Happy people are always similar: The evidence from brain morphological and functional inter-subject correlations.

A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.

Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

Minimizing Undesired Side Reactions Induced by Nanoscale Conductive Carbon Enables Stable Cycling of Semi-Solid Li-Ion Full Batteries.

Semi-solid lithium-ion batteries (SSLIBs) based on "slurry-like" electrodes hold great promise to enable low-cost and sustainable energy storage. However, the development of the SSLIBs has long been hindered by the lack of high-performance anodes. Here the origin of low initial Coulombic efficiency (iCE, typically <60%) is elucidated in the graphite-based semi-solid anodes (in the non-flowing mode) and develop rational strategies to minimize the irreversible capacity loss. It is discovered that Ketjen black (KB), a nanoscale conductive additive widely used in SSLIB research, induces severe electrolyte decomposition during battery charge due to its large surface area and abundant surface defects. High iCEs up to 92% are achieved for the semi-solid graphite anodes by replacing KB with other low surface-area, low-defect conductive additives. A semi-solid full battery (LiFePO4 vs graphite, in the non-flowing mode) is further demonstrated with stable cycle performance over 100 cycles at a large areal capacity of 6 mAh cm-2 and a pouch-type semi-solid full cell that remains functional even when it is mechanically abused. This work demystifies the SSLIBs and provides useful physical insights to further improve their performance and durability.

Distant metastasis identification based on optimized graph representation of gene interaction patterns.

Metastasis is a major cause of cancer morbidity and mortality, and most cancer deaths are caused by cancer metastasis rather than by the primary tumor. The prediction of metastasis based on computational methods has not been explored much in the previous research. In this study, we proposed a graph convolutional network embedded with a graph learning (GL) module, named glmGCN, to predict the distant metastasis of cancer. Both the mRNA and lncRNA expressions were used to provide more genetic information than using the mRNA alone and we used them to construct gene interaction graph representation to consider the effect of genetic interaction. Then, the prediction of the cancer metastasis was performed under a GCN framework, which extracted informative and advanced features from the built non-regular graph structures. Particularly, a GL module was embedded in the proposed glmGCN to learn an optimal graph representation of the gene interaction. We firstly constructed the protein-protein interaction network to represent the initial gene(node) relationship graph. Then, through the GL module, a new graph representation was built which optimally learned the gene interaction strength. Finally, the GCN was adopted to identify the distant metastasis cases. It is worth mentioning that the proposed method pays more attentions on the gene-gene relation than the previous GCN-based method, so more accurate prediction performance can be obtained. The glmGCN was trained based on two types of cancer and was further validated using two other cancer types. A series of experiments have shown that the effectiveness of the proposed method. The implementation for the proposed method is available at https://github.com/RanSuLab/Metastasis-glmGCN.

An essential role for mannan degradation in both cell growth and secondary cell wall formation.

Coordination of secondary cell wall deposition and cell expansion during plant growth is required for cell development, particularly in vascular tissues. Yet the fundamental coordination process has received little attention. We observed that the Arabidopsis endo-1,4-mannanase gene, AtMAN6, is involved in the formation of cell walls in vascular tissues. In the inflorescence stem, the man6 mutant had smaller vessel cells with thicker secondary cell walls and shorter fiber cells. Elongation growth was reduced in the root, and secondary cell wall deposition in vessel cells occurred early. Overexpression of AtMAN6 resulted in the inverse phenotypes of the man6 mutant. AtMAN6 was discovered on the plasma membrane and was specifically expressed in vessel cells during its early development. The AtMAN6 protein degraded galactoglucomannan to produce oligosaccharides, which caused secondary cell wall deposition in vessel and fiber cells to be suppressed. Transcriptome analysis revealed that the expression of genes involved in the regulation of secondary cell wall synthesis was changed in both man6 mutant and AtMAN6 overexpression plants. AtMAN6's C-terminal cysteine repeat motif (CCRM) was found to facilitate homodimerization and is required for its activity. According to the findings, the oligosaccharides produced by AtMAN6 hydrolysis may act as a signal to mediate this coordination between cell growth and secondary cell wall deposition.

Recent advances of 3-fucosyllactose in health effects and production.

Human milk oligosaccharides (HMOs) have been recognized as gold standard for infant development. 3-Fucosyllactose (3-FL), being one of the Generally Recognized as Safe HMOs, represents a core trisaccharide within the realm of HMOs; however, it has received comparatively less attention in contrast to extensively studied 2'-fucosyllactose. The objective of this review is to comprehensively summarize the health effects of 3-FL, including its impact on gut microbiota proliferation, antimicrobial effects, immune regulation, antiviral protection, and brain maturation. Additionally, the discussion also covers the commercial application and regulatory approval status of 3-FL. Lastly, an organized presentation of large-scale production methods for 3-FL aims to provide a comprehensive guide that highlights current strategies and challenges in optimization.

Mendelian randomization study on association between grip strength and BMD in different age groups.

INTRODUCTION: This study aimed to use the Mendelian randomization study method to verify the causal relationship between grip strength and bone mineral density (BMD) in different ages and different parts of the body. MATERIALS AND METHODS: The analysis was based on pooled data from genome-wide association studies (GWAS). Hand grip strength (right) was used as the exposure variable and total body bone mineral density (BMD) of different age groups was used as the outcome variable. Single-nucleotide polymorphisms highly correlated with exposure variables were used as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis method, and the Mendelian randomization Egger (MR-Egger) regression and weighted median methods were used as supplementary evidence for the IVW results. Horizontal pleiotropy and heterogeneity tests were conducted to ensure the stability of the results. RESULTS: Analyzing the GWAS data on osteoporosis as the outcome variable, the IVW analysis showed that osteoporosis risk was associated with decreased grip strength in the 45-60 age group and the risk of declining lumbar spine BMD was associated with decreased grip strength. However, there was no significant correlation between the risk of osteoporosis in other age groups and changes in grip strength. CONCLUSION: A causal relationship exists between decreased grip strength and osteoporosis risk in people aged 45-60 years. The risk of BMD declining in the lumbar spine was associated with reduced grip strength.

Effectiveness of Global Leadership Initiative on Malnutrition and Subjective Global Assessment for diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers.

Malnutrition significantly hampers wound healing processes. This study aimed to compare the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) and Subjective Global Assessment (SGA) in diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers (DFU). GLIM criteria were evaluated for sensitivity (SE), specificity (SP), positive predictive value, negative predictive value and kappa (κ) against SGA as the reference. Modified Poisson regression model and the DeLong test investigated the association between malnutrition and non-healing ulcers over 6 months. This retrospective cohort study included 398 patients with DFU, with a mean age of 66·3 ± 11·9 years. According to SGA and GLIM criteria, malnutrition rates were 50·8 % and 42·7 %, respectively. GLIM criteria showed a SE of 67·3 % (95 % CI 60·4 %, 73·7 %) and SP of 82·7 % (95 % CI 76·6 %, 87·7 %) in identifying malnutrition, with a positive predictive value of 80·0 % and a negative predictive value of 71·1 % (κ = 0·50) compared with SGA. Multivariate analysis demonstrated that malnutrition, as assessed by SGA, was an independent risk factor for non-healing (relative risk (RR) 1·84, 95 % CI 1·45, 2·34), whereas GLIM criteria were associated with poorer ulcer healing in patients with estimated glomerular filtration rate ≥ 60 ml/min/1·73m2 (RR: 1·46, 95 % CI 1·10, 1·94). SGA demonstrated a superior area under the receiver's operating characteristic curve for predicting non-healing compared with GLIM criteria (0·70 (0·65-0·75) v. 0·63 (0·58-0·65), P < 0·01). These findings suggest that both nutritional assessment tools effectively identify patients with DFU at increased risk, with SGA showing superior performance in predicting non-healing ulcers.

Impact of Perioperative Empathic Care on Postoperative Psychological Status in Patients with Cervical Cancer.

Objective: To evaluate the effectiveness of perioperative empathic care for patients with cervical cancer and its impact on their postoperative recovery and psychological well-being. Methods: A total of 196 patients diagnosed with cervical cancer and treated at our hospital between December 2019 and January 2021 were recruited and assigned via random number table method to receive either conventional nursing care (conventional group) or empathic care (experimental group), with 98 cases in each group. The inclusion criteria for cervical cancer patients were FIGO stage I-III, aged 18-65 years, and no prior cancer treatment. The empathic care provided to the experimental group involved enhanced communication, emotional support, and shared decision-making. Outcome measures included postoperative recovery indices, numeric rating scale (NRS) scores, Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS) scores, Hamilton depression scale (HAMD) scores, and Strategies Used by People to Promote Health (SUPPH) scores. Results: Independent t tests were used to analyze the differences in postoperative recovery indices between the two groups. Patients in the experimental group who received empathic care had significantly shorter mean time to passing gas (2.35 ± 0.61 days vs. 3.41 ± 0.56 days, P < .05), shorter mean time to postoperative defecation (3.28 ± 0.71 days vs. 4.75 ± 0.63 days, P < .05), and shorter mean length of hospital stay (7.18 ± 1.04 days vs. 11.52 ± 1.25 days, P < .05) compared to the conventional group.Before the nursing intervention, there were no significant differences between the two groups in NRS scores, PSQI scores, SAS scores, HAMD scores, and SUPPH scores (all P > .05). After the nursing intervention, ANOVA was used to analyze the differences. Patients in the experimental group had lower mean NRS scores (2.96 ± 0.84 vs. 4.36 ± 1.02, P < .05), lower mean PSQI scores (8.45 ± 1.11 vs. 12.15 ± 1.52, P < .05), lower mean SAS scores (33.08 ± 3.35 vs. 47.65 ± 4.32, P < .05), and lower mean HAMD scores (30.44 ± 3.37 vs. 41.82 ± 4.05, P < .05) compared to the conventional group. Conclusion: This study demonstrates that perioperative empathic care can significantly improve postoperative recovery and psychological well-being in patients with cervical cancer. Patients receiving empathic care exhibited faster return of gastrointestinal function, shorter hospital stays, and better outcomes on measures of pain, sleep quality, anxiety, and depression. These findings suggest that incorporating empathic care into standard oncology nursing practice could have a positive impact on patient experience and clinical outcomes. Beyond the benefits for individual patients, widespread adoption of empathic care approaches has the potential to enhance the overall quality of cancer care, improve resource utilization, and contribute to more holistic, patient-centered models of healthcare delivery. Further research is warranted to evaluate the long-term effects of empathic care and its applicability across diverse oncology populations.

Effectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Spinocerebellar Ataxia Type 3.

OBJECTIVE: To investigate the effectiveness of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on improvement of clinical symptoms in patients with spinocerebellar ataxia type 3 (SCA3). METHODS: Sixteen SCA3 participants diagnosed by genetic testing were enrolled in this sham-controlled and double-blind trial. They received either a 2-week 10-Hz rTMS intervention or sham stimulation targeting the vermis and cerebellum. The Scale for Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale were completed at baseline and poststimulation. RESULTS: Compared with baseline, the HF-rTMS group demonstrated a significant improvement in the total Scale for Assessment and Rating of Ataxia ( P < 0.0001) and the International Cooperative Ataxia Rating Scale scores ( P = 0.002). After 2-week treatment, the real group exhibited decreasing pattern in 3 subgroups, especially for limb kinetic function ( P < 0.0001). CONCLUSIONS: Short-term HF-rTMS treatment is a potentially promising and feasible tool for rehabilitation in patients with SCA3. Studies with long-term follow-up need to be carried out in the future and further need to assess gait, limb kinetic function, speech and oculomotor disorders.

Three new antinociceptive diterpenoids from the fruits of Rhododendron molle.

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity.

Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.

Diabetic complications pose a significant threat to life and have a negative impact on quality of life in individuals with diabetes. Among the various factors contributing to the development of these complications, endothelial dysfunction plays a key role. The main mechanism underlying endothelial dysfunction in diabetes is oxidative stress, which adversely affects the production and availability of nitric oxide (NO). Flavonoids, a group of phenolic compounds found in vegetables, fruits, and fungi, exhibit strong antioxidant and anti-inflammatory properties. Several studies have provided evidence to suggest that flavonoids have a protective effect on diabetic complications. This review focuses on the imbalance between reactive oxygen species and the antioxidant system, as well as the changes in endothelial factors in diabetes. Furthermore, we summarize the protective mechanisms of flavonoids and their derivatives on endothelial dysfunction in diabetes by alleviating oxidative stress and modulating other signaling pathways. Although several studies underline the positive influence of flavonoids and their derivatives on endothelial dysfunction induced by oxidative stress in diabetes, numerous aspects still require clarification, such as optimal consumption levels, bioavailability, and side effects. Consequently, further investigations are necessary to enhance our understanding of the therapeutic potential of flavonoids and their derivatives in the treatment of diabetic complications.

Wood of trees: Cellular structure, molecular formation, and genetic engineering.

Wood is an invaluable asset to human society due to its renewable nature, making it suitable for both sustainable energy production and material manufacturing. Additionally, wood derived from forest trees plays a crucial role in sequestering a significant portion of the carbon dioxide fixed during photosynthesis by terrestrial plants. Nevertheless, with the expansion of the global population and ongoing industrialization, forest coverage has been substantially decreased, resulting in significant challenges for wood production and supply. Wood production practices have changed away from natural forests toward plantation forests. Thus, understanding the underlying genetic mechanisms of wood formation is the foundation for developing high-quality, fast-growing plantation trees. Breeding ideal forest trees for wood production using genetic technologies has attracted the interest of many. Tremendous studies have been carried out in recent years on the molecular, genetic, and cell-biological mechanisms of wood formation, and considerable progress and findings have been achieved. These studies and findings indicate enormous possibilities and prospects for tree improvement. This review will outline and assess the cellular and molecular mechanisms of wood formation, as well as studies on genetically improving forest trees, and address future development prospects.

Parental psychological control and depression, anxiety among adolescents: The mediating role of bedtime procrastination and moderating role of neuroticism.

Studies have shown that maladaptive parenting styles, particularly parental psychological control may be an important risk factor for emotional problems in adolescence. However, the potential mechanisms behind this association are still not fully understood. To fill the research gap, this study investigated the relationship between parental psychological control and depression and anxiety among adolescents. It also explored the mediating effect of bedtime procrastination and the moderating effect of neuroticism through a moderated mediation analysis. A sample of 665 adolescents (331 girls) were recruited from two secondary schools in southern China. All participants completed standardized self-report questionnaires measuring the severity of parental psychological control, bedtime procrastination, depression, anxiety, and neuroticism. Data were analyzed using SPSS 25.0 and PROCESS macros. The results indicated that parental psychological control had a positive predictive effect on depression and anxiety among adolescents. Bedtime procrastination partially mediated the relationship between parental psychological control and depression, as well as parental psychological control and anxiety. Neuroticism was found to play a moderating role in the path from bedtime procrastination to depression and from bedtime procrastination to anxiety, with these effects being stronger for adolescents with higher levels of neuroticism. This study advances a deeper understanding of how and when or for whom parental psychological control is related to adolescents' severe depression and anxiety. Our findings suggest that intervention programs or strategies aimed at reducing parental psychological control and assisting adolescents in establishing healthy sleep hygiene practices should be developed to decrease the risk of depression and anxiety in adolescents.

Evolutionary analysis of SLC10 family members and insights into function and expression regulation of lamprey NTCP.

The Na ( +)-taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier family 10 (SLC10), which consists of 7 members (SLC10a1-SLC10a7). NTCP is a transporter localized to the basolateral membrane of hepatocytes and is primarily responsible for the absorption of bile acids. Although mammalian NTCP has been extensively studied, little is known about the lamprey NTCP (L-NTCP). Here we show that L-NTCP follows the biological evolutionary history of vertebrates, with conserved domain, motif, and similar tertiary structure to higher vertebrates. L-NTCP is localized to the cell surface of lamprey primary hepatocytes by immunofluorescence analysis. HepG2 cells overexpressing L-NTCP also showed the distribution of L-NTCP on the cell surface. The expression profile of L-NTCP showed that the expression of NTCP is highest in lamprey liver tissue. L-NTCP also has the ability to transport bile acids, consistent with its higher vertebrate orthologs. Finally, using a farnesoid X receptor (FXR) antagonist, RT-qPCR and flow cytometry results showed that L-NTCP is negatively regulated by the nuclear receptor FXR. This study is important for understanding the adaptive mechanisms of bile acid metabolism after lamprey biliary atresia based on understanding the origin, evolution, expression profile, biological function, and expression regulation of L-NTCP.

A Comparative Study of Prevalence and Associated Factors of Social Support Among Chinese Shidu Parents and Non-Shidu Parents.

The number of parents in China who have lost their only child, referred to as shidu parents, currently exceeds one million and is increasing by approximately 76,000 annually. Shidu parents face a unique challenge in long-term care, primarily stemming from the sudden and tragic loss of their only child, which leads to a substantial decrease in their social support network. A multi-stage, stratified, and cluster sampling method was employed across various economic belts. Linear regression analysis was utilized to examine factors associated with the social support status of shidu and non-shidu parents. The level of social support decreases as the severity of depression increases. Shidu parents with grandchildren tend to have good social support. The city of Hangzhou exhibits relatively high levels of social support. Married individuals typically report higher levels of social support. It is recommended to prioritize shidu parents without grandchildren as a primary focus for government and societal support. Key recommendations include strengthening social skills training and developing social support networks. Drive economic development, particularly in relatively underdeveloped regions. Strengthen social organizations and community development. Enhancing access to support services, leveraging technology, and encouraging volunteerism for non-married parents.

PWSC: a novel clustering method based on polynomial weight-adjusted sparse clustering for sparse biomedical data and its application in cancer subtyping.

BACKGROUND: Clustering analysis is widely used to interpret biomedical data and uncover new knowledge and patterns. However, conventional clustering methods are not effective when dealing with sparse biomedical data. To overcome this limitation, we propose a hierarchical clustering method called polynomial weight-adjusted sparse clustering (PWSC). RESULTS: The PWSC algorithm adjusts feature weights using a polynomial function, redefines the distances between samples, and performs hierarchical clustering analysis based on these adjusted distances. Additionally, we incorporate a consensus clustering approach to determine the optimal number of classifications. This consensus approach utilizes relative change in the cumulative distribution function to identify the best number of clusters, resulting in more stable clustering results. Leveraging the PWSC algorithm, we successfully classified a cohort of gastric cancer patients, enabling categorization of patients carrying different types of altered genes. Further evaluation using Entropy showed a significant improvement (p = 2.905e-05), while using the Calinski-Harabasz index demonstrates a remarkable 100% improvement in the quality of the best classification compared to conventional algorithms. Similarly, significantly increased entropy (p = 0.0336) and comparable CHI, were observed when classifying another colorectal cancer cohort with microbial abundance. The above attempts in cancer subtyping demonstrate that PWSC is highly applicable to different types of biomedical data. To facilitate its application, we have developed a user-friendly tool that implements the PWSC algorithm, which canbe accessed at http://pwsc.aiyimed.com/ . CONCLUSIONS: PWSC addresses the limitations of conventional approaches when clustering sparse biomedical data. By adjusting feature weights and employing consensus clustering, we achieve improved clustering results compared to conventional methods. The PWSC algorithm provides a valuable tool for researchers in the field, enabling more accurate and stable clustering analysis. Its application can enhance our understanding of complex biological systems and contribute to advancements in various biomedical disciplines.

Reducing shape errors in the discrete dipole approximation using effective media.

The discrete dipole approximation (DDA) simulates optical properties of particles with any given shape based on the volume discretization. These calculations cost a large amount of time and memory to achieve high accuracy, especially for particles with large sizes and complex geometric structures, such as mixed black-carbon aerosol particles. We systematically study the smoothing of the DDA discretization using the effective medium approximation (EMA) for boundary dipoles. This approach is tested for optical simulations of spheres and coated black-carbon (BC) aggregates, using the Lorenz-Mie and multiple-sphere T-Matrix as references. For spheres, EMA significantly improves the DDA accuracy of integral scattering quantities (up to 60 times), when the dipole size is only several times smaller than the sphere diameter. In these cases, the application of the EMA is often comparable to halving the dipole size in the original DDA, thus reducing the simulation time by about an order of magnitude for the same accuracy. For a coated BC model based on transmission electron microscope observations, the EMA (specifically, the Maxwell Garnett variant) significantly improves the accuracy when the dipole size is larger than » of the monomer diameter. For instance, the relative error of extinction efficiency is reduced from 4.7% to 0.3% when the dipole size equals that of the spherical monomer. Moreover, the EMA-DDA achieves the accuracy of 1% for extinction, absorption, and scattering efficiencies using three times larger dipoles than that with the original DDA, corresponding to about 30 times faster simulations.

Spatial organization of pathway enzymes via self-assembly to improve 2'-fucosyllactose biosynthesis in engineered Escherichia coli.

As one of the most abundant components in human milk oligosaccharides, 2'-fucosyllactose (2'-FL) possesses versatile beneficial health effects. Although most studies focused on overexpressing or fine-tuning the expression of pathway enzymes and achieved a striking increase of 2'-FL production, directly facilitating the metabolic flux toward the key intermediate GDP-l-fucose seems to be ignored. Here, multienzyme complexes consisting of sequential pathway enzymes were constructed by using specific peptide interaction motifs in recombinant Escherichia coli to achieve a higher titer of 2'-FL. Specifically, we first fine-tuned the expression level of pathway enzymes and balanced the metabolic flux toward 2'-FL synthesis. Then, two key enzymes (GDP-mannose 4,6-dehydratase and GDP- l-fucose synthase) were self-assembled into enzyme complexes in vivo via a short peptide interaction pair RIAD-RIDD (RI anchoring disruptor-RI dimer D/D domains), resulting in noticeable improvement of 2'-FL production. Next, to further strengthen the metabolic flux toward 2'-FL, three pathway enzymes were further aggregated into multienzyme assemblies by using another orthogonal protein interaction motif (Spycatcher-SpyTag or PDZ-PDZlig). Intracellular multienzyme assemblies remarkably enlarged the flux toward 2'-FL biosynthesis and showed a 2.1-fold increase of 2'-FL production compared with a strain expressing free-floating and unassembled enzymes. The optimally engineered strain EZJ23 accumulated 4.8 g/L 2'-FL in shake flask fermentation and was capable of producing 25.1 g/L 2'-FL by fed-batch cultivation. This work provides novel approaches for further improvement and large-scale production of 2'-FL and demonstrates the effectiveness of spatial assembly of pathway enzymes to improve the production of valuable products in the engineered host strain.