Shoot-to-root translocated GmNN1/FT2a triggers nodulation and regulates soybean nitrogen nutrition.

Symbiotic nitrogen fixation (SNF) provides sufficient nitrogen (N) to meet most legume nutrition demands. In return, host plants feed symbionts carbohydrates produced in shoots. However, the molecular dialogue between shoots and symbionts remains largely mysterious. Here, we report the map-based cloning and characterization of a natural variation in GmNN1, the ortholog of Arabidopsis thaliana FLOWERING LOCUS T (FT2a) that simultaneously triggers nodulation in soybean and modulates leaf N nutrition. A 43-bp insertion in the promoter region of GmNN1/FT2a significantly decreased its transcription level and yielded N deficiency phenotypes. Manipulating GmNN1/GmFT2a significantly enhanced soybean nodulation, plant growth, and N nutrition. The near-isogenic lines (NILs) carrying low mRNA abundance alleles of GmNN1/FT2a, along with stable transgenic soybeans with CRISPR/Cas9 knockouts of GmNN1/FT2a, had yellower leaves, lower N concentrations, and fewer nodules than wild-type control plants. Grafting together with split-root experiments demonstrated that only shoot GmNN1/FT2a was responsible for regulating nodulation and thereby N nutrition through shoot-to-root translocation, and this process depends on rhizobial infection. After translocating into roots, shoot-derived GmNN1/FT2a was found to interact with GmNFYA-C (nuclear factor-Y subunit A-C) to activate symbiotic signaling through the previously reported GmNFYA-C-ENOD40 module. In short, the description of the critical soybean nodulation regulatory pathway outlined herein sheds novel insights into the shoot-to-root signaling required for communications between host plants and root nodulating symbionts.

Bioinformatics-based analysis of programmed cell death pathway and key prognostic genes in gastric cancer: Implications for the development of therapeutics.

BACKGROUND: Gastric cancer (GC) represents a major global health burden as a result of its high incidence and poor prognosis. The present study examined the role of the programmed cell death (PCD) pathway and identified key genes influencing the prognosis of patients with GC. METHODS: Bioinformatics analysis, machine learning techniques and survival analysis were systematically integrated to identify core prognostic genes from the The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset. A prognostic model was then developed to stratify patients into high-risk and low-risk groups, and further validated in the GSE84437 dataset. The model also demonstrated clinical relevance with tumor staging and histopathology. Immune infiltration analysis and the potential benefits of immunotherapy for each risk group were assessed. Finally, subgroup analysis was performed based on the expression of three key prognostic genes. RESULTS: Three core prognostic genes (CAV1, MMP9 and MAGEA3) were identified. The prognostic model could effectively differentiate patients into high-risk and low-risk groups, leading to significantly distinct survival outcomes. Increased immune cell infiltration was observed in the high-risk group, and better potential for immunotherapy outcomes was observed in the low-risk group. Pathways related to cancer progression, such as epithelial-mesenchymal transition and tumor necrosis factor-α signaling via nuclear factor-kappa B, were enriched in the high-risk group. By contrast, the low-risk group showed a number of pathways associated with maintenance of cell functionality and immune responses. The two groups differed in gene mutation patterns and drug sensitivities. Subgroup analysis based on the expression of the three key genes revealed two distinct clusters with distinct survival outcomes, tumor immune microenvironment characteristics and pathway enrichment. CONCLUSIONS: The present study offers novel insights into the significance of PCD pathways and identifies key genes associated with the prognosis of patients with GC. This robust prognostic model, along with the delineation of distinct risk groups and molecular subtypes, provides valuable tools for risk stratification, treatment selection and personalized therapeutic interventions for GC.

Transcriptomic analysis reveals the regulatory mechanisms of messenger RNA (mRNA) and long non-coding RNA (lncRNA) in response to waterlogging stress in rye (Secale cereale L.).

BACKGROUND: Waterlogging stress (WS) negatively impacts crop growth and productivity, making it important to understand crop resistance processes and discover useful WS resistance genes. In this study, rye cultivars and wild rye species were subjected to 12-day WS treatment, and the cultivar Secale cereale L. Imperil showed higher tolerance. Whole transcriptome sequencing was performed on this cultivar to identify differentially expressed (DE) messenger RNAs (DE-mRNAs) and long non-coding RNAs (DE-lncRNAs) involved in WS response. RESULTS: Among the 6 species, Secale cereale L. Imperil showed higher tolerance than wild rye species against WS. The cultivar effectively mitigated oxidative stress, and regulated hydrogen peroxide and superoxide anion. A total of 728 DE-mRNAs and 60 DE-lncRNAs were discovered. Among these, 318 DE-mRNAs and 32 DE-lncRNAs were upregulated, and 410 DE-mRNAs and 28 DE-lncRNAs were downregulated. GO enrichment analysis discovered metabolic processes, cellular processes, and single-organism processes as enriched biological processes (BP). For cellular components (CC), the enriched terms were membrane, membrane part, cell, and cell part. Enriched molecular functions (MF) terms were catalytic activity, binding, and transporter activity. LncRNA and mRNA regulatory processes were mainly related to MAPK signaling pathway-plant, plant hormone signal transduction, phenylpropanoid biosynthesis, anthocyanin biosynthesis, glutathione metabolism, ubiquitin-mediated proteolysis, ABC transporter, Cytochrome b6/f complex, secondary metabolite biosynthesis, and carotenoid biosynthesis pathways. The signalling of ethylene-related pathways was not mainly dependent on AP2/ERF and WRKY transcription factors (TF), but on other factors. Photosynthetic activity was active, and carotenoid levels increased in rye under WS. Sphingolipids, the cytochrome b6/f complex, and glutamate are involved in rye WS response. Sucrose transportation was not significantly inhibited, and sucrose breakdown occurs in rye under WS. CONCLUSIONS: This study investigated the expression levels and regulatory functions of mRNAs and lncRNAs in 12-day waterlogged rye seedlings. The findings shed light on the genes that play a significant role in rye ability to withstand WS. The findings from this study will serve as a foundation for further investigations into the mRNA and lncRNA WS responses in rye.

Global prevalence and factors associated with preoperative depression in women undergoing breast surgery: a meta-analysis and meta-regression.

PURPOSE: Depression is one of the main psychological responses experienced by patients with breast cancer perioperatively. Therefore, this review aimed to synthesize the prevalence rate of depression preoperatively among patients with breast cancer. METHODS: Six databases were searched for published articles, which recruited female patients aged 18 years and above, diagnosed with breast cancer and planned for breast surgery. Grey literatures were searched from ProQuest Theses and Dissertations, Science.gov and CogPrints. Studies published in English from the inception of databases to January 2023 were considered. Two reviewers screened, extracted, and appraised the data independently. Joanna Briggs Institute data collection form was used for data collection. Hoy's Risk of Bias Tool was utilized to assess the individual study's quality. Review Manager 5.4 software was utilized for meta-analysis. Subgroup analyses were conducted to explore the reasons for any heterogeneity. Publication bias was evaluated by Egger's test and funnel plot. RESULTS: Twenty studies involving 32,143 patients with breast cancer were included. Meta-analyses revealed an overall preoperative prevalence of 30% among all studies. Subgroup analyses showed that studies conducted in the Middle East and North Africa used purposive sampling, with patients undergoing mastectomy and lumpectomy and with moderate risk of bias reported higher prevalence of preoperative depression (54%, 44%, 40%, and 49%, respectively) as compared to other respective subgroups. CONCLUSION: The high prevalence of preoperative depression among women with breast cancer indicated the need for health care professionals to provide more psychological support to them.

Potential transceptor AtNRT1.13 modulates shoot architecture and flowering time in a nitrate-dependent manner.

Compared with root development regulated by external nutrients, less is known about how internal nutrients are monitored to control plasticity of shoot development. In this study, we characterize an Arabidopsis thaliana transceptor, NRT1.13 (NPF4.4), of the NRT1/PTR/NPF family. Different from most NRT1 transporters, NRT1.13 does not have the conserved proline residue between transmembrane domains 10 and 11; an essential residue for nitrate transport activity in CHL1/NRT1.1/NPF6.3. As expected, when expressed in oocytes, NRT1.13 showed no nitrate transport activity. However, when Ser 487 at the corresponding position was converted back to proline, NRT1.13 S487P regained nitrate uptake activity, suggesting that wild-type NRT1.13 cannot transport nitrate but can bind it. Subcellular localization and ß-glucuronidase reporter analyses indicated that NRT1.13 is a plasma membrane protein expressed at the parenchyma cells next to xylem in the petioles and the stem nodes. When plants were grown with a normal concentration of nitrate, nrt1.13 showed no severe growth phenotype. However, when grown under low-nitrate conditions, nrt1.13 showed delayed flowering, increased node number, retarded branch outgrowth, and reduced lateral nitrate allocation to nodes. Our results suggest that NRT1.13 is required for low-nitrate acclimation and that internal nitrate is monitored near the xylem by NRT1.13 to regulate shoot architecture and flowering time.

An Exploratory Study of Alternative Time Frames and Descriptors for EQ-5D-5L in Obstructive Airway Diseases Using Mixed Methods.

OBJECTIVES: EQ-5D-5L with its recall time of "today" may limit its ability to capture episodic symptoms and exacerbations in chronic obstructive airway diseases (OAD). We examined whether longer time frames and changing the intensity response scales to frequency scales could improve the measurement properties of EQ-5D-5L. METHODS: We used a mixed-method design starting with in-depth interviews with 20 patients and clinicians to elicit preferred time frames using concept elicitation techniques and content analyses. We then administered the top 4 preferred variants using 1- and 4-weeks' time frames with the original intensity or an alternative frequency response scale alongside EQ-5D-5L and St George Respiratory Questionnaire to OAD patients during 2 different visits. We compared the ceiling effects and construct validity by testing a priori hypotheses in relation to St George Respiratory Questionnaire and clinical outcomes via correlation and receiver operating characteristic (ROC) analyses, respectively. Follow-up patients were categorized into "better," "stable," and "worse" groups to assess reliability using intraclass correlation coefficient (ICC) or Cohen's Kappa (k) and responsiveness using ROC analysis. RESULTS: A total of 184 patients (mean [SD] age: 54[18]; female: 37.0%) completed baseline assessments. A total of 120 patients also completed follow-up assessments (mean [SD] interval: 2.8 [1.7] months). The ceilings were lower in the variants compared with EQ-5D-5L (P < .001). Reliability of the variants were comparable to or higher than EQ-5D-5L. The c-statistic values derived from ROC analyses of the variants were consistently higher than EQ-5D-5L. CONCLUSIONS: Use of longer time frames with the original intensity or the frequency response scales may improve EQ-5D-5L's psychometric properties in OAD patients.

The Ceiling Effects of EQ-5D-3L and 5L in General Population Health Surveys: A Systematic Review and Meta-Analysis.

OBJECTIVES: This review aims to examine the ceiling effects of EQ-5D-3L (3L) and EQ-5D-5L (5L) in general adult populations and identify the factors influencing these effects. METHODS: We searched 8 databases for observational studies published in English from inception to 24 July 2023. Ceiling effects were calculated by dividing the number of participants reporting full health at dimension or profile level by the total sample size. Subgroup analysis and meta-regression using the metafor package in R software were performed. RESULTS: We identified 94 studies from 70 articles, including 4 543 647 adults across 37 countries. The global pooled proportion of individuals reporting full health ("11111") was 56% (95% CI 51%-62%) for 3L and 49% (95% CI 44%-54%) for 5L. The self-care dimension showed the highest ceiling effects (3L: 97%; 5L: 94%), whereas pain/discomfort had the lowest (3L: 69%; 5L: 60%). The ceiling effects in East/South-East Asia were higher than in Europe by 25% (95% CI 18%-32%) in 3L and 9% (95% CI -2%-20%) in 5L. Adjusting for mean age and proportion of males, significant regional differences persisted in the overall profile level of 3L, in all 3L dimensions (except for self-care), and 5L dimensions (except for pain/discomfort and anxiety/depression). CONCLUSIONS: This review highlights significant ceiling effects in the EQ-5D, especially in Asian populations. The 5L version exhibited fewer ceiling effects than the 3L, indicating its superiority for general population surveys. Further research is crucial to understand the disparities in self-reported health outcomes between Asians and other populations.

Cobalt-catalyzed amination of aziridines and azetidines toward 1,2- and 1,3-diamines.

Diamines play important roles in synthetic organic chemistry and thus facilitate life and materials sciences. Herein we report a cobalt-catalyzed ring opening, nucleophilic amination of aziridines and azetidines with N-fluorosulfonamides toward a wide range of 1,2- and 1,3-diamine derivatives in moderate to good yields under mild conditions.

Association of a healthy ageing index with health-related outcomes in a multi-ethnic cohort from Singapore.

BACKGROUND: The global population is ageing rapidly and it is important to promote healthy ageing. The Healthy Ageing Index (HAI) is a comprehensive measure of health, but there is limited research on its association with other age-related outcomes. The management of an aging population necessitates considerations even among generally healthy adults, as age-related diseases often remain unaccounted for until later stages of life. This study explores the association of risk factors with HAI and its association with peripheral artery disease (PAD), muscle strength, health-related quality of life (HRQoL), and psychological distress in the Singapore Multi-Ethnic Cohort study. METHODS: This cross-sectional study involved 1909 participants (median (Q1, Q3) age: 53 (48, 60) years and 59.3% females) from Singapore Multi-Ethnic Cohort study. The risk factors of HAI included age, gender, ethnicity, education level, smoking, alcohol consumption, employment, BMI and past medical histories. PAD was assessed using ankle-brachial index (ABI), handgrip strength (HGS), HRQoL with the EQ-5D-5 L questionnaire and psychological distress via the Kessler Psychological Distress Scale (K10). HAI components were assessed using relevant marker tests. RESULTS: Older age, Malay and Indian ethnicities, unemployment, high BMI and histories of CHD, hypercholesterolaemia, tumours and TIA/stroke were associated with lower HAI scores indicative of poorer health. Higher HAI scores were associated with females and higher education levels. Lower HAI scores were significantly associated with low ABI, high K10 scores, mobility and anxiety/depression dimensions of EQ-5D-5 L. CONCLUSION: The most important factors associated with HAI were age, sex, ethnicity, education, unemployment, BMI and a history of health conditions. Lower HAI scores were significantly associated with PAD, lower HRQoL and psychological distress. Thus, the HAI demonstrates promise as an evaluation method for assessing PAD, overall muscle strength and HRQoL in a population-based setting.

Functional Characterization of the First Bona Fide Phytoene Synthase in Red Algae from Pyropia yezoensis.

The formation of phytoene by condensing two geranylgeranyl diphosphate molecules catalyzed by phytoene synthase (PSY) is the first committed and rate-limiting step in carotenoid biosynthesis, which has been extensively investigated in bacteria, land plants and microalgae. However, this step in macroalgae remains unknown. In the present study, a gene encoding putative phytoene synthase was cloned from the economic red alga Pyropia yezoensis-a species that has long been used in food and pharmaceuticals. The conservative motifs/domains and the tertiary structure predicted using bioinformatic tools suggested that the cloned PyPSY should encode a phytoene synthase; this was empirically confirmed by pigment complementation in E. coli. This phytoene synthase was encoded by a single copy gene, whose expression was presumably regulated by many factors. The phylogenetic relationship of PSYs from different organisms suggested that red algae are probably the progeny of primary endosymbiosis and plastid donors of secondary endosymbiosis.

Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein-protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management.

Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials.

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No adverse event signals were detected in the treatment groups. Conclusion and Relevance: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.

BZW2 Modulates Lung Adenocarcinoma Progression through Glycolysis-Mediated IDH3G Lactylation Modification.

Histone lactylation (Hla) is a metabolically stress-related histone modification that featured in specific gene expression regulation. However, the role of Hla in the pathogenesis of lung adenocarcinoma (LUAD) remains unexplored. Through bioinformatics analysis, we found that BZW2 exhibited an elevated level of expression in LUAD tissues, which was associated with a poor prognosis. Flow cytometry and TUNEL assay were used to analyze the apoptosis of LUAD cells and tissues, respectively. The effect of the cell function experiment on the LUAD cell phenotype was analyzed. An XF 96 Extracellular Flux Analyzer measured the ECAR value, and kits were used to detect lactate production and glucose consumption. Animal experiments were performed for further verification. Cell experiments showed that BZW2 fostered the malignant progression of LUAD by promoting glycolysis-mediated lactate production and lactylation of IDH3G. In a compelling in vivo validation, the inhibition of Hla could suppress the malignant progression of LUAD. Knockdown of BZW2 combined with 2-DG treatment significantly repressed tumor growth in mice. BZW2 could regulate the progression of LUAD through glycolysis-mediated IDH3G lactylation, offering a theoretical basis for the targeted treatment of LUAD with glycolysis and Hla.

Elucidating the role of T-cell exhaustion-related genes in colorectal cancer: a single-cell bioinformatics perspective.

Colorectal cancer (CRC) remains a significant global health issue. In this study, the role of T-cell exhaustion-related genes (TEXs) in CRC was investigated using single-cell and bulk RNA-seq analysis. This research involved extensive data analysis using multiple databases, including the TCGA-COAD cohort, GSE14333, and GSE39582. Through single-cell analysis, distinct cell populations within CRC samples were identified and classified T-cells into four subgroups: regulatory T-cells (Tregs), conventional CD4+ T-cells (CD4+ T conv), CD8+ T, and CD8+ T exhausted cells. Intercellular communication networks and signaling pathways associated with TEXs using computational tools such as CellChat and PROGENy. Additionally, TEX-related alterations in tumor gene pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Prognostic models were developed, and their correlation with immune infiltration was assessed. The study revealed the presence of distinct cell populations within CRC, with TEXs playing a crucial role in the tumor microenvironment. CD8+ T exhausted cells exhibited expression of specific markers, indicating their involvement in tumor immune evasion. CellChat and PROGENy analyses revealed intricate communication networks and signaling pathways associated with TEXs, including RNA splicing and viral carcinogenesis. Furthermore, the prognostic risk model developed on the basis of TEXs demonstrated its efficacy in stratifying CRC patients. This risk model exhibited strong correlations with immune infiltration by various effector immune cells, highlighting the influence of TEXs on the tumor immune response. The complex interactions and signaling pathways underlying TEX-associated immune dysregulation in CRC were revealed by employing advanced analytical approaches. The development of a prognostic risk model based on TEXs offers a promising tool for prognostic stratification in patients with CRC. Furthermore, the correlations observed between TEXs and immune infiltration provide valuable insights into the potential of TEXs as therapeutic targets and highlight the need for further investigation into TEX-mediated immune evasion mechanisms. This study thus provides valuable insights into the role of TEXs in CRC.

CRISPR-Cas9 screening identified lethal genes enriched in necroptosis pathway and of prognosis significance in osteosarcoma.

BACKGROUND: The present study aimed to identify indispensable genes associated with tumor cell viability according to the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) datasets, which may support new therapeutic targets for patients with osteosarcoma. METHODS: The transcriptome patterns between tumor and normal tissues, which were obtained from the Therapeutically Applicable Research to Generate Effective Treatments dataset, were overlapped with the genomics associated with cell viability screened by CRISPR-Cas9 technology. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were employed to determine enrichment pathways related to lethal genes. Least absolute shrinkage and selection operator (LASSO) regression was employed to construct a risk model related to lethal genes for predicting clinical outcomes of osteosarcoma. Univariate and multivariate Cox regressions were conducted to assess the prognostic value of this feature. Weighted gene co-expression network analysis was performed to identify modules associated with patients with high-risk score. RESULTS: In total, 34 lethal genes were identified in this investigation. These genes were enriched in the necroptosis pathway. The risk model based on LASSO regression algorithm distinguishes patients with high-risk score from patients with low-risk score. Compared with low-risk patients, high-risk patients showed a shorter overall survival rate in both the training and validation sets. The time-dependent receiver operating characteristic curves of 1, 3 and 5 years displayed that the risk score has great prediction performance. The necroptosis pathway represents the main difference in biological behavior between the high-risk group and the low-risk group. Meanwhile, CDK6 and SMARCB1 may serve as important targets for detecting osteosarcoma progression. CONCLUSIONS: The present study developed a predictive model that outperformed classical clinicopathological parameters for predicting the clinical outcomes of osteosarcoma patients and identified specific lethal genes, including CDK6 and SMARCB1, as well as the necroptosis pathway. These findings may serve as potential targets for future osteosarcoma treatments.

Molecular mechanisms of rapid-acting antidepressants: New perspectives for developing antidepressants.

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.

Effect of Bushen Tiansui Decoction on Delayed Fracture Healing: A Systematic Review and Meta-analysis.

This review aimed to validate the therapeutic potential of Bushen Tiansui decoction (BSTSD), a traditional Chinese formulation, in treating delayed union of fractures. Comprehensive database searches identified randomized controlled trials up to September 13, 2022, assessing BSTSD's efficacy in delayed fracture healing. Outcomes were bone metabolism indexes and Harris hip scores. Quality and risk assessments were conducted using the Cochrane Collaboration's tools. Data were analyzed using RevMan software, with sensitivity analysis through Stata. BSTSD significantly improved bone GLA protein (SMD=1.76, P<0.00001) and alkaline phosphatase (SMD=1.31, P<0.00001). Additionally, Harris hip scores for pain, function, deformity, and motion showed marked improvement. BSTSD treatment also demonstrated enhanced clinical efficiency (RR=1.27, P<0.00001) with fewer complications. Sensitivity analyses indicated consistent results. BSTSD shows promise in treating delayed fracture unions, yet conclusions necessitate further high-quality research for validation.

Mother-Infant Group Intervention on Maternal Depression and Bonding: A Quasi-Experimental Study.

OBJECTIVES: Parent-Infant Psychotherapy (PIP) aims at improving the interaction between parents and their infants. Group intervention has advantages in facilitating universality, support, and social learning. However, the researches on PIP adoption in a group format are limited. This study aims to explore the outcome of a mother-infant group on bonding and maternal depression. METHODS: Eighty-two infant mothers with subjective distress on parenting or depressed mood were recruited to participate in the intervention group (IG). Another sample of one hundred and ninety-four postpartum women was recruited as the control group (CG). Instruments for outcome measure were the Mother-Infant Bonding Scale, Edinburgh Postnatal Depression Scale (EPDS), Beck Depression Inventory-Second Edition (BDI-II), and Social Network Interaction System Questionnaire. Twelve courses of mother-infant groups were conducted for IG women. Each course consisted of twelve 90-min sessions. IG women joined the intervention with their infants and replied to the instruments at baseline, post-intervention, and follow-up. CG women replied to the instruments at similar intervals. Primary data analyses were performed by the intent-to-treat analysis, ANOVA, and GEE. RESULTS: Relative to CG participants, the IG women experienced significant benefits in most mother-infant bonding scores at both post-intervention and follow-up (ps = .000 - .026). IG women also experienced a greater reduction in follow-up depressive symptoms measured by EPDS (p = .023). However, no significant reduction was noted on BDI-II. CONCLUSIONS: Mother-infant group intervention has preliminary effects on improving bonding and reducing depressive symptoms for women with infants. Further studies are warranted to replicate the results.

Literature indicates detrimental impacts of adverse bonding and maternal depression on children development. Parent-infant group psychotherapy suggests a positive effect on facilitating bonding and reducing depression severity. However, the evidence is limited and inconclusive. Since the treatment has never been applied in Taiwan, its effect and feasibility on Taiwanese women is unknown. The results established a preliminary positive outcome of parent-infant group on maternal bonding and depression. Also, by the first practice, we observe the participants have well motivation to join intervention with their infants and with other women. Parent-infant group is a promising treatment that warranted further exploration.

Circ-BICC1 Knockdown Alleviates Lipopolysaccharide (LPS)-Induced WI-38 Cell Injury Through miR-338-3p/MYD88 Axis.

Circular RNAs (circRNAs) play important roles in human diseases, including infantile pneumonia. In this article, we aimed to investigate the functions of circ-BICC1 in lipopolysaccharide (LPS)-induced injury of WI-38 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circ-BICC1, BICC1, microRNA-338-3p (miR-338-3p), and myeloid differentiation primary response 88 (MYD88). Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry analysis were conducted to evaluate cell viability, proliferation, and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used for the concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The levels of oxidative stress markers were detected with commercial kits. Dual-luciferase reporter assay was adopted to analyze the interaction between circ-BICC1 and miR-338-3p, as well as MYD88 and miR-338-3p. Western blot assay was employed for the protein level of MYD88. Circ-BICC1 level was increased in pneumonia patients' blood samples and LPS-treated WI-38 cells. LPS treatment suppressed WI-38 cell viability and promoted cell apoptosis, inflammation, and oxidative stress. Circ-BICC1 knockdown reversed the effect of LPS-induced WI-38 cell injury. For mechanism analysis, circ-BICC1 could function as the sponge for miR-338-3p and miR-338-3p inhibition reversed the effect of circ-BICC1 knockdown on LPS-induced WI-38 cell injury. MYD88 was identified as the target of miR-338-3p. MiR-338-3p overexpression relieved LPS-induced injury of WI-38 cells, while the impact was abolished by elevating MYD88. Circ-BICC1 silencing remitted LPS-triggered WI-38 cell damage by adsorbing miR-338-3p and regulating MYD88.

Enzymatic Glucose Fiber Sensor for Glucose Concentration Measurement with a Heterodyne Interferometry.

In this study, we developed a glucose fiber sensor incorporating heterodyne interferometry to measure the phase difference produced by the chemical reaction between glucose and glucose oxidase (GOx). Both theoretical and experimental results showed that the amount of phase variation is inversely proportional to glucose concentration. The proposed method provided a linear measurement range of the glucose concentration from 10 mg/dL to 550 mg/dL. The experimental results indicated that the sensitivity is proportional to the length of the enzymatic glucose sensor, and the optimum resolution can be obtained at a sensor length of 3 cm. The optimum resolution of the proposed method is better than 0.6 mg/dL. Moreover, the proposed sensor demonstrates good repeatability and reliability. The average relative standard deviation (RSD) is better than 10% and satisfied the minimum requirement for point-of-care devices.