Search

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecalmicrobiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the longterm safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor. Methods: We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML. The DHRGs were explored through multiple in silico approaches including genomic and functional analysis, survival analysis, immune infiltration, miRNA coexpression and stemness features analyses to reveal their prognostic importance in AML. Furthermore, using different ML algorithms, prognostic models were constructed and validated using the DHRGs. At the end molecular docking studies were performed to identify potential drug candidates targeting the selected DHRGs. Results: We identified a total of 80 DHRGs by comparing the differentially expressed genes derived between AML patients and normal controls and high-risk AML genes identified by Cox regression. Genetic and epigenetic alteration analyses of the DHRGs revealed a significant association of their copy number variations and methylation status with overall survival (OS) of AML patients. Out of the 137 models constructed using different ML algorithms, the combination of Ridge and plsRcox maintained the highest mean C-index and was used to build the final model. When AML patients were classified into low- and high-risk groups based on DHRGs, the low-risk group had significantly longer OS in the AML training and validation cohorts. Furthermore, immune infiltration, miRNA coexpression, stemness feature and hallmark pathway analyses revealed significant differences in the prognosis of the low- and high-risk AML groups. Drug sensitivity and molecular docking studies revealed top 5 drugs, including carboplatin and austocystin-D that may significantly affect the DHRGs in AML. Conclusion: The findings from the current study identified a set of high-risk genes that may be used as prognostic and therapeutic markers for AML patients. In addition, significant use of the ML algorithms in constructing and validating the prognostic models in AML was demonstrated. Although our study used extensive bioinformatics and machine learning methods to identify the hub genes in AML, their experimental validations using knock-out/-in methods would strengthen our findings. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to propose a three-dimensional (3D) augmented reality navigation method with point cloud–based image-patient registration that could merge virtual images in the real environment for dental implants using a 3D image overlay and to evaluate its feasibility. Materials and Methods: A total of 12 rapid prototyping mandibular models were fabricated using a 3D printing method and were divided into two groups: 3D augmented reality–guided group and traditional two-dimensional (2D) image-guided group. A point cloud–based preoperative image-to-patient registration method was introduced to replace the traditional point-to-point registration. After the registration, dental implant surgery was performed in the two model groups using an augmented reality–guided navigation method and a traditional two-dimensional image-guided navigation method. The planned and actual postoperative implant positions were compared for measuring positional implantation errors. The surgery time was also recorded and compared between the two groups. Results: In the model experiment, the root-mean-square deviation of registration was 0.54 mm, and the implant surgery results showed < 1.5-mm mean linear deviation and < 5.5-degree angular deviation. The augmented reality–guided implantation showed smaller horizontal, vertical, and angular errors in the apical areas of the central incisor and the canine region. The surgery time using the augmented reality–guided navigation method was significantly shorter than that using the two-dimensional (2D) image-guided navigation method (P < .05). Moreover, the volunteer experiment demonstrated that the preoperative 3D models in situ accurately overlaid onto the surgical site. Conclusion: The proposed point cloud–based registration method can achieve excellent registration accuracy. Dental implant placement guided by the proposed 3D augmented reality navigation method showed better accuracy and applicability, as well as higher efficiency, than the traditional 2D image navigation method. [ABSTRACT FROM AUTHOR]

Aims: In this study, we aimed to identify cuproptosis-associated ferroptosis genes in the atherosclerosis microarray of the Gene Expression Omnibus (GEO) database and to explore hub gene-mediated immune infiltration in atherosclerosis. Background: Immune infiltration plays a crucial role in atherosclerosis development. Ferroptosis is a mode of cell death caused by the iron-dependent accumulation of lipid peroxides. Cuproptosis is a recently discovered type of programmed cell death. No previous studies have examined the mechanism of cuproptosis-associated ferroptosis gene regulation in immune infiltration in atherosclerosis. Methods: We searched the qualified atherosclerosis gene microarray in the GEO database, integrated it with ferroptosis and cuproptosis genes, and calculated the correlation coefficients. We then obtained the cuproptosis-associated ferroptosis gene matrix and screened differentially expressed genes. Subsequently, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and protein-protein interaction network analysis of differentially expressed genes. We also screened hub genes according to the Matthews correlation coefficient (MCC) algorithm. We conducted enrichment analysis of hub genes to explore their functions and predict related microRNAs (P < 0.05). We also used the single-sample gene set enrichment analysis (ssGSEA) algorithm to analyze the relationships between hub genes and immune infiltration, and used immune-associated hub genes to construct a risk model. Finally, we used the drug prediction results and molecular docking technology to explore potential therapeutic drugs targeting the hub genes. Results: Seventy-eight cuproptosis-associated ferroptosis genes were found to be involved in the cellular response to oxidative and chemical stress, and to be enriched in multiple pathways, including ferroptosis, glutathione metabolism, and atherosclerosis. Ten hub genes were identified with the MCC algorithm; according to the ssGSEA algorithm, these genes were closely associated with immune infiltration, thus indicating that cuproptosis-associated ferroptosis genes may participate in atherosclerosis by mediating immune infiltration. The receiver operating characteristic curve indicated that the model had a good ability to predict atherosclerosis risk. The results of drug prediction (adjusted P < 0.001) and molecular docking showed that glutathione may be a potential therapeutic drug that targets the hub genes. Conclusion: Cuproptosis-associated ferroptosis genes are associated with immune infiltration in atherosclerosis. [ABSTRACT FROM AUTHOR]

Human society operates on large-scale cooperation. However, individual differences in cooperativeness and incentives to free ride on others’ cooperation make large-scale cooperation fragile and can lead to reduced social welfare. Thus, how individual cooperation spreads through human social networks remains puzzling from ecological, evolutionary, and societal perspectives. Here, we identify oxytocin and costly punishment as biobehavioral mechanisms that facilitate the propagation of cooperation in social networks. In three laboratory experiments (n = 870 human participants: 373 males, 497 females), individuals were embedded in heterogeneous networks and made repeated decisions with feedback in games of trust (n = 342), ultimatum bargaining (n = 324), and prisoner’s dilemma with punishment (n = 204). In each heterogeneous network, individuals at central positions (hub nodes) were given intranasal oxytocin (or placebo). Giving oxytocin (vs matching placebo) to central individuals increased their trust and enforcement of cooperation norms. Oxytocin-enhanced norm enforcement, but not elevated trust, explained the spreading of cooperation throughout the social network. Moreover, grounded in evolutionary game theory, we simulated computer agents that interacted in heterogeneous networks with central nodes varying in terms of cooperation and punishment levels. Simulation results confirmed that central cooperators’ willingness to punish noncooperation allowed the permeation of the network and enabled the evolution of network cooperation. These results identify an oxytocininitiated proximate mechanism explaining how individual cooperation facilitates network-wide cooperation in human society and shed light on the widespread phenomenon of heterogeneous composition and enforcement systems at all levels of life. [ABSTRACT FROM AUTHOR]

In materials, energy can propagate by means of two limiting regimes: diffusive and ballistic. Ballistic energy transport can be fast and efficient and often occurs with a constant speed. Using twodimensional infrared spectroscopy methods, we discovered ballistic energy transport via individual polyethylene chains with a remarkably high speed of 1440 m/s and the mean free path length of 14.6 Å in solution at room temperature. Whereas the transport via the chains occurs ballistically, the mechanism switches to diffusive with the effective transport speed of 130 m/s at the end-groups attached to the chains. A unifying model of the transport in molecules is presented with clear time separation and additivity among the transport along oligomeric fragments, which occurs ballistically, and the transport within the disordered fragments, occurring diffusively. The results open new avenues for making novel elements for molecular electronics, including ultrafast energy transporters, controlled chemical reactors, and sub-wavelength quantum nanoseparators. [ABSTRACT FROM AUTHOR]

Aim: To compare cervical small cell carcinoma (SmCC) with squamous cell carcinoma (SCC) in patient characteristics and survival outcomes. Methods: Cervical SmCC and SCC patients in Surveillance, Epidemiology, and End Results database from 2004 to 2015 were enrolled. Propensity-score matching analysis (PSM) paired subjects with similar background variables. Cox regression, Kaplan-Meier and stratified analyses were conducted before and after PSM. Results: Cervical SmCC patients showed a higher rate of larger tumor size, advanced grade disease, lymph node involvement and distant metastasis (p < 0.001). Before and after PSM, SmCC histology and advanced Federation International of Gynecology and Obstetrics stages (p < 0.001) were principal prognostic factors of survival, and cervical SmCC was associated with worse survival in all stages (stage I-IV). Conclusion: SmCC was an independent poor prognostic factor in cervical cancer patients. [ABSTRACT FROM AUTHOR]

Sustaining cooperation in social dilemmas is a fundamental objective in the social and biological sciences. Although providing a punishment option to community members in the public goods game (PGG) has been shown to effectively promote cooperation, this has some serious disadvantages; these include destruction of a society's physical resources as well as its overall social capital. A more efficient approach may be to instead employ a reward mechanism. We propose an endogenous reward mechanism that taxes the gross income of each round's PGG play and assigns the amount to a fund; each player then decides how to distribute his or her share of the fund as rewards to other members of the community. Our mechanism successfully reverses the decay trend and achieves a high level of contribution with budget-balanced rewards that require no external funding, an important condition for practical implementation. Simulations based on type-specific estimations indicate that the payoff-based conditional cooperation model explains the observed treatment effects well. [ABSTRACT FROM AUTHOR]

Polyoxometalates (POMs) are inorganic clusters that possess potential anti-bacterial, anti-viral, and anti-tumor activities. Herein, the in vitro anti-proliferation activities of K12[V18O42(H2O)]⋅6H2O (V18) have been investigated on the MCF-7 and MDA-MB-231 cell lines. The results indicated that V18 could inhibit the proliferation of MCF-7 (IC50, 11.95 μM at 48 h) in a dose-dependent manner compared to the positive control, 5-fluorouracil (5-Fu, p < 0.05). The anti-proliferation activity of V18 might be mediated by arrest of the MCF-7 cells in the G2/M phase and induction of apoptosis and necrosis. Moreover, V18 can effectively quench the fluorescence of ctDNA. The binding mode between them may be groove or outside stacking binding. V18 can also effectively quench the intrinsic fluorescence of bovine serum albumin (BSA) and human serum albumin (HSA) via static quenching, and changed the conformation of BSA and HSA. [ABSTRACT FROM AUTHOR]

Communities are common in complex networks and play a significant role in the functioning of social, biological, economic, and technological systems. Despite widespread interest in detecting community structures in complex networks and exploring the effect of communities on collective dynamics, a deep understanding of the emergence and prevalence of communities in social networks is still lacking. Addressing this fundamental problem is of paramount importance in understanding, predicting, and controlling a variety of collective behaviors in society. An elusive question is how communities with common internal properties arise in social networks with great individual diversity. Here, we answer this question using the ultimatum game, which has been a paradigm for characterizing altruism and fairness. We experimentally show that stable local communities with different internal agreements emerge spontaneously and induce social diversity into networks, which is in sharp contrast to populations with random interactions. Diverse communities and social norms come from the interaction between responders with inherent heterogeneous demands and rational proposers via local connections, where the former eventually become the community leaders. This result indicates that networks are significant in the emergence and stabilization of communities and social diversity. Our experimental results also provide valuable information about strategies for developing network models and theories of evolutionary games and social dynamics. [ABSTRACT FROM AUTHOR]

A novel 16-channel fixed frequency Doppler backward scattering (DBS) reflectometer system has been developed on the HL-2A tokamak. This system is based on the filter-based feedback loop microwave source (FFLMS) technique, which has lower phase noise and lower power variation compared with present tunable frequency generation and comb frequency array generation techniques [J. C. Hillesheim et al. Rev. Sci. Instrum. 80, 083507 (2009) and W. A. Peebles et al. Rev. Sci. Instrum. 81, 10D902 (2010)]. The 16-channel DBS system is comprised of four × four-frequency microwave transmitters and direct quadrature demodulation receivers. The working frequencies are 17-24 GHz and 31-38 GHz with the frequency interval of 1 GHz. They are designed to measure the localized intermediate wave-number (k⊥ρ ~ 1-2, k⊥ ~ 2-9 cm-1) density fluctuations and the poloidal rotation velocity profile of turbulence. The details of the system design and laboratory tests are presented. Preliminary results of Doppler spectra measured by the multi-channel DBS reflectometer systems are obtained. The plasma rotation and turbulence distribution during supersonic molecular beam injection are analyzed. [ABSTRACT FROM AUTHOR]

Magnetic tunnel junction nanopillar with interfacial perpendicular magnetic anisotropy (PMA-MTJ) becomes a promising candidate to build up spin transfer torque magnetic random access memory (STT-MRAM) for the next generation of non-volatile memory as it features low spin transfer switching current, fast speed, high scalability, and easy integration into conventional complementary metal oxide semiconductor (CMOS) circuits. However, this device suffers from a number of failure issues, such as large process variation and tunneling barrier breakdown. The large process variation is an intrinsic issue for PMA-MTJ as it is based on the interfacial effects between ultra-thin films with few layers of atoms; the tunneling barrier breakdown is due to the requirement of an ultra-thin tunneling barrier (e.g., <1 nm) to reduce the resistance area for the spin transfer torque switching in the nanopillar. These failure issues limit the research and development of STT-MRAM to widely achieve commercial products. In this paper, we give a full analysis of failure mechanisms for PMA-MTJ and present some eventual solutions from device fabrication to system level integration to optimize the failure issues. [ABSTRACT FROM AUTHOR]

Background: Ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation. Their secondary structures are crucial for the RNA functionality, and the prediction of the secondary structures is widely studied. Our previous research shows that cutting long sequences into shorter chunks, predicting secondary structures of the chunks independently using thermodynamic methods, and reconstructing the entire secondary structure from the predicted chunk structures can yield better accuracy than predicting the secondary structure using the RNA sequence as a whole. The chunking, prediction, and reconstruction processes can use different methods and parameters, some of which produce more accurate predictions than others. In this paper, we study the prediction accuracy and efficiency of three different chunking methods using seven popular secondary structure prediction programs that apply to two datasets of RNA with known secondary structures, which include both pseudoknotted and non-pseudoknotted sequences, as well as a family of viral genome RNAs whose structures have not been predicted before. Our modularized MapReduce framework based on Hadoop allows us to study the problem in a parallel and robust environment. Results: On average, the maximum accuracy retention values are larger than one for our chunking methods and the seven prediction programs over 50 non-pseudoknotted sequences, meaning that the secondary structure predicted using chunking is more similar to the real structure than the secondary structure predicted by using the whole sequence. We observe similar results for the 23 pseudoknotted sequences, except for the NUPACK program using the centered chunking method. The performance analysis for 14 long RNA sequences from the Nodaviridae virus family outlines how the coarse-grained mapping of chunking and predictions in the MapReduce framework exhibits shorter turnaround times for short RNA sequences. However, as the lengths of the RNA sequences increase, the fine-grained mapping can surpass the coarse-grained mapping in performance. Conclusions: By using our MapReduce framework together with statistical analysis on the accuracy retention results, we observe how the inversion-based chunking methods can outperform predictions using the whole sequence. Our chunk-based approach also enables us to predict secondary structures for very long RNA sequences, which is not feasible with traditional methods alone. [ABSTRACT FROM AUTHOR]

Activation of the RhoA/ROCK signaling pathway has been shown to contribute to dissociation-induced apoptosis of embryonic and neural stem cells. We previously demonstrated that approximately 1 out of 40 Lin-Sca-1+CD49fhigh (LSC) prostate basal epithelial cells possess the capacities of stem cells for self-renewal and multi-lineage differentiation. We show here that treating LSC cells with the ROCK kinase inhibitor Y-27632 increases their cloning efficiency by 8 fold in an in vitro prostate colony assay. Y-27632 treatment allows prostate colony cells to replate efficiently, which does not occur otherwise. Y-27632 also increases the cloning efficiency of prostate stem cells in a prostate sphere assay and a dissociated prostate cell regeneration assay. The increased cloning efficiency is due to the suppression of the dissociation-induced, RhoA/ROCK activation-mediated apoptosis of prostate stem cells. Dissociation of prostate epithelial cells from extracellular matrix increases PTEN activity and attenuates AKT activity. Y-27632 treatment alone is sufficient to suppress cell dissociationinduced activation of PTEN activity. However, this does not contribute to the increased cloning efficiency, because Y-27632 treatment increases the sphere-forming unit of wild type and Pten null prostate cells to a similar extent. Finally, knocking down expression of both ROCK kinases slightly increases the replating efficiency of prostate colony cells, corroborating that they play a major role in the Y-27632 mediated increase in cloning efficiency. Our study implies that the numbers of prostate cells with stem/progenitor activity may be underestimated based on currently employed assays, supports that dissociation-induced apoptosis is a common feature of embryonic and somatic stem cells with an epithelial phenotype, and highlights the significance of environmental cues for the maintenance of stem cells. [ABSTRACT FROM AUTHOR]

Dicer is an RNase III enzyme essential for microRNA maturation. Dicer ablation in diverse tissues has been shown to block tissue differentiation, induce cell apoptosis, impair specialized cellular function, and perturb organ structures. To gain insight into the role of microRNAs in prostate tissue function and homeostasis, we conditionally disrupted Dicer activity in the mouse prostate using an ARR2PB-Cre. We demonstrated that Dicer activity is disrupted in both prostatic basal/stem cells and differentiated luminal cells. Dicer knockout murine prostates are smaller in size and mass and develop epithelial hypotrophy in ventral prostates by 4 months. Dicer ablation induces increased apoptosis in the prostate, predominantly in the differentiated luminal cells. Paradoxically, a concurrent increase in proliferation is observed in both basal/stem cells and luminal cells, presumably due to compensatory growth of the cells devoid of homologous recombination in response to the elevated cellular apoptosis. We have previously shown that Lin(CD31CD45Ter119)-Sca-1+CD49fhigh (LSC) cells enrich for prostate stem cell activity. Through proliferation and differentiation, some LSC cells are capable of forming prostate spheres composed of cells at various stages of differentiation. Although LSC cells were expanded by threefold in Dicer knockout mice, the sphere-forming units of Dicer knockout prostate cells decreased by more than half compared with wild-type cells. In addition, most prostate spheres in the Dicer knockout culture were derived from cells that did not undergo homologous recombination. Our results demonstrate a critical role of microRNAs for the proliferative capacity of prostate stem cells and the maintenance of prostate homeostasis. STEM CELLS 2010;28:1260–1269 [ABSTRACT FROM AUTHOR]

Purpose: Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS[SUP+]) is one of the most common medically intractable epilepsies. Although the pathogenesis of HS[SUP+1] still remains highly controversial, genetics may play a role as a predisposing factor. Previous evidence in a Japanese population shows that the homozygotes for allele 2 at position -511 of the interleukin (IL)-1β gene promoter region (IL-1β-5 11*2/2) confers susceptibility to the development of HS. However, this result has not been confirmed in populations of European ancestry. Given that the discrepancy may be attributed to ethnic differences, our aim in this study was to test the validity of a previous report in another Asian population. Methods: This study consisted of total 112 nonlesional TLE patients of Chinese ancestry, and 115 ethnically matched control subjects. A 304-base pair fragment in position of IL-1β-511 was amplified by polymerase chain reaction (PCR). The PCR products were digested with restriction enzyme AvaI, and run on a 12% polyacrylamide gel. We compared the frequency of this gene variation among 67 refractory TLE-HS[SUP+] patients, 45 patients without HS (TLE-HS), and normal control subjects. Results: The heterozygous type (-5I1*1/2) is the most common genotype in our patient groups and controls. Allele 1(-511C) and allele 2(-511T) showed equal frequency (∼50%), which is similar to that (46%) in Japanese. Analysis of genotype and allele distribution showed no significant difference among the three groups (p > 0.05). Conclusions: In contrast with the lower frequency in the white population (35 and 34%) and higher rate in the population of African ancestry (60%), the allele-511T frequency in our present study is ∼50%, indicating differences in the distribution of allele frequencies in IL-1β-511 among different ethnic groups. [ABSTRACT FROM AUTHOR]

We describe a method to construct water-soluble porphyrinic nanospheres with enhanced photo-physical properties as a result of precluding (via intra-molecular host-guest interactions) the individual porphyrins units from aromatic-aromatic stacking. [ABSTRACT FROM AUTHOR]

The intermittent behavior of a quasi-coherent density fluctuation is observed in a laboratory plasma. The quasi-coherent fluctuation is localized but intermittent events are observed in the whole region of plasma. Conditional averaging shows the intermittent events propagate from the central region of the magnetized plasma column to the peripheral region. Auto-correlation function of fluctuations and Hurst analysis reveal the intermittency is highly auto-correlated and the Hurst parameter reaches to 0.8, indicating the existence of self-similar behavior and long-range time correlation, and self-organized criticality dynamics might be the mechanism. Cross-bicoherence between different radii shows the nonlinear coupling between the quasi-coherent fluctuation and ambient turbulence, which will contribute to the generation of intermittency of turbulence. [ABSTRACT FROM AUTHOR]