Management tools used to reduce entanglement risk, for example temporary area restrictions on fishing, can have negative economic consequences for fishing communities. Balancing whale protection with sustaining productive fisheries is therefore a challenge experienced worldwide. In the California Current Ecosystem, ecosystem indicators have been used to understand the environmental dynamics that lead to increased whale entanglement risk in a lucrative crab fishery. However, an assessment of socio-economic risk for this fishery, as in many other regions, is missing. We estimate retrospectively the losses from ex-vessel revenue experienced by commercial Dungeness crab fishers in California during two seasons subject to whale entanglement mitigation measures using a Linear-Cragg hurdle modeling approach which incorporated estimates of pre-season crab abundance. In the 2020 fishing season, our results suggest total revenues would have been $14.4 million higher in the Central Management Area of California in the absence of closures and other disturbances. In the 2019 fishing season, our results suggest ex-vessel revenues would have been $9.4 million higher in the Central Management Area and $0.3 million higher in the Northern Management Area. Our evaluation should motivate the development of strategies which maximize whale protection whilst promoting productive, sustainable and economically-viable fisheries.

This study investigated the extent to which biological maturation selection biases existed according to playing position in national-level youth soccer. A total of 159 players from the U13 to U16 age groups in the Football Association of Ireland’s national talent pathway and international representative squads had their relative biological maturity status assessed using the Khamis-Roche method for the percentage of predicted adult height at the time of observation. Players were categorised as goalkeeper (GK), central defender (CD), full-back (FB), centre defensive midfielder (CDM), centre midfielder (CM), centre attacking midfielder (CAM), wide midfielder (WM) or centre forward (CF). A series of one-sampled means t-tests were used to examine the degree to which biological maturation selection biases existed across playing positions. A non-parametric Kruskal-Wallis test was used to evaluate inter-positional differences. A small to very large selection bias in favour of early maturing players existed for GK (D = 0.7), CD (D = 1.65), FB (D = 0.49), CM (D = 0.62), WM (D = 0.78), and CF (D = 0.76) (p < 0.05). Maturational selection biases did not exist for CDM or CAM. Moreover, CD were significantly more advanced in maturation compared to FB, CDM and CAM (p < 0.05). This study supports the contention that maturation selection biases exist in youth soccer, but the magnitude of this bias is highly dependent upon playing position. The very strong maturity selection biases at the national level evidenced in this investigation highlight the need for Football Associations to explore strategies, such as futures programmes, to help to retain talented, yet late maturing athletes.

The study aimed to evaluate the occurrence of some heavy metals in agricultural soil in the Hau Giang province, Vietnam. The geographical accumulation index (Igeo), pollutant load index (PLI) and ecological risk index (RI) are used to assess the pollution levels and potential ecological risks due to the presence of heavy metals in agricultural soil. The results showed that the mean concentrations of Cu, Pb and Zn in the soil ranged from 16.25-40.32, 18.05-29.92 and 52.78-147.22 mg/kg, respectively, within the limits of QCVN 03-MT:2015/BTNMT. Cluster analysis showed that Pb originated from the process of using fertilizers, especially phosphate fertilizers in farming. Cu and Zn possibly share a common origin from the use of pesticides and fungicides in agricultural production. The Igeo value of Cu, Pb and Zn gradually increases in the order of Cu < Zn < Pb. The PLI (1.03-1.97) reflected that the soil in the study area is moderately polluted. The RI (14.80-25.33) represented a low potential ecological risk. In particular, position D3 had the highest level of pollution and risk among the study sites. Pb had the highest level of accumulation in soil with the highest single ecological risk factor; thus, measures should be taken to limit the source of Pb generation. The results of the study also indicated that ingestion route is the main exposure pathway by which heavy metals can be harmful to humans.

Oral mucosal disease is a general term for a type of disease that mainly affects the oral mucosa and surrounding soft tissues. In the treatment of oral mucosal diseases, due to the particularity of the anatomical location, the use of topical administration is relatively simple and convenient; drugs can easily accumulate in the lesions, and at the same time, they can also avoid adverse reactions caused by systemic drug delivery. Topical administration has become an important and even preferred option for the treatment of oral mucosal diseases. There are various types of topically used drugs for oral mucosal diseases, such as glucocorticoids (triamcinolone acetonide), immunomodulatory drugs (tacrolimus), antiseptic drugs (chlorhexidine), pain relievers (lidocaine) and proprietary Chinese medicines (aloe vera gel). Among these drugs, although the most widely used liquid formulations such as gargles and sprays are easy to use, they are not conducive to local retention of drugs due to the particularity of the oral environment and function. Based on this, researchers have continuously improved the dosage form of the drug, and developed a series of semi-solid pharmaceutical preparations such as gels and ointments, some of which have exerted good curative effects in clinical work. In addition, although films, patches and other solid oral mucosal topical pharmaceutical preparations have few clinical applications, they have also been widely researched and described and are expected to become the mainstream dosage form in the future. In general, with the improvement of dosage forms, topical administration is playing an increasingly important role in the treatment of oral mucosal diseases. Therefore, combined with basic research and clinical reports, this article reviews the application of topical drug delivery in the treatment of oral mucosal diseases.

BackgroundAdolescents who use alcohol and other drugs on school campuses are at heightened risk for adverse consequences to their health and wellbeing. Schools have historically turned to punitive approaches as a first-line response to substance use. However, punishment is an ineffective deterrent for substance use and may cause harm and increase inequities. iDECIDE (Drug Education Curriculum: Intervention, Diversion, and Empowerment) was developed as a scalable and youth-centered drug education and diversion program that can be used as a skills-based alternative to punishment. We aim to evaluate the effectiveness of the iDECIDE curriculum as an alternative to punishment (ATP) for school-based substance use infractions in the context of a large pragmatic clinical effectiveness study.MethodsWe will conduct a Type 1, hybrid effectiveness-implementation trial. Using a stepped wedge design with approximately 90 middle and high schools in Massachusetts, we will randomly allocate the timing of implementation of the iDECIDE curriculum compared to standard disciplinary response over approximately 36 months. We will test the overarching hypothesis that student-level outcomes (knowledge of drug effects and attitudes about substance use; frequency of substance use; school connectedness) improve over time as schools transition from a standard disciplinary response to having access to iDECIDE. The secondary aims of this trial are to (1) explore whether change in student-level outcomes vary according to baseline substance use, number of peers who use alcohol or other drugs, age, gender, and school urbanicity, and (2) determine the acceptability and feasibility of the iDECIDE curriculum through qualitative stakeholder interviews.DiscussionSubstance use continues to be a major and rapidly evolving problem in schools. The importance of moving away from punishment to more restorative approaches is widely accepted; however, scalable alternatives have not yet been identified. This will be the first study to our knowledge to systematically evaluate an ATP for students who violate the school substance use policy and is well poised to have important implications for policy making.

Introduction The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was ‘Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?’ This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.Methods and analysis We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.Ethics and dissemination This study was approved by the Yorkshire and The Humber—Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.Trial registration number ISRCTN41647111.

Albinism is a unique problem encountered in tissue culture experiments, but the underlying mechanism remains unclear in most bamboo species. In this study, we identified the putative regulatory genes in an albino mutant of Bambusa oldhamii using comparative physiology and transcriptome analysis. The degeneration of chloroplasts, low chlorophyll (Chl) content and reduced photosynthetic capacity were observed in albinotic B. oldhamii compared to normal lines. A total of 6191 unigenes were identified that were clearly differentially expressed between albino and normal lines by transcriptome sequencing. Most genes related to chloroplast development (such as Psa, Psb) and pigment biosynthesis (such as LHC, GUN4, ZEP) were downregulated significantly in albinotic lines, which might be responsible for the albino phenotype. Moreover, some transcription factors (TFs) such as PIF and GLK1 were identified to be involved in chloroplast development and Chl synthesis, indicating the involvement of putative regulatory pathways PIF-LHC and GLK1-LHC/Psa/Psb in albinotic B. oldhamii. Finally, the downregulation of some stress responsive TFs (like ICE1 and EREB1) suggested a reduction in stress resistance of albinotic B. oldhamii. The above findings provided new insights into the molecular mechanism of albinism in bamboo.

Here the authors revealed a role for the protein deacetylase SIRT2 in Golgi stress, particularly induced by bacterial infection. Shigella secrete effector proteins such as IcsB, which transfers fatty acyl groups to modify host proteins to evade host immune surveillance. The upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella.

Abstract Background Small intestinal bacterial overgrowth (SIBO) is a condition of unknown prevalence characterized by an excessive amount of bacteria in the small bowel, typically resulting in vague gastrointestinal symptoms with bloating being most commonly reported. Here we describe a severe case of SIBO leading to small bowel necrosis requiring surgical intervention. Case presentation A 55-year-old Hispanic female with gastric outlet obstruction secondary to a newly diagnosed gastric adenocarcinoma, receiving neoadjuvant chemotherapy, developed bloody gastrostomy output and rapidly progressing nausea and abdominal distention 3 days after jejunostomy tube placement and initiation of jejunal enteral nutrition. Imaging revealed diffuse pneumatosis and portal venous gas. Surgical exploration confirmed segmental bowel necrosis requiring resection. Histologic findings were consistent with SIBO. Conclusions Presentation of severe SIBO in the setting of intestinal stasis secondary to gastric outlet after initiation of enteral feeds is a rare phenomenon. Early recognition and diagnosis of SIBO is critical in minimizing patient morbidity and mortality.

Abstract Introduction The optimal preoperative preparation for elective colorectal cancer surgery has been debated in academic circles for decades. Previously, several expert teams have conducted studies on whether preoperative mechanical bowel preparation and oral antibiotics can effectively reduce the incidence of postoperative complications, such as surgical site infections and anastomotic leakage. Most of the results of these studies have suggested that preoperative mechanical bowel preparation for elective colon surgery has no significant effect on the occurrence of surgical site infections and anastomotic leakage. Methods/design This study will examine whether oral antibiotic bowel preparation (OABP) influences the incidence of anastomotic leakage after surgery in a prospective, multicentre, randomized controlled trial that will enrol 1500 patients who require colon surgery. The primary endpoint, incidence of anastomotic leakage, is based on 2.3% in the OABP ± mechanical bowel preparation (MBP) group in the study by Morris et al. Patients will be randomized (1:1) into two groups: the test group will be given antibiotics (both neomycin 1 g and metronidazole 0.9 g) the day before surgery, and the control group will not receive any special intestinal preparation before surgery, including oral antibiotics or mechanical intestinal preparation. All study-related clinical data, such as general patient information, past medical history, laboratory examination, imaging results, and surgery details, will be recorded before surgery and during the time of hospitalization. The occurrence of postoperative fistulas, including anastomotic leakage, will be recorded as the main severe postoperative adverse event and will represent the primary endpoint. Ethics and dissemination Ethics approval was obtained from the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200173). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Protocol was revised on November 22, 2021, version 4.0. Trial registration ChiCTR2000035550 . Registered on 13 Aug 2020.

Objective To explore the expression and distribution of runt-related transcription factor (RUNX) family in lesions of psoriasis vulgaris (PV), and analyze the correlation between its levels and markers of proliferation, apoptosis and immunity. Methods The transcript levels of RUNX1, 2 and 3 were analyzed in normal skin from 14 healthy controls (HC) and lesions from 17 patients with PV by gene array from a published database. The protein levels and distribution of RUNX1, 2, and 3 were examined by immunohistochemistry (IHC) in normal skin from 11 HC and lesions from 11 patients with chronic eczema (CE) and 12 patients with PV. The correlation between RUNX and other genes in the gene array was analyzed by R, and GO enrichment analysis was performed. Results Compared with HC, the transcript levels of RUNX1 were down-regulated (HC: 0.61±0.06, PV: 0.54±0.02, P

The combination of hyaluronic acid (HA) and BMP-2 has been reported to promote bone regeneration. However, the interaction of endothelial cells and bone marrow mesenchymal stem cells (BMSCs) during HA + BMP-2 treatment is not fully understood. This study aimed to analyze the direct effect of HA, as well as the paracrine effect of HA-treated endothelial cells, on the BMP-2-mediated osteogenic differentiation of BMSCs. The angiogenic differentiation potential of HA at different molecular weights and different concentrations was tested. The direct effect of HA, as well as the indirect effect of HA-treated human umbilical cord endothelial cells (HUVECs, i.e., conditioned medium (CM)-based co-culture) on the BMP-2-mediated osteogenic differentiation of BMSCs was analyzed using alkaline phosphatase (ALP) staining and activity, alizarin red S (ARS) staining, and RT-qPCR of osteogenic markers. Angiogenic differentiation markers were also analyzed in HUVECs after treatment with HA + BMP-2. The bone regeneration potential of BMP-2 and HA + BMP-2 was analyzed in a rat ectopic model. We found that 1600 kDa HA at 300 µg/mL promoted tube formation by HUVECs in vitro and upregulated the mRNA expression of the angiogenic markers CD31, VEGF, and bFGF. HA inhibited, but conditioned medium from HA-treated HUVECs promoted, the BMP-2-mediated osteogenic differentiation of BMSCs, as indicated by the results of ALP staining and activity, ARS staining, and the mRNA expression of the osteogenic markers RUNX-2, ALP, COLI, and OPN. HA + BMP-2 (50 ng/mL) upregulated the expression of the angiogenesis-related genes VEGF and bFGF in HUVECs and bone regeneration in vivo compared to BMP-2 treatment. In conclusion, the paracrine effect of hyaluronic acid-treated endothelial cells promotes BMP-2-mediated osteogenesis, suggesting the application potential of HA + BMP-2 in bone tissue engineering.

The flexibility of insect wings should be considered in the design of bionic micro flapping-wing aircraft. The honeybee is an ideal biomimetic object because its wings are small and possess a concise vein pattern. In this paper, we focus on resilin, an important flexible factor in honeybees’ forewings. Both resilin joints and resilin stripes are considered in the finite element model, and their mechanical behaviors are studied comprehensively. Resilin was found to increase the static deflections in chordwise and spanwise directions by 1.4 times and 1.9 times, respectively. In modal analysis, natural frequencies of the first bending and first torsional modes were found to be decreased significantly—especially the latter, which was reduced from 500 Hz to 217 Hz—in terms of resilin joints and stripes, closely approaching flapping frequency. As a result, the rotational angle amplitude in dynamic responses is remarkable, with an amplification ratio of about six. It was also found that resilin joints and stripes together lead to well-cambered sections and improve the stress concentrations in dynamic deformation. As resilin is widespread in insect wings, the study could help our understanding of the flexible mechanism of wing structure and inspire the development of flexible airfoils.

Vat photopolymerization (VP), including stereolithography (SLA), digital light processing (DLP), and volumetric printing, employs UV or visible light to solidify cell-laden photoactive bioresin contained within a vat in a point-by-point, layer-by-layer, or volumetric manner. VP-based bioprinting has garnered substantial attention in both academia and industry due to its unprecedented control over printing resolution and accuracy, as well as its rapid printing speed. It holds tremendous potential for the fabrication of tissue- and organ-like structures in the field of regenerative medicine. This review summarizes the recent progress of VP in the fields of tissue engineering and regenerative medicine. First, it introduces the mechanism of photopolymerization, followed by an explanation of the printing technique and commonly used biomaterials. Furthermore, the application of VP-based bioprinting in tissue engineering was discussed. Finally, the challenges facing VP-based bioprinting are discussed, and the future trends in VP-based bioprinting are projected.

Background: Previous studies have demonstrated a direct correlation between pacemaker programming mode and exercise capacity on a long-term follow-up. In the present study we aimed to test whether reprogramming of the pacemaker can produce immediate effects on patients' exercise capacity. Methods: The exercise capacity of 33 patients wearing dual-chamber pacemakers was evaluated by cardiopulmonary exercise test at 24-hour intervals in two programming modes: initially in the single-chamber ventricular pacing mode with a fixed 60bpm rate, and in the second phase in dual chamber pacing mode with exercise adaptable rate, up to 130bpm. Results: The maximum O2 consumption (VO2 max: 12.82±2.70 mL/kg/min vs 14.52±3.25 mL/kg/min, p=0.02), the O2 consumption at the time of the anaerobic threshold (10.76±2.25 mL/kg/min vs 12.30±2.84 mL/kg/min, p=0.008), the duration of exercise (456.76±116.85 seconds vs 510.57±129.56 seconds, p=0.04) and the maximum workload (84.39±17.89W vs 96.36±24.09W, p=0.01) were significantly lower when the pacemakers were programmed in the single chamber ventricular fixed-rate pacing mode compared to the dual chamber rate adaptive pacing mode. Conclusion: Cardiac pacemaker reprogramming is able to exert immediate effects on exercise capacity. Dual chamber pacing with adaptable rate during physical exercise is superior to single chamber fixed rate pacing.

Abstract Background Molecular breeding accelerates the speed of animal breeding. Screening molecular markers that can affect economic traits through genome-wide association studies (GWAS) can provide a theoretical basis for molecular breeding. At present, a large number of molecular markers have been screened in poultry research, but few reports on how molecular markers affect economic traits exist. It is particularly important to reveal the action mechanisms of molecular markers, which can provide more accurate information for molecular breeding. Results The aim of this study was to investigate the relationships between two indels (NUDT15-indel-2777 and NUDT15-indel-1673) in the promoter region of NUDT15 and growth and carcass traits in chickens and to explore the regulatory mechanism of NUDT15. Significant differences were found in genotype and allele frequencies among commercial broilers, commercial laying hens and dual-purpose chickens. The results of association analyses showed that these two indel loci could significantly affect growth traits, such as body weight, and carcass traits. Tissue expression profiling at E12 showed that the expression of NUDT15 was significantly higher in skeletal muscle, and time-expression profiling of leg muscle showed that the expression of NUDT15 in myoblasts was significantly higher in the E10 and E12 proliferation stages than in other stages. Promoter activity analysis showed that pro-1673-I and pro-1673-D significantly inhibited promoter activity, and the promoter activity of pro-1673-D was significantly lower than that of pro-1673-I. In addition, when NUDT15 was overexpressed or underwent interference in chicken primary myoblasts (CPMs), NUDT15 could inhibit the proliferation of CPMs. Conclusion The results suggest that the studied indels in the promoter region of NUDT15 may regulate the proliferation of CPMs by affecting NUDT15 expression, ultimately affecting the growth and carcass traits of chickens. These indel polymorphisms may be used together as molecular markers for improving economic traits in chickens.