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Breast cancer is one of the most common malignant tumors in women all over the world. Mastectomy is the most effective treatment, but there are serious problems such as high tumor recurrence rate and side effects of chemotherapy. Therefore, there is an urgent need for a therapeutic strategy that can effectively promote postoperative wound healing and inhibit local tumor recurrence. In this study, a 3D printing scaffold based on carbon dots-curcumin nano-drug release (CCNPs) was developed as a local drug delivery platform (named CCNACA using CCNPs, Sodium alginate, Nanoclay and Caffeic Acid grafted Chitosan as raw materials), which has the ability to visualize drug release. The 14-day drug release test in vitro showed that the tumor inhibition rate of CCNACA scaffolds on breast cancer cells (MCF-7) was 73.77 ± 1.68 %. And the CCNACA scaffolds had good long-term antibacterial (Escherichia coli and Staphylococcus aureus) activity. Animal experiments have shown that implanting CCNACA scaffolds into surgical defects can inhibit postoperative residual cancer cells, reduce inflammation, promote angiogenesis, and repair tissue defects caused by surgery. In summary, the local drug delivery system of this manuscript has great potential in wound healing and prevention of tumor recurrence after breast cancer surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

High-sensitivity C-reactive protein (hs-CRP) is an inflammatory biomarker and can accurately predict the development of cardiovascular disease (CVD). We synthesized a core-shell structure PPy-Au nanocomposite in situ by chemically oxidizing pyrrole (Py) with HAuCl 4 and the produced Au nanoparticles realized the doping in the polymerization. Analysis of morphology and energy spectrum as well as electrochemical characterization confirmed the successful one-pot synthesis. The conductive polymers with porous structure provide abundant sites for anti-CRP binding and effectively enhanced the sensitivity of the label-free BSA/anti-CRP/PPy-Au/GCE immunosensor. Its analytical performance was observed using differential pulse voltammetry (DPV), with a linear range from 0.0005 to 60 μg mL -1 and a detection limit of 0.17 ng mL -1 . The platform demonstrated satisfactory selectivity, stability, and reproducibility. To validate its clinical application, we detected CRP in human serum samples with a recovery rate of 101.00-105.95% and investigated the consistency of the developed method and immunoturbidimetry with a deviation between -1.2% and +3.2%, suggesting great potential for use in point-of-care testing (POCT)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Steroids have been attracting global attention given potential carcinogenic and endocrine-disrupting effects, yet the environmental status of steroids, especially their metabolites, in estuarine environment remain largely unexplored. This study investigated 31 steroids and metabolites in suspended particulate matter (SPM), water phase and sediments of the Pearl River Estuary (PRE) during the dry and wet seasons to elucidate their spatiotemporal patterning, partitioning behavior, and environmental fate. The results showed that natural steroids predominated in SPM and sediments while the metabolites predominated in water. The spatial distribution of steroids and metabolites varied seasonally, with hydrophobicity and environmental factors influencing phase partitioning in the estuary. Furthermore, a natural steroid, progesterone (P) could serve as a trustworthy chemical indicator to estimate the concentrations of steroids and metabolites in the PRE. Importantly, the mass budget of P was estimated using an improved multi-box mass balance model, revealing that outflow to the South China Sea was the primary sink of P in water (∼87%) and degradation was the primary sink of P in sediments (∼68%) of the PRE. Overall, this study offers insightful information about the distribution and environmental fate of steroids and metabolites in estuarine environment, with implications for future management strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stenotrophomonas maltophilia is a rapidly evolving multidrug-resistant opportunistic pathogen that can cause serious infections in immunocompromised patients. Although phage therapy is one of promising strategies for dealing with MDR bacteria, the main challenges of phage therapeutics include accumulation of phage resistant mutations and acquisition of the phage defense systems. To systematically evaluate the impact of (pro)phages in shaping genetic and evolutionary diversity of S. maltophilia, we collected 166 S. maltophilia isolates from three hospitals in southern China to analyze its pangenome, virulence factors, prophage regions, and anit-viral immune systems. Pangenome analysis indicated that there are 1328 saturated core genes and 26961 unsaturated accessory genes in the pangenome, suggesting existence of highly variable parts of S. maltophilia genome. The presence of genes in relation to T3SS and T6SS mechanisms suggests the great potential to secrete toxins by the S. maltophilia population, which is contrary to the conventional notion of low-virulence of S. maltophilia. Additionally, we characterized the pan-immune system maps of these clinical isolates against phage infections and revealed the co-harboring of CBASS and anti-CBASS in some strains, suggesting a never-ending arms race and the co-evolutionary dynamic between bacteria and phages. Furthermore, our study predicted 310 prophage regions in S. maltophilia with high genetic diversity. Six viral defense systems were found to be located at specific position of the S. maltophilia prophage genomes, indicating potential evolution of certain site/region similar to bacterial 'defense islands' in prophage. Our study provides novel insights into the S. maltophilia pangenome in relation to phage-defense mechanisms, which extends our understanding of bacterial-phage interactions and might guide the application of phage therapy in combating S. maltophilia infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

C-di-GMP is a bacterial second messenger implicated in the regulation of many key functions including antibiotic tolerance and biofilm formation. Our understanding of how c-di-GMP exerts its action via receptors to modulate different biological functions is still limited. Here we used a c-di-GMP affinity pull-down assay coupled to LC-MS/MS to identify c-di-GMP-binding proteins in the opportunistic pathogen Stenotrophomonas maltophilia. This analysis identified Smlt3238 (SodA), a protein of the superoxide dismutase family, as a c-di-GMP-binding protein. Microscale thermophoresis showed that purified SodA protein bound c-di-GMP with an estimated dissociation constant (Kd) value of 141.5 μM. Using various in vivo and in vitro experiments, we demonstrated that c-di-GMP modulates the enzyme activity of SodA directly. Circular dichroism experiments revealed that SodA protein gradually altered its basic structure with increasing levels of c-di-GMP. Phenotypic experiments conducted in the presence of a range of intracellular c-di-GMP levels showed that SodA function is modulated by c-di-GMP. The findings thus identify a novel c-di-GMP binding protein that governs oxidative stress tolerance in S. maltophilia., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Three unusual oleanane-derived triterpenoids, stytontriterpenes A-C (1-3), were isolated from the resin of Styrax tonkinensis together with an oleanane-lactone (stytontriterpene D, 4). Their structures and absolute configurations were characterised using a combination of spectroscopic analysis, electronic circular dichroism, and theoretical calculations. 1 and 2 belong to nor-oleanane with rare spiro D/E rings and 3 contains one infrequent C 32 scaffold. 1 considerably suppressed the number of adhered leukemic monocytes (THP-1) to human umbilical vein endothelial cells and attenuated the upregulations of mRNA and protein levels of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 at 5 μM, suggesting that 1 might be a promising anti-vascular inflammatory chemical for atherosclerosis therapy. Plausible biosynthetic pathways for 1-4 are also proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Global trends in mitral valve surgery (MVSx) suggest increasing repair compared with replacement, especially in the United States and European countries. The relative use, and outcomes of, MV repair and replacement in Australia are unknown., Methods: New South Wales residents who underwent isolated MVSx between 2001 and 2017 were identified from the Admitted-Patient-Data-Collection database. Mortality outcomes were tracked to 31 Dec 2018 and adjusted based on age, sex, urgency of operation, and comorbidity status., Results: The study cohort comprised 5,693 patients: 2020 (35%) underwent repair (MVr), 1,656 (29%) underwent mechanical replacement (mech.MVR), and 2017 (35%) underwent bioprosthetic replacement (bio.MVR). Respective median ages [interquartile range] were 67 yo [59-75 yo], 64 yo [55-71 yo], and 75 yo [68-80 yo] (p<0.001 across groups). Between 2001 and 2017, total MVSx increased steadily with population growth. Whereas the relative use of MVr remained static (34% to 38%), that for bio.MVR (22% to 50%) and mech.MVR (45% to 13%) changed significantly. MVr had the best outcome with 1.2% in-hospital, 2.5% 1-year, and 21.6% total cumulative mortality during a median follow-up of 6.5 years. Compared to MVr, the adjusted hazard ratio (aHR) for mech.MVR and bio.MVR for long-term mortality were 1.41 (95% confidence interval [CI]=1.24-1.61) and 1.73 (95% CI=1.53-1.95), respectively. Heart failure and sepsis were the main cardiovascular and noncardiovascular causes of death in all groups., Conclusion: In this statewide Australian cohort examined over 17 years, MVr is potentially underutilised despite having superior outcomes to MVR. Access to quality dataset which provides the indication for MVSx and quantitative clinical factors is critical to further improve MVr coverage and outcome MVSx., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

We report the fabrication of a facile sensor using heme conjugated with gold nanoparticles (AuNPs) in situ on a glass carbon electrode (GCE) for the ultrasensitive determination of biotin without antibody or streptavidin. The use of heme and AuNPs as dual amplifiers allows a very broad detection range from 0.0050 to 50.0000 μmol·L -1 and a very low detection limit of 0.0016 μmol·L -1 . The mechanistic aspects were elucidated using electrochemical analyses and frontier orbital calculations showing that the electrooxidation of biotin involves a one-electron and a one-proton transfer, generating biotin sulfoxide. The heme/AuNPs/GCE sensor exhibited excellent selectivity, reproducibility and stability, indicating high robustness. The recovery was between 97.20 and 105.70% with RSD less than 8.71%, suggesting good practicability. Our studies demonstrate that this approach can be used to detect and quantify biotin in a range of foods, including milk, infant formula, flour, orange juice, mango juice, egg white and egg yolk. Furthermore, all measurements do not require any intricate preparation or pre-treatment of the foods, thus representing a great potential for point-of-care testing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Single component white-light-emitting (SCWLE) materials are extremely desired in the field of solid-state lighting. However, pure-phosphorescent SCWLE has rarely been reported. Herein, one halogen-bonding-containing MOF [Cd(5-BIPA)(phen)] ( 1 ) has been synthesized, which shows efficient white-light emission originating from dual phosphorescence bands with different wavelengths and lifetimes. The fabrication of a phosphor-converted white-light-emitting diode device driven by pulsing current enables this MOF to be a promising phosphor.

Diabetic foot ulcers are one of the most serious of the numerous complications of diabetes mellitus, causing great physical trauma and financial stress to patients, and accelerating wound healing in diabetic patients remains one of the major clinical challenges. Exosomes from adipose-derived stem cells can directly and indirectly promote wound healing. However, due to the low retention rate of exosomes in the wound, exosome treatment is difficult to achieve the expected effect. Therefore, it is of great significance to synthesize a composite scaffold that can stably load exosomes and has antibacterial properties. In this study, fresh pig skin was decellularized to obtain decellularized matrix (dECM). Secondly, quaternized chitosan (Qcs) was modified with quaternary ammonium salt to make it soluble in water after quaternization. Finally, Gel-dECM-Qcs (GDQ) bioink was prepared by adding acellular matrix and quaternized chitosan with temperature sensitive gelatin (Gel) as carrier. Tissue engineered composite scaffolds were then prepared by extrusion 3D printing technology. Subsequently, the physicochemical properties, biocompatibility and antimicrobial capacity of the composite scaffolds were determined, and the data showed that the composite scaffolds had good mechanical properties, biocompatibility and antimicrobial capacity, and the maximum stress of the composite scaffolds was 1.16 ± 0.05 MPa, the composite scaffolds were able to proliferate and adhered to the L929 cells, and the kill rates of composite scaffolds against E. coli and S. aureus after incubation for 24 h were 93.24 ± 1.22 % and 97.34 ± 0.23 %, respectively. Overall, the GDQ composite scaffolds have good mechanical properties adapted to skin bending, its good biocompatibility can promote the growth and migration of fibroblasts, reshape injured tissues, accelerate the wound healing, and excellent antimicrobial ability can inhibit the growth of E. coli and S. aureus, reducing the impact of bacterial infections on wounds. Moreover, the composite scaffolds have the potential to be used as exosom-loaded hydrogel dressings, which provides a basis for the subsequent research on the repair of diabetic foot ulcers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: High-quality cardiopulmonary resuscitation (CPR) is a key element in the rescue of cardiac arrest patients but is difficult to achieve in circumstances involving aerosol transmission, such as the COVID-19 pandemic., Methods: This prospective randomized crossover trial included 30 experienced health care providers to evaluate the impact of personal protective equipment (PPE) on CPR quality and rescuer safety. Participants were asked to perform continuous CPR for 5 minutes on a manikin with three types of PPE: level D-PPE, level C-PPE, and PAPR. The primary outcome was effective chest compression per minute. Secondary outcomes were the fit factor by PortaCount, vital signs and fatigue scores before and after CPR, and perceptions related to wearing PPE. Repeated-measures ANOVA was used, and a two-tailed test value of 0.05 was considered statistically significant., Results: The rates of effective chest compressions for 5 minutes with level D-PPE, level C-PPE, and PAPRs were 82.0 ± 0.2%, 78.4 ± 0.2%, and 78.0 ± 0.2%, respectively ( p = 0.584). The fit-factor test values of level C-PPE and PAPRs were 182.9 ± 39.9 vs. 198.9 ± 9.2 ( p < 0.001). The differences in vital signs before and after CPR were not significantly different among the groups. In addition, the fatigue and total perception scores of wearing PPE were significantly higher for level C-PPE than PAPRs: 3.8 ± 1.6 vs. 3.0 ± 1.6 ( p < 0.001) and 27.9 ± 5.4 vs. 26.0 ± 5.3 ( p < 0.001), respectively., Conclusion: PAPRs are recommended when performing CPR in situations where aerosol transmission is suspected. When PAPRs are in short supply, individual fit-tested N95 masks are an alternative. This trial is registered with NCT04802109., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Cheng-Hsin Cheng et al.)

Objectives: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children., Methods: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes., Results: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups ( P >0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment ( P <0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment ( P <0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level ( P <0.05), the FGF23 level was positively correlated with the IGF-1 level ( P <0.05), and the Klotho level was positively correlated with the FGF23 level ( P <0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point ( P >0.05)., Conclusions: The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.

The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response., (© 2023. The Author(s).)

Motivation: Cell function is regulated by gene regulatory networks (GRNs) defined by protein-mediated interaction between constituent genes. Despite advances in experimental techniques, we can still measure only a fraction of the processes that govern GRN dynamics. To infer the properties of GRNs using partial observation, unobserved sequential processes can be replaced with distributed time delays, yielding non-Markovian models. Inference methods based on the resulting model suffer from the curse of dimensionality., Results: We develop a simulation-based Bayesian MCMC method employing an approximate likelihood for the efficient and accurate inference of GRN parameters when only some of their products are observed. We illustrate our approach using a two-step activation model: an activation signal leads to the accumulation of an unobserved regulatory protein, which triggers the expression of observed fluorescent proteins. With prior information about observed fluorescent protein synthesis, our method successfully infers the dynamics of the unobserved regulatory protein. We can estimate the delay and kinetic parameters characterizing target regulation including transcription, translation, and target searching of an unobserved protein from experimental measurements of the products of its target gene. Our method is scalable and can be used to analyze non-Markovian models with hidden components., Availability and Implementation: Our code is implemented in R and is freely available with a simple example data at https://github.com/Mathbiomed/SimMCMC., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Taiwan's unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors., Methods: A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan. In total, 491 responses were included in the analyses., Results: Respondents (65% female, aged 41.9 ± 11.4 years, with 68% having a Bachelor's degree) reported a moderate anti-doping knowledge score of 37.2 ± 4.9, ranging from 21 to 48 (out of 51). Fifteen per cent of them had the experience of being counselled about drug use in sports. Higher knowledge scores were observed in younger respondents, showing an age-dependent effect (p < 0.001). Individuals practising in southern Taiwan (compared to northern Taiwan) and those working at clinics (compared to hospitals) exhibited lower knowledge. Most of the respondents (90%) knew that stimulant ephedrine is prohibited in sports, but few had recognised diuretic furosemide (38%) and CHM (7%) containing β 2 -agonist higenamine. Approximately 90% of respondents agreed with the need for anti-doping education., Conclusions: This study highlights the heterogeneity of anti-doping knowledge among pharmacy professionals and provides practical relevance in organising future educational topics and research-based activities., (© 2023. The Author(s).)

To investigate the presence of hop stunt viroid (HSVd) in mulberry ( Morus alba ) plants in China, HSVd was detected by reverse transcription (RT)-PCR using dsRNAs extracted from symptomatic or asymptomatic mulberry leaf samples collected from a mulberry field located in Zhenjiang, China, as a template and the primer pairs for HSVd detection. The primer pairs were designed based on the conserved sequence of 25 HSVd variants deposited in the GenBank database. Four out of a total of 53 samples were HSVd-positive, confirming that HSVd is present in mulberry plants in China. The consensus full-length nucleotide (nt) sequence of two HSVd variants determined by sequencing the HSVd variants in these four HSVd-positive samples consisted of 296 nt and shared the highest nt identity of 96.8% with that from plum in Turkey but relatively low identity with those from mulberry in Iran (87.3 to 90.8%). Phylogenetic analysis showed that these HSVd variants clustered together with those of the HSVd-hop group. Analysis of the infectivity and pathogenicity to hosts by the constructed Agrobacterium -mediated dimeric head-to-tail HSVd cDNA infectious clones demonstrated that one of the HSVd variants identified in this study infects the natural host, mulberry plants, and also infects experimental plants, cucumber, and tomato. It probably induces stunting symptoms in HSVd-infected tomatoes but does not induce symptoms on mulberry leaves or in cucumbers. Although HSVd infecting mulberry has been found in Iran, Italy, and Lebanon, this is the first study to report this viroid in naturally infected mulberry plants in China., Competing Interests: The author(s) declare no conflict of interest.

The CRISPR-Cas system has emerged as the most efficient genome editing technique for a wide range of cells. Delivery of the Cas9-sgRNA ribonucleoprotein complex (Cas9 RNP) has gained popularity. The objective of this study was to develop a quantitative polymerase chain reaction (qPCR)-based assay to quantify the double-strand break reaction mediated by Cas9 RNP. To accomplish this, the dextransucrase gene ( dsr ) from Leuconostoc citreum was selected as the target DNA. The Cas9 protein was produced using recombinant Escherichia coli BL21, and two sgRNAs were synthesized through in vitro transcription to facilitate binding with the dsr gene. Under optimized in vitro conditions, the 2.6 kb dsr DNA was specifically cleaved into 1.1 and 1.5 kb fragments by both Cas9-sgRNA365 and Cas9-sgRNA433. By monitoring changes in dsr concentration using qPCR, the endonuclease activities of the two Cas9 RNPs were measured, and their efficiencies were compared. Specifically, the specific activities of dsr 365RNP and dsr 433RNP were 28.74 and 34.48 (unit/μg RNP), respectively. The versatility of this method was also verified using different target genes, uracil phosphoribosyl transferase ( upp ) gene, of Bifidobacterium bifidum and specific sgRNAs. The assay method was also utilized to determine the impact of high electrical field on Cas9 RNP activity during an efficient electroporation process. Overall, the results demonstrated that the qPCR-based method is an effective tool for measuring the endonuclease activity of Cas9 RNP.

Background: Robot-assisted gait training is incorporated into guidelines for stroke rehabilitation. It is a promising tool combined with conventional therapy for low ambulatory patients. The heavy weight and bulky appearance of a robotic exoskeleton limits its practicality. On the other hand, soft robotic exosuit (SRE) based on its light weight and inconspicuous property, is better tolerated by patients in daily life. The aim of this study is to review the efficacy of the SRE with regard to walking ability and biomechanical properties in stroke patients., Methods: Electronic searches were carried out in PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database. Clinical trials that investigated the effectiveness of SREs on ambulation ability in patients with post-stroke hemiparesis were eligible. Qualitative data synthesis was subsequently performed., Results: Nine studies were identified as relevant, involving a total of 83 patients. For the assessment of SRE efficacy, outcome measures were walking ability and biomechanical properties. In terms of both immediate effect and training effect, SREs improved the walking speed, walking distance, peak ankle dorsiflexion angle during swing phase, peak paretic propulsion, stride length and compensated gait in stroke patients., Conclusions: SRE improved the ambulation ability of stroke patients in terms of walking ability and biomechanical properties. The small number of studies limits the generalizability of interpretation. More controlled studies with better quality are required to reach a more solid conclusion on this issue., (© 2023. BioMed Central Ltd., part of Springer Nature.)

C-reactive protein (CRP) is a protein biomarker for acute phase response. Herein, we fabricate a highly sensitive electrochemical immunosensor for CRP on a screen-printed carbon electrode (SPCE) with indole as a novel electrochemical probe and Au nanoparticles for signal amplification. Amongst, indole appeared as transparent nanofilms on the electrode surface, and underwent a one-electron and one-proton transfer to form oxindole during the oxidation process. Upon optimization of experimental conditions, a logarithmic correlation between CRP concentration (0.0001-100 μg∙mL -1 ) and response current was revealed with a detection limit of 0.03 ng∙mL -1 and a sensitivity of 5.7055 μA∙μg -1 ∙mL∙cm -2 . The sensor exhibited exceptionally distinction selectivity, reproducibility and stability of the electrochemical immunosensor studied. The recovery rate of CRP in human serum samples determined by the standard addition method, ranged between 98.2-102.2%. Overall, the developed immunosensor is promising, and has the potential for CRP detection in real human serum samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Effective communication that integrates the value of patient-centered care is important in healthcare encounters. Communication skills training (CST) has been indicated as effective in improving patient-centered communication behaviors. However, there is a paucity of studies on the impact of CST among Malaysian hospital pharmacists., Objective: This study aimed to evaluate the effects of a patient-centered CST program on patient-centered communication scores, communication self-efficacy, and attitudes toward concordance among pharmacists in public hospitals., Methods: A communication skills training (CST) program was conducted among hospital pharmacists. This training intervention was developed based on patient-centered communication frameworks and techniques, namely the Four Habits Model and motivational interviewing. A pre-test/post-test quasi-experimental design was implemented for the evaluation. Pharmacists underwent pre-test/post-test audiotaped simulated consultations and completed questionnaires, including the Revised United States-Leeds Attitudes Toward Concordance scale (RUS-LATCon) and Communication Self-Efficacy scale. The Four Habits Coding Scheme (FHCS) was used to evaluate patient-centered communication scores from the audiotapes, and the Wilcoxon signed-rank test was used to analyze for differences in the pre- and post-intervention scores., Results: A total of 38 pharmacists from four tertiary hospitals participated in this study and completed the pre-test. However, due to the impact of COVID-19, only 23 pharmacists completed the post-test data collection. Improvements were noted in the FHCS scores post-training, including items related to exploring patients' concerns, acceptability, and barriers to treatment. Based on the questionnaire, there was an improvement in recognizing patients' needs and potential medication uncertainty and an increase in the overall communication self-efficacy scores after the training., Conclusions: CST may help improve the adoption of patient-centered communication in pharmacists' consultations with patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Fever can occur after acute myocardial infarction (MI). The influence of body temperature (BT) after hospital arrival on patients with acute MI has rarely been investigated., Methods: Patients who were diagnosed with acute MI in the emergency department (ED) of a tertiary teaching hospital between 1 January 2020 and 31 December 2020 were enrolled. Based on the tympanic temperature obtained at the ED triage, patients were categorized into normothermic (35.5°C-37.5°C), hypothermic (< 35.5°C), or hyperthermic (> 37.5°C) groups. The primary outcome was in-hospital cardiac arrest (IHCA), while the secondary outcomes were adverse events. Statistical significance was set at p < 0.05., Results: There were 440 enrollees; significant differences were found among the normothermic (n = 369, 83.9%), hypothermic (n = 27, 6.1%), and hyperthermic (n = 44, 10.0%) groups in the triage respiratory rate (median [IQR]) (20.0 [4.0] cycles/min versus 20.0 [4.0] versus 20.0 [7.5], p = 0.009), triage heart rate (88.0 [29.0] beats/min versus 82.0 [28.0] versus 102.5 [30.5], p < 0.001), presence of ST-elevation MI (42.0% versus 66.7% versus 31.8%, p = 0.014), need for cardiac catheterization (87.3% versus 85.2% versus 72.7%, p = 0.034), initial troponin T level (165.9 [565.2] ng/L versus 49.1 [202.0] versus 318.8 [2002.0], p = 0.002), peak troponin T level (343.8 [1405.9] ng/L versus 218.7 [2318.2] versus 832.0 [2640.8], p = 0.003), length of ICU stay (2.0 [3.0] days versus 3.0 [8.0] versus 3.0 [9.5], p = 0.006), length of hospital stay (4.0 [4.5] days versus 6.0 [15.0] versus 10.5 [10.8], p < 0.001), and infection during hospitalization (19.8% versus 29.6% versus 63.6%, p < 0.001) but not in IHCA (7.6% versus 14.8% versus 11.4%, p = 0.323) or any adverse events (50.9% versus 48.1% versus 63.6%, p = 0.258). Multivariable analysis showed no significant association of triage BT with IHCA or any major complication., Conclusion: Triage BT did not show a significant association with IHCA or adverse events in patients with acute MI. However, triage BT could be associated with different clinical presentations and should warrant further investigation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy., Materials and Methods: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO 2 peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive., Results: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO 2 peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO 2 peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO 2 peak., Conclusion: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender ® (QV0 dietary formula) in vitro and in vivo, respectively . QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender ® daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender ® . Significantly enhanced tumor apoptosis was observed in the Defender ® -treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender ® were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis., Competing Interests: Author KQ, the owner of QGS, provided the QV0 and Defender® in the study. He was not involved in the experiment and data interpretation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Zhang, Yu, Zhuang, Ke, Johnson, Rath, Lee, Klebe, Kao, Qin, Pham, Vuong and Cheng.)

Huntington's disease (HD) is a progressive and devastating neurodegenerative disease marked by inheritable CAG nucleotide expansion. For offspring of HD patients carrying abnormal CAG expansion, biomarkers that predict disease onset are crucially important but still lacking. Alteration of brain ganglioside patterns has been observed in the pathology of patients carrying HD. Here, by using a novel and sensitive ganglioside-focused glycan array, we examined the potential of anti-glycan auto-antibodies for HD. In this study, we collected plasma from 97 participants including 42 control (NC), 16 pre-manifest HD (pre-HD), and 39 HD cases and measured the anti-glycan auto-antibodies by a novel ganglioside-focused glycan array. The association between plasma anti-glycan auto-antibodies and disease progression was analyzed using univariate and multivariate logistic regression. The disease-predictive capacity of anti-glycan auto-antibodies was further investigated by receiver operating characteristic (ROC) analysis. We found that anti-glycan auto-antibodies were generally higher in the pre-HD group when compared to the NC and HD groups. Specifically, anti-GD1b auto-antibody demonstrated the potential for distinguishing between pre-HD and control groups. Moreover, in combination with age and the number of CAG repeat, the level of anti-GD1b antibody showed excellent predictability with an area under the ROC curve (AUC) of 0.95 to discriminate between pre-HD carriers and HD patients. With glycan array technology, this study demonstrated abnormal auto-antibody responses that showed temporal changes from pre-HD to HD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rotor syndrome is a rare, benign, inherited disorder that is commonly associated with mild hyperbilirubinemia. It is caused by bi-allelic pathological variants in both SLCO1B1 and SLCO1B3 genes, causing defective OATP1B1 and OATP1B3 in the sinusoidal membrane and interrupted bilirubin uptake of the hepatocytes. We report five Taiwanese pediatric and adult patients aged 5-32 years presenting with conjugated hyperbilirubinemia, and were found to have genetic variants of SLCO1B1 and SLCO1B3. Two also had history of prolonged neonatal jaundice. Genetic analysis using panel-based next generation sequencing revealed three patients with homozygous mutations c.1738C>T (p.R580∗) in SLCO1B1 and a transposon LINE-1 insertion in SLCO1B3, one patient with homozygous mutations for another haplotype, c.757C>T (p.R253∗) in SLCO1B1 and c.1747+1G>A in SLCO1B3. Another patient had heterozygous c.1738C>T (p.R580∗) in SLCO1B1 linked with a LINE-1 insertion in SLCO1B3, and heterozygous c.757C>T (p.R253∗) in SLCO1B1 linked with c.1747+1G>A in SLCO1B3. In conclusion, we present the first time of genetic diagnosis of Rotor syndrome in Taiwan. Advanced genetic testing has enhanced the diagnosis of rare diseases with mild symptoms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Wearable robotic devices have been strongly put into use in both the clinical and research fields of stroke rehabilitation over the past decades. This study aimed to explore the effectiveness of soft robotic gloves (SRGs) towards improving the motor recovery and functional abilities in patients with post-stroke hemiparesis. Five major bibliographic databases, PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database, were all reviewed for enrollment regarding comparative trials prior to 7 March 2023. We included adults with stroke and compared their rehabilitation using SRGs to conventional rehabilitation (CR) on hand function in terms of the Fugl-Meyer Upper Extremity Motor Assessment (FMA-UE), Fugl-Meyer Distal Upper Extremity Motor Assessment (FMA-distal UE), box and blocks test score, grip strength test, and the Jebsen-Taylor hand function test (JTT). A total of 8 studies, comprising 309 participants, were included in the analysis. Compared to CR, rehabilitation involving SRGs achieved better FMA-UE (MD 6.52, 95% CI: 3.65~9.39), FMA-distal UE (MD 3.27, 95% CI: 1.50~5.04), and JJT (MD 13.34, CI: 5.16~21.53) results. Subgroup analysis showed that stroke latency of more than 6 months and training for more than 30 min offered a better effect as well. In conclusion, for patients with stroke, rehabilitation using SRGs is recommended to promote the functional abilities of the upper extremities.

Robotic-exoskeleton-assisted gait rehabilitation improves lower limb strength and functions in post-stroke patients. However, the predicting factors of significant improvement are unclear. We recruited 38 post-stroke hemiparetic patients whose stroke onsets were <6 months. They were randomly assigned to two groups: a control group receiving a regular rehabilitation program, and an experimental group receiving in addition a robotic exoskeletal rehabilitation component. After 4 weeks of training, both groups showed significant improvement in the strength and functions of their lower limbs, as well as health-related quality of life. However, the experimental group showed significantly better improvement in the following aspects: knee flexion torque at 60°/s, 6 min walk test distance, and the mental subdomain and the total score on a 12-item Short Form Survey (SF-12). Further logistic regression analyses showed that robotic training was the best predictor of a greater improvement in both the 6 min walk test and the total score on the SF-12. In conclusion, robotic-exoskeleton-assisted gait rehabilitation improved lower limb strength, motor performance, walking speed, and quality of life in these stroke patients.

Polysaccharides have been successfully used as immunogens for the development of vaccines against bacterial infection; however, there are no oligosaccharide-based vaccines available to date and no previous studies of their processing and presentation. We reported here the intracellular enzymatic processing and antigen presentation of an oligosaccharide-conjugate cancer vaccine prepared from the glycan of Globo-H (GH), a globo-series glycosphingolipid (GSL). This oligosaccharide-conjugate vaccine was shown to elicit antibodies against the glycan moieties of all three globo-series GSLs that are exclusively expressed on many types of cancer and their stem cells. To understand the specificity and origin of cross-reactivity of the antibodies elicited by the vaccine, we found that the vaccine is first processed by fucosidase 1 in the early endosome of dendritic cells to generate a common glycan antigen of the GSLs along with GH for MHC class II presentation. This work represents the first study of oligosaccharide processing and presentation and is expected to facilitate the design and development of glycoconjugate vaccines based on oligosaccharide antigens.

Purpose of Review: Heart failure leads to high mortality. The failing myocardium cannot often be rescued as heart regeneration is mostly compromised by disease progress. Stem cell therapy is a strategy under development to replace the impaired myocardium for recovery after heart injury., Recent Findings: Many studies have provided evidence of the beneficial effects of pluripotent stem cell-derived cardiomyocyte (CM) implantation into diseased rodent hearts, but there are still many challenges and limitations to replicating the same effects in large animal models for preclinical validation. In this review, we summarize progress in the use of pluripotent stem cell-derived CMs in large animal models based on three key parameters: species selection, cell source, and delivery. Most importantly, we discuss the current limitations and challenges that need to be solved to advance this technology to the translational stage., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Respiratory diseases are the 2nd leading cause of death globally. The current treatments for chronic lung diseases are only supportive. Very few new classes of therapeutics have been introduced for lung diseases in the last 40 years, due to the lack of reliable lung models that enable rapid, cost-effective, and high-throughput testing. To accelerate the development of new therapeutics for lung diseases, we established two classes of lung-mimicking models: (i) healthy, and (ii) diseased lungs - COPD., Methods: To establish models that mimic the lung complexity to different extents, we used five design components: (i) cell type, (ii) membrane structure/constitution, (iii) environmental conditions, (iv) cellular arrangement, (v) substrate, matrix structure and composition. To determine whether the lung models are reproducible and reliable, we developed a quality control (QC) strategy, which integrated the real-time and end-point quantitative and qualitative measurements of cellular barrier function, permeability, tight junctions, tissue structure, tissue composition, and cytokine secretion., Results: The healthy model is characterised by (i) continuous tight junctions, (ii) physiological cellular barrier function, (iii) a full thickness epithelium composed of multiple cell layers, and (iv) the presence of ciliated cells and goblet cells. Meanwhile, the disease model emulates human COPD disease: (i) dysfunctional cellular barrier function, (ii) depletion of ciliated cells, and (ii) overproduction of goblet cells. The models developed here have multiple competitive advantages when compared with existing in vitro lung models: (i) the macroscale enables multimodal and correlative characterisation of the same model system, (ii) the use of cells derived from patients that enables the creation of individual models for each patient for personalised medicine, (iii) the use of an extracellular matrix proteins interface, which promotes physiological cell adhesion and differentiation, (iv) media microcirculation that mimics the dynamic conditions in human lungs., Conclusion: Our model can be utilised to test safety, efficacy, and superiority of new therapeutics as well as to test toxicity and injury induced by inhaled pollution or pathogens. It is envisaged that these models can also be used to test the protective function of new therapeutics for high-risk patients or workers exposed to occupational hazards., (© 2023. Crown.)

Geriatric community centers often offer nutrition lectures to older adults. In order to make learning more interesting and pragmatic, we developed group activity sessions. This undertaking was tested for its efficacy in changes of frailty status and several other geriatric health parameters. A cluster-randomized controlled trial was conducted between September 2018 and December 2019 at 13 luncheon-providing community strongholds in Taipei, Taiwan. During the 3-month intervention period, 6 experimental strongholds received a weekly 1 h exercise workout and 1 h nutrition activities aiming at achieving the recommendations of the Taiwanese Daily Food Guide for elderlies; the other 7 received a weekly 1 h exercise workout and 1 h other activities. Dietary intakes and frailty status were the primary outcomes. Secondary outcomes included working memory and depression. The measurements were performed at baseline, 3 months, and 6 months. The nutrition intervention significantly reduced the intake of refined grains and roots ( p = 0.003) and increased that of non-refined grains and roots ( p = 0.008), dairy products ( p < 0.0001), and seeds and nuts (at borderline, p = 0.080) at 3 months. Some, but not all, of these changes were maintained at 6 months. Performance improvements included the frailty status score ( p = 0.036) and forward digit span ( p = 0.004), a working memory parameter, at 3 months. Only the forward digit span remained improved ( p = 0.007) at 6 months. The 3-month nutrition group activities combined with exercise sessions improved the frailty status and working memory more than exercise alone. The dietary and frailty improvements were accompanied by improved dietary intakes and advanced behavioral stages. However, the improved frailty status backslid after intervention ceased, suggesting that boosting activities are needed for maintaining the intervention effect.

Background: Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression.  Phosphorylation of ATG4B is crucial for activation of its protease activity.  However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC)., Methods: The ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays., Results: ATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox's regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells., Conclusions: Our results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC., (© 2023. The Author(s).)

DNA is a universal and programmable signal of living organisms. Here we develop cell-based DNA sensors by engineering the naturally competent bacterium Bacillus subtilis (B. subtilis) to detect specific DNA sequences in the environment. The DNA sensor strains can identify diverse bacterial species including major human pathogens with high specificity. Multiplexed detection of genomic DNA from different species in complex samples can be achieved by coupling the sensing mechanism to orthogonal fluorescent reporters. We also demonstrate that the DNA sensors can detect the presence of species in the complex samples without requiring DNA extraction. The modularity of the living cell-based DNA-sensing mechanism and simple detection procedure could enable programmable DNA sensing for a wide range of applications., (© 2023. The Author(s).)

Decellularized extracellular matrix is one form of natural material in tissue engineering. The process of dECM retains the tissue microstructure, provides good cell adhesion sites, maintains most of biological signals that promotes the survival and differentiation ability of cells. In this study, sheep kidney was decellularized followed by histochemical staining, elemental analysis and scanning electron microscopy characterizations. The dECM scaffold was prepared with different sequences of freeze drying technology, crosslinking and the water absorption, porosity, mechanical strength with subsequent thermogravimetric analysis, Infrared spectroscopy and biocompatibility tests. Our results indicated that these decellularized treatments of sheep kidney can effectively remove DNA and retain uniform pore size distribution. After crosslinking the scaffold's water absorption decreased from 987.56 ± 40.21% to 934.39 ± 39.61%, the porosity decreased from 89.64 ± 3.2% to 85.09 ± 17.63%, and the compression modulus increased from 304.32 ± 25.43 kPa to 459.53 ± 38.92 kPa, with thermal process the percentage of weight loss decreased from 66.57% to 44.731%, in addition, the composition didn't change significantly, crosslinking could also promote the stability. In terms of biocompatibility, the number of viable cells increased significantly with the days. In conclusion, the crosslinked decellularized sheep kidney extracellular matrix scaffold reduced water absorption and porosity slightly, but has a significant increase in mechanical properties, and presented excellent biocompatibility which are beneficial to cell adhesion, growth and differentiation.

Background: Post-stroke spasticity is a cause of gait dysfunction and disability. Focal vibration (FV) of agonist-antagonist upper limb muscle pairs reduces flexor spasticity; however, its effects on ankle plantarflexor spasticity are uncertain., Objective: To assess the effects of focal vibration administered by a trained operator to the ankle plantarflexor and dorsiflexor muscles on post-stroke lower limb spasticity., Methods: A randomized, single-blind controlled trial of 64 participants with stroke and plantarflexor spasticity assigned to 3 groups by centralized, computer-generated randomization (1:1:1): 1) physiotherapy alone (CON), 2) physiotherapy+gastrocnemius vibration (FV&#95;GM) and 3) physiotherapy+tibialis anterior vibration (FV&#95;TA). Physiotherapists and assessors were blinded to group assignment. The experimental groups underwent 15, 20-min vibration sessions at 40 Hz. We performed evaluations at baseline and after the final treatment: Modified Ashworth Scale (MAS), Clonus scale, Functional Ambulation Categories (FAC), Fugl-Meyer Assessment - Lower Extremity (FMA&#95;LE), Modified Barthel Index (MBI), and electromyography and ultrasound elastography. Primary outcome was remission rate (number and proportion of participants) of the MAS., Results: MAS remission rate was higher in FV&#95;GM and FV&#95;TA than CON groups (CON vs. FV&#95;GM: p=0.009, odds ratio 0.15 [95% confidence interval 0.03-0.67]; CON vs. FV&#95;TA: p=0.002, 0.12 [0.03-0.51]). Remission rate was higher in the experimental than CON groups for the Clonus scale (CON vs. FV&#95;GM: p<0.001, OR 0.07 [95% CI 0.01-0.31]; CON vs. FV&#95;TA: p=0.006, 0.14 [95% CI 0.03-0.61]). FAC remission rate was higher in the FV&#95;TA than the CON (p=0.009, 0.18 [0.05-0.68]) and FV&#95;GM (p=0.014, 0.27 [0.07-0.99]) groups. Ultrasound variables of the paretic medial gastrocnemius decreased more in FV&#95;GM than CON and FV&#95;TA groups (shear modulus: p=0.006; shear wave velocity: p=0.008)., Conclusions: Focal vibration reduced post-stroke spasticity of the plantarflexor muscles. Vibration of the tibialis anterior improved ambulation more than vibration of the gastrocnemius or physiotherapy alone. Gastrocnemius vibration may reduce spasticity by changing muscle stiffness., Competing Interests: Declaration of Competing Interest None declared No preprints available, (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The skin plays an important role in vitamin D synthesis, humoral balance, temperature regulation, and waste excretion. Due to the complexity of the skin, fluids loss, bacterial infection, and other life-threatening secondary complications caused by skin defects often lead to the damage of skin functions. 3D bioprinting technology, as a customized and precise biomanufacturing platform, can manufacture dressings and tissue engineering scaffolds that accurately simulate tissue structure, which is more conducive to wound healing. In recent years, with the development of emerging technologies, an increasing number of 3D-bioprinted wound dressings and skin tissue engineering scaffolds with multiple functions, such as antibacterial, antiinflammatory, antioxidant, hemostatic, and antitumor properties, have significantly improved wound healing and skin treatment. In this article, we review the process of wound healing and summarize the classification of 3D bioprinting technology. Following this, we shift our focus on the functional materials for wound dressing and skin tissue engineering, and also highlight the research progress and development direction of 3D-bioprinted multifunctional wound healing materials., Competing Interests: The authors declare no conflict of interest., (Copyright:© 2023, 10.18063/ijb.757.)

The molecular and ecological factors shaping horizontal gene transfer (HGT) via natural transformation in microbial communities are largely unknown, which is critical for understanding the emergence of antibiotic-resistant pathogens. We investigate key factors shaping HGT in a microbial co-culture by quantifying extracellular DNA release, species growth, and HGT efficiency over time. In the co-culture, plasmid release and HGT efficiency are significantly enhanced than in the respective monocultures. The donor is a key determinant of HGT efficiency as plasmids induce the SOS response, enter a multimerized state, and are released in high concentrations, enabling efficient HGT. However, HGT is reduced in response to high donor lysis rates. HGT is independent of the donor viability state as both live and dead cells transfer the plasmid with high efficiency. In sum, plasmid HGT via natural transformation depends on the interplay of plasmid properties, donor stress responses and lysis rates, and interspecies interactions., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Mild cognitive impairment (MCI) is a prodrome of Alzheimer's disease pathology. Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods. Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases. This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI. Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls, and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays. Correlation of cognitive performance with the serum exosomal protein level was determined. Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls. We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis. Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients. Exosomal fibulin-1, with an area under the curve value of 0.81, may be a biomarker for an MCI diagnosis. The exosomal protein signature from MCI patients reflected the cell adhesion molecule category. In particular, higher exosomal fibulin-1 levels correlated with lower cognitive performance. Thus, this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI., Competing Interests: None

Bone tissue engineering is a novel and efficient repair method for bone tissue defects, and the key step of the bone tissue engineering repair strategy is to prepare non-toxic, metabolizable, biocompatible, bone-induced tissue engineering scaffolds of suitable mechanical strength. Human acellular amniotic membrane (HAAM) is mainly composed of collagen and mucopolysaccharide; it has a natural three-dimensional structure and no immunogenicity. In this study, a polylactic acid (PLA)/Hydroxyapatite (nHAp)/Human acellular amniotic membrane (HAAM) composite scaffold was prepared and the porosity, water absorption and elastic modulus of the composite scaffold were characterized. After that, the cell-scaffold composite was constructed using newborn Sprague Dawley (SD) rat osteoblasts to characterize the biological properties of the composite. In conclusion, the scaffolds have a composite structure of large and small holes with a large pore diameter of 200 μm and a small pore diameter of 30 μm. After adding HAAM, the contact angle of the composite decreases to 38.7°, and the water absorption reaches 249.7%. The addition of nHAp can improve the scaffold's mechanical strength. The degradation rate of the PLA+nHAp+HAAM group was the highest, reaching 39.48% after 12 weeks. Fluorescence staining showed that the cells were evenly distributed and had good activity on the composite scaffold; the PLA+nHAp+HAAM scaffold has the highest cell viability. The adhesion rate to HAAM was the highest, and the addition of nHAp and HAAM could promote the rapid adhesion of cells to scaffolds. The addition of HAAM and nHAp can significantly promote the secretion of ALP. Therefore, the PLA/nHAp/HAAM composite scaffold can support the adhesion, proliferation and differentiation of osteoblasts in vitro which provide sufficient space for cell proliferation, and is suitable for the formation and development of solid bone tissue.

Epstein-Barr virus (EBV) replicates its genome in the nucleus and undergoes tegumentation and envelopment in the cytoplasm. We are interested in how the single-stranded DNA binding protein BALF2, which executes its function and distributes predominantly in the nucleus, is packaged into the tegument of virions. At the mid-stage of virus replication in epithelial TW01-EBV cells, a small pool of BALF2 colocalizes with tegument protein BBLF1, BGLF4 protein kinase, and the cis -Golgi marker GM130 at the perinuclear viral assembly compartment (AC). A possible nuclear localization signal (NLS) between amino acids 1100 and 1128 (C29), which contains positive charged amino acid 1113 RRKRR 1117 , is able to promote yellow fluorescent protein (YFP)-LacZ into the nucleus. In addition, BALF2 interacts with the nucleocapsid-associated protein BVRF1, suggesting that BALF2 may be transported into the cytoplasm with nucleocapsids in a nuclear egress complex (NEC)-dependent manner. A group of proteins involved in intracellular transport were identified to interact with BALF2 in a proteomic analysis. Among them, the small GTPase Rab1A functioning in bi-directional trafficking at the ER-Golgi interface is also a tegument component. In reactivated TW01-EBV cells, BALF2 colocalizes with Rab1A in the cytoplasmic AC. Expression of dominant-negative GFP-Rab1A(N124I) diminished the accumulation of BALF2 in the AC, coupling with attenuation of gp350/220 glycosylation. Virion release was significantly downregulated by expressing dominant-negative GFP-Rab1A(N124I). Overall, the subcellular distribution of BALF2 is regulated through its complex interaction with various proteins. Rab1 activity is required for proper gp350/220 glycosylation and the maturation of EBV. IMPORTANCE Upon EBV lytic reactivation, the virus-encoded DNA replication machinery functions in the nucleus, while the newly synthesized DNA is encapsidated and transported to the cytoplasm for final virus assembly. The single-stranded DNA binding protein BALF2 executing functions within the nucleus was also identified in the tegument layer of mature virions. Here, we studied the functional domain of BALF2 that contributes to the nuclear targeting and used a proteomic approach to identify novel BALF2-interacting cellular proteins that may contribute to virion morphogenesis. The GTPase Rab1, a master regulator of anterograde and retrograde endoplasmic reticulum (ER)-Golgi trafficking, colocalizes with BALF2 in the juxtanuclear concave region at the midstage of EBV reactivation. Rab1 activity is required for BALF2 targeting to the cytoplasmic assembly compartment (AC) and for gp350/220 targeting to cis -Golgi for proper glycosylation and virion release. Our study hints that EBV hijacks the bi-directional ER-Golgi trafficking machinery to complete virus assembly.

Craniofacial bone regeneration is a coupled process of angiogenesis and osteogenesis, which, associated with infection, still remains a challenge in bone defects after trauma or tumor resection. 3D tissue engineering scaffolds with multifunctional-therapeutic properties can offer many advantages for the angiogenesis and osteogenesis of infected bone defects. Hence, in the present study, a microchannel networks-enriched 3D hybrid scaffold composed of decellularized extracellular matrix (dECM), gelatin (Gel), quaterinized chitosan (QCS) and nano-hydroxyapatite (nHAp) (dGQH) was fabricated by an extrusion 3D bioprinting technology. And enlightened by the characteristics of natural bone microstructure and the demands of vascularized bone regeneration, the exosomes (Exos) isolated from human adipose derived stem cells as angiogenic and osteogenic factors were then co-loaded into the desired dGQH 20 hybrid scaffold based on an electrostatic interaction. The results of the hybrid scaffolds performance characterization showed that these hybrid scaffolds exhibited an interconnected pore structure and appropriate degradability (>61% after 8 weeks of treatment), and the dGQH 20 hybrid scaffold displayed the highest porosity (83.93 ± 7.38%) and mechanical properties (tensile modulus: 62.68 ± 10.29 MPa, compressive modulus: 16.22 ± 3.61 MPa) among the dGQH hybrid scaffolds. Moreover, the dGQH 20 hybrid scaffold presented good antibacterial activities (against 94.90 ± 2.44% of Escherichia coli and 95.41 ± 2.65% of Staphylococcus aureus , respectively) as well as excellent hemocompatibility and biocompatibility. Furthermore, the results of applying the Exos to the dGQH 20 hybrid scaffold showed that the Exo promoted the cell attachment and proliferation on the scaffold, and also showed a significant increase in osteogenesis and vascularity regeneration in the dGQH@Exo scaffolds in vitro and in vivo . Overall, this novel dECM/Gel/QCS/nHAp hybrid scaffold laden with Exo has a considerable potential application in reservation of craniofacial bone defects., (© 2023 IOP Publishing Ltd.)

Carbon nanotubes (CNTs), as kinds of conductive carbon nanomaterials, were widely applied in neural tissue engineering due to their excellent electrical conductivity and good biocompatibility. In this study, the carboxyl-modified multi-walled carbon nanotubes (mMWCNTs) were introduced into sodium alginate/gelatin (Alg/Gel) scaffolds to optimize the function of the hybrid scaffolds. The Alg/Gel/mMWCNTs conductive scaffolds with mMWCNTs content of 1%, 3%, and 5% were prepared by freeze-drying, respectively. Following this, the physicochemical properties and biocompatibility of the hybrid scaffolds at different magnetic field intensities were evaluated. The conductive scaffolds were characterized by Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). In general, the mMWCNTs addition improved the hydrophilic, electrical conductivity and mechanical properties of the composite scaffold, and PC12 cells showed a trend of gradual increase over culture time. Particularly, the Alg/Gel-1%C scaffold exhibited the best cell proliferation behavior. Briefly, the surface contact angle decreased from 74 ± 1° to 60 ± 3°, the electrical conductivity and compressive modulus increased to 1.32 × 10 -3 ± 2.1 × 10 -4 S/cm and 1.40 ± 0.076 Mpa, the G1 phase from 55.67 ± 1.86% to 59.77 ± 0.94% and the G2 phase from 10.32 ± 0.35% to 13.93 ± 1.26%，respectively. In the SEM images, PC12 cells were well-shaped and densely distributed. Therefore, the Alg/Gel/mMWCNTs conductive scaffold has potential as a tissue engineering scaffold in nerve regeneration., Competing Interests: Conflicts of Interest The authors have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Studies have reported increasing triple valve surgery (TVS, defined as concomitant aortic, mitral and tricuspid valves surgery) incidence and improved postoperative survival. The epidemiology and outcome of TVS is not known in Australia., Methods: From the Admission-Patient-Data-Collection registry, all New South Wales residents who underwent cardiac valve surgery between 1 July 2001 and 31 December 2018 were identified, with cause-specific mortality tracked from the death registry., Results: Triple valve surgery comprised 1.2% (347/28,667 cases) of all valvular surgeries. Volumes rose from eight cases-per-annum in 2002 to a peak of 37 in 2012, and between 23 and 30 cases-per-annum since. Mean (±SD) age of study cohort (n=340 persons) was 68.2±15.2 years (50% male); 20.3% had concomitant coronary-artery-bypass-surgery (males vs females: 29.4% vs 11.2%, p<0.001). Main surgery on aortic and mitral valves was replacement (95.9% and 70.6% respectively). Tricuspid valve annuloplasty was performed in 90.6% of patients. Cumulative in-hospital, 180-day, and total mortality (mean follow-up=4.9±4.0 yrs) was 7.4%, 11.8% and 42.6%, respectively. Heart failure (24.0% in-hospital, 22.5% post-discharge) and sepsis (24.0% in-hospital, 20.0% post-discharge) were the main cause-specific deaths. There was no in-hospital stroke-related death. Age (median >72 yrs; hazard ratio [HR]=1.95, 95%CI=1.37-2.79), malignancy (HR=6.35, 95%CI=2.21-18.26), heart failure (HR=1.79, 95%CI=1.25-2.57) and chronic kidney disease (CKD) (HR=2.21, 95%CI=1.39-3.51) (all p<0.005) were independent predictors during intermediate-term follow-up., Conclusions: Triple valve surgery remains rare in Australia and is associated with high mortality. Multi-centred collaboration and access to comprehensive clinical data are required to identify the drivers of poor outcome., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Hydrogen transfer (HT) is of crucial importance in biochemistry and atmospheric chemistry. Here, HT processes involved in the dissociation reaction of dimethyl disulfide radical cations (DMDS˙ + , CH 3 SSCH 3 ˙ + ) are investigated using quantum chemical calculations. Four HTs from the C to S atom and one HT from the S to S atom are observed and the most probable paths are proposed in the dissociation channel from DMDS˙ + to CH n S + ( n = 2-4). The mechanisms of all these five HTs are described as hydrogen atom transfer (HAT) and four of them are accompanied by electron transfer (ET). Considering the catalytic effect of water molecules existing in organisms and the atmosphere, five HT processes in the dissociation of the [DMDS + H 2 O]˙ + complex are further explored, which show lower free energy barriers. With the participation of water molecules acting as a base, two HTs from the C to the S atom, which have the largest decrease in energy barriers, are characterized as concerted proton-coupled electron transfer (cPCET). These results can be extended to understand the mechanism of the HT process during the dissociation of disulfide and help provide a strategy to design a rare cPCET mechanism for the activation of the C-H bond.

The production and use of hexabromocyclododecanes (HBCDs) have been strictly limited due to their persistence, toxicity and bioaccumulation. However, the release of HBCDs from related products and wastes would continue for a long time, which may cause many environmental problems. In this study, we investigated the occurrence and distribution of HBCDs and microplastics (MPs) in aquatic organisms inhabiting different substrates. HBCDs were measurable in the seawater, sediment, expanded polystyrene (EPS) substrates and organism samples. Mostly, the concentrations of HBCDs in organisms inhabiting EPS buoys were significantly higher than those of the same species inhabiting other substrates. Meanwhile, the diastereomeric ratio (α/γ) of HBCDs in organisms inhabiting EPS buoys was closer to that in EPS buoys. The fugacity values of HBCDs in EPS buoys were much higher than those in other media, implying that HBCDs can be transferred from EPS buoys to other media. Additionally, MPs derived from EPS buoys would be mistaken as food and ingested by aquatic organisms. The transfer of HBCDs from EPS buoys to aquatic organisms can be achieved by aqueous and dietary exposures. In combination, the contribution of MP ingestion to HBCDs for aquatic organisms should be very limited. These results supported EPS buoys as an important source of HBCDs for the aquatic ecosystem. To effectively control HBCDs pollution, it is necessary to discontinue or reduce the use of EPS buoys., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed., (© 2023. The Author(s).)