Tuning the Electronic Structures of Anchor Sites to Achieve Zero-Valence Single-Atom Catalysts for Advanced Hydrogenation.

Single-atom catalysts (SACs) have recently become highly attractive for selective hydrogenation reactions owing to their remarkably high selectivity. However, compared to their nanoparticle counterparts, atomically dispersed metal atoms in SACs often show inferior activity and are prone to aggregate under reaction conditions. Here, by theoretical calculations, we show that tuning the local electronic structures of metal anchor sites on g-C3N4 by doping B atoms (BCN) with relatively lower electronegativity allows achieving zero-valence Pd SACs with reinforced metal-support orbital hybridizations for high stability and upshifted Pd 4d orbitals for high activity in H2 activation. The precise synthesis of Pd SACs on BCN supports with varied B contents substantiated the theoretical prediction. A zero-valence Pd1/BCN SAC was achieved on a BCN support with a relatively low B content. It exhibited much higher stability in a H2 reducing environment, and more strikingly, a hydrogenation activity, approximately 10 and 34 times greater than those high-valence Pd1/g-C3N4 and Pd1/BCN with a high B content, respectively.

Fluctuation of flavor quality in roasted duck: The consequences of raw duck preform's repetitive freeze-thawing.

This study aimed to investigate the changes in flavor quality of roasted duck during repetitive freeze-thawing (FT, -20 ℃ for 24 h, then at 4 ℃ for 24 h for five cycles) of raw duck preforms. HS-SPME/GC-MS analysis showed that more than thirty volatile flavor compounds identified in roasted ducks fluctuated with freeze-thawing of raw duck preforms, while hexanal, nonanal, 1-octen-3-ol, and acetone could as potential flavor markers. Compared with the unfrozen raw duck preforms (FT-0), repetitive freeze-thawing increased the protein/lipid oxidation and cross-linking of raw duck preforms by maintaining the higher carbonyl contents (1.40 âˆ¼ 3.30 nmol/mg), 2-thiobarbituric acid reactive substances (0.25 âˆ¼ 0.51 mg/kg), schiff bases and disulfide bond (19.65 âˆ¼ 30.65 µmol/g), but lower total sulfhydryl (73.37 âˆ¼ 88.94 µmol/g) and tryptophan fluorescence intensity. Moreover, A lower protein band intensity and a transformation from α-helixes to ß-sheets and random coils were observed in FT-3 âˆ¼ FT-5. The obtained results indicated that multiple freeze-thawing (more than two cycles) of raw duck preforms could be detrimental to the flavor quality of the roasted duck due to excessive oxidation and degradation.

Research progress of chilled meat freshness detection based on nanozyme sensing systems.

It is important to develop rapid, accurate, and portable technologies for detecting the freshness of chilled meat to meet the current demands of meat industry. This report introduces freshness indicators for monitoring the freshness changes of chilled meat, and systematically analyzes the current status of existing detection technologies which focus on the feasibility of using nanozyme for meat freshness sensing detection. Furthermore, it examines the limitations and foresees the future development trends of utilizing current nanozyme sensing systems in evaluating chilled meat freshness. Harmful chemicals are produced by food spoilage degradation, including biogenic amines, volatile amines, hydrogen sulfide, and xanthine, which have become new freshness indicators to evaluate the freshness of chilled meat. The recognition mechanisms are clarified based on the special chemical reaction with nanozyme or directly inducting the enzyme-like catalytic activity of nanozyme.

Development of a rhodamine-based fluorescent probe for ATP detection for potential applications in meat freshness assessment.

Adenosine triphosphate (ATP) plays a vital role in physiological processes and is an essential indicator of microbial content in food. Herein, a new sensitive, rapid and water-soluble probe for ATP detection was developed. Rhodamine B and pentaethylenehexamine were employed to design and synthesise the probe rhodamine-pentaethylenehexamine (RP) for selective ATP detection. The synthesised probe RP was characterized using Fourier transform infrared, NMR and dynamic light scattering size distributions. Upon the addition of ATP, the probe exhibited a distinct change in fluorescence intensity, with fluorescence emission at 580 nm. A linear relationship was observed between fluorescence intensity and ATP concentrations at 0-50 µmol/L, with a limit of detection of 10.97 × 10-9 mol/L. The results of the zeta potential and molecular dynamics simulation demonstrated that the detection mechanism of the probe RP is associated with the electrostatic adsorption interaction between the multi-positively charged sites of RP and the negatively charged triphosphate structure of ATP. Our study provides new insights into improving charge site identification in small molecule detection. Furthermore, the successful detection of ATP on meat surfaces indicates that RP has the potential to assess meat freshness.

RNA-seq transcriptome analysis provides new insights into the negative effects of tannic acid on the intestinal function of Brandt's voles (Lasiopodomys brandtii).

Tannic acid (TA), a significant plant secondary metabolite, is contained in the daily food of Brandt's voles. Its adverse effect on gut function has been shown in earlier research, but the underlying molecular mechanisms remain uncertain. In this study, male Brandt's vole (13 weeks old) were divided into two groups and given 0 (control) or 1,200 (TA-treated) mg•kg-1 TA for 18 days. Then RNA sequencing was used to conduct a thorough transcriptome analysis on the duodenum, jejunum, and ileum of Brandt's voles. Results showed that TA significantly increased serum total cholesterol concentration (P < 0.05) and decreased the nutrient digestibility (P < 0.05) of Brandt's voles. Furthermore, there were 174 differentially expressed genes (DEGs) in the duodenum, 96 DEGs in the jejunum, and 88 DEGs in the ileum between the control and TA-treated groups. Enrichment analysis revealed that many genes associated with bile secretion, fat digestion and absorption, innate immune response, and tight junction such as ABCG2, ABCG8, PEAK1, and IFR2, etc. were altered after TA treatment, which were verified by quantitative real-time PCR. These findings suggested that TA can change the expression of intestinal genes, thereby, altering nutrition metabolism and immunological function, eventually hindering the growth of Brandt's voles. The results of this study provide a theoretical basis for explaining how TA affects the gut function of Brandt's voles at the molecular level.

Application of the New Irrigation Protocol to Reduce Recurrence Rate in the Management Of Periprosthetic Joint Infection.

OBJECTIVE: Irrigation is a conventional treatment for acute and chronic periprosthetic joint infections (PJI). However, there has been no unified standard for irrigation during surgery for PJI in the past, and the efficacy is uncertain. The purpose of this study is to create a new irrigation protocol to enhance the infection control rate and reduce the postoperative recurrence rate of PJI patients. METHODS: We conducted a single-institution retrospective review with a total of 56 patients who underwent revision total hip or knee arthroplasties due to PJI from January 2011 to January 2022. Conventional irrigation (CI) was used in 32 cases, and standard operating procedure of irrigation (SOPI) was used in 24. The CI protocol carries out an empirical irrigation after debridement, which is quite random. Our SOPI protocol clearly stipulates the soaking concentration and time of hydrogen peroxide and povidone-iodine. The irrigation is carried out three times, and tissue samples are taken from multiple parts before and after irrigation, which are sent for microbial culture. The important statistical indicators were the rate of positive microbiological culture and postoperative recurrence rate with an average follow-up of 24 average months. RESULTS: The drainage volume was lower in the SOPI group than in the CI group on postoperative day 3 (p < 0.01) and 7 (p = 0.016). In addition, the percentage of positive microbiological cultures after the third irrigation was less than that before (p < 0.01) and after (p < 0.01) the first irrigation. The most common causative organism was Staphylococcus aureus, which was detected in 25.0% and 12.5% of the SOPI and CI groups, respectively. The failure rate at the final follow-up was 8.3% and 31.3% (p = 0.039) for the SOPI and CI groups, respectively. CONCLUSION: Compared with the traditional CI method, SOPI standardized the soaking time of hydrogen peroxide and povidone-iodine, increased the frequency of and irrigation, and proved that microorganisms were almost completely removed through the microbial culture of multiple tissues. SOPI has the potential to become a standardized irrigation process worthy of promotion, effectively reducing the postoperative recurrence rate of PJI patients.

Separated Electron-Phonon and Phonon-Phonon Scatterings Across Interface in Thin Film LaCoO3 /SrTiO3.

Electron-phonon coupling (EPC) and phonon-phonon scattering (PPS) are at the core of the microscopic physics mechanisms of vast quantum materials. However, to date, there are rarely reports that these two processes can be spatially separated, although they are usually temporally detached with different characteristic lifetimes. Here, by employing ultrafast spectroscopy to investigate the photo-carrier ultrafast dynamics in a LaCoO3 thin film on a (100) SrTiO3 substrate, intriguing evidence is found that the two interactions are indeed spatially separated. The EPC mainly occurs in the thin film, whereas PPS is largely in the substrate, especially at the several atomic layers near the interface. Across-interface penetration and decay of optical phonons into acoustic phonons thus naturally occur. An EPC strength λEg  = 0.30 is also obtained and an acoustic phonon mode at 45.3 GHz is observed. The finding lays out a cornerstone for future quantum nano device designs.

Identification of anterior cruciate ligament fibroblasts and their contribution to knee osteoarthritis progression using single-cell analyses.

The mechanical properties of the anterior cruciate ligament (ACL) in the knee have been highlighted, but its role in the regulation of the joint microenvironment remains unclear, especially in the progression of Knee Osteoarthritis (KOA). Here, single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) data were integrated to reveal the transcriptional and epigenomic landscape of ACL in normal and OA states. We identified a novel subpopulation of fibroblasts in ACL, which provides new insights into the role of the ACL in knee homeostasis and disease. Degeneration of the ACL during OA mechanically alters the knee joint homeostasis and influences the microenvironment by regulating inflammatory- and osteogenic-related factors, thereby contributing to the progression of KOA. Additionally, the specific mechanism by which these Inflammation-associated Fibroblasts (IAFs) regulate KOA progression was uncovered, providing new foundation for the development of targeted treatments for KOA.

Exoskeleton-Assisted Sit-to-Stand Training Improves Lower-Limb Function Through Modifications of Muscle Synergies in Subacute Stroke Survivors.

Abnormal muscle synergies during sit-to-stand (STS) transitions have been observed post-stroke, which are associated with deteriorated lower-limb function and mobility. Although exoskeletons have been used in restoring lower-limb function, their effects on muscle synergies and lower-limb motor recovery remain unclear. Here, we characterized normal muscle synergy patterns during STS activity in ten healthy adults as a reference, comparing with pathological muscle synergy patterns in ten participants with subacute stroke. Moreover, we assessed the effects of a 3-week exoskeleton-assisted STS training intervention on muscle synergies and clinical scores in seven stroke survivors. We also investigated correlations between neuromuscular complexity of muscle synergies and clinical scores. Our results showed that the STS task involved three motor modules representing distinct biomechanical functions among healthy subjects. In contrast, stroke participants showed 3 abnormal modules for the paretic leg and 2 modules for the non-paretic leg. After the intervention, muscle synergies partially shifted towards the normal pattern observed in healthy subjects on the paretic side. On the non-paretic side, the synergy modules increased to three and neuromuscular coordination improved. Furthermore, the significant intervention-induced increases in Fugl-Meyer Assessment of Lower Extremity and Berg Balance Scale scores were associated with improved muscle synergies on the non-paretic side. These results indicate that the paretic side demonstrates abnormal changes in muscle synergies post-stroke, while the non-paretic side can synergistically adapt to post-stroke biomechanical deviations. Our data show that exoskeleton-based training improved lower-limb function post-stroke by inducing modifications in muscle synergies.

Effects of repetitive peripheral magnetic stimulation for the upper limb after stroke: Meta-analysis of randomized controlled trials.

Introduction: Repetitive peripheral magnetic stimulation (rPMS) can stimulate profound neuromuscular tissues painlessly to evoke action potentials in motor axons and induce muscle contraction for treating neurological conditions. It has been increasingly used in stroke rehabilitation as an easy-to-administer approach for therapeutic neuromodulation. Objective: We performed this meta-analysis of randomized controlled trials to systematically evaluate the effects of rPMS for the upper limb in patients with stroke, including motor impairment, muscle spasticity, muscle strength, and activity limitation outcomes. Methods: The meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, EMBASE, Web of Science, Cochrane Library, and Physiotherapy Evidence Database (PEDro) were searched for articles published before June 2022. Forest plots were employed to estimate the pooled results of the included studies, and the I2 statistical analysis was used to identify the source of heterogeneity. Publication bias was examined by Egger's regression tests or visual inspection of the funnel plots. Results: The database searches yielded 1052 potential eligible literature; of them, five randomized controlled trials met the eligible criteria, involving a total of 188 participants. Patients in the rPMS group showed better improvement in motor impairment as measured by the FM-UE (MD: 5.39 [95% CI, 4.26 to 6.52]; P < 0.001; I2 = 0%) compared with the control group. Among the secondary outcomes, no difference was found in the improvement of muscle spasticity (SMD: 0.36 [95% CI, -0.05 to 0.77]; P = 0.08; I2 = 41%). There was a significant difference in the proximal (SMD: 0.58 [95% CI, 0.10 to 1.06]; P = 0.02; I2 = 0%) but not the distal muscle strength (SMD: 1.18 [95% CI, -1.00 to 3.36]; P = 0.29; I2 = 93%). Moreover, the activity limitation outcomes were significantly improved with rPMS intervention (SMD: 0.59 [95% CI, 0.08 to 1.10]; P = 0.02; I2 = 0%). Conclusion: This meta-analysis showed that rPMS might improve upper limb motor impairment, proximal muscle strength, and activity limitation outcomes but not muscle spasticity and distal strength in patients after stroke. Due to the limited number of studies, further randomized clinical trials are still warranted for more accurate interpretation and clinical recommendation.

SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice.

BACKGROUND: Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS). METHODS: Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood-brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice. RESULTS: Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1ß, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1ß, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein. CONCLUSIONS: Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.

Insight from untargeted metabolomics: Revealing the potential marker compounds changes in refrigerated pork based on random forests machine learning algorithm.

Data on changes in non-volatile components and metabolic pathways during pork storage were inadequately investigated. Herein, an untargeted metabolomics coupled with random forests machine learning algorithm was proposed to identify the potential marker compounds and their effects on non-volatile production during pork storage by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). A total of 873 differential metabolites were identified based on analysis of variance (ANOVA). Bioinformatics analysis shows that the key metabolic pathways for protein degradation and amino acid transport are amino acid metabolism and nucleotide metabolism. Finally, 40 potential marker compounds were screened using the random forest regression model, innovatively proposing the key role of pentose-related metabolism in pork spoilage. Multiple linear regression analysis revealed that d-xylose, xanthine, and pyruvaldehyde could be key marker compounds related to the freshness of refrigerated pork. Therefore, this study could provide new ideas for the identification of marker compounds in refrigerated pork.

Novel insights from protein degradation: Deciphering the dynamic evolution of biogenic amines as a quality indicator in pork during storage.

Biogenic amines (BAs) have drawn great attention as important markers for monitoring food quality. However, the BAs content in protein degradation profiles during pork storage was inadequately investigated. In this work, the Longissimus lumborum and Breast and flank of pork were collected, and their peptides contents, free amino acids (FAAs) contents, BAs contents, and several characteristic physicochemical indexes were monitored during storage at 4 °C. As a result, the differences of nutritional components in the Longissimus lumborum and Breast and flank could not affect the shelf life of refrigerated pork. There are 161 small peptides in the Longissimus lumborum of pork identified by LC-MS. As verified, arginine, glutamic acid, valine, and alanine could serve as four indicative amino acids during protein degradation in pork, and the arginine degradation pathway is more complex. Redundancy analysis confirmed that putrescine and cadaverine were significantly related to the precursor FAAs content, and their sum value could be used as a novel quality indicator instead of the biogenic amine index (BAI). Finally, the above prediction was also verified by the other species (beef, mutton and chicken) to improve the index system of meat quality evaluation in cold chain logistics.

Altered frontoparietal activity in acoustic startle priming tasks during reticulospinal tract facilitation: An fNIRS study.

Background: Because it is one of the important pathways for promoting motor recovery after cortical injury, the function of the reticulospinal tract (RST) has received increasing attention in recent years. However, the central regulatory mechanism of RST facilitation and reduction of apparent response time is not well understood. Objectives: To explore the potential role of RST facilitation in the acoustic startle priming (ASP) paradigm and observe the cortical changes induced by ASP reaching tasks. Methods: Twenty healthy participants were included in this study. The reaching tasks were performed with their left and right hands. Participants were instructed to get ready after the warning cue and complete the reach as soon as they heard the Go cue. Half of the testing trials were set as control trials with an 80-dB Go cue. The other half of the trials had the Go cue replaced with 114-dB white noise to evoke the StartleReact effect, inducing reticulospinal tract facilitation. The response of the bilateral sternocleidomastoid muscle (SCM) and the anterior deltoid was recorded via surface electromyography. Startle trials were labeled as exhibiting a positive or negative StartleReact effect, according to whether the SCM was activated early (30-130 ms after the Go cue) or late, respectively. Functional near-infrared spectroscopy was used to synchronously record the oxyhemoglobin and deoxyhemoglobin fluctuations in bilateral motor-related cortical regions. The ß values representing cortical responses were estimated via the statistical parametric mapping technique and included in the final analyses. Results: Separate analyses of data from movements of the left or right side revealed significant activation of the right dorsolateral prefrontal cortex during RST facilitation. Moreover, left frontopolar cortex activation was greater in positive startle trials than in control or negative startle trials during left-side movements. Furthermore, decreased activity of the ipsilateral primary motor cortex in positive startle trials during ASP reaching tasks was observed. Conclusion: The right dorsolateral prefrontal cortex and the frontoparietal network to which it belongs may be the regulatory center for the StartleReact effect and RST facilitation. In addition, the ascending reticular activating system may be involved. The decreased activity of the ipsilateral primary motor cortex suggests enhanced inhibition of the non-moving side during the ASP reaching task. These findings provide further insight into the SE and into RST facilitation.

Macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling.

Aseptic prosthesis loosening (APL) is one of the most prevalent complications associated with arthroplasty. The main cause is the periprosthetic osteolysis induced by wear particles. However, the specific mechanisms of crosstalk between immune cells and osteoclasts/osteoblasts during osteolysis are unclear. In this study, we report the role and mechanism of macrophage-derived exosomes in wear particle-induced osteolysis. The results of exosomes up-taken experiments revealed that osteoblast and mature osteoclasts capture macrophage-derived exosomes (M-Exo). Next-generation sequencing and RT-qPCR on M-Exo revealed that exosomal microRNA miR-3470b was downregulated in wear particle-induced osteolysis. The results of analysis on Luciferase reporter assays/fluorescence in situ hybridization (FISH)/immunofluorescence (IF)/immunohistochemistry (IHC) and co-culture experiments demonstrated that wear particles induced osteoclast differentiation by increasing the expression of NFatc1 via M-Exo miR-3470b targeting TAB3/ NF-κB signaling. We also illustrate that engineered exosomes enriching miR-3470b facilitated to suppressed the osteolysis; the microenvironment enriching with miR-3470b could suppress wear particle-induced osteolysis via inhibition of TAB3/ NF-κB in vivo. In summary, our findings indicate that macrophage-derived exosomes transfer to osteoclasts to induce osteolysis in wear particle-induced APL. Engineering exosomes enriching with miR-3470b might be a novel strategy for the targeting treatment of bone resorption-related diseases.

Tannic Acid Induces Intestinal Dysfunction and Intestinal Microbial Dysregulation in Brandt's Voles (Lasiopodomys brandtii).

Brandt's vole (Lasiopodomys brandtii) is a small herbivorous mammal that feeds on plants rich in secondary metabolites (PSMs), including tannins. However, plant defense mechanisms against herbivory by Brandt's voles are not clearly established. This study aimed to investigate the effects of dietary tannic acid (TA) on the growth performance, intestinal morphology, digestive enzyme activities, cecal fermentation, intestinal barrier function, and gut microbiota in Brandt's voles. The results showed that TA significantly hindered body weight gain, reduced daily food intake, changed the intestinal morphology, reduced digestive enzyme activity, and increased the serum zonulin levels (p < 0.05). The number of intestinal goblet and mast cells and the levels of serum cytokines and immunoglobulins (IgA, IgG, TNF-α, IL-6, and duodenal SlgA) were all reduced by TA (p < 0.05). Moreover, TA altered ß-diversity in the colonic microbial community (p < 0.05). In conclusion, the results indicate that TA could damage the intestinal function of Brandt's voles by altering their intestinal morphology, decreasing digestive ability and intestinal barrier function, and altering microbiota composition. Our study investigated the effects of natural PSMs on the intestinal function of wildlife and improved our general understanding of plant-herbivore interactions and the ecological role of PSMs.

Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors.

Background: To explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD. Methods: In this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace. Results: Globally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. "Rehabilitation", "Genetics & Heredity", "Nanoscience & Nanotechnology", "Biochemistry & Molecular biology", "Psychology", "Neurosciences", and "Environmental Sciences" were the hotspots and frontier disciplines of ASD risk factors. Conclusions: Disease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem.

Immediate and short-term effects of continuous theta burst transcranial magnetic stimulation over contralesional premotor area on post-stroke spasticity in patients with severe hemiplegia: Study protocol for a randomized controlled trial.

Background: Post-stroke spasticity is an important complication that greatly affects survivors' functional prognosis and daily activities. Increasing evidence points to aberrant contralesional neuromodulation compensation after brain injury as a possible culprit for increased spasticity in patients with severe stroke. Hyperactivity of the contralesional premotor area (cPMA) was supposed to be highly correlated with this progression. This study aims to demonstrate the immediate and short-term efficacy of continuous theta-burst stimulation (cTBS) targeting cPMA on upper limb spasticity in severe subacute stroke patients. Methods: This trial is a single-center, prospective, three-group randomized controlled trial. Forty-five eligible patients will be recruited and randomized into three groups: the sham-cTBS group (sham cTBS targeting contralesional PMA), the cTBS-cM1 group (cTBS targeting contralesional M1), and the cTBS-cPMA group (cTBS targeting contralesional PMA). All subjects will undergo comprehensive rehabilitation and the corresponding cTBS interventions once a day, five times a week for 4 weeks. Clinical scales, neurophysiological examinations, and neuroimaging will be used as evaluation tools in this study. As the primary outcome, clinical performance on muscle spasticity of elbow/wrist flexor/extensors and upper-limb motor function will be evaluated with the modified Ashworth scale and the Fugl-Meyer Assessment of Upper Extremity Scale, respectively. These scale scores will be collected at baseline, after 4 weeks of treatment, and at follow-up. The secondary outcomes were neurophysiological examinations and Neuroimaging. In neurophysiological examinations, motor evoked potentials, startle reflex, and H reflexes will be used to assess the excitability of the subject's motor cortex, reticulospinal pathway, and spinal motor neurons, respectively. Results of them will be recorded before and after the first cTBS treatment, at post-intervention (at 4 weeks), and at follow-up (at 8 weeks). Neuroimaging tests with diffusion tensor imaging for all participants will be evaluated at baseline and after the 4-week treatment. Discussion: Based on the latest research progress on post-stroke spasticity, we innovatively propose a new neuromodulation target for improving post-stroke spasticity via cTBS. We expected that cTBS targeting cPMA would have significant immediate and short-term effects on spasticity and related neural pathways. The effect of cTBS-cPMA may be better than that of cTBS via conventional cM1. The results of our study will provide robust support for the application of cTBS neuromodulation in post-stroke spasticity after a severe stroke. Clinical trial registration: This trial was registered with chictr.org.cn on June 13, 2022 (protocol version). http://www.chictr.org.cn/showproj.aspx?proj=171759.

Hyaluronan size alters chondrogenesis of mesenchymal stem cells cultured on tricalcium phosphate-collagen-hyaluronan scaffolds.

Hyaluronan (HA) provides a favorable environment for chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). A previous report from our group indicated that addition of HA increases the chondro-inductive capacity of scaffolds. Therefore, this study aimed to investigate whether the Mw of the HA could affect chondrogenesis of BMSCs seeded on TCP-COL-HA scaffolds. Human BMSCs (hBMSCs) and rabbit BMSCs (rBMSCs) were isolated and expanded. TCP-COL scaffolds and TCP-COL-HA scaffolds with two different HA Mws were assessed for their capacity to induce cartilage regeneration from hBMSCs in vitro and in vivo. The results showed that about 96.96% of hBMSCs expressed CD44. Moreover, Hyal-1 and chondrogenic marker genes expressions were increased in hMSCs seeded on TCP-COL-HA scaffolds, and blocking the HA-CD44 interaction with an anti-CD44 antibody reduced the expression levels of Hyal-1 and chondrogenic marker genes. Additionally, TCP-COL-HA scaffolds with 2000 kDa Mw showed greater induction of BMSC chondrogenesis induction compared with those with 80 kDa Mw. Similar results were observed in an ectopic implantation nude mouse model. In a rabbit osteochondral defect repair model, rBMSCs seeded on TCP-COL-HA scaffolds with 2000 kDa Mw showed greater cartilage regeneration than those seeded with 80 kDa Mw. In addition, hBMSC-seeded TCP-COL-HA scaffolds with 2000 kDa Mw showed a significantly higher mechanical strength than those with 80 kDa Mw. Collectively, these results indicate that the Mw of HA could affect chondrogenesis of BMSCs seeded on TCP-COL-HA scaffolds. The TCP-COL-HA scaffolds might be used as allogenic off the shelf products in cartilage tissue engineering in future.