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Abstract People readily change their behavior to comply with others. However, to which extent they will internalize the social influence remains elusive. In this preregistered electroencephalogram (EEG) study, we investigated how learning from one’s in-group or out-group members about facial attractiveness would change explicit attractiveness ratings and spontaneous neural representations of facial attractiveness. Specifically, we quantified the neural representational similarities of learned faces with prototypical attractive faces during a face perception task without overt social influence and intentional evaluation. We found that participants changed their explicit attractiveness ratings to both in-group and out-group influences. Moreover, social conformity updated spontaneous neural representation of facial attractiveness, an effect particularly evident when participants learned from their in-group members and among those who perceived tighter social norms. These findings offer insights into how group affiliations and individual differences in perceived social norms modulate the internalization of social influence.

Abstract Background Skeletal muscles are vital for daily function, yet assessing their injuries remain challenging. We aimed to elucidate the effectiveness of 68Ga-FAPI-04 in evaluating skeletal muscle remodeling. Results C2C12 cells were subjected to graded H2O2 stimulation in vitro, revealing an initial rise and subsequent decline in fibroblast activation protein (FAP) expression as H2O2 concentration increased. In vivo, a murine triceps surae injury model was created using various solutions to simulate normal repair, mild repair failure, and severe repair failure. Assessments were conducted on days 1, 3, 7, and 14 using PET, MRI, and ultrasound. With 68Ga-FAPI-04, the normal and mild repair failure groups showed significantly higher SUVmax and T/B ratios on day 1 compared to the severe repair failure group. These values gradually decreased in the normal repair group, becoming negligible after day 7. MRI results for the normal repair group showed low to moderate signal intensity by day 7. A clinical study retrospectively evaluated post-hip arthroplasty patient images at intervals of 1 month, 2–3 months, 5–6 months, and over 7 months. In these patients, 18F-FDG SUVmax and volume remained relatively stable over time, while 68Ga-FAPI-04 SUVmax initially increased, then decreased, with a consistent reduction in volume. Conclusion In skeletal muscle injuries, FAP demonstrates a distinctive mechanism of action, and 68Ga-FAPI-04, in comparison to other tests, more precisely captures alterations in lesion site uptake intensity and volume. Trial registration Trial registration: ChiCTR2000041204. Registered 22 December 2020, https://www.chictr.org.cn/showproj.html?proj=66211

Abstract People often change their evaluations upon learning about their peers’ evaluations, i.e., social learning. Given sleep’s vital role in consolidating daytime experiences, sleep may facilitate social learning, thereby further changing people’s evaluations. Combining a social learning task and the sleep-based targeted memory reactivation technique, we asked whether social learning-induced evaluation updating can be modulated during sleep. After participants had indicated their initial evaluation of snacks, they learned about their peers’ evaluations while hearing the snacks’ spoken names. During the post-learning non-rapid-eye-movement sleep, we re-played half of the snack names (i.e., cued snack) to reactivate the associated peers’ evaluations. Upon waking up, we found that the social learning-induced evaluation updating further enlarged for both cued and uncued snacks. Examining sleep electroencephalogram (EEG) activity revealed that cue-elicited delta-theta EEG power and the overnight N2 sleep spindle density predicted post-sleep evaluation updating for cued but not for uncued snacks. These findings underscore the role of sleep-mediated memory reactivation and the associated neural activity in supporting social learning-induced evaluation updating.

Despite the potential link between stress-induced reward dysfunctions and the development of mental problems, limited human research has investigated the specific impacts of chronic stress on the dynamics of reward processing. Here we aimed to investigate the relationship between chronic academic stress and the dynamics of reward processing (i.e., reward anticipation and reward consumption) using event-related potential (ERP) technology. Ninety healthy undergraduates who were preparing for the National Postgraduate Entrance Examination (NPEE) participated in the study and completed a two-door reward task, their chronic stress levels were assessed via the Perceived Stress Scale (PSS). The results showed that a lower magnitude of reward elicited more negative amplitudes of cue-N2 during the anticipatory phase, and reward omission elicited more negative amplitudes of FRN compared to reward delivery especially in high reward conditions during the consummatory phase. More importantly, the PSS score exhibited a U-shaped relationship with cue-N2 amplitudes regardless of reward magnitude during the anticipatory phase; and FRN amplitudes toward reward omission in high reward condition during the consummatory phase. These findings suggest that individuals exposed to either low or high levels of chronic stress, as opposed to moderate stress levels, exhibited a heightened reward anticipation, and an augmented violation of expectations or affective response when faced with relatively more negative outcomes.

Abstract Collagen possesses high biocompatibility with all tissue and cell types in the body, enabling the creation of multifunctional composite materials for medical applications. In biomedical engineering, naturally-sourced collagen is often combined with diverse organic and inorganic bioactive components to eliminate defects and disorders in fields including orthopedics, dermatology, and more. At the same time, medical-related infection issues and the precise treatment needs of patients require collagen composite biomaterials to have antibacterial properties and customized structures. This paper reviews the antibacterial functionalization of collagen composite biomaterials in recent years, including the combination with inorganic or organic antibacterial agents, which is beneficial for preventing and controlling biological contamination in medical applications. Then, the existing problems and future development directions for the architecturalization of collagen composite materials with 3D printing were discussed, providing guidance for personalized customization of multifunctional materials to meet the specific needs of patients in the future. Graphical Abstract

Background and purpose The associations of fundamental motor skills (FMS), health-related physical fitness (e.g., cardiorespiratory fitness, CRF), and moderate-vigorous physical activity (MVPA) have been demonstrated in Western children, but these associations have not yet been validated in a sample of Chinese children. The aims of this study, therefore, were to examine the association between FMS subdomains and MVPA in a sample of Chinese children and to evaluate whether this association is mediated by CRF. Methods A cross-sectional study consisting of 311 children aged 8–12 years (49.2% girls; mean age = 9.9 years) from Shanghai was conducted. FMS, CRF and MVPA were assessed using the Test of Gross Motor Development-3rd Edition, Progressive Aerobic Cardiovascular Endurance Run and ActiGraph GT3X accelerometers. Preacher & Hayes’s bootstrap method was used to test the mediating effects of CRF on the association between FMS and MVPA. Results CRF fully mediated the association between total FMS and MVPA in girls (indirect effects, b = 0.21, 95% CI [0.07–0.37]), while the mediation was only partial in boys (indirect effects, b = 0.12, 95% CI [0.01–0.26]). CRF fully mediated the association between locomotor skills and MVPA in girls (indirect effects, b = 0.27, 95% CI [0.09– 0.51]), whereas CRF partially mediated the association between object control skills and MVPA in boys (indirect effects, b = 0.15, 95% CI [0.18–0.35]). Conclusion In order to better design and implement sex-specific interventions aiming to increase MVPA, it is essential to consider FMS subdomains and CRF alongside the sex differences in the association between them.

Abstract Background Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. Results Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. Conclusions Two novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

Abstract Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the mitochondrial unfolded protein response (UPRmt) in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, which may provide a new insight into the mechanisms of antitumor drug functions.

Treatment of articular cartilage remains a great challenge due to its limited self-repair capability. In tissue engineering, a scaffold with both mechanical strength and regenerative capacity has been highly desired. This study developed a double-network scaffold based on natural biomaterials of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) using three-dimensional (3D) printing technology. Structural and mechanical characteristics of the scaffold was first investigated. To enhance its ability of recruiting endogenous bone marrow mesenchymal stem cells (BMSCs), the scaffold was conjugated with a proven BMSC-specific-affinity peptide E7, and its biocompatibility and capacity of cell recruitment were assessed in vitro. Animal experiments were conducted to evaluate cartilage regeneration after transplantation of the described scaffolds. The SF/HA scaffolds exhibited a hierarchical macro-microporous structure with ideal mechanical properties, and offered a 3D spatial microenvironment for cell migration and proliferation. In vitro experiments demonstrated excellent biocompatibility of the scaffolds to support BMSCs proliferation, differentiation, and extracellular matrix production. In vivo, superior capacity of cartilage regeneration was displayed by the SF/MAHA + E7 scaffold as compared with microfracture and unconjugated SF/MAHA scaffold based on macroscopic, histologic and imaging evaluation. In conclusion, this structurally and functionally optimized SF/MAHA + E7 scaffold may provide a promising approach to repair articular cartilage lesions in situ.

Abstract Real-time imaging of transient structure of the electronic excited state is fundamentally critical to understand and control ultrafast molecular dynamics. The ejection of electrons from the inner-shell and valence level can lead to the population of different excited states, which trigger manifold ultrafast relaxation processes, however, the accurate imaging of such electronic state-dependent structural evolutions is still lacking. Here, by developing the laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, snapshots of the vibrational wave-packets of the excited (A) and ground states (X) of D2O+ are captured simultaneously with sub-10 picometre and few-femtosecond precision. We visualise that θ DOD and ROD are significantly increased by around 50∘ and 10 pm, respectively, within approximately 8 fs after initial ionisation for the A state, and the ROD further extends 9 pm within 2 fs along the ground state of the dication in the present condition. Moreover, the ROD can stretch more than 50 pm within 5 fs along autoionisation state of dication. The accuracies of the results are limited by the simulations. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards to make a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.

Abstract Background Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored. Main body Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed. Conclusion OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

Degenerative tendon injuries are common clinical problems associated with overuse or aging, and understanding the mechanisms of tendon injury and regeneration can contribute to the study of tendon healing and repair. As a transcription factor, Mohawk (Mkx) is responsible for tendons development, yet, the roles of which in tendon damage remain mostly elusive. In this study, using Mkx overexpressed mice on long treadmill as an in vivo model and MkxOE Achilles tenocytes stimulated by equiaxial stretch as an in vitro model, we anaylsed the effects of Mkx overexpression on the tendon. Mkx and tendon tension strength were decreased after the expose to excessive mechanical forces, and Mkx overexpression protected the tendon from damage. Moreover, we revealed that the Wnt/β-catenin activation, inflammation, and Runx2 expression were increased at the injured Achilles tendon, upregulated Mkx significantly reversed the increased Wnt/β-catenin pathway, Tnf-α, Il-1β, and Il-6 levels, and reduced tendon cell damage. However, Wnt3a, IWR and BIO had not significantly affected the Mkx expression in achilles tenocytes. In conclusion, Mkx is involved in tendon healing and protects the tendon from damage through suppressing Wnt/β-catenin pathway, suggesting Mkx/Wnt/β-catenin pathway may be potential therapeutic targets for tendon damage.

Coupled nuclear and electronic dynamics within a molecule are key to understanding a broad range of fundamental physical and chemical processes. Although probing the coupled vibrational and electronic dynamics was demonstrated, it has so far been challenging to observe the coupling interactions between the rotational and electronic degrees of freedom. Here, we report the first observation of Coriolis coupling, a coupling interaction between nuclear rotational angular momentum and electronic axial angular momentum, during laser-induced molecular fragmentation by tracing the electronic structure of a dissociating [Formula: see text] molecule. We observe that the electron density changes its shape from that of a molecular σ orbital to a nearly isotropic shape as the internuclear distance goes up to ∼20 Å, which results from the transition between nearly degenerate electronic states associated with different rotational angular momenta. Our experiment demonstrates that the breaking of a chemical bond does not occur suddenly during molecular dissociation. Instead, it lasts for a long time of several hundred femtoseconds due to the Coriolis coupling interaction. Our experiment can be extended to complicated molecules, holding the potential of revealing yet unobserved electron–nuclear coupling interactions during ultrafast processes.

Abstract The study of molecular valence electron dynamics and their coupling with nuclear motion is one of the frontiers of ultrafast physics and ultrafast chemistry. With time-resolved strong-field ion momentum spectroscopy, we study electron valence and nucleus wavepacket evolution on a femtosecond timescale. Two orientation-dependent bond-breaks of N2O molecules from the same electronic state are studied, and the influence of orbital hybridization and polarization effect during molecular breaking is analyzed based on the measured time-resolved asymmetric Pzsum distributions, allowing a visual representation of electron localization during the dissociation of molecules into ions and atoms. Comparison of experimental and theoretical results on orientation-dependent dissociation dynamics allows us to understand how nuclear motions evolve during fragmentation and to control ultrafast molecular reactions.

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Here, we employed the targeted memory reactivation (TMR) paradigm to unobtrusively replaying auditory memory cues during human participants' slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found temporally segregated and functionally distinct item-specific neural representations: the early post-cue EEG activity (within 0 to 2,000 ms) contained comparable item-specific representations for memory cues and control cues, signifying effective processing of auditory cues. Critically, the later EEG activity (2,500 to 2,960 ms) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, indicating memory reprocessing. Moreover, these later item-specific neural representations were supported by concurrently increased spindles, particularly for items that had not been tested prior to sleep. These findings elucidated how external memory cues triggered item-specific neural representations during SWS and how such representations were linked to successful long-term memory. These results will benefit future research aiming to perturb specific memory episodes during sleep.

Abstract In clinical practice, repairing osteochondral defects presents a challenge due to the varying biological properties of articular cartilages and subchondral bones. Thus, elucidating how spatial microenvironment‐specific biomimetic scaffolds can be used to simultaneously regenerate osteochondral tissue is an important research topic. Herein, a novel bioinspired double‐network hydrogel scaffold produced via 3D printing with tissue‐specific decellularized extracellular matrix (dECM) and human adipose mesenchymal stem cell (MSC)‐derived exosomes is described. The bionic hydrogel scaffolds promote rat bone marrow MSC attachment, spread, migration, proliferation, and chondrogenic and osteogenic differentiation in vitro, as determined based on the sustained release of bioactive exosomes. Furthermore, the 3D‐printed microenvironment‐specific heterogeneous bilayer scaffolds efficiently accelerate the simultaneous regeneration of cartilage and subchondral bone tissues in a rat preclinical model. In conclusion, 3D dECM‐based microenvironment‐specific biomimetics encapsulated with bioactive exosomes can serve as a novel cell‐free recipe for stem cell therapy when treating injured or degenerative joints. This strategy provides a promising platform for complex zonal tissue regeneration whilst holding attractive clinical translation potential.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by pervasive deficits in social interaction, communication impairments, and the presence of restricted and repetitive behaviors. This complex disorder is a significant public health concern due to its escalating incidence and detrimental impact on quality of life. Currently, extensive investigations are underway to identify prospective susceptibility or predictive biomarkers, employing a physiological biomarker-based framework. However, knowledge regarding physiological biomarkers in relation to Autism is sparse. We performed a scoping review to explore putative changes in physiological activities associated with behaviors in individuals with Autism. We identified studies published between January 2000 and June 2023 from online databases, and searched keywords included electroencephalography (EEG), magnetoencephalography (MEG), electrodermal activity markers (EDA), eye-tracking markers. We specifically detected social-related symptoms such as impaired social communication in ASD patients. Our results indicated that the EEG/ERP N170 signal has undergone the most rigorous testing as a potential biomarker, showing promise in identifying subgroups within ASD and displaying potential as an indicator of treatment response. By gathering current data from various physiological biomarkers, we can obtain a comprehensive understanding of the physiological profiles of individuals with ASD, offering potential for subgrouping and targeted intervention strategies.

Purpose Urgent start peritoneal dialysis (USPD) is an effective therapeutic method for end-stage renal disease (ESRD). However, whether it is safe to initiate peritoneal dialysis (PD) within 24 h unclear. We examined the short-term outcomes of a break-in period (BI) of 24 h for patients undergoing USPD.Methods This real-world, multicenter, retrospective cohort study evaluated USPD patients from five centers from January 2013 to August 2020. Patients were divided into BI ≤ 24 h or BI > 24 h groups. The Primary outcomes included incidence of mechanical and infectious complications. The secondary outcome was technique failure. Moreover, we presented a subgroup analysis for patients who did not receive temporary hemodialysis (HD).Results A total of 871 USPD patients were included: 470 in the BI ≤ 24 h and 401 in the BI > 24 h groups. Mechanical and infectious complications did not differ between the two groups across the follow-up timepoints (2 weeks, 1 month, 3 months, and 6 months) (p > 0.05). Multiple logistic regression analysis revealed that BI ≤ 24 h was not an independent risk factor for mechanical complications, catheter migration, or infectious complications (p > 0.05). A BI ≤ 24 h was not an independent significant risk factor for technique failure by multivariate Cox regression analysis (p > 0.05). The subgroup analysis of patients who did not receive temporary HD returned the same results.Conclusion Initiating PD within 24 h of catheter insertion was not associated with increased mechanical complications, infectious complications, or technique failures.

This study demonstrates a role of cholesterol metabolism-related gene, Lrp3, in cartilage degeneration and osteoarthritis pathogenesis. LRP3 positively regulates cartilage extracellular matrix metabolism by targeting syndecan-4 via Ras signalling, implicating the cholesterol-LRP3-SDC4 axis in osteoarthritic cartilage degeneration.

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5′ untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8+ T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.

In the present study, 24 rabbits were firstly used to evaluate the apoptosis index and matrix degeneration after untreated adult meniscal tears. Vertical tears (0.25 cm in length) were prepared in the avascular zone of the anterior horn. Specimens were harvested at 1, 3, 6, 12 weeks postoperatively. The apoptosis index around tear sites stayed at a high level throughout the whole follow-up period. The depletion of glycosaminoglycans (GAG) and aggrecan at the tear site was observed, while the deposition of COL I and COL II was not affected, even at the last follow-up of 12 weeks after operation. The expression of SOX9 decreased significantly; no cellularity was observed at the wound interface at all timepoints. Secondly, another 20 rabbits were included to evaluate the effects of anti-apoptosis therapy on rescuing meniscal cells and enhancing meniscus repair. Longitudinal vertical tears (0.5 cm in length) were made in the meniscal avascular body. Tears were repaired by the inside-out suture technique, or repaired with sutures in addition to fibrin gel and blank silica nanoparticles, or silica nanoparticles encapsulating apoptosis inhibitors (z-vad-fmk). Samples were harvested at 12 months postoperatively. We found the locally administered z-vad-fmk agent at the wound interface significantly alleviated meniscal cell apoptosis and matrix degradation, and enhanced meniscal repair in the avascular zone at 12 months after operation. Thus, local administration of caspase inhibitors (z-vad-fmk) is a promising therapeutic strategy for alleviating meniscal cell loss and enhancing meniscal repair after adult meniscal tears in the avascular zone.

Abstract Pancreatic ductal adenocarcinomas (PDAC) is one of the stiffest malignancies with strong solid stresses. Increasing stiffness could alter cellular behavior and trigger internal signaling pathways and is strongly associated with a poor prognosis in PDAC. So far, there has been no report on of an experimental model that can rapidly construct and stably maintain a stiffness gradient dimension in both vitro and in vivo. In this study, a gelatin methacryloyl (GelMA)‐based hydrogel was designed for in vitro and in vivo PDAC experiments. The GelMA‐based hydrogel has porous, adjustable mechanical properties and excellent in vitro and in vivo biocompatibility. The GelMA‐based in vitro 3D culture method can effectively form a gradient and stable extracellular matrix stiffness, affecting cell morphology, cytoskeleton remodeling, and malignant biological behaviors such as proliferation and metastasis. This model is suitable for in vivo studies with long‐term maintenance of matrix stiffness and no significant toxicity. High matrix stiffness can significantly promote PDAC progression and tumor immunosuppression. This novel adaptive extracellular matrix rigidity tumor model is an excellent candidate for further development as an in vitro and in vivo biomechanical study model of PDAC or other tumors with strong solid stresses.

Background: Vogt-Koyanagi-Harada (VKH) disease is a common and easily blinded uveitis entity, with choroid being the main involved site. Classification of VKH disease and its different stages is crucial because they differ in clinical manifestations and therapeutic interventions. Wide-field swept-source optical coherence tomography angiography (WSS-OCTA) provides the advantages of non-invasiveness, large-field-of-view, high resolution, and ease of measuring and calculating choroid, offering the potential feasibility of simplified VKH classification assessment based on WSS-OCTA.Methods: 15 healthy controls (HC), 13 acute-phase and 17 convalescent-phase VKH patients were included, undertaken WSS-OCTA examination with a scanning field of 15 × 9 mm2. 20 WSS-OCTA parameters were then extracted from WSS-OCTA images. To classify HC and VKH patients in acute and convalescent phases, two 2-class VKH datasets (HC and VKH) and two 3-class VKH datasets (HC, acute-phase VKH, and convalescent-phase VKH) were established by the WSS-OCTA parameters alone or in combination with best-corrected visual acuity (logMAR BCVA) and intraocular pressure (IOP), respectively. A new feature selection and classification method that combines an equilibrium optimizer and a support vector machine (called SVM-EO) was adopted to select classification-sensitive parameters among the massive datasets and to achieve outstanding classification performance. The interpretability of the VKH classification models was demonstrated based on SHapley Additive exPlanations (SHAP).Results: Based on pure WSS-OCTA parameters, we achieved classification accuracies of 91.61% ± 12.17% and 86.69% ± 8.30% for 2- and 3-class VKH classification tasks. By combining the WSS-OCTA parameters and logMAR BCVA, we achieved better classification performance of 98.82% ± 2.63% and 96.16% ± 5.88%, respectively. Through SHAP analysis, we found that logMAR BCVA and vascular perfusion density (VPD) calculated from the whole field of view region in the choriocapillaris (whole FOV CC-VPD) were the most important features for VKH classification in our models.Conclusion: We achieved excellent VKH classification performance based on a non-invasive WSS-OCTA examination, which provides the possibility for future clinical VKH classification with high sensitivity and specificity.

In our last study [J. Phys. B At. Mol. Opt. Phys. 54, 125,102 (2021).], we reported the ab initio calculation of the full-dimensional potential energy surfaces of water molecule including 9 A’ and 9 A” states in Cs symmetry. In this study, we performed additional non-adiabatic semi-classical studies based on the potential energy surfaces. Our simulation successfully repeated the near picosecond lifetime of the F∼1A′ state measured by time resolved photo-electron spectra experiment [Chinese J. Chem. Phys. 32, 53 (2019)]. We also determined the dissociation branching ratio including H + OH(X, A), H + H + O and H2+O channels. In addition, the reaction path corresponding to H2+O (1S) channel is clearly marked out, which is found in recent free-electron laser experiment [Nat. Commun. 12, 6,303 (2021)].

Abstract Studies have shown that Tai Chi and conventional exercise can modify the brain through distinct mechanisms, resulting in different brain adaptations. Therefore, it is conceivable to speculate that these two exercise modalities may have different effects on improving cognitive function. This study was a parallel group, assessor-blinded, pilot randomized controlled trial comparing the effects of Tai Chi and conventional exercise on improving cognitive function in older persons with mild cognitive impairment (MCI). A total of 34 adults aged ≥ 50 years with MCI were randomized (1:1:1) to the Tai Chi group (TC, n = 10, 3 sessions of 60-min Yang-style Tai Chi training per week for 24 weeks), conventional exercise group (EX: n = 12, 3 sessions of 60-min fitness training per week for 24 weeks), or control group (CON: n = 12, no intervention). Global cognitive function assessed by the Hong Kong version of the Montreal Cognitive Assessment (MoCA-HK) and performance in various cognitive domains were examined at baseline, and 12 and 24 weeks of the intervention. Both exercise groups showed improved global cognitive function as measured by MoCA-HK compared with the control group after 12 and 24 weeks of the intervention, (all P

Purpose: This study aimed to describe the national prevalence of Chinese children and adolescents who met the World Health Organization muscle-strengthening exercise (MSE) recommendations and identify correlates of meeting the MSE recommendations. Methods: Cross-sectional data from the 2019 Physical Activity and Fitness in China—The Youth Study, a nationally representative sample of Chinese children and adolescents (n = 80,413; mean age = 13.7 years; 53.9% girls) and their parents, were analyzed. Children and adolescents who reported engaging ≥3 days (up to 7 days) of MSE per week were classified as meeting the MSE recommendations. MSE, demographics, lifestyle behaviors (sport participation, moderate-to-vigorous physical activity, screen time, and sleep duration), exercise intention, peer and parental support, and parental MSE participation were assessed through self-reports. Logistic regression models were used to determine the correlates of meeting the MSE recommendations. The analyses were completed in 2020. Results: Overall, 39.3% of children and adolescents met the MSE recommendations. Girls, 10th–12th graders, minorities, those from lower income households and those from families with lower parental education were less likely to meet the MSE recommendations. Children and adolescents who were proficient in ≥2 sports were more likely to meet the MSE recommendations (adjusted odds ratio (aOR) = 1.44, 95% confidence interval (95%CI): 1.26–1.65), as were those with more moderate-to-vigorous physical activity (aOR = 1.57, 95%CI: 1.53–1.61). Additionally, children and adolescents with high exercise intention (aOR = 1.60, 95%CI: 1.51–1.69), those whose parents met the adult MSE recommendations (aOR = 1.46, 95%CI: 1.40–1.52), and those who received high peer (aOR = 1.27, 95%CI: 1.20–1.34) and parental support (aOR = 1.07, 95%CI: 1.04–1.12) were more likely to meet the MSE recommendations. Conclusion: Less than two-fifths of Chinese children and adolescents met the World Health Organization MSE recommendations. The correlates identified in our study can help inform the development of school and community based strategies and policies to enhance participation in MSE and improve muscular fitness of all Chinese children and adolescents.

Background: Synovium has been confirmed to be the primary contributor to meniscal repair. Particulated Juvenile Allograft Cartilage (PJAC) has demonstrated promising clinical effect on repairing cartilage. The synergistic effect of synovium and PJAC transplant on meniscal fibrocartilaginous repair is unclear. We hypothesize that the transplantation of synovium and PJAC synergistically facilitates meniscal regeneration and the donor cells within graft tissues still survive in the regenerated tissue at the last follow up (16 weeks postoperatively). Methods: The study included 24 mature female rabbits, which were randomly divided into experimental and control groups. A cylindrical full-thickness defect measuring 2.0 ​mm was prepared in the avascular portion of the anterior horn of medial meniscus in both knees. The synovium and PJAC transplant were harvested from juvenile male rabbits (2 months after birth). The experimental group received synovium and PJAC transplant encapsulated with fibrin gel. The control groups received synovium transplant encapsulated with fibrin gel, pure fibrin gel and nothing. The macroscopic, imageological and histological evaluations of repaired tissue were performed at 8 weeks and 16 weeks postoperatively. The in situ hybridization (ISH) of male-specific sex-determining region Y-linked (SRY) gene was performed to detect the transplanted cells. Results: The regenerated tissue in experimental group showed superior structural integrity, superficial smoothness, and marginal integration compared to control groups at 8 weeks or 16 weeks postoperatively. More meniscus-like fibrochondrocytes filled the repaired tissue in the experimental group, and the matrix surrounding these cell clusters demonstrated strongly positive safranin O and type 2 collagen immunohistochemistry staining. By SRY gene ISH, the positive SRY signal of experimental group could be detected at 8 weeks (75.72%, median) and 16 weeks (48.69%, median). The expression of SOX9 in experimental group was the most robust, with median positive rates of 65.52% at 8 weeks and 67.55% at 16 weeks. Conclusion: The transplantation of synovium and PJAC synergistically facilitates meniscal regeneration. The donor cells survive for at least 16 weeks in the recipient. The translational potential of this article: This study highlighted the positive effect of PJAC and synovium transplant on meniscal repair. We also clarified the potential repair mechanisms reflected by the survival of donor cells and upregulated expression of meniscal fibrochondrocytes related genes. Thus, based on our study, further clinical experiments are needed to investigate synovium and PJAC transplant as a possible treatment to meniscal defects.

Heart failure with preserved ejection fraction (HFpEF) is defined as HF with left ventricular ejection fraction (LVEF) not less than 50%. HFpEF accounts for more than 50% of all HF patients, and its prevalence is increasing year to year with the aging population, with its prognosis worsening. The clinical assessment of cardiac function and prognosis in patients with HFpEF remains challenging due to the normal range of LVEF and the nonspecific symptoms and signs. In recent years, new echocardiographic techniques have been continuously developed, particularly speckle-tracking echocardiography (STE), which provides a sensitive and accurate method for the comprehensive assessment of cardiac function and prognosis in patients with HFpEF. Therefore, this article reviewed the clinical utility of STE in patients with HFpEF.

Although advances in protein assembly preparation have provided a new platform for drug delivery during tissue engineering, achieving long-term controlled exosome delivery remains a significant challenge. Diffusion-dominated exosome release using protein hydrogels results in burst release of exosomes. Here, a fibroin-based cryo-sponge was developed to provide controlled exosome release. Fibroin chains can self-assemble into silk I structures under ice-cold conditions when annealed above the glass transition temperature. Exosome release is enzyme-responsive, with rates primarily determined by enzymatic degradation of the scaffolds. In vivo experiments have demonstrated that exosomes remain in undigested sponge material for two months, superior to their retention in fibrin glue, a commonly used biomaterial in clinical practice. Fibroin cryo-sponges were implanted subcutaneously in nude mice. The exosome-containing sponge group exhibited better neovascularization and tissue ingrowth effects, demonstrating the efficacy of this exosome-encapsulating strategy by realizing sustained release and maintaining exosome bioactivity. These silk fibroin cryo-sponges containing exosomes provide a new platform for future studies of exosome therapy.

Background/ObjectivePhysical activity (PA) has been suggested to reduce screen time. This study aimed to explore the associations of physical education (PE), muscle-strengthening exercise (MSE), and sport participation with screen time.MethodsA multi-cluster sampling design was used to select 13,677 school-attending adolescents that participated in the Youth Risk Behavior Surveillance 2019 survey. Adolescents self-reported their frequency of PE attendance, participations in MSE, sport participation and hours for screen time. Additionally, participants provided demographic information including sex, age, race, grade, and weight status.ResultsCollectively, there were beneficial associations between participating in MSE for 4 (OR = 1.31, CI: 1.02–1.68), 5 (OR = 1.65, CI: 1.31–2.08), 6 (OR = 2.23, CI: 1.47–3.36), 7 (OR = 1.62, CI: 1.30–2.01) days and video or computer game hours. Similarly, beneficial associations between participating in 1 team sport (OR = 1.23, CI: 1.06–1.42), 2 team sports (OR = 1.61, CI: 1.33–1.95), 3 or more team sports (OR = 1.45, CI: 1.16–1.83) and video or computer game hours were observed. Participating in 1 team sport (OR = 1.27, CI: 1.08–1.48), 2 teams sport (OR = 1.41, CI: 1.09–1.82), 3 or more team sport (OR = 1.40, CI: 1.03–1.90) also increased the odds for meeting guidelines for television viewing hours. Only 2 days of PE attendance (OR = 1.44, CI: 1.14–1.81) was significantly associated with video or computer game hours.ConclusionThe promotion of sports participation appears to be an important component for reducing excess screen time in adolescents. Further, MSE may have beneficial effects on reducing time spent on the computer and playing video games.

Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.

Live-attenuated rotavirus vaccine has shown low protection in underdeveloped or developing countries. However, the inactivated rotavirus vaccine may have the potential to overcome some of these challenges. In the present study, the immunogenicity and protective efficacy of a bivalent inactivated rotavirus vaccine by parenteral administration were elevated in a neonatal rhesus monkey model. A bivalent inactivated rotavirus vaccine containing G1P[8] (ZTR-68 strain) and G9P[8] (ZTR-18 strain) was administered to pregnant rhesus monkeys twice at an interval of 14 days. Neutralizing antibodies against RV strains ZTR-68, ZTR-18, SA11, WA, UK, and Gottfried emerged in pregnant rhesus monkeys and were transplacentally transmitted to the offspring. In the vaccine group, clinical symptoms of diarrhea, viral load in the gut tissue and histopathological changes were significantly reduced in the neonatal rhesus monkeys following oral challenge with the SA11 strain.

Abstract Rosette‐type submerged macrophytes are widely distributed across a range of water depths in shallow lakes and play a key role in maintaining ecosystem structures and functions. However, little is known about the rapid adaptive responses of such macrophytes to variations in water depth, especially at the juvenile stage. Here, we conducted a short‐term in situ mesocosm experiment, in which the juveniles of Vallisneria natans were exposed to a water depth gradient ranging from 20 to 360 cm. Twenty‐two leaf‐related traits were examined after 4 weeks of growth in a shallow lake. Most (18) traits of V. natans generally showed high plasticity in relation to water depth. Specifically, juveniles allocated more biomass to leaves and had higher specific leaf area, leaf length‐to‐width ratio, chlorophyll content, and carotenoids content in deep waters, displaying trait syndrome associated with high resource acquisition. In contrast, V. natans juveniles in shallow waters had higher leaf dry matter content, leaf soluble carbohydrate content, carotenoids per unit chlorophyll, and peroxidase activity, pertaining to resource conservation. Notably, underwater light intensity was found to be the key factor explaining the trait plasticity along the water depth gradient, and 1.30 mol photons m−2 d−1 (at 270 cm) could be the optimal irradiance level based on the total biomass of V. natans juveniles. The present study highlights the significance of leaf trait plasticity for rosette‐type macrophytes in response to variations in water depth and sheds new light on the differences between trade‐offs in deep‐ and shallow‐water areas.

Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) membrane. The ADM membranes were harvested from Sprague-Dawley (SD) rats through standard decellularization procedures. The characterization of the scaffolds was measured, including the morphology and physical properties of the ADM membrane. The in vitro experiments included the cell distribution, chondrogenic matrix quantification, and viability evaluation of the scaffolds. Adult male New Zealand white rabbits were used for the in vivo evaluation. Isolated microfracture was performed in the control (MF group) in the left knee and the tested ADM group was included as an experimental group when an ADM scaffold was implanted through matching with the defect after microfracture in the right knee. At 6, 12, and 24 weeks post-surgery, the rabbits were sacrificed for further research. The ADM could adsorb water and had excellent porosity. The bone marrow stem cells (BMSCs) grew well when seeded on the ADM scaffold, demonstrating a characteristic spindle-shaped morphology. The ADM group exhibited an excellent proliferative capacity as well as the cartilaginous matrix and collagen production of the BMSCs. In the rabbit model, the ADM group showed earlier filling, more hyaline-like neo-tissue formation, and better interfacial integration between the defects and normal cartilage compared with the microfracture (MF) group at 6, 12, and 24 weeks post-surgery. In addition, neither intra-articular inflammation nor a rejection reaction was observed after the implantation of the ADM scaffold. This study provides a promising biomaterial-based strategy for cartilage repair and is worth further investigation in large animal models.

Despite the well-established treatment effectiveness of exercise, cognitive behavioral therapy for insomnia (CBT-I), and pharmacotherapy on improving sleep, there have been no studies to compare their long-term effectiveness, which is of clinical importance for sustainable management of chronic insomnia. This study compared the long-term effectiveness of these three interventions on improving sleep in adults with chronic insomnia. MEDLINE, PsycINFO, Embase, and SPORTDiscus were searched for eligible reports. Trials that investigated the long-term effectiveness of these three interventions on improving sleep were included. The post-intervention follow-up of the trial had to be ≥6 months to be eligible. The primary outcome was the long-term effectiveness of the three interventions on improving sleep. Treatment effectiveness was the secondary outcome. A random-effects network meta-analysis was carried out using a frequentist approach. Thirteen trials were included in the study. After an average post-intervention follow-up period of 10.3 months, both exercise (SMD, −0.29; 95% CI, −0.57 to −0.01) and CBT-I (−0.48; −0.68 to −0.28) showed superior long-term effectiveness on improving sleep compared with control. Temazepam was the only included pharmacotherapy, which demonstrated superior treatment effectiveness (−0.80; −1.25 to −0.36) but not long-term effectiveness (0.19; −0.32 to 0.69) compared with control. The findings support the use of both exercise and CBT-I for long-term management of chronic insomnia, while temazepam may be used for short-term treatment.

Therapeutic strategies based on utilizing endogenous BMSCs have been developed for the regeneration of bone, cartilage, and ligaments. We previously found that E7 peptide (EPLQLKM) could enhance BMSC homing in bio-scaffolds and, therefore, promote cartilage regeneration. However, the profile and mechanisms of E7 peptide in cartilage regeneration remain elusive. In this study, we examined the effect of E7 peptide on the BMSC phenotype, including adhesion, viability and chondrogenic differentiation, and its underlying mechanism. The konjac glucomannan microsphere (KGM), a carrier material that is free of BMSC adhesion ability, was used as the solid base of E7 peptide to better explore the independent role of E7 peptide in BMSC behavior. The results showed that E7 peptide could support BMSC adhesion and viability in a comparable manner to RGD and promote superior chondrogenic differentiation to RGD. We examined differentially expressed genes of BMSCs induced by E7 compared to RGD. Subsequently, a real-time PCR validated the significantly upregulated expression of lncRNA H19, and the knockdown of lncRNA H19 or miR675, a downstream functional unit of H19, could significantly obscure the chondrogenic differentiation induced by E7. In conclusion, this study confirmed the independent role of E7 in the adhesion and viability of BMSCs and revealed the pro-chondrogenic effect of E7 on BMSCs via the H19/miR675 axis. These results could help establish new therapeutic strategies based on employing endogenous BMSCs for cartilage tissue regeneration.

Abstract Background The primary aim of this systematic review and meta-analysis was to compare postoperative pain, analgesic consumption, and complications after fascia iliaca block (FIB) versus control for patients undergoing primary total hip arthroplasty (THA). Second, we compared the outcomes of FIB versus placebo. Finally, we sought to evaluate pain and analgesic consumption after preoperative and postoperative FIB. Methods We performed a systematic literature search in MEDLINE, Embase, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov , and CENTRAL through February 2021 to identify randomized controlled trials (RCTs) that evaluated the efficacy of FIB versus control for patients undergoing primary THA. All analyses were conducted on intent-to-treat data with a random-effects model. Results Twelve RCTs with a total of 815 patients were included. There was no difference in postoperative pain (P = 0.64), analgesic consumption (P = 0.14), or complication rate (P = 0.99) between FIB and control groups. Moreover, no difference in postoperative pain (P = 0.26), analgesic consumption (P = 0.06), or complication rate (P = 0.71) was found between FIB and placebo. Moreover, sensitivity analysis suggested that no significant difference in postoperative pain, analgesic consumption, or complication rate was present between FIB and control in studies that used preoperative and postoperative FIB. Conclusion FIB was not found to be superior to placebo or various anesthetic techniques for patients undergoing primary THA, as measured by postoperative pain, analgesic consumption, and complications.

BackgroundThe optimal break-in period (BI) of urgent-start peritoneal dialysis (USPD) initiation for patients with end-stage renal disease (ESRD) and diabetes is unclear. We aimed to explore the safety and applicability of a BI ≤24 h in patients with ESRD and diabetes.MethodsWe used a retrospective cohort design wherein we recruited patients with ESRD and diabetes who underwent USPD at five institutions in China between January 2013 and August 2020. The enrolled patients were grouped according to BI. The primary outcomes were mechanical and infectious complication occurrences, whereas the secondary outcome was technique survival.ResultsWe enrolled 310 patients with diabetes, of whom 155 and 155 patients were in the BI ≤24 h and BI >24 h groups, respectively. The two groups showed a comparable incidence of infectious and mechanical complications within 6 months after catheter insertion (p>0.05). Logistic regression analysis revealed that a BI ≤24 h was not an independent risk factor for mechanical or infectious complications. Kaplan–Meier estimates showed no statistically significant between-group differences in technique survival rates (p>0.05). Cox multivariate regression analysis revealed that a BI ≤24 h was not an independent risk factor for technique failure.ConclusionUSPD initiation with a BI ≤24 h may be safe and feasible for patients with ESRD and diabetes.

Populus alba × Populus glandulosa (84K poplar) is model material with excellent genetic engineering resource and ornamental value. In our study, AmRosea1 (Antirrhinum majus) was overexpressed in 84K poplar, and the transgenic 84K (AM) poplar with high content of anthocyanin exhibited red pigmentation leaves. The transcriptome analysis between wild type (WT) and AM showed that 170 differentially expressed genes (DEGs) (86 up-regulated and 84 down-regulated) were found, and some DEGs were involved in flavone and flavonol biosynthesis, flavonoid biosynthesis and anthocyanin biosynthesis. The metabolome analysis showed that 13 anthocyanins-related differentially accumulated metabolites (DAMs) were detected in AM. The correlation analysis between DEGs and DAMs were performed, and the results revealed that 18 DEGs, including 11 MYB genes, two BZ1 genes, one FG2 gene, one ANS gene, and three IF7MAT genes, were negatively or positively correlated with 13 DAMs. The phylogenetic analysis demonstrated that there was high homology between AmRosea1 and PagMYB113, and MYB113 co-expressed with BZ1, ANS and DFR directly. Our results elucidated the molecular mechanism of plant color change mediated by anthocyanin biosynthesis pathway, which laid the foundation for the development and utilization of colorful woody plant.

Abstract Corynebacterium glutamicum is widely used as microbial cell factory for various bioproducts, but its genomic editing efficiency needs to be improved. In this study, a highly efficient CRISPR/Cas9-assisted genomic editing system for C. glutamicum was constructed. This system mainly involves a plasmid and can be used for both gene insertion and deletion in the chromosome of C. glutamicum. The recombinant plasmid for the target gene containing all the editing elements, and first constructed it in E. coli, then purified and transformed it into C. glutamicum. This temperature-sensitive plasmid was cured at high temperature after the genomic editing was completed in C. glutamicum. Using this genetic editing system, the genetic editing efficiency in C. glutamicum ATCC 13032 could reach 95%. The whole work of editing could be done in 8–9 days and showed most time-saving compared to the reported. Using this system, the native promoter of gdhA1 in ATCC 13032 has been replaced with the strong promoter PtacM, and more than 10 genes in ATCC 13032 have been deleted. The results demonstrate that this CRISPR/Cas9-assisted system is highly efficient and very suitable for genome editing in C. glutamicum.

Abstract Background Venous thromboembolism (VTE) in ovarian cancer (OC) patients has been widely investigated, but our knowledge on the role of VTE in OC patients receiving chemotherapy is limited. The aim of our study was to investigate the prevalence, risk factors, and prognostic value of chemotherapy-associated VTE in OC. Methods Three databases (PubMed, Embase, and the Cochrane Library) were systematically searched from inception to October 14, 2020. The primary outcome was the prevalence of VTE in OC patients receiving chemotherapy. The risk factors and prognostic value of VTE were the secondary outcomes. The pooled prevalence of VTE was estimated using the generic inverse-variance method. The statistical heterogeneity was evaluated with Cochran’s Q test and I 2 statistic. Funnel plot, Begg’s test, and Egger’s test were used to assess the potential publication bias in the meta-analysis. Results A total of eleven observational studies with 4759 OC patients were included. The pooled prevalence of VTE was 9% (95% CI, 0.06–0.12) in OC patients receiving chemotherapy. The results of subgroup analysis and sensitivity analysis were basically consistent with the overall pooled estimate. Multiple significant risk factors associated with VTE were also identified including advanced age, D-dimer > 0.5 mg/mL, and tumor diameter > 10 cm. Only two included studies reported the prognostic value of VTE in OC patients receiving chemotherapy, but with inconsistent results. Funnel plot showed that there existed potential publication bias, which was further verified by statistical test, but the results of the trim-and-fill method showed the pooled estimate kept stable after adding two “missing” studies. Conclusions This current study revealed that the pooled prevalence of chemotherapy-related VTE in OC was approximately 9% in OC patients. Risk factors for chemotherapy-related VTE were also identified which may contribute to targeting potentially preventative measures for VTE in OC.

Abstract Background Although studies have reported the sex differences in injury patterns among recreational skiers, the findings are still conflicting. This study aims to analyse the sex differences of orthopaedic knee injuries that occurred during alpine skiing. Methods A total of 306 recreational alpine skiers (125 females and 181 males) who sustained knee surgeries between June 2016 and December 2018 participated in this study. Age, height, weight, and physical activity level of the patients were recorded. The orthopaedic knee injury patterns were analysed based on the diagnosis given by the physicians. Results Male skiers (17.13%) had a higher proportion of multiple knee ligament injuries than females (6.40%). The combined anterior cruciate ligament (ACL) and medial collateral ligament injury were the most common injury types in both females and males, with ACL injury being more prevalent for females (79.20%) than that in males (56.35%). The proportion of female skiers (17.6%) with vigorous-intensity activity level was significantly lower than that of males (30.9%). Female skiers had lower body height, body weight, and body mass index than male skiers (P

Chlorogenic acid (CGA) is an antibacterial agent that can be isolated from Eucommia ulmoides Oliver, a Chinese medicinal and edible plant food. The inhibitory effect of CGA on bacterial growth and stiffness of the outer membrane (OM) had been reported, while more evidence were required to elucidate its impairment of cell wall. In this study, the morphological and physiochemical changes of Salmonella cells under CGA treatment were investigated. Firstly, the minimum inhibitory concentration (MIC) of CGA against Salmonella was assayed. Later, the permeability of OM and activity of the proteins released were measured and observed to reveal the alteration of OM characteristic and cellular morphology. Finally, reactive oxygen species and cell membrane fluidity were analyzed, respectively, to elucidate how CGA damaged cell surface. The results showed that MIC of CGA against Salmonella was 6.25 mg/L. Under sub-lethal doses of CGA, the OM permeability and the release of soluble proteins were enhanced evidently, and Salmonella cells showed more deformed and shrunken, confirming the impairment of cellular integrity under CGA. Finally, the possible cause of cell surface damage was investigated. the fluidity of the membrane was increased upon CGA treatment, which may the possible cause of OM by CGA.

Meniscus damage is a common trauma that often arises from sports injuries or menisci tissue degeneration. Current treatment methods focus on the repair, replacement, and regeneration of the meniscus to restore its original function. The advance of tissue engineering provides a novel approach to restore the unique structure of the meniscus. Recently, mesenchymal stem cells found in tissues including bone marrow, peripheral blood, fat, and articular cavity synovium have shown specific advantages in meniscus repair. Although various studies explore the use of stem cells in repairing meniscal injuries from different sources and demonstrate their potential for chondrogenic differentiation, their meniscal cartilage-forming properties are yet to be systematically compared. Therefore, this review aims to summarize and compare different sources of mesenchymal stem cells for meniscal repair and regeneration.

Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood. We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with porcine circovirus type 2 (PCV2) and Campylobacter. Campylobacter infection significantly decreased species richness and Shannon diversity index of colonic microbiota together with a significant increase in the proportion of Campylobacter and Enterobacteriaceae, whereas no significant difference on the above indexes was observed in piglets infected with PCV2 compared with healthy piglets. PCV2 and Campylobacter infection could disturb the homeostasis of colonic microbiota through deterioration of ecological network within microbial community, and specially Campylobacter performed as a module hub in ecological networks. The microbial dysbiosis caused metabolic dysfunction and led to a remarkable reduction in production of short chain fatty acids, following by a higher pH level in colon cavity. Campylobacter infection disturbed the function of colonic tract barrier observed in terms of significant lower relative expression of claudin-1, occluding, and zonula occludens protein-1 genes, and PCV2 infection induced intestinal inflammation together with a higher permeability of colon. Generally, these results suggested that PCV2 and Campylobacter infection could induce microbial dysbiosis and metabolic dysfunction, and cause intestinal disorder, all of which finally were associated to contribute to the diarrhea of early-weaning piglets.