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Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged ≥50 (hip) or ≥38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64±8 years), baseline NRS was 3.2±2.3 in the CG and 3.5±2.4 in the IG; HOOS/KOOS-ADL was 71.6±17.7 and 69.4±17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans

Efficacy of a multimodal conservative rehabilitation program for bladder control in individuals with incomplete spinal cord injury: A randomized controlled trial.

ObjectiveThe study aimed to evaluate the efficacy of a multimodal intervention on urodynamic outcomes, urinary incontinence severity, and pelvic floor muscle strength in individuals with overactive bladder after incomplete spinal cord injury.MethodsA single-blind randomized controlled trial was conducted on 74 male participants diagnosed with overactive bladder and incomplete spinal cord injury. Participants were randomly assigned to an experimental group or a control group. Treatment was conducted for 8 weeks, three sessions per week. Outcomes were assessed at baseline, post-intervention, and the 8-week follow-up.ResultsThe experimental group showed significantly greater improvements in the measured outcomes compared with the control group (P&#x2009;<&#x2009;0.001).ConclusionIncorporating a multimodal regimen demonstrated significant efficacy in enhancing bladder capacity, continence, and muscle function in individuals with overactive bladder due to incomplete spinal cord injury.Clinical trial registry (ID: NCT07008157).https://clinicaltrials.gov/study/NCT07008157?cond=Spinal%20Cord%20Injuries&intr=Multimodal%20Rehabilitation%20Program&viewType=Card&rank=1.

Humans

Transcriptomic insights into exogenous fatty acid-enhanced halotolerance in Zygosaccharomyces rouxii.

BACKGROUND: High salinity restricts microbial growth during brine-based food fermentation. Although exogenous unsaturated fatty acids improve the salt tolerance of Zygosaccharomyces rouxii, the associated transcriptional mechanisms remain unclear. This study investigated the transcriptomic response of Z. rouxii CGMCC 3791 to palmitoleic acid (C16:1) under high salt conditions. RESULTS: Cells were cultured in yeast extract peptone dextrose (YPD) containing 120&#x2009;g&#x2009;L-1 NaCl, with or without 20&#x2009;&#x3bc;g&#x2009;mL-1 C16:1. They were analyzed by RNA sequencing. Principal component analysis clearly separated the two treatments. Using q&#x2009;<&#x2009;0.05 and |log2 fold change|&#x2009;>&#x2009;1, 23 differentially expressed genes were identified - three upregulated and 20 downregulated. INO1, MLS1, POX1, MEP2, and SOD5 were among the major responsive genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that peroxisome-associated functions, lipid metabolism, oxidative stress responses, nitrogen utilization, and mitogen-activated protein kinase (MAPK) signaling were the principal C16:1-responsive processes. CONCLUSION: Exogenous C16:1 elicited a focused transcriptional adjustment rather than broad transcriptome-wide reprogramming in salt-stressed Z. rouxii. The results indicated that peroxisome-linked lipid processes and redox regulation were candidate mechanisms underlying fatty-acid-associated halotolerance and provided targets for improving the robustness of high-salt food fermentation. &#xa9; 2026 Society of Chemical Industry.

Zygosaccharomyces rouxii

Complex evolutionary history of Rosales mediated by extensive incomplete lineage sorting and hybridization.

The angiosperm order Rosales still represents a major challenge for phylogenetic reconstruction. Although its circumscription is now well-defined, phylogenetic relationships among families are still uncertain. Here, we used nuclear, plastid, and mitochondrial genomic data from 33 species representing all nine families to further clarify interfamilial relationships and the group's evolutionary history. We detected significant phylogenetic conflict among the three datasets. Further analyses at the nuclear level identified incomplete lineage sorting (ILS) as the main cause of unstable phylogenetic positions among families. The discordant placements of Rhamnaceae and Elaeagnaceae based on plastid and mitochondrial data are caused by ancient hybridization events, potentially involving differences in organellar inheritance. Our molecular dating confirms earlier suggestions that the ancient rapid diversification of the three Rosaceae subfamilies could be the main reason for the difficulties in resolving their phylogenetic relationships. Our findings provide new insights into the interfamilial relationships of Rosales and demonstrate that the evolutionary history of this order was shaped by ancient and rapid radiation as well as extensive ILS and reticulate evolution. They also suggest that previous attempts to clarify interfamilial relationships in this order were hampered by combining nuclear and organellar sequence data, leading to inconsistent topologies observed across earlier studies.

Phylogeny

Effect of Motor-Control Exercises on Scapulohumeral and Scapulothoracic Muscle Activations in Athletes With Secondary Subacromial Impingement Syndrome.

CONTEXT: Unbalanced or uncoordinated activity across either the scapulohumeral or the scapulothoracic muscle may impair scapulohumeral rhythm during arm elevation. OBJECTIVE: To compare the effects of progressive resistance exercises (PREs), integrated with and without facilitatory motor-control exercises (MCEs), on scapulohumeral and scapulothoracic myoelectric activities in overhead athletes diagnosed with secondary subacromial impingement syndrome (SAIS). DESIGN: Randomized controlled clinical trial. SETTING: Neuromuscular Rehabilitation Research Center. PATIENTS OR OTHER PARTICIPANTS: Overhead athletes diagnosed with secondary SAIS were assigned randomly to 3 parallel groups: 2 intervention groups and 1 control group. INTERVENTIONS: All groups received contemporary physical therapy modalities every other day for 8 weeks. Intervention groups I and II also completed scapulohumeral and scapulothoracic PREs, integrated, respectively, with and without facilitatory MCEs targeting infraspinatus and lower trapezius muscles. MAIN OUTCOME MEASURES: Scapulohumeral and scapulothoracic myoelectric activities were recorded during scapular arm abduction between 80&#xb0; and 110&#xb0; before and after the prescribed treatment protocols. RESULTS: Scapulohumeral and scapulothoracic PREs reduced the corresponding myoelectric activities during scapular arm abduction within the groups (P &#x2264; .02, partial &#x3b7;2 &#x2265; 0.127). Facilitatory biofeedback-guided exercises integrated into PREs preserved scapulohumeral and scapulothoracic myoelectric activities (P &#x2264; .03), excluding teres minor myoelectric activity (P > .99). CONCLUSIONS: Scapulohumeral and scapulothoracic PREs reduced the corresponding muscle activations during scapular arm abduction in overhead athletes with secondary SAIS. Facilitatory MCEs targeting infraspinatus and lower trapezius muscles, integrated into PREs, preserved scapulohumeral and scapulothoracic muscle activations.

Humans

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n&#x202f;=&#x202f;56) compared to Enriched Supportive Therapy (n&#x202f;=&#x202f;43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group&#x202f;&#xd7;&#x202f;time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans

Acetic acid-induced translational repression involves eIF2B body formation and Ded1 sequestration into stress granules in yeast.

Elucidating the physiological impact of acetic acid stress and the corresponding yeast responses is essential for advancing fundamental biology and improving industrial alcoholic fermentation. Despite numerous genome-wide studies, information on the effects of acetic acid stress on yeast translational regulation remains limited. We found that a sublethal concentration of acetic acid (35 mM, 0.2% v/v) causes translational repression, accompanied by the formation of eIF2B bodies and the phosphorylation of eIF2&#x3b1;, both of which are involved in the regulation of translation initiation. Acetic acid also caused the sequestration of Ded1, a DEAD-box RNA helicase crucial for translation initiation, into stress granules. Removal of acetic acid restored translational activity and the proper localization of eIF2B and Ded1, indicating the reversibility of acetic acid-induced translational repression. Furthermore, when yeast cells were pretreated with 0.05% acetic acid, translational repression under subsequent 0.2% acetic acid stress was attenuated in wild-type cells but not in hrk1&#x394; cells. This indicates that Hrk1, a Pma1 activator, is required to sufficiently enhance tolerance to acetic acid-induced translational repression. These findings provide novel insights into the physiological effects of acetic acid stress on translational activity and translation-related factors in yeast cells.

Saccharomyces cerevisiae

Comparative genomic and proteomic analysis reveals orthogroup structured evolution of tick protease inhibitors.

Protease inhibitors (PIs) play central roles in regulating endogenous proteolysis and host-parasite interactions in ticks. However, the evolutionary architecture underlying their diversification across tick lineages remains insufficiently resolved. Here, we performed a genome-wide comparative analysis of predicted proteomes from 14 tick species to systematically characterize PI repertoires. In total, 4931 putative PIs were identified and grouped into 20 families using the MEROPS classification system. Further, PI families such as Antistasin, WAP-type, and Pacifastin, which have not previously been systematically reported in tick genomes, were classified. Orthogroup inference demonstrated that PI expansion is structured at the level of evolutionary lineages rather than uniformly across families. By stratifying orthogroups according to duplication burden and taxonomic conservation, we identified a broadly conserved single-copy core under strong purifying selection. Motif level analysis of serpin reactive center loops further revealed conservation of inhibitory specificity within single copy orthogroups and diversification of key functional residues in duplication-associated lineages. Integration of secretion prediction and tissue-resolved proteomics from Hyalomma anatolicum and Rhipicephalus microplus demonstrated that evolutionary stratification is reflected at the protein level. Together, these findings provide an orthogroup-resolved evolutionary framework linking duplication dynamics, molecular evolution, and tissue-level protein deployment. This integrative approach offers a systematic basis for prioritizing conserved and diversified PI lineages for future functional and anti-tick intervention studies.

Animals

The spatial and temporal distribution of Staphylococcus aureus along a tropical Hawaiian watershed.

Staphylococcus aureus is a leading cause of community-acquired skin and soft-tissue infections worldwide. One major route of exposure is recreating in marine waters, but knowledge is limited regarding the drivers of S. aureus in surface waters that discharge into marine environments. This study explores spatial and temporal distributions of S. aureus, including antimicrobial-resistant and virulence genes, using both culture-dependent and molecular techniques across a tropical Hawaiian watershed with a gradient of human influence. Negative binomial generalized linear mixed models revealed that the interaction between spatial and temporal factors was the strongest predictor of S. aureus and associated genes. Cultured S. aureus was highest at mid-watershed sites in summer, which included a popular swimming hole, suggesting human shedding as a significant source. Molecular detection of S. aureus (femA gene) yielded concentrations two orders of magnitude higher than cultured concentrations and peaked at estuarine sites with the greatest nutrients and water residence times. In the winter at upstream sites with no public access, staphylococci antibiotic-resistant (mecA) and S. aureus virulence gene (etb) were elevated, indicating highly pathogenic S. aureus strains in surface waters may originate from zoonotic sources. Our findings indicate that human and zoonotic sources contribute antibiotic-resistant and virulent S. aureus to watersheds, with streams facilitating environmental transmission to marine waters. This watershed-scale assessment enables the prediction of spatial and temporal conditions associated with elevated S. aureus concentrations, thereby reducing exposure and infections.

Staphylococcus aureus

Comparative Transcriptomics Reveals Shared Downstream Pathways in Craniofacial Pathology.

Treacher Collins syndrome and Nager syndrome are craniofacial developmental disorders caused by defects in ribosome biogenesis and RNA splicing, respectively, yet they exhibit overlapping abnormalities affecting neural crest cell-derived craniofacial structures. To investigate shared downstream pathogenic mechanisms, we performed a comparative transcriptomic analysis of zebrafish polr1c and sf3b4 mutant models from our previous studies. Comparative analysis identified 17 shared differentially expressed genes (DEGs) between polr1c and sf3b4 mutants, with the majority of shared genes dysregulated in the same direction, indicating a coordinated rather than random transcriptional response. Gene ontology analysis identified ATP-dependent protein folding chaperone activity as the only shared molecular function, driven in part by upregulation of hsp90aa1.2, indicating a common proteostasis response. Because chaperone activity is linked to extracellular matrix (ECM) protein processing, we cross-referenced DEGs from both mutants against the curated zebrafish matrisome. Three of the 17 shared DEGs (serpinh1b, il11a, and lepa) were matrisome-associated and upregulated in both mutants. Serpinh1b, a collagen-specific chaperone, was strongly expressed in craniofacial cartilage and mesenchymal populations during pharyngeal arch development and exhibited nearly identical fold changes in both mutants. Il11a is of particular interest because its receptor, IL11RA, is known to be associated with human craniosynostosis, suggesting potential relevance to craniofacial development. Together, it is possible to hypothesize that shared chaperone-associated transcriptional changes, together with altered ECM-related gene expression, may contribute to polr1c- and sf3b4-associated craniofacial disorders, warranting further functional validation.

Extracellular Matrix

Effect of Global Postural Re-Education in Individuals With Text Neck Syndrome: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: This study investigated the effect of Global Postural Re-Education (GPR) versus conventional physical therapy in text neck syndrome (TNS). A prospective, single-blinded, parallel-group randomized controlled trial design was used. METHODS: Sixty participants with TNS (aged 18-40&#xa0;years) were randomly assigned to either conventional treatment or GPR plus conventional treatment. Both groups received supervised therapy for three sessions per week over 4&#xa0;weeks. Outcome measures included craniovertebral and shoulder angles assessed by photogrammetry, pain intensity via Visual Analog Scale, and Cervical Range of Motion via a smartphone application (Clinometer). Measured before and after the intervention. RESULTS: Within-group analyses showed significant improvements in pain and CROM in both groups (p&#xa0;<&#xa0;0.001). However, the between-group analysis revealed no superiority of GPR for pain or CROM (p&#xa0;>&#xa0;0.05). In contrast, GPR demonstrated statistically significant superiority in postural correction, with greater improvements in craniovertebral angle (MD: 2.14&#xb0;; 95% CI: 0.69-3.59; p&#xa0;=&#xa0;0.005) and shoulder angle (MD: 3.2&#xb0;; 95% CI: 0.33-6.07; p&#xa0;=&#xa0;0.03), exceeding MCID thresholds and indicating clinically meaningful benefits. However, these findings should be interpreted with caution because of the longer session duration in the GPR group. DISCUSSION: Incorporating Global Postural Reeducation (GPR) into conventional treatment provided significant additional benefits for postural parameters (craniovertebral and shoulder angles) in individuals with text neck syndrome. However, GPR demonstrated no added superiority over conventional treatment alone regarding pain intensity and cervical range of motion outcomes.

Humans

Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% &#x2265;3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

Humans

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or &#x2265;2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (&#x2265;160-179 and/or &#x2265;100-109 mmHg), and severe (&#x2265;180 and/or &#x2265;110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or &#x2265;2 blood pressures &#x2265; 140 and/or &#x2265;90 mmHg at &#x2265;20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans

Meta-Analysis of the Efficacy of Ultrasound-Guided Mammotome Minimally Invasive Surgery and Traditional Open Surgery in the Therapy of Benign Breast Tumors.

ObjectiveTo systematically analyze the efficacy of ultrasound-guided mammotome minimally invasive surgery and traditional open surgery in the therapy of benign breast tumors.MethodsA computerized search retrieved original literature on the therapeutic effects of ultrasound-guided mammotome minimally invasive surgery and traditional open surgery for benign breast tumors from authoritative databases, including CNKI, Wanfang, VIP, Web of Science, PubMed, ScienceDirect, Cochrane Library, and Embase. The search covered from database inception to January 2024, using a strategy of subject terms combined with free terms. The retrieved literature was screened, data were extracted, and quality was evaluated. Meta-analysis was performed using RevMan 5.4 software.ResultsA total of 8 literatures were included in the study, and a total of 1909 patients with benign breast tumors were found from 2018 to 2023. The results of meta-analysis showed that the operation time [MD = -12.79, 95%CI (-14.04, -11.55), P < 0.00001], intraoperative blood loss [MD = -11.55, 95%CI (-14.74, -8.36), P < 0.00001], healing time [MD = -2.73, 95%CI (-4.03, -1.43), P < 0.00001] and complication rate [MD = 0.17, 95%CI (0.12, 0.26), P < 0.00001] was apparently different from traditional open surgery (P < 0.05).ConclusionUltrasound-guided mammotome minimally invasive surgery can effectively shorten the operation time of patients with benign breast tumors, reduce intraoperative blood loss, promote healing, and reduce the risk of complications. The effect is better than that of traditional open surgery.

Humans

The Effect of Game-Based Virtual Reality Rehabilitation and Its Impact on Upper Extremity Function After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often results in prolonged recovery and limited shoulder function. Conventional physical therapy rehabilitation programs require sustained patient engagement; however, adherence is frequently low. Game-based virtual reality (VR) offers an interactive and engaging environment that may enhance rehabilitation outcomes. OBJECTIVE: To evaluate the effect of a game-based VR program on the function of the upper limb in patients following ARCR. METHODS: A randomized controlled trial was conducted with patients who underwent ARCR. Participants were randomized into two groups: game-based VR or conventional rehabilitation. Outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand score, pain severity by the Numerical Pain Rating Scale, range of motion measures, and muscle strength testing. Assessments were performed at baseline and at 6 weeks and 12 weeks post surgery. RESULTS: Results have shown significant within-group improvements in pain, function, range of motion, and isometric muscle strength across all time points (P < 0.05). Between-group analysis revealed greater improvements in pain, function, flexion range, and abduction and external rotation strength in the experimental group at both time points (P < 0.05). Abduction range improved significantly only at 12 weeks (P = 0.02), whereas external rotation range showed no significant difference between groups at either time point (P > 0.05). CONCLUSION: The findings indicate that integrating game-based VR rehabilitation provides additional benefits over conventional therapy in improving pain and upper extremity function following ARCR. These findings support the use of VR as an effective alternative to the conventional rehabilitation for postoperative rehabilitation.

Humans

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer

The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency and promotes leaf regeneration.

Transformation is an indispensable tool for plant genetics and functional genomics. Although stable transformation in maize is no longer a major obstacle, there remains a need for accessible and efficient methods for academic laboratories. Here, we present the GGB&#xa0;system, a rapid and efficient approach optimized for immature embryo transformation in B104 and other maize lines. This system combines two distinct morphogenetic regulators, the wheat GRF4-GIF1 chimera and the maize BABY BOOM (BBM) transcription factor (hence the name "GGB") with a modified QuickCorn protocol, enabling regeneration of transformed maize plantlets in c. 2 months with an efficiency 7-fold higher than when compared to either morphogenic factor used in isolation. Expression of both regulators did not significantly affect development, eliminating the need to excise them after regeneration. However, transmission of the transgenic GGB construct through pollen was significantly reduced, potentially aiding transgenic line containment. We show that the GGB system is adaptable for CRISPR-Cas9 editing and reporter line generation. Furthermore, stable GGB transformants exhibited high leaf regeneration capacity via somatic embryogenesis. RNA-seq time-course profiling of GGB leaf cultures identified additional factors that could promote regeneration and led to the discovery of asparagine and trehalose as additional media components that significantly enhanced leaf regeneration.

Zea mays

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC