Human iPSC 4R tauopathy model uncovers modifiers of tau propagation.

Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer's Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.

Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration.

Tau (MAPT) drives neuronal dysfunction in Alzheimer disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize Tau interactomes modified by neuronal activity and mutations that cause frontotemporal dementia (FTD) in human induced pluripotent stem cell (iPSC)-derived neurons. We established interactions of Tau with presynaptic vesicle proteins during activity-dependent Tau secretion and mapped the Tau-binding sites to the cytosolic domains of integral synaptic vesicle proteins. We showed that FTD mutations impair bioenergetics and markedly diminished Tau's interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity. These multimodal and dynamic Tau interactomes with exquisite spatial resolution shed light on Tau's role in neuronal function and disease and highlight potential therapeutic targets to block Tau-mediated pathogenesis.

Mapping the differential impact of spontaneous and conversational laughter on brain and mind: an fMRI study in autism.

Spontaneous and conversational laughter are important socio-emotional communicative signals. Neuroimaging findings suggest that non-autistic people engage in mentalizing to understand the meaning behind conversational laughter. Autistic people may thus face specific challenges in processing conversational laughter, due to their mentalizing difficulties. Using fMRI, we explored neural differences during implicit processing of these two types of laughter. Autistic and non-autistic adults passively listened to funny words, followed by spontaneous laughter, conversational laughter, or noise-vocoded vocalizations. Behaviourally, words plus spontaneous laughter were rated as funnier than words plus conversational laughter, and the groups did not differ. However, neuroimaging results showed that non-autistic adults exhibited greater medial prefrontal cortex activation while listening to words plus conversational laughter, than words plus genuine laughter, while autistic adults showed no difference in medial prefrontal cortex activity between these two laughter types. Our findings suggest a crucial role for the medial prefrontal cortex in understanding socio-emotionally ambiguous laughter via mentalizing. Our study also highlights the possibility that autistic people may face challenges in understanding the essence of the laughter we frequently encounter in everyday life, especially in processing conversational laughter that carries complex meaning and social ambiguity, potentially leading to social vulnerability. Therefore, we advocate for clearer communication with autistic people.

Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.

Optofluidic tunable filters using ionic liquid electrolyte capacitors.

Tunable optical filter is a basic component for most optical systems. This study reports a unique design of Fabry-Pérot (FP) tunable filter by using an ionic liquid solution. The tunable filter consists of two neighboring regions: capacitor region and FP region. The former is in the form of electrolyte capacitor and the latter remains transparent as an FP cavity for light transmission. When the capacitor region is applied with a bias voltage, it attracts the ions from the FP region and thus reduces the ion concentration of the FP region, resulting in a change of the refractive index and eventually a shift of transmission peak of the FP cavity. Among four electrolyte solutions studied, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF6) exhibits the best overall performance, such as low insertion loss (3.2 dB), large side mode suppression ratio (23 dB) and high stability (drift <0.2 nm). Additionally, a wavelength tuning of 0.17 nm/V is achieved over 0-17 V, providing a tunable range of 3 nm. This device features low bias voltage, no mechanical movement, easy fabrication and seamless integration with microfluidics systems, and may find potential applications in spectral analyzers and lab-on-a-chip biosensing systems.

Unraveling the Heat- and UV-Induced Degradation of Mixed Halide Perovskite Thin Films via Surface Analysis Techniques.

In recent years, organic-inorganic hybrid perovskite materials have become one of the most promising materials in the new generation of solar cells. These perovskites can provide excellent photoelectric properties after a simple fabrication process. Although perovskite solar cells have achieved high power conversion efficiency, instability concerns regarding material exposure to heat, moisture, air, and UV light present hindrances to commercialization. In this study, three kinds of perovskites (MAPbI3, MAPbI3-xBrx, and MAPbI3-xClx) were used to investigate the crystal stability upon exposure to heat and UV light. SEM, XRD, and FTIR were used to observe the surface morphology, crystal structure, and functional groups of the perovskite thin films. XPS was used to examine the surface composition and chemical state of the perovskite thin films under different conditions. Among these three types of perovskites, it was found that the MAPbI3-xBrx crystal demonstrated the best stability. ToF-SIMS was used to confirm the molecular distribution of the MAPbI3-xBrx films upon exposure to heat and UV light at different depths. ToF-SIMS revealed that [Pb]+ and [PbI]+ aggregated at the interface between the perovskite and ITO substrate after 14 days of thermal treatment. On the other hand, [Pb]+ and [PbI]+ were distributed uniformly after 3 days of UV exposure. This study systematically analyzed and revealed the thermal- and UV-induced degradation process of three perovskite films by using surface analysis techniques. It was concluded that bromine-doped perovskite films had better stability, and UV light caused more severe damage than heat.

Hormone replacement therapy and periodontitis progression in postmenopausal women: A prospective cohort study.

OBJECTIVE: This study aimed to investigate the responses of periodontal environment to hormone replacement therapy (HRT) in postmenopausal women with or without periodontitis. BACKGROUND: HRT is a common and effective strategy for controlling menopausal symptoms, while the changes of periodontal environment under it, particularly in postmenopausal women with periodontitis, remain unclear. METHODS: As a prospective cohort study, a total of 97 postmenopausal women receiving HRT were screened, including 47 with and 50 without periodontitis. Correspondingly, 97 women did not receiving HRT were screened as controls during the same period. The full-mouth sulcus bleeding index (SBI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured using periodontal probes. The levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the gingival crevicular fluid were measured using enzyme-linked immunosorbent assay. In addition, cone beam computed tomography was performed to measure the alveolar bone height (ABH) and bone mineral density (BMD). RESULTS: In postmenopausal women without periodontitis, no significantly changes on periodontal parameters were observed after HRT. In women with stage II periodontitis, SBI, BOP, IL-6, and TNF-α were significant decreased after one year and two years of HRT. Compared to the controls, women with stage II periodontitis who underwent HRT had significantly lower CAL and ABH and higher BMD in the second year. The incidence of at least one site with CAL increase ≥1 mm between baseline and 2 years was significantly lower in the HRT group than in the control group in women with stage II periodontitis. In addition, HRT was significantly associated with a decrease in SBI, BOP, IL-6, and TNF-α in the first year and with a decrease in CAL, SBI, BOP, IL-6, and ABH and an increase in BMD in the second year. CONCLUSIONS: In postmenopausal women with stage II periodontitis, HRT is associated with the alleviation of inflammation within two years and the remission of alveolar bone loss in the second year. HRT appears to decrease the incidence of CAL increase ≥1 mm within 2 years in women with periodontitis by inhibiting inflammation and alveolar bone loss.

Tracking the temporal dynamics of the face-like inversion effect as revealed by Chinese characters using magnetoencephalography.

The neural basis of configural processing has been extensively studied by exploiting face inversion during recognition, and growing evidence has revealed that word inversion also involves changes in configuration. However, the neural dynamics of face-like inversion effects remain unclear. Here, we tracked the temporal dynamics of neural responses that were sensitive to inversion during Chinese character recognition as they occurred during face recognition using multivariate decoding and temporal generalization analyses. We recorded magnetoencephalography while participants performed a one-back task for faces, compound characters, and simple characters with upright and inverted orientations. We showed that the inversion effect (inverted versus upright) can be decoded at occipitotemporal sensors for all stimulus types over and across time points, with a stronger impact on faces and compound characters than on simple characters. The inversion effect occurred earlier and lasted longer for faces than for characters, and the effect was also stronger for compound characters than for simple characters. Finally, we demonstrated inversion effects in the event-related field for all stimulus types and identified their sources in the ventral occipitotemporal areas. Overall, this study provides novel evidence for the temporal dynamics of the face-like inversion effect occurring during Chinese character recognition.

Performance of 21 Early Warning System scores in predicting in-hospital deterioration among undifferentiated admitted patients managed by ambulance services.

BACKGROUND: The optimal Early Warning System (EWS) scores for identifying patients at risk of clinical deterioration among those transported by ambulance services remain uncertain. This retrospective study compared the performance of 21 EWS scores to predict clinical deterioration using vital signs (VS) measured in the prehospital or emergency department (ED) setting. METHODS: Adult patients transported to a single ED by ambulances and subsequently admitted to the hospital between 1 January 2019 and 18 April 2019 were eligible for inclusion. The primary outcome was 30-day mortality; secondary outcomes included 3-day mortality, admission to intensive care or coronary care units, length of hospital stay and emergency call activations. The discriminative ability of the EWS scores was assessed using the area under the receiver operating characteristic curve (AUROC). Subanalyses compared the performance of EWS scores between surgical and medical patient types. RESULTS: Of 1414 patients, 995 (70.4%) (53.1% male, mean age 68.7±17.5 years) were included. In the ED setting, 30-day mortality was best predicted by VitalPAC EWS (AUROC 0.71, 95% CI (0.65 to 0.77)) and National Early Warning Score (0.709 (0.65 to 0.77)). All EWS scores calculated in the prehospital setting had AUROC <0.70. Rapid Emergency Medicine Score (0.83 (0.73 to 0.92)) and New Zealand EWS (0.88 (0.81 to 0.95)) best predicted 3-day mortality in the prehospital and ED settings, respectively. EWS scores calculated using either prehospital or ED VS were more effective in predicting 3-day mortality in surgical patients, whereas 30-day mortality was best predicted in medical patients. Among the EWS scores that achieved AUROC ≥0.70, no statistically significant differences were detected in their discriminatory abilities to identify patients at risk of clinical deterioration. CONCLUSIONS: EWS scores better predict 3-day as opposed to 30-day mortality and are more accurate when estimated using VS measured in the ED. The discriminatory performance of EWS scores in identifying patients at higher risk of clinical deterioration may vary by patient type.

Patterns of Mental Health Service Utilisation: A Population-Based Linkage of Over 17 Years of Health Administrative Records.

A cross-sectoral partnership was formed in 2021 in support of the recommendations in an audit on access to state-funded mental health services. In this first paper, we aimed to describe the demographic and service utilisation of adults with a mental health diagnosis in the Western Australian state-funded health system from 2005 to 2021. Inpatient, emergency department, specialised (ambulatory) community mental health service, and death records were linked in individuals aged ≥ 18 years with a mental health diagnosis in Western Australia. Altogether, 392,238 individuals with at least one mental health service contact between 1st January 2005 and 31st December 2021 were included for analysis. Females, Aboriginal and/or Torres Strait Islander people, and those who lived outside major cities or in the most disadvantaged areas were more likely to access state-funded mental health services. While the number of individuals who accessed community mental health services increased over time (from 28,769 in 2005 to 50,690 in 2021), the percentage increase relative to 2005 was notably greater for emergency department attendances (127% for emergency department; 76% for community; and 63% for inpatient). Conditions that contributed to the increase for emergency department were mainly alcohol disorder, reaction to severe stress and adjustment disorders, and anxiety disorders. Sex differences were observed between conditions. The pattern of access increased for emergency department and the community plus emergency department combination. This study confirmed that the patterns of access of state-funded mental health services have changed markedly over time and the potential drivers underlying these changes warrant further investigation.

Motivation, injury prevention, and the incidence of sports injuries: A three-wave longitudinal test of self-determination theory.

This study applied self-determination theory (SDT) as a psychological framework to examine whether psychological need support and autonomous motivation are predictive of sports injury preventive behaviors and the incidence of sports injuries. 2042 secondary school students (mean age = 14.33, male = 44.3%) from China completed a survey of the study variables (using established scales) at three time points (baseline, 1-month follow-up, 3-month follow-up). Structural equation modeling examined the core tenets of SDT by testing if the change-scores of the SDT variables (i.e., psychological need support from PE teachers, students' motivation, and students' behavioral adherence) between baseline and 1-month follow-up, were predictive of sports injury incidence assessed at 3-month follow-up. Our model demonstrated acceptable goodness-of-fit parameters (CFI = 0.97, TLI = 0.96, RMSEA = 0.03, and SRMR = 0.05). The relationships between psychological need support, autonomous motivation, and behavioral adherence were both positive and significant. These SDT variables predicted the future incidence of sports injuries following the motivational pathways of SDT. Our study provides evidence of the predictive power of SDT variables on sports injury preventive behaviors and the incidence of sports injuries: Students who perceive their PE teachers as psychological need supportive possess higher autonomous motivation and behavioral adherence towards sports injury prevention, and are also less likely to encounter sports injuries in the future.

Exogenous progesterone short-termly affects the periodontal environment in perimenopausal women.

OBJECTIVE: This study aimed to evaluate the effects of exogenous progesterone in the periodontal environment of perimenopausal women. METHODS: Either with or without periodontitis, 100 perimenopausal women received 3 months of progesterone treatment, as well as age-matched 100 perimenopausal and 100 postmenopausal women without treatments were enrolled (N = 50). The gingival index (GI), probing depth (PD), clinical attachment level (CAL), and tooth mobility (TM), as well the gingival crevicular fluid (GCF) levels of IL-6 and TNF-α were analyzed. RESULTS: Periodontitis showed higher GI, PD, and CAL than non-periodontitis at perimenopausal and postmenopausal periods. In women without periodontitis, the GI and PD, and the GCF levels of IL-6 and TNF-α were increased by 3 months of progesterone treatment, but recovered from the 6th month in the absence of progesterone. In women with periodontitis, only the PD was short-termly increased by progesterone treatment. For those without progesterone treatment, the GI, PD, and TM were not significantly different between perimenopausal and postmenopausal women either with periodontitis or not. CONCLUSIONS: Exogenous progesterone short-termly exacerbated the inflammation and PD in perimenopausal women without periodontitis, and the PD in those with periodontitis.

LncRNA KCNQ1OT1/miR-496/HMGB1 Signaling Axis Promotes Invasion and Migration of Non-small Cell Lung Cancer Cells.

Enhanced invasion and migration of non-small cell lung cancer (NSCLC) cells is the major cause of metastasis and poor prognosis in NSCLC. This study was conducted to investigate the role and mechanism of lncRNA KCNQ1OT1 in the proliferation, invasion, and migration of NSCLC cells. The expression of KCNQ1OT1 in NSCLC was analyzed in the StarBase database, and the target miRNA of KCNQ1OT1 as well as the target genes of the miRNA was predicted. Then, the mRNA expression levels of KCNQ1OT1, miR-496, and HMGB1 were detected in clinical tissue samples and cells by qRT-PCR assay. Besides, the protein levels of HMGB1 were detected by Western blot. MTT assay, transwell assay, and scratch assay were used to determine the proliferation, invasion, and migration ability of NSCLC cells, respectively. Correlation analysis was performed to assess the correlation between the expression of KCNQ1OT1, miR-496, and HMGB1 in clinical NSCLC samples. Dual-luciferase reporter gene assay was conducted to analyze the interaction between KCNQ1OT1 and miR-496 and between miR-496 and HMGB1. The database results showed that KCNQ1OT1 was highly expressed in NSCLC. Similarly, we found that the expression level of KCNQ1OT1 was significantly higher in NSCLC tissues and cells than that in the corresponding normal tissues and cells. The results of MTT assay, transwell assay, and scratch assay demonstrated that KCNQ1OT1 significantly enhanced the proliferation, invasion, and migration of NSCLC cells. Further mechanism exploration revealed that KCNQ1OT1 could sponge miR-496, and miR-496 directly targeted and regulated the expression of HMGB1. The expression of miR-496 and either KCNQ1OT1 or HMGB1 were negatively correlated in NSCLC, while the expression of KCNQ1OT1 and HMGB1 were positively correlated. Compared with normal paracancer tissues, miR-496 was much lower and HMGB1 was much higher expressed in NSCLC tissues. The results of cotransfection also further demonstrated that miR-496 inhibitor or sh-HMGB1 cotransfected with sh-KCNQ1OT1 could significantly decrease or increase the ability of sh-KCNQ1OT1 to inhibit the proliferation, invasion, and migration of H1299 cells, respectively. In conclusion, lncRNA KCNQ1OT1 promotes the invasion and migration of NSCLC cells through miR-496/HMGB1 signaling axis.

Patient Use, Experience, and Satisfaction With Telehealth in an Australian Population (Reimagining Health Care): Web-Based Survey Study.

BACKGROUND: The COVID-19 pandemic triggered a rapid scale-up of telehealth services in Australia as a means to provide continued care through periods of physical restrictions. The factors that influence engagement in telehealth remain unclear. OBJECTIVE: The purpose of this study is to understand the experience of Australian people who engaged in a telehealth consultation during the pandemic period (2020-2021) and the demographic factors that influence engagement. METHODS: A web-based survey was distributed to Australians aged over 18 years that included 4 questions on frequency and type of clinical consultation, including with a general practitioner (GP), specialist, allied health, or nurse; 1 question on the experience of telehealth; and 2 questions on the quality of and satisfaction with telehealth. Statistical analysis included proportion of responses (of positive responses where a Likert scale was used) and regression analyses to determine the effect of demographic variables. RESULTS: Of the 1820 participants who completed the survey, 88.3% (1607/1820) had engaged in a health care consultation of some type in the previous 12 months, and 69.3% (1114/1607) of those had used telehealth. The most common type of consultation was with a GP (959/1114, 86.1%). Older people were more likely to have had a health care consultation but less likely to have had a telehealth consultation. There was no difference in use of telehealth between metropolitan and nonmetropolitan regions; however, people with a bachelor's degree or above were more likely to have used telehealth and to report a positive experience. A total of 87% (977/1114) of participants agreed or strongly agreed that they had received the information they required from their consultation, 71% (797/1114) agreed or strongly agreed that the outcome of their consultation was the same as it would have been face-to-face, 84% (931/1114) agreed or strongly agreed that the doctor or health care provider made them feel comfortable, 83% (924/1114) agreed or strongly agreed that the doctor or health care provider was equally as knowledgeable as providers they have seen in person; 57% (629/1114) of respondents reported that they would not have been able to access their health consultation if it were not for telehealth; 69% (765/1114) of respondents reported that they were satisfied with their telehealth consultation, and 60% (671/1114) reported that they would choose to continue to use telehealth in the future. CONCLUSIONS: There was a relatively high level of engagement with telehealth over the 12 months leading up to the study period, and the majority of participants reported a positive experience and satisfaction with their telehealth consultation. While there was no indication that remoteness influenced telehealth usage, there remains work to be done to improve access to older people and those with less than a bachelor's degree.

A multilevel social-ecological network approach for reconciling coastal saltmarsh conservation and development.

In a large-scale region, governance for connectivity in an ecological system often conflicts with management boundaries, causing inefficiencies. Collaboration among management organizations in different areas can help overcome this problem. However, few studies quantified the collaborations' practical relationship with connectivity, considering that some potentially connected paths are easy to neglect by managers. In this paper, collaborations among government agencies in project application process were analyzed, and a multilevel social-ecological network analysis (SENA) approach was developed to identify the collaboration's effect on genetically connected coastal areas. The network framework and methods were shown in a case of coastal saltmarsh conservation and development in the Yellow River Delta, China. Collaboration patterns in conservation and development networks were analyzed and compared among local, subregional, and regional government agencies working in genetically connected coastal areas. Project information flow, reflecting communication frequency and decision-making chances among government agencies was quantified and correlated with ecological connectivity to inform governance effects. Results showed areas with the potential to realize social-ecological alignment, where collaborative networks were measured by network density (percentage of connected network edges). The current reveals that development has more significant potential than conservation at most levels to overcome the misalignment of the social-ecological system, also known as scale mismatch. Empirical evidence also showed a correlation between communication capacity in development networks and improved ecological conditions. The multilevel SENA advanced in this paper can be used for natural resource management when connectivity plays a major role.

Developing a digital game for excel skills learning in higher education - a comparative study analyzing differences in learning between digital games and textbook learning.

In higher education, many universities in Taiwan let college students learn excel in a self-directed way. The current axle of the Excel curriculum mainly relies on self-directed learning. In the study, we designed the digital game "Legendary Wizard Excel" and took a certified Excel textbook as the research tool. The game we designed integrated the role-play with cognitive scaffolding to help learners learn Excel skills, whereas the textbook we used was "Excel Expert" in the Microsoft Office Specialist. We compared the Learning Effectiveness, Flow Status, and Technology Acceptance Model with 187 college students between two tools, and found that: (1) The game reached a high Technology Acceptance Model; (2) Both groups of learners had significant improvements in learning effectiveness and were engaged in the activity; (3) On learning effectiveness, learners in game-based learning groups achieved higher than learners in textbook groups; (4) Learners in game-based learning groups engaged better in the activity than learners in textbook groups. Therefore, in the future, we looked forward to bringing our results to higher education levels and workplace training to enhance the Excel skills.

Biology, Bias, or Both? The Contribution of Sex and Gender to the Disparity in Cardiovascular Outcomes Between Women and Men.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide for both men and women. However, CVD is understudied, underdiagnosed, and undertreated in women. This bias has resulted in women being disproportionately affected by CVD when compared to men. The aim of this narrative review is to explore the contribution of sex and gender on CVD outcomes in men and women and offer recommendations for researchers and clinicians. RECENT FINDINGS: Evidence demonstrates that there are sex differences (e.g., menopause and pregnancy complications) and gender differences (e.g., socialization of gender) that contribute to the inequality in risk, presentation, and treatment of CVD in women. To start addressing the CVD issues that disproportionately impact women, it is essential that these sex and gender differences are addressed through educating health care professionals on gender bias; offering patient-centered care and programs tailored to women's needs; and conducting inclusive health research.

Mitochondrial protein LETM1 and its-mediated CTMP are potential therapeutic targets for endometrial cancer.

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is an important mitochondrial protein, while its function in endometrial cancer remains unknown. This study aimed to explore the function of LETM1 in endometrial cancer and reveal the underlying mechanisms involving carboxy-terminal modulator protein (CTMP). Immunohistochemistry was performed to detect the expression of LETM1 and CTMP in normal, atypical hyperplastic and endometrial cancer endometrial tissues. LETM1 and CTMP were silenced in two endometrial cancer cell lines (ISK and KLE), which were verified by western blot. Cell viability, colony number, migration and invasion were detected by cell counting kit-8, colony formation, wound healing and trans-well assays, respectively. A xenograft mouse model was established to determine the antitumor potential of LETM1/CTMP silencing in vivo . In addition, CTMP was overexpressed to evaluate its regulatory relationship with LETM1 in endometrial cancer cells. The expression of LETM1 and CTMP proteins were higher in endometrial cancer tissues than atypical hyperplastic tissues and were higher in atypical hyperplastic tissues than normal tissues. LETM1 and CTMP were also upregulated in ISK and KLE cells. Silencing of LETM1 or CTMP could decrease the viability, colony number, migration and invasion of endometrial cancer cells and the weight and volume of tumor xenografts. In addition, CTMP was downregulated by LETM1 silencing in KLE cells, and its overexpression enhanced the malignant characteristics of si-LETM1-transfected KLE cells. Silencing of LETM1 inhibits the malignant progression of endometrial cancer through downregulating CTMP.

Lower-Limb Muscle Activity During Aquatic Treadmill Running in Individuals With Anterior Cruciate Ligament Reconstruction.

INTRODUCTION: While anterior cruciate ligament (ACL) tears are commonly managed with ACL reconstruction (ACL-R), 35% of ACL-R individuals fail to return to the preinjury elite sport level. Persistent neuromuscular deficits in the hamstrings and quadriceps have been observed. It has been proposed that aquatic therapy can be used to optimize neuromuscular control after ACL-R. OBJECTIVES: (1) To compare muscle activity in ACL-R individuals during aquatic treadmill (ATM) running at different water depths and (2) to compare muscle activity during ATM running between ACL-R and healthy individuals. METHODS: A total of 38 participants, including 18 ACL-R individuals (mean postoperative time [SD] = 25.8 [25.0] mo) and 20 healthy individuals were recruited. Muscle activity of biceps femoris (BF), rectus femoris (RF), tibialis anterior, and medial gastrocnemius during land treadmill and ATM running at mid-shin, mid-thigh, and waist levels were recorded using surface electromyography (sEMG).  The sEMG signals of the selected muscles were normalized and expressed in % Maximal Voluntary Contraction (%MVC). Muscle activity of the ACL-R, ACL-contralateral, and healthy control limbs at different water depths was compared. RESULTS: Among the 3 groups, the ACL-R group demonstrated the most prominent percentage increase of 101.97% (P = .001) at mid-shin level, 139.66% (P = .001) at mid-thigh level, and 141.97% (P < .001) at waist level, respectively, in %MVC when compared to land. In the ACL-R group, muscle activity of BF in the stance phase (BFSt) was significantly higher than the control group on land at all water depths. Muscle activity of RF in the swing phase (RFSw) in the ACL-R group significantly increased in all water depths immersion when compared to land, respectively. CONCLUSION: This study showed an increasing trend in muscle activity of BFSt and RFSw in ACL-R individuals during ATM running at increased water depths. ATM running could be implemented as neuromuscular training in rehabilitation after ACL-R.

Effectiveness of an online short-term audio-based mindfulness program on negative emotions during the COVID-19 pandemic: Latent growth curve analyses of anxiety and moderated mediation effects of anxiety between mindfulness and negative affect.

This pilot study aims to explore the effects and mechanisms of a mindfulness-based intervention on negative emotions in community settings during the COVID-19 pandemic. Participants (N = 100) were randomized into an intervention group (n = 50) and a waitlist control group (n = 50). Participants in the mindfulness group underwent 3 weeks (21 sessions) of an online audio-based mindfulness-based intervention program and completed the online measures four times whereas those in the waitlist control group needed to complete the measures twice. Participants completed measures of the Hospital Anxiety and Depression Scale and Positive and Negative Affect Schedule. The results of the measures of the two groups were compared. Moderated mediation analysis was used to analyze intervention outcomes on negative affect through anxiety. Unconditional quadratic latent growth analysis was used to test the growth trajectories of anxiety. The results showed that this intervention program was effective at improving positive affect and at reducing depression, anxiety, and negative affect. The baseline anxiety moderator was found to be significant, and indirect effects of anxiety post-intervention were found between the mindfulness-based intervention and negative affect. Anxiety levels of participants were not at the same starting point and had similar but non-quadratic growth trajectories. The mindfulness-based intervention program was effective at promoting mental wellbeing and reducing mental problems in community settings in China. Mindfulness practices were beneficial to people with different anxiety levels but had more obvious benefits on anxiety and a negative affect for participants with low anxiety levels. Clinical trial registration: ISRCTN16205138 on 26/02/2021.