OCIAD2 promotes pancreatic cancer progression through the AKT signaling pathway.

BACKGROUND: OCIAD2（Ovarian carcinoma immunoreactive antigen-like protein 2） is a protein reported in various cancers. However, the role of OCIAD2 has not been explored in pan-cancer datasets. The purpose of this research lies in analyzing the expression level and prognostic-related value of OCIAD2 in different human cancers, as well as revealing the underlying mechanism in specific cancer type (pancreatic adenocarcinoma, PAAD). METHODS: The correlation between OCIAD2 expression level and clinical relevance in different human cancers was investigated from bioinformatical perspective (GTEx and TCGA). The OCIAD2 expression level and clinical significance in PAAD were explored in GEO datasets and tissue microarray. Functional experiments were used to determine the OCIAD2 cell functions in vitro and in vivo. GSEA, western blot and immunohistochemistry were used to uncover the potential mechanism. RESULTS: OCIAD2 expression level was closely correlated with clinical relevance in many cancer types through pan-cancer analysis, and we found OCIAD2 was highly expressed in PAAD and associated with poorer prognosis. OCIAD2 acted as the promotor of Warburg effect and influenced PAAD cells proliferation, migration and apoptosis. Mechanistically, OCIAD2 upregulation may boost glycolysis in PAAD via activating the AKT signaling pathway in PAAD. CONCLUSIONS: In PAAD, OCIAD2 promotes Warburg effect via AKT signaling pathway and targeting cancer cells metabolic reprogramming could be a potential treatment.

Novel Bifunctional Conjugates Targeting PD-L1/PARP7 as Dual Immunotherapy for Potential Cancer Treatment.

Bifunctional conjugates targeting PD-L1/PARP7 were designed, synthesized, and evaluated for the first time. Compounds B3 and C6 showed potent activity against PD-1/PD-L1 interaction (IC50 = 0.426 and 0.342 µM, respectively) and PARP7 (IC50 = 2.50 and 7.05 nM, respectively). They also displayed excellent binding affinity with hPD-L1, approximately 100-200-fold better than that of hPD-1. Both compounds restored T-cell function, leading to the increase of IFN-γ secretion. In the coculture assay, B3 and C6 enhanced the killing activity of MDA-MB-231 cells by Jurkat T cells in a concentration-dependent manner. Furthermore, B3 and C6 displayed significant in vivo antitumor efficacy in a melanoma B16-F10 tumor mouse model, more than 5.3-fold better than BMS-1 (a PD-L1 inhibitor) and RBN-2397 (a PARP7i clinical candidate) at the dose of 25 mg/kg, without observable side effects. These results provide valuable insight and understanding for developing bifunctional conjugates for potential anticancer therapy.

Chronic restraint stress induces depression-like behaviors and alterations in the afferent projections of medial prefrontal cortex from multiple brain regions in mice.

INTRODUCTION: The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated. METHODS: In the present study, C57BL/6 J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively. RESULTS: The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala. CONCLUSION: Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.

The effect of a mindfulness and motivational interviewing-oriented physical-psychological integrative intervention for community-dwelling spinal cord injury survivors: a mixed-methods randomized controlled trial.

OBJECTIVE: To evaluate the feasibility, acceptability, and efficacy of a mindfulness and motivational interviewing-oriented physical-psychological integrated intervention in community-dwelling spinal cord injury (SCI) survivors. DESIGN: A mixed-methods randomized controlled trial. SETTING: Local organizations of handicapped in Hong Kong. PARTICIPANTS: Community-dwelling adults with SCI (N = 72). INTERVENTIONS: Participants in the intervention group (n = 36) received video-guided exercise for daily practice and online group psychological (mindfulness and motivational interviewing-oriented) weekly sessions for eight weeks. Participants in the control group (n = 36) received an eight-week online group didactic education on lifestyle discussions and general health suggestions. MAIN OUTCOMES MEASURES: Primary outcomes included quality of life, physical activity, depression, and chronic pain. Secondary outcomes included exercise self-efficacy and mindfulness. Outcomes were measured at baseline, post-intervention, and three-month follow-up. Focus-group interviews were conducted post-intervention. RESULTS: The recruitment, retention, and adherence rates were 84.7%, 100%, and 98.6%, respectively. The intervention showed significant positive effects on preventing declines in quality of life at three-month follow-up [Cohen's d = 0.70 (0.22, 1.18)]. Positive trends manifested in physical activity, depression, chronic pain, and exercise self-efficacy. Three qualitative categories were identified: subjective improvements in exercise, physical, and social well-being; perceived changes in mindfulness and mental well-being; and intervention facilitators and barriers. CONCLUSIONS: The mindfulness and motivational interviewing-oriented physical-psychological integrated intervention is feasible and acceptable. The significant prolonged effect in maintaining quality of life and positive impacts on physical and psychosocial well-being indicate its value to address major health challenges of community-dwelling SCI survivors.

Naringenin restricts the colonization and growth of Ralstonia solanacearum in tobacco mutant KCB-1.

Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first demonstrated that the roots of bacterial wilt-resistant tobacco mutant KCB-1 can limit the growth and reproduction of Ralstonia solanacearum. Secondly, we demonstrated that KCB-1 specifically induced an upregulation of naringenin content in root metabolites and root secretions. Further experiments showed that naringenin can disrupt the structure of R. solanacearum, inhibit the growth and reproduction of R. solanacearum, and exert a controlling effect on bacterial wilt. Exogenous naringenin application activated the resistance response in tobacco by inducing the burst of reactive oxygen species and salicylic acid deposition, leading to transcriptional reprogramming in tobacco roots. Additionally, both external application of naringenin in CB-1 and overexpression of the Nicotiana tabacum chalcone isomerase (NtCHI) gene, which regulates naringenin biosynthesis, in CB-1 resulted in a higher complexity of their inter-root bacterial communities than in untreated CB-1. Further analysis showed that naringenin could be used as a marker for resistant tobacco. The present study provides a reference for analyzing the resistance mechanism of bacterial wilt-resistant tobacco and controlling tobacco bacterial wilt.

The effect of adding real-time postural feedback in balance and mobility training in older adults: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to systematically review the additional value of providing real-time postural feedback during balance and mobility training in older people. METHODS: PubMed, Embase, CINAHL, and Web-of-Science were searched from inception to August 2023. Studies comparing the effectiveness of feedback-based versus non-feedback-based postural balance or mobility training on balance or mobility outcomes were selected. Similar outcomes were pooled in meta-analyses using a random-effect model. The quality of evidence for available outcomes was rated by Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Eight studies were identified with 203 subjects. Two studies showed that providing postural feedback immediately improved stability in static balance and gait. For the post-training effect, however, no significant change was found in trunk movement during single-leg standing (i.e., pitch angle, MD=0.65, 95 %CI=-0.77 to 2.07, low-quality; roll angle, MD=0.96, 95 %CI=-0.87 to 2.80, moderate-quality), in the Mini-BESTest (MD=1.88, 95 %CI=-0.05 to 3.80, moderate-quality), and in balance confidence (MD=0.29, 95 %CI=-3.43 to 4.2, moderate-quality). A worsened functional reach distance was associated with providing feedback during balance training (MD=-3.26, 95 %CI=-6.31 to -0.21, high-quality). Meta-analyses on mobility outcomes were mostly insignificant, except for the trunk-roll angle of walking (MD=0.87, 95 %CI=0.05 to 1.70, low-quality) and trunk-pitch angle of walking with head-turning (MD=1.87, 95 %CI=0.95 to 2.79, moderate-quality). CONCLUSION: Adding real-time postural feedback to balance and mobility training might immediately improve stability in balance and mobility in older people. However, mixed results were reported for its post-training effect.

Charge Carrier Regulation for Efficient Blue Quantum-Dot Light-Emitting Diodes Via a High-Mobility Coplanar Cyclopentane[b]thiopyran Derivative.

The performance of blue quantum dot light-emitting diodes (QLEDs) is limited by unbalanced charge injection, resulting from insufficient holes caused by low mobility or significant energy barriers. Here, we introduce an angular-shaped heteroarene based on cyclopentane[b]thiopyran (C8-SS) to modify the hole transport layer poly-N-vinylcarbazole (PVK), in blue QLEDs. C8-SS exhibits high hole mobility and conductivity due to the π···π and S···π interactions. Introducing C8-SS to PVK significantly enhanced hole mobility, increasing it by 2 orders of magnitude from 2.44 × 10-6 to 1.73 × 10-4 cm2 V-1 s-1. Benefiting from high mobility and conductivity, PVK:C8-SS-based QLEDs exhibit a low turn-on voltage (Von) of 3.2 V. More importantly, the optimized QLEDs achieve a high peak power efficiency (PE) of 7.13 lm/W, which is 2.65 times that of the control QLEDs. The as-proposed interface engineering provides a novel and effective strategy for achieving high-performance blue QLEDs in low-energy consumption lighting applications.

Total Syntheses and Absolute Stereochemical Correction of Negundin B, Vitexin 1, and Vitexin 6.

A highly adaptable asymmetric synthetic route toward dihydronaphthalene lignans was developed, with its application to the syntheses of negundin B and vitexin 1/6 described herein. This developed pathway proceeded through an enantioselective aldol reaction to establish the contiguous stereocenters present in the final structures with subsequent functional group transformations yielding (-)-negundin B and (-)-vitexin 1/6. The enantioselective synthesis of vitexin 1/6 allowed the correction of absolute configuration, which has been widely incorrectly reported.

Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

Advances in prosthetics and orthotics.

Over the past years, the field of prosthetics and orthotics has seen incredible innovations that used to be perceived as science fiction. This editorial aims to shed light on such exciting developments, exploring how they are addressing the challenges faced by individuals with limb impairments and musculoskeletal conditions.

Associations between spinal flexibility and bracing outcomes in adolescent idiopathic scoliosis: a literature review.

OBJECTIVES: To identify the existing assessment methods used to measure the spinal flexibility of adolescents with idiopathic scoliosis before bracing and to evaluate the predictive effect of spinal flexibility on bracing outcomes. METHODS: A broad literature search was performed in the PubMed, Web of Science, EMBASE, CINAHL, Scopus, and Cochrane Library databases to obtain relevant information about spinal flexibility and bracing outcomes. All literature was retrieved by October 14, 2023. The inclusion and exclusion criteria were meticulously determined. The quality of each included study and the level of evidence were evaluated by the Quality in Prognosis Studies (QUIPS) method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system, respectively. RESULTS: After screening 1863 articles retrieved from databases, a total of 14 studies with 2261 subjects were eligible for the final analysis in this review. Overall, nine methods of flexibility assessment were identified, including supine radiographs, supine lateral bending radiographs, lateral bending radiographs but without clear positions, hanging radiographs, fulcrum bending physical method, and ultrasound imaging in the positions of supine, prone, sitting with side bending and prone with side bending. In addition, five studies demonstrated that flexibility had a strong correlation with in-brace correction, and eleven studies illustrated that spinal flexibility was a predictive factor of the bracing outcomes of initial in-brace Cobb angle, initial in-brace correction rate, curve progression, and curve regression. The results of GRADE demonstrated a moderate-evidence rating for the predictive value of spinal flexibility. CONCLUSION: Supine radiography was the most prevalent method for measuring spinal flexibility at the pre-brace stage. Spinal flexibility was strongly correlated with the in-brace Cobb angle or correction rate, and moderate evidence supported that spinal flexibility could predict bracing outcomes.

Reliability, Validity, and Identification Ability of a Commercialized Waist-Attached Inertial Measurement Unit (IMU) Sensor-Based System in Fall Risk Assessment of Older People.

Falls are a prevalent cause of injury among older people. While some wearable inertial measurement unit (IMU) sensor-based systems have been widely investigated for fall risk assessment, their reliability, validity, and identification ability in community-dwelling older people remain unclear. Therefore, this study evaluated the performance of a commercially available IMU sensor-based fall risk assessment system among 20 community-dwelling older recurrent fallers (with a history of ≥2 falls in the past 12 months) and 20 community-dwelling older non-fallers (no history of falls in the past 12 months), together with applying the clinical scale of the Mini-Balance Evaluation Systems Test (Mini-BESTest). The results show that the IMU sensor-based system exhibited a significant moderate to excellent test-retest reliability (ICC = 0.838, p < 0.001), an acceptable level of internal consistency reliability (Spearman's rho = 0.471, p = 0.002), an acceptable convergent validity (Cronbach's α = 0.712), and an area under the curve (AUC) value of 0.590 for the IMU sensor-based receiver-operating characteristic (ROC) curve. The findings suggest that while the evaluated IMU sensor-based system exhibited good reliability and acceptable validity, it might not be able to fully identify the recurrent fallers and non-fallers in a community-dwelling older population. Further system optimization is still needed.

Effectiveness and learning experience from undergraduate nursing students in surgical nursing skills course: a quasi- experimental study about blended learning.

BACKGROUND: Blended learning is increasingly being adopted, and yet a gap remains in the related literature pertaining to its skill performance, learning engagement and inner experience in undergraduate surgical nursing skills course. OBJECTIVES: To investigate the changes in skills performance and learning engagement in the application of blended learning, and what it actually brings to nursing students. DESIGN: The study uses a historical control, two-armed, mixed and quasi-experimental design. METHODS: The blended learning version of the course was offered to the 2019 class of 334 nursing undergraduates. Quantitative and qualitative data were collected after the course to obtain a comprehensive understanding of the course effects compared with the 304 nursing undergraduates of grade 2017 who adapted traditional learning. Quantitative data were analyzed by descriptive and inferential statistics using IBM SPSS 26.0, and qualitative data were encoded using Nvivo11.0. RESULTS: There were significant differences in skill performance and learning engagement between the class of 2017 and 2019 (p < 0.001). Combined with further analysis of the interview data, 3 first-level nodes and 8 secondary nodes were determined. Students' opinions, comments and suggestions on the application of blended learning are refreshing. CONCLUSION: Moving forward with blended learning: opportunities and challenges go hand in hand. Researchers need to continually modify their research designs to respond to variable educational environments.

A feasibility study of applying two-dimensional photogrammetry for screening and monitoring of patients with adolescent idiopathic scoliosis in clinical practice.

Standing posteroanterior radiographs have been the golden standard to quantify the severity of scoliosis deformity. However, it exposes ionizing radiation to scoliosis patients, and cannot be used for routine screening and monitoring. This study aimed to develop a protocol of measuring postural indexes by using the noninvasive and radiation-free two-dimensional (2D) photogrammetry method and identify its clinical value in scoliosis screening and monitoring. The five postural indexes were measured from the posterior view of 110 participants. One-way ANOVA with post hoc Tukey HSD/Games-Howell analysis was used to compare the differences between the participants in the scoliosis group and the non-scoliosis group. Pearson coefficients of correlation were analyzed to identify the relationships between Cobb angles and each of the five quantitative postural indexes. Based on 2D photogrammetry, the postural indexes of C7 deviation (p = 0.02), shoulder alignment (p < 0.001), scapula alignment (p < 0.001), waist angle discrepancy (p < 0.001), and PSIS alignment (p < 0.001) could significantly differentiate scoliosis and non-scoliosis patients during screening. The waist angle discrepancy (r = 0.4, p = 0.01; r = 0.8, p = 0.03; r = 0.7, p = 0.01) and shoulder alignment (r = 0.6, p = 0.03) had moderate to strong positive correlations with the Cobb angles, which supported their clinical values in monitoring scoliotic curvature changes of adolescent idiopathic scoliosis (AIS) patients.

Muscular and Kinematic Responses to Unexpected Translational Balance Perturbation: A Pilot Study in Healthy Young Adults.

Falls and fall-related injuries are significant public health problems in older adults. While balance-controlling strategies have been extensively researched, there is still a lack of understanding regarding how fast the lower-limb muscles contract and coordinate in response to a sudden loss of standing balance. Therefore, this pilot study aims to investigate the speed and timing patterns of multiple joint/muscles' activities among the different challenges in standing balance. Twelve healthy young subjects were recruited, and they received unexpected translational balance perturbations with randomized intensities and directions. Electromyographical (EMG) and mechanomyographical (MMG) signals of eight dominant-leg's muscles, dominant-leg's three-dimensional (3D) hip/knee/ankle joint angles, and 3D postural sways were concurrently collected. Two-way ANOVAs were used to examine the difference in timing and speed of the collected signals among muscles/joint motions and among perturbation intensities. This study has found that (1) agonist muscles resisting the induced postural sway tended to activate more rapidly than the antagonist muscles, and ankle muscles contributed the most with the fastest rate of response; (2) voluntary corrective lower-limb joint motions and postural sways could occur as early as the perturbation-induced passive ones; (3) muscles reacted more rapidly under a larger perturbation intensity, while the joint motions or postural sways did not. These findings expand the current knowledge on standing-balance-controlling mechanisms and may potentially provide more insights for developing future fall-prevention strategies in daily life.

Reliability and validity of assessing lower-limb muscle architecture of patients with cerebral palsy (CP) using ultrasound: A systematic review.

AIMS: To investigate the reliability, validity, and level of evidence of applying ultrasound in assessing the lower-limb muscles of patients with cerebral palsy (CP). METHOD: Publications in Medline, PubMed, Web of Science, and Embase were searched on May 10, 2023, to identify and examine relevant studies investigating the reliability/validity of ultrasound in evaluating the architecture of CP lower-limb muscles systematically, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. RESULTS: Out of 897 records, 9 publications with 111 CP participants aged 3.8-17.0 years were included (8 focused on intra-rater and inter-rater reliability, 2 focused on validity, and 4 were with high quality). The ultrasound-based measurements of muscle thickness (intra-rater only), muscle length, cross-sectional area, muscle volume, fascicle length, and pennation angle showed high reliability, with the majority of intraclass correlation coefficient (ICC) values being larger than 0.9. Moderate-to-good correlations between ultrasound and magnetic resonance imaging measurements existed in muscle thickness and cross-sectional area (0.62 ≤ ICC ≤ 0.82). INTERPRETATION: Generally, ultrasound has high reliability and validity in evaluating the CP muscle architecture, but this is mainly supported by moderate and limited levels of evidence. More high-quality future studies are needed.

Advances in Biomechanics-Based Motion Analysis.

Motion patterns in humans have been closely associated with neurological/musculoskeletal/behavioral/psychological health issues and competitive sports performance [...].

Can Computer-Aided Design and Computer-Aided Manufacturing Integrating with/without Biomechanical Simulation Improve the Effectiveness of Spinal Braces on Adolescent Idiopathic Scoliosis?

The CAD/CAM technology has been increasingly popular in manufacturing spinal braces for patients with adolescent idiopathic scoliosis (AIS) in clinics. However, whether the CAD/CAM-manufactured braces or the CAD/CAM-manufactured braces integrating with biomechanical simulation could improve the in-brace correction angle of spinal braces in AIS patients, compared to the manually manufactured braces, has remained unclear. The purpose of this systematic review and meta-analysis was to compare the in-brace correction angle of (1) computer-aided design and computer-aided manufacturing (CAD/CAM)-manufactured braces or (2) the CAD/CAM-manufactured braces integrating with biomechanical simulation with that of (3) manually manufactured braces. The Web of Science, OVID, EBSCO, PUBMED, and Cochrane Library databases were searched for relevant studies published up to March 2023. Five randomized controlled trials (RCTs) or randomized controlled crossover trials were included for qualitative synthesis, and four of them were included for meta-analysis. The meta-analysis effect sizes of the in-brace correction angle for CAD/CAM versus manual method, and CAD/CAM integrating with biomechanical simulation versus the manual method in the thoracic curve group and the thoracolumbar/lumbar curve group were 0.6° (mean difference [MD], 95% confidence intervals [CI]: -1.06° to 2.25°), 1.12° (MD, 95% CI: -8.43° to 10.67°), and 3.96° (MD, 95% CI: 1.16° to 6.76°), respectively. This review identified that the braces manufactured by CAD/CAM integrating with biomechanical simulation did not show sufficient advantages over the manually manufactured braces, and the CAD/CAM-manufactured braces may not be considered as more worthwhile than the manually manufactured braces, based on the in-brace correction angle. More high-quality clinical studies that strictly follow the Scoliosis Research Society (SRS) guidelines with long-term follow-ups are still needed to draw more solid conclusions and recommendations for clinical practice in the future.

Reducing Contact Resistance in Organic Field-Effect Transistors: A Comprehensive Comparison between 2D and Microrod Single Crystals.

A comprehensive comparison of organic single crystals based on a single material but with different dimensions provides a unique approach to probe their carrier injection mechanism. In this report, both two-dimensional (2D) and microrod single crystals with the same crystalline structure of an identical thiopyran derivative, 7,14-dioctylnaphtho[2,1-f:6,5-f']bis(cyclopentane[b]thiopyran) (C8-SS), are grown on a glycerol surface with the space-confined method. Organic field-effect transistors (OFETs) based on the 2D C8-SS single crystal exhibit superior performance compared with those based on the microrod single crystal, particularly in their contact resistance (RC). It is demonstrated that the resistance of the crystal bulk in the contact region plays a key role in RC of the OFETs. Thus, among the 30 devices tested, the microrod OFETs typically appear contact-limited, whereas the 2D OFETs possess significantly reduced RC arising from the tiny thickness of the 2D single crystal. The 2D OFETs show high operational stability and high channel mobility up to 5.7 cm2/V·s. The elucidation of the contact behavior highlights the merits and great potential of 2D molecular single crystals in organic electronics.