Inhibition of HDAC activity directly reprograms murine embryonic stem cells to trophoblast stem cells.

Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.

Manufacturing biodegradable lignocellulosic films with tunable properties from spent coffee grounds: A sustainable alternative to plastics.

Manufacturing biodegradable lignocellulosic films from spent coffee grounds (SCG) as an alternative to commercial plastics is a viable solution to address plastic pollution. Here, the biodegradable lignocellulosic films from SCG were fabricated via a sequential alkaline treatment and ionic liquid-based dissolution process. The alkaline treatment process could swell the cell wall of SCG, change its carbohydrates and lignin contents, and enhance its solubility in ionic liquids. The prepared SCG films with different lignin contents exhibited outstanding UV blocking capability (42.07-99.99 % for UVB and 20.96-99.99 % for UVA) and light scattering properties, good surface hydrophobicity (water contact angle = 63.2°-88.7°), enhanced water vapor barrier property (2.28-6.79 × 10-12 g/m·s·Pa), and good thermal stability. Moreover, the SCG films exhibit excellent mechanical strength (51.10-81.56 MPa, tensile strength) and biodegradability (fully degraded within 30 days when buried in soil) compared to commercial plastic. The SCG films represent a promising alternative that can replace non-biodegradable plastics.

A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among people with HIV.

Inflammation underlies many conditions causing excess morbidity and mortality among people with HIV (PWH). A handful of single-trait epigenome-wide association studies (EWAS) have suggested that inflammation is associated with DNA methylation (DNAm) among PWH. Multi-trait EWAS may further improve statistical power and reveal pathways in common between different inflammatory markers. We conducted single-trait EWAS of three inflammatory markers (soluble CD14, D-dimers, and interleukin 6) in the Veteran Aging Cohort Study (n = 920). The study population was all male PWH with an average age of 51 years, and 82.3% self-reported as Black. We then applied two multi-trait EWAS methods-CPASSOC and OmniTest-to combine single-trait EWAS results. CPASSOC and OmniTest identified 189 and 157 inflammation-associated DNAm sites respectively, of which 112 overlapped. Among the identified sites, 56% were not significant in any single-trait EWAS. Top sites were mapped to inflammation-related genes including IFITM1 , PARP9 and STAT1 . These genes were significantly enriched in pathways such as "type I interferon signaling" and "immune response to virus". We demonstrate that multi-trait EWAS can improve the discovery of inflammation-associated DNAm sites, genes, and pathways. These DNAm sites suggest molecular mechanisms in response to inflammation associated with HIV and might hold the key to addressing persistent inflammation in PWH.

Identification and characterization of ACR gene family in maize for salt stress tolerance.

Background: Members of the ACR gene family are commonly involved in various physiological processes, including amino acid metabolism and stress responses. In recent decades, significant progress has been made in the study of ACR genes in plants. However, little is known about their characteristics and function in maize. Methods: In this study, ACR genes were identified from the maize genome, and their molecular characteristics, gene structure, gene evolution, gene collinearity analysis, cis-acting elements were analyzed. qRT-PCR technology was used to verify the expression patterns of the ZmACR gene family in different tissues under salt stress. In addition, Ectopic expression technique of ZmACR5 in Arabidopsis thaliana was utilized to identify its role in response to salt stress. Results: A total of 28 ZmACR genes were identified, and their molecular characteristics were extensively described. Two gene pairs arising from segmented replication events were detected in maize, and 18 collinear gene pairs were detected between maize and 3 other species. Through phylogenetic analysis, three subgroups were revealed, demonstrating distinct divergence between monocotyledonous and dicotyledonous plants. Analysis of ZmACR cis-acting elements revealed the optional involvement of ZmACR genes in light response, hormone response and stress resistance. Expression analysis of 8 ZmACR genes under salt treatment clearly revealed their role in the response to salt stress. Ectopic overexpression of ZmACR5 in Arabidopsis notably reduced salt tolerance compared to that of the wild type under salt treatment, suggesting that ZmACR5 has a negative role in the response to salt stress. Conclusion: Taken together, these findings confirmed the involvement of ZmACR genes in regulating salt stress and contributed significantly to our understanding of the molecular function of ACR genes in maize, facilitating further research in this field.

Long-term care for community-dwelling older adults: A systematic review of clinical practice guidelines and consensus statements.

This review identified clinical practice guidelines (CPGs) and consensus statements (CSs) that include recommendations on long-term care for community-dwelling older adults. Additionally, it assessed their quality using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool to determine high-quality guidelines and synthesis recommendations from high-quality guidelines and evaluate the quality of these guidelines using the AGREE-Recommendation Excellence (AGREE-REX) tool. A systematic search was performed (November 2023) in MEDLINE, PubMed, Guidelines International Network (GIN), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Registered Nurses' Association of Ontario (RNAO), National Guideline Clearinghouse (NGC), and Scottish Intercollegiate Guidelines Network (SIGN). Two reviewers independently selected and assessed the articles using AGREE II. A meeting was held to appraise the quality of the guidelines (AGREE II mean score >70 %) using AGREE-REX. The analysis included 14 CPGs and 2 CSs. Of these, 7 CPGs reached the standard of >70 %, the 'Scope and purpose' domain obtained the highest score with 85.43 (± 17.87), and the 'Applicability' domain scored lowest with 46.93 (± 26.74). Regarding the score of AGREE-REX, the seven CPGs were considered as 'moderate', with the 'Clinical Applicability' domain having the highest score of 61.29 % (±10.80) and the 'Values and Preferences' domain having the lowest score of 38.14 % (±9.26). Four themes were synthesised from the seven high-quality CPGs: planning and delivering person-centred home care, cognitive impairment, and screening for impaired vision and falls. The quality of CPGs and CSs on long-term care for community-dwelling older adults has room for improvement, and higher-quality guidelines are required to meet the long-term care needs of community-dwelling older adults.

Establishment and validation of an artificial intelligence web application for predicting postoperative in-hospital mortality in patients with hip fracture: a National cohort study of 52,707 cases.

BACKGROUND: In-hospital mortality following hip fractures is a significant concern, and accurate prediction of this outcome is crucial for appropriate clinical management. Nonetheless, there is a lack of effective prediction tools in clinical practice. By utilizing artificial intelligence and machine learning techniques, this study aims to develop a predictive model that can assist clinicians in identifying geriatric hip fracture patients at a higher risk of in-hospital mortality. METHODS: A total of 52,707 geriatric hip fracture patients treated with surgery from 90 hospitals were included in this study. The primary outcome was postoperative in-hospital mortality. The patients were randomly divided into two groups, with a ratio of 7:3. The majority of patients, assigned to the training cohort, were used to develop the AI models. The remaining patients, assigned to the validation cohort, were used to validate the models. Various machine learning algorithms, including logistic regression (LR), decision tree (DT), naïve Bayesian (NB), neural network (NN), eXGBoosting machine (eXGBM), and random forest (RF), were employed for model development. A comprehensive scoring system, incorporating 10 evaluation metrics, was developed to assess the prediction performance, with higher scores indicating superior predictive capability. Based on the best machine learning-based model, an AI application was developed on the Internet. In addition, a comparative testing of prediction performance between doctors and the AI application. FINDINGS: The eXGBM model exhibited the best prediction performance, with an AUC of 0.908 (95% CI: 0.881-0.932), as well as the highest accuracy (0.820), precision (0.817), specificity (0.814), and F1 score (0.822), and the lowest Brier score (0.120) and log loss (0.374). Additionally, the model showed favorable calibration, with a slope of 0.999 and an intercept of 0.028. According to the scoring system incorporating 10 evaluation metrics, the eXGBM model achieved the highest score (56), followed by the RF model (48) and NN model (41). The LR, DT, and NB models had total scores of 27, 30, and 13, respectively. The AI application has been deployed online at https://in-hospitaldeathinhipfracture-l9vhqo3l55fy8dkdvuskvu.streamlit.app/ , based on the eXGBM model. The comparative testing revealed that the AI application's predictive capabilities significantly outperformed those of the doctors in terms of AUC values (0.908 vs. 0.682, P <0.001). CONCLUSIONS: The eXGBM model demonstrates promising predictive performance in assessing the risk of postoperative in-hospital mortality among geriatric hip fracture patients. The developed AI model serves as a valuable tool to enhance clinical decision-making.

Efficacy and safety of traditional Chinese medicine decoction as an adjuvant treatment for diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study aimed to assess the efficacy and safety of traditional Chinese medicine decoction as an adjunctive treatment for diabetic nephropathy in systematic evaluations. Methods: A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering the period from January 2013 to July 2023. The search was restricted to randomized controlled trials (RCTs) conducted within the past decade that investigated the use of TCM decoction as an adjunctive treatment for diabetic nephropathy. The control group received western medicine treatment, while the intervention group received TCM decoction in addition to the conventional treatment. Endnote and Excel were employed for literature management and data organization, and Revman 5.3 and Stata 16 software were used for the analyses. Results: 66 RCTs involving 6,951 participants were included in this study. The clinical efficacy of TCM decoction as an adjunctive treatment for diabetic nephropathy was found to be significantly higher than that of the control group (OR = 3.12, 95% CI [2.70, 3.60], I2 = 0%, p < 0.00001). The incidence of adverse events did not differ significantly between the intervention group and the control group (OR = 0.94, 95% CI [0.60, 1.48], I2 = 0%, p = 0.94). According to the secondary outcomes of renal function and blood glucose indicators, the intervention group showed better therapeutic efficacy compared to the control group. The most frequently used TCM categories were tonifying medicine, blood-activating medicine, astringent medicine, diuretic medicine, heat-clearing medicine, and laxative medicine. Among them, the top five frequently used Chinese medicine were Astragalus mongholicus Bunge [Fabaceae; Astragali mongholici radix](58 times), Salvia miltiorrhiza Bunge [Lamiaceae; Radix et rhizoma salviae miltiorrhizae] (42 times), Dioscorea oppositifolia L. [Dioscoreaceae; Dioscoreae rhizoma] (38 times), Poria cocos (Schw.) Wolf [Polyporaceae; Poria] (38 times), and Cornus officinalis Siebold & Zucc. [Cornaceae; Corni fructus] (35 times). Conclusion: The combined use of TCM decoction with western medicine in the treatment of diabetic nephropathy can enhance clinical effectiveness and 2 This is a provisional file, not the final typeset article achieve superior therapeutic effects in comparison to western medicine alone, without significant risks. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier [CRD42022529144].

Anatomical variations of the brachial plexus in adult cadavers: A descriptive study and clinical significance.

BACKGROUND: Brachial plexus injury is recognized as one of the most severe clinical challenges due to the complex anatomical configuration of the brachial plexus and its propensity for variation, which complicates safe clinical interventions. This study aimed to ascertain the prevalence and characterize the types of brachial plexus variations, and to elucidate their clinical implications. MATERIALS AND METHODS: We conducted meticulous dissections of 60 formalin-fixed cadavers' upper arm, axilla and lower neck to reveal and assess the roots, trunks, divisions, cords, and branches of the brachial plexus. The pattern of branching was noted by groups of dissecting medical students and confirmed by the senior anatomists. The variations discovered were record and photographed using a digital camera for further analysis. RESULTS: Variations in the brachial plexus were identified in 40 of the 60 cadavers, yielding a prevalence rate of 66.7%. These variations were classified into root anomalies (2.1%), trunk anomalies (8.5%), division anomalies (2.1%), and cord anomalies (4.3%). Notably, anomalies in communicating branches were observed in 39 cadavers (83.0%): 14 with bilateral anomalies, 14 with anomalies on the left side, and 11 on the right side. These communicating branches formed connections between the roots and other segments, including trunks, cords, and terminal nerves, and involved the median, musculocutaneous, and ulnar nerves. CONCLUSION: The frequency and diversity of brachial plexus variations, particularly in communicating branches, are significant in cadavers. It is imperative that these variations are carefully considered during the diagnostic process, treatment planning, and prior to procedures such as supraclavicular brachial plexus blocks and nerve transfers, to mitigate the risk of iatrogenic complications.

Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters.

The XBB.1.5 subvariant has garnered significant attention due to its exceptional immune evasion and transmissibility. Significantly, the evolutionary trajectory of SARS-CoV-2 has shown continual progression, with a recent global shift observed from XBB to BA.2.86, exemplified by the emergence of the predominant JN.1 subvariant. This phenomenon highlights the need for vaccines that can provide broad-spectrum antigenic coverage. In this study, we utilized a NS1-deleted (dNS1) influenza viral vector to engineer an updated live-attenuated vectored vaccine called dNS1-XBB-RBD. This vaccine encodes the receptor-binding domain (RBD) protein of the XBB.1.5 strain. Our findings demonstrate that the dNS1-XBB-RBD vaccine elicits a similar systemic and mucosal immune response compared to its prototypic form, dNS1-RBD. In hamsters, the dNS1-XBB-RBD vaccine provided robust protection against the SARS-CoV-2 immune-evasive strains XBB.1.9.2.1 and Beta. Remarkably, nasal vaccination with dNS1-RBD, which encodes the ancestor RBD gene, also effectively protected hamsters against both the XBB.1.9.2.1 and Beta strains. These results provide valuable insights about nasal influenza-vectored vaccine and present a promising strategy for the development of a broad-spectrum vaccine against COVID-19 in the future.

Chitinase 3-like 1 expression associated with lymphatic metastasis and prognosis in urothelial carcinoma of the bladder.

Objectives: Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods: We employed an RNA-sequencing cohort (n = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA-BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results: In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P < 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1+ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (P < 0.001) and recurrence-free survival (P = 0.006). CHI3L1+ stromal cells were positively associated with D2-40+ lymphatic vessel density (P < 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all P < 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways. Conclusion: Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.

Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated. METHODS: We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells' infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate. RESULTS: In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G-Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy. CONCLUSIONS: Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Rapid generation of fragrant thermo-sensitive genic male sterile rice with enhanced disease resistance via CRISPR/Cas9.

MAIN CONCLUSION: The three, by mutagenesis produced genes OsPi21, OsXa5, and OsBADH2, generated novel lines exhibiting desired fragrance and improved resistance. Elite sterile lines are the basis for hybrid rice breeding, and rice quality and disease resistance become the focus of new sterile lines breeding. Since there are few sterile lines with fragrance and high resistance to blast and bacterial blight at the same time in hybrid rice production, we here integrated the simultaneous mutagenesis of three genes, OsPi21, OsXa5, and OsBADH2, into Zhi 5012S, an elite thermo-sensitive genic male sterile (TGMS) variety, using the CRISPR/Cas9 system, thus eventually generated novel sterile lines would exhibit desired popcorn-like fragrance and improved resistance to blast and bacterial blight but without a loss in major agricultural traits such as yield. Collectively, this study develops valuable germplasm resources for the development of two-line hybrid rice with disease resistance, which provides a way to rapid generation of novel TGMS lines with elite traits.

An Automated Deep Learning-Based Framework for Uptake Segmentation and Classification on PSMA PET/CT Imaging of Patients with Prostate Cancer.

Uptake segmentation and classification on PSMA PET/CT are important for automating whole-body tumor burden determinations. We developed and evaluated an automated deep learning (DL)-based framework that segments and classifies uptake on PSMA PET/CT. We identified 193 [18F] DCFPyL PET/CT scans of patients with biochemically recurrent prostate cancer from two institutions, including 137 [18F] DCFPyL PET/CT scans for training and internally testing, and 56 scans from another institution for external testing. Two radiologists segmented and labelled foci as suspicious or non-suspicious for malignancy. A DL-based segmentation was developed with two independent CNNs. An anatomical prior guidance was applied to make the DL framework focus on PSMA-avid lesions. Segmentation performance was evaluated by Dice, IoU, precision, and recall. Classification model was constructed with multi-modal decision fusion framework evaluated by accuracy, AUC, F1 score, precision, and recall. Automatic segmentation of suspicious lesions was improved under prior guidance, with mean Dice, IoU, precision, and recall of 0.700, 0.566, 0.809, and 0.660 on the internal test set and 0.680, 0.548, 0.749, and 0.740 on the external test set. Our multi-modal decision fusion framework outperformed single-modal and multi-modal CNNs with accuracy, AUC, F1 score, precision, and recall of 0.764, 0.863, 0.844, 0.841, and 0.847 in distinguishing suspicious and non-suspicious foci on the internal test set and 0.796, 0.851, 0.865, 0.814, and 0.923 on the external test set. DL-based lesion segmentation on PSMA PET is facilitated through our anatomical prior guidance strategy. Our classification framework differentiates suspicious foci from those not suspicious for cancer with good accuracy.

Targeting PNPO to suppress tumor growth via inhibiting autophagic flux and to reverse paclitaxel resistance in ovarian cancer.

Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC.

Correction: Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy.

Correction for 'Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy' by Junyu Chen et al., Mater. Horiz., 2024, 11, 2010-2020, https://doi.org/10.1039/D3MH01884A.

Nanobody in a Double "Y"-Shaped Assembly: A Promising Candidate for Lateral Flow Immunoassays.

Derived from camelid heavy-chain antibodies, nanobodies (Nbs) are the smallest natural antibodies and are an ideal tool in biological studies because of their simple structure, high yield, and low cost. Nbs possess significant potential for developing highly specific and user-friendly diagnostic assays. Despite offering considerable advantages in detection applications, knowledge is limited regarding the exclusive use of Nbs in lateral flow immunoassay (LFIA) detection. Herein, we present a novel double "Y" architecture, achieved by using the SpyTag/SpyCatcher and Im7/CL7 systems. The double "Y" assemblies exhibited a significantly higher affinity for their epitopes, as particularly evident in the reduced dissociation rate. An LFIA employing double "Y" assemblies was effectively used to detect the severe acute respiratory syndrome coronavirus-2 N protein, with a detection limit of at least 500 pg/mL. This study helps broaden the array of tools available for the development of Nb-based diagnostic techniques.

Can irisin be developed as the molecular evolutionary clock based on the origin and functions?

Irisin, a myokine identified in 2012, has garnered research interest for its capacity to induce browning of adipocytes and improve metabolic parameters. As such, the potential therapeutic applications of this exercise-induced peptide continue to be explored. Though present across diverse animal species, sequence analysis has revealed subtle variation in the irisin protein. In this review, we consider the effects of irisin on disease states in light of its molecular evolution. We summarize current evidence for irisin's influence on pathologies and discuss how sequence changes may inform development of irisin-based therapies. Furthermore, we propose that the phylogenetic variations in irisin could potentially be leveraged as a molecular clock to elucidate evolutionary relationships.

Optimizing tendon repair and regeneration: how does the in vivo environment shape outcomes following rupture of a tendon such as the Achilles tendon?

Risk for rupture of the Achilles tendon, and other tendons increases with age. Such injuries of tissues that function in high load environments generally are believed to heal with variable outcome. However, in many cases, the healing does not lead to a good outcome and the patient cannot return to the previous level of participation in active living activities, including sports. In the past few years, using proteomic approaches and other biological techniques, reports have appeared that identify biomarkers that are prognostic of good outcomes from healing, and others that are destined for poor outcomes using validated criteria at 1-year post injury. This review will discuss some of these recent findings and their potential implications for improving outcomes following connective tissue injuries, as well as implications for how clinical research and clinical trials may be conducted in the future where the goal is to assess the impact of specific interventions on the healing process, as well as focusing the emphasis on regeneration and not just repair.

Review of Droplet Printing Technologies for Flexible Electronic Devices: Materials, Control, and Applications.

Flexible devices have extensive applications in areas including wearable sensors, healthcare, smart packaging, energy, automotive and aerospace sectors, and other related fields. Droplet printing technology can be utilized to print flexible electronic components with micro/nanostructures on various scales, exhibiting good compatibility and wide material applicability for device production. This paper provides a comprehensive review of the current research status of droplet printing technologies and their applications across various domains, aiming to offer a valuable reference for researchers in related areas.