The cuproptosis-related signature predicts the prognosis and immune microenvironments of primary diffuse gliomas: a comprehensive analysis.

BACKGROUND: Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. METHODS: We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. RESULTS: Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. CONCLUSION: The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

Evidence for continent-wide convergent evolution and stasis throughout 150 y of a biological invasion.

The extent to which evolution can rescue a species from extinction, or facilitate range expansion, depends critically on the rate, duration, and geographical extent of the evolutionary response to natural selection. Adaptive evolution can occur quickly, but the duration and geographical extent of contemporary evolution in natural systems remain poorly studied. This is particularly true for species with large geographical ranges and for timescales that lie between "long-term" field experiments and the fossil record. Here, we introduce the Virtual Common Garden (VCG) to investigate phenotypic evolution in natural history collections while controlling for phenotypic plasticity in response to local growing conditions. Reconstructing 150 y of evolution in Lythrum salicaria (purple loosestrife) as it invaded North America, we analyze phenology measurements of 3,429 herbarium records, reconstruct growing conditions from more than 12 million local temperature records, and validate predictions across three common gardens spanning 10° of latitude. We find that phenological clines have evolved repeatedly throughout the range, during the first century of evolution. Thereafter, the rate of microevolution stalls, recapitulating macroevolutionary stasis observed in the fossil record. Our study demonstrates that preserved specimens are a critical resource for investigating limits to evolution in natural populations. Our results show how natural selection and trade-offs measured in field studies predict adaptive divergence observable in herbarium specimens over 15 decades at a continental scale.

Multiple traces and altered signal-to-noise in systems consolidation: Evidence from the 7T fMRI Natural Scenes Dataset.

The brain mechanisms of memory consolidation remain elusive. Here, we examine blood-oxygen-level-dependent (BOLD) correlates of image recognition through the scope of multiple influential systems consolidation theories. We utilize the longitudinal Natural Scenes Dataset, a 7-Tesla functional magnetic resonance imaging human study in which ∼135,000 trials of image recognition were conducted over the span of a year among eight subjects. We find that early- and late-stage image recognition associates with both medial temporal lobe (MTL) and visual cortex when evaluating regional activations and a multivariate classifier. Supporting multiple-trace theory (MTT), parts of the MTL activation time course show remarkable fit to a 20-y-old MTT time-dynamical model predicting early trace intensity increases and slight subsequent interference (R2 > 0.90). These findings contrast a simplistic, yet common, view that memory traces are transferred from MTL to cortex. Next, we test the hypothesis that the MTL trace signature of memory consolidation should also reflect synaptic "desaturation," as evidenced by an increased signal-to-noise ratio. We find that the magnitude of relative BOLD enhancement among surviving memories is positively linked to the rate of removal (i.e., forgetting) of competing traces. Moreover, an image-feature and time interaction of MTL and visual cortex functional connectivity suggests that consolidation mechanisms improve the specificity of a distributed trace. These neurobiological effects do not replicate on a shorter timescale (within a session), implicating a prolonged, offline process. While recognition can potentially involve cognitive processes outside of memory retrieval (e.g., re-encoding), our work largely favors MTT and desaturation as perhaps complementary consolidative memory mechanisms.

Age-dependent functional development pattern in neonatal brain: An fMRI-based brain entropy study.

The relationship between brain entropy (BEN) and early brain development has been established through animal studies. However, it remains unclear whether the BEN can be used to identify age-dependent functional changes in human neonatal brains and the genetic underpinning of the new neuroimaging marker remains to be elucidated. In this study, we analyzed resting-state fMRI data from the Developing Human Connectome Project, including 280 infants who were scanned at 37.5-43.5 weeks postmenstrual age. The BEN maps were calculated for each subject, and a voxel-wise analysis was conducted using a general linear model to examine the effects of age, sex, and preterm birth on BEN. Additionally, we evaluated the correlation between regional BEN and gene expression levels. Our results demonstrated that the BEN in the sensorimotor-auditory and association cortices, along the 'S-A' axis, was significantly positively correlated with postnatal age (PNA), and negatively correlated with gestational age (GA), respectively. Meanwhile, the BEN in the right rolandic operculum correlated significantly with both GA and PNA. Preterm-born infants exhibited increased BEN values in widespread cortical areas, particularly in the visual-motor cortex, when compared to term-born infants. Moreover, we identified five BEN-related genes (DNAJC12, FIG4, STX12, CETN2, and IRF2BP2), which were involved in protein folding, synaptic vesicle transportation and cell division. These findings suggest that the fMRI-based BEN can serve as an indicator of age-dependent brain functional development in human neonates, which may be influenced by specific genes.

Characterizing normal perinatal development of the human brain structural connectivity.

Early brain development is characterized by the formation of a highly organized structural connectome, which underlies brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development, inherently low signal quality, imaging difficulties, and high inter-subject variability. These factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational method based on spatio-temporal averaging in the image space for determining such baselines. We used this method to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in the perinatal stage. We observed increases in measures of network integration and segregation, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. Our proposed method also showed considerable agreement with an alternative technique based on connectome averaging. The new computational method and results of this study can be useful for assessing normal and abnormal development of the structural connectome early in life.

Mechanical Control of Polar Patterns in Wrinkled Thin Films via Flexoelectricity.

Intriguing topological polar structures in oxide nanofilms have drawn growing attention owing to their immense potential applications in nanoscale electronic devices. Here, we report a novel route to mechanically manipulate polar structures via flexoelectricity in wrinkled thin films. Our results present a flexoelectric polar transition from a nonpolar state to uniaxial polar stripes, biaxial meronlike or antimeronlike polar structures, and polar labyrinths by varying wrinkle morphologies. The evolution mechanisms and the outstanding mechanical tunability of these flexoelectric polar patterns were investigated theoretically and numerically. This strategy based on flexoelectricity for generating nontrivial polar structures will no longer rely on the superlattice structure and can be widely applicable to all centrosymmetric or noncentrosymmetric materials, providing a broader range of material and structure candidates for polar topologies.

Policy and weather influences on mobility during the early US COVID-19 pandemic.

As the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to proliferate across the globe, it is a struggle to predict and prevent its spread. The successes of mobility interventions demonstrate how policies can help limit the person-to-person interactions that are essential to infection. With significant community spread, experts predict this virus will continue to be a threat until safe and effective vaccines have been developed and widely deployed. We aim to understand mobility changes during the first major quarantine period in the United States, measured via mobile device tracking, by assessing how people changed their behavior in response to policies and to weather. Here, we show that consistent national messaging was associated with consistent national behavioral change, regardless of local policy. Furthermore, although human behavior did vary with outdoor air temperature, these variations were not associated with variations in a proxy for the rate of encounters between people. The independence of encounters and temperatures suggests that weather-related behavioral changes will, in many cases, be of limited relevance for SARS-CoV-2 transmission dynamics. Both of these results are encouraging for the potential of clear national messaging to help contain any future pandemics, and possibly to help contain COVID-19.

Living Materials Based Dynamic Information Encryption via Light-Inducible Bacterial Biosynthesis of Quantum Dots.

Microbial biosynthesis, as an alternative method for producing quantum dots (QDs), has gained attention because it can be conducted under mild and environmentally friendly conditions, distinguishing it from conventional chemical and physical synthesis approaches. However, there is currently no method to selectively control this biosynthesis process in a subset of microbes within a population using external stimuli. In this study, we have attained precise and selective control over the microbial biosynthesis of QDs through the utilization of an optogenetically engineered Escherichia coli (E. coli). The recombinant E. coli is designed to express smCSE enzyme, under the regulation of eLightOn system, which can be activated by blue light. The smCSE enzymes use L-cysteine and Cd2+ as substrates to form CdS QDs. This system enables light-inducible bacterial biosynthesis of QDs in precise patterns within a hydrogel for information encryption. As the biosynthesis progresses, the optical characteristics of the QDs change, allowing living materials containing the recombinant E. coli to display time-dependent patterns that self-destruct after reading. Compared to static encryption using fluorescent QD inks, dynamic information encryption based on living materials offers enhanced security.

22R- but not 22S-hydroxycholesterol is recruited for diosgenin biosynthesis.

Diosgenin is an important compound in the pharmaceutical industry and it is biosynthesized in several eudicot and monocot species, herein represented by fenugreek (a eudicot), and Dioscorea zingiberensis (a monocot). Formation of diosgenin can be achieved by the early C22,16-oxidations of cholesterol followed by a late C26-oxidation. This study reveals that, in both fenugreek and D. zingiberensis, the early C22,16-oxygenase(s) shows strict 22R-stereospecificity for hydroxylation of the substrates. Evidence against the recently proposed intermediacy of 16S,22S-dihydroxycholesterol in diosgenin biosynthesis was also found. Moreover, in contrast to the eudicot fenugreek, which utilizes a single multifunctional cytochrome P450 (TfCYP90B50) to perform the early C22,16-oxidations, the monocot D. zingiberensis has evolved two separate cytochrome P450 enzymes, with DzCYP90B71 being specific for the 22R-oxidation and DzCYP90G6 for the C16-oxidation. We suggest that the DzCYP90B71/DzCYP90G6 pair represent more broadly conserved catalysts for diosgenin biosynthesis in monocots.

Preparation of N-doped cellulose-based hydrothermal carbon using a two-step hydrothermal induction assembly method for the efficient removal of Cr(VI) from wastewater.

Cr(VI) pollution is a growing problem that causes the deterioration of the environment and human health. We report the development of an effective adsorbent for the removal of Cr(VI) from wastewater. N-doped cellulose-based hydrothermal carbon (N-CHC) was prepared via a two-step hydrothermal method. The morphology and structural properties of N-CHC were investigated by various techniques. N-CHC has many O and N groups, which are suitable for Cr(VI) adsorption and reduction. Intermittent adsorption experiments showed that N-CHC had an adsorption capacity of 151.05 mg/g for Cr(VI) at pH 2, indicating excellent adsorption performance. Kinetic and thermodynamic analyses indicates that the adsorption of Cr(VI) on N-CHC follows a monolayer uniform adsorption process, which is a spontaneous endothermic process dominated by chemical interaction and limited by diffusion within particles. In a multi-ion system (Pb2+, Cd2+, Mn7+, Cl-, and SO42-), the selectivity of N-CHC toward Cr(VI) was 82.62%. In addition, N-CHC demonstrated excellent reuse performance over seven adsorption-desorption cycles; the Cr(VI) removal rate of N-CHC in 5-20 mg/L wastewater was >99.87%, confirming the potential of N-CHC for large-scale applications. CN/C-OR, pyridinic-N, and pyrrolic-N were found to play a critical role in the adsorption process. This study provides a new technology for Cr(VI) pollution control that could be utilized in large-scale production and other environmental applications.

Oral membrane-biomimetic nanoparticles for enhanced endocytosis and regulation of tumor-associated macrophage.

Enterocyte uptake with high binding efficiency and minor endogenous interference remains a challenge in oral nanocarrier delivery. Enterocyte membrane-biomimetic lipids may universally cooperate with endogenous phosphatidyl choline via a biorthogonal group. In this study, we developed a sophorolipid-associated membrane-biomimetic choline phosphate-poly(lactic-co-glycolic) acid hybrid nanoparticle (SDPN). Aided by physical stability in the gastrointestinal tract and rapid mucus diffusion provided by association with sophorolipid, these nanoparticles show improved endocytosis, driven by dipalmitoyl choline phosphate-phosphatidyl choline interaction as well as its optimized membrane fluidity and rigidity. Luteolin- and silibinin-co-loaded with SDPN alleviated breast cancer metastasis in 4T1 tumor-bearing mice by regulating the conversion of tumor-associated M2 macrophages into the M1 phenotype and reducing the proportion of the M2-phenotype through co-action on STAT3 and HIF-1α. In addition, SDPN reduces angiogenesis and regulates the matrix barrier in the tumor microenvironment. In conclusion, this membrane-biomimetic strategy is promising for improving the enterocyte uptake of oral SDPN and shows potential to alleviate breast cancer metastasis.

Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling.

Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for the treatment of metastatic breast cancer. Despite the good anti-cancer activity of garcinone E (GE), there are no reports on its therapeutic effects on breast cancer metastasis. The objective of this study was to examine the anti-cancer effects of GE on metastatic breast cancer. RAW 264.7 and THP-1 cells were polarized to M2 macrophages by IL-4/IL-13 in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were used to explore the effect of GE on breast cancer growth and metastasis in vivo. In vitro studies showed that GE dose-dependently suppressed IL-4 + IL-13-induced expression of CD206 in both RAW 264.7 cells and differentiated THP-1 macrophages. However, GE did not affect the LPS + IFN-γ-induced polarization to the M1-like macrophages in vitro. GE inhibited the expression of the M2 macrophage specific genes in RAW 264.7 cells, and simultaneously impaired M2 macrophage-induced breast cancer cell proliferation and migration, and angiogenesis. In animal studies, GE significantly suppressed tumor growth, angiogenesis, and lung metastasis in 4T1 tumor-bearing mice, without causing toxicity. In both tumor and lung tissues, the proportion of M2-like TAMs was significantly decreased while the proportion of M1-like TAMs was markedly increased by GE treatment. Mechanistically, GE inhibited phosphorylation of STAT6 in vitro and in vivo. Our results demonstrate for the first time that GE suppresses breast cancer growth and pulmonary metastasis by modulating M2-like macrophage polarization through the STAT6 signaling pathway.

Ex vivo detection of mandibular incisors' root canal morphology using cone-beam computed tomography with 4 different voxel sizes and micro-computed tomography.

BACKGROUND: In recent years, cone-beam computed tomography (CBCT) has been widely used to evaluate patients' root canal anatomy due to its high resolution and noninvasive nature. As voxel size is one of the most important parameters affecting CBCT image quality, the current study evaluated the diagnostic potential of CBCT with 4 different voxel sizes in the detection of double root canal systems and accessory canals (ACs) in permanent mandibular incisors. METHODS: A total of 106 extracted mandibular permanent incisors were collected from the dental clinics, and then were scanned by using micro-CT with a voxel size of 9 µm. The teeth were then fixed in the tooth sockets of human dry mandibles and scanned by using a CBCT device with 4 different voxel sizes (300, 200, 250, and 125 µm). Four observers detected in blind the root canal morphology of the teeth according to the CBCT images, and the presence or absence of a double root canal system, and the presence or absence of ACs, were scored according to a 5-point scale, respectively. Receiver operating characteristic (ROC) analysis was performed, and DeLong test was used to compare the area under the curve (AUC) values and the micro-CT data was taken as a gold standard. RESULTS: Among 106 sample teeth, 25 specimens with a double root canal system were identified by the micro-CT. ROC curve analysis of the data obtained by the four observers showed that in the detection of double root canal systems, the AUC values ranged from 0.765 to 0.889 for 300 µm voxel size, from 0.877 to 0.926 for 250 µm voxel size, from 0.893 to 0.967 for 200 µm voxel size, and from 0.914 to 0.967 for 125 µm voxel size (all p < 0.01). In general, we observed a trend that the AUC values, sensitivity, and specialty increased with the decrease in the voxel size, and significantly higher AUC values were detected in 125 µm voxel size images. In the detection of ACs, ROC curve analysis showed that among the four observers, the AUC values ranged from 0.554 to 0.639 for 300 µm voxel size, from 0.532 to 0.654 for 250 µm voxel size, from 0.567 to 0.626 for 200 µm voxel size, and from 0.638 to 0.678 for 125 µm voxel size. CBCT images at a voxel size of 125 µm had a weak diagnostic potential (AUC: 0.5-0.7, all p < 0.05) in the detection of AC, with a lower sensitivity ranging from 36.8 to 57.9% and a higher specialty ranging from 73.6 to 98.8%. CONCLUSIONS: CBCT with 300 µm voxel size could only provide moderate diagnostic accuracy in the detection of a double canal system in mandibular incisors. CBCT with a voxel size of 125 µm exhibited high diagnostic value in the detection of double canal systems, while showing low but statistically significant value in the detection of ACs.

A micro-computed tomographic analysis of the root canal systems in the permanent mandibular incisors in a Chinese population.

BACKGROUND: Comprehensive understanding of the root canal system complexity is critical important for successful root canal therapy. A double root canal system may be present in permanent mandibular incisors with a variable incidence in different ethnic populations. Ignorance or improper management of this canal variation can lead to treatment failure. This in vitro study aimed to identify the anatomic features of root canal systems in the mandibular incisors in a Chinese population by using micro-CT. METHODS: A total of 106 permanent mandibular incisors (53 central incisors and 53 lateral incisors) were collected from a native Chinese population. The teeth were scanned by a micro-CT scanner and then reconstructed three-dimensionally. The canal configurations were detected by Vertucci's classification, and the number and location of the accessory canals were also identified. The long (D) and short diameters (d) of the main and accessory canals were measured and D/d ratio was calculated at different root levels (cemento-enamel junction [CEJ] level, mid-root level and 1, 2, 3 and 4 mm from the apex). The root canal curvatures in the double-canaled mandibular incisors were measured at the proximal view by using modified Schneider's method. Chi-square test or Fisher's exact test was used for comparison of occurrence rates. Comparison of means from multiple groups was performed by using one-way ANOVA and LSD post-hoc test. RESULTS: In regard to the occurrence of double root canals, gender difference was neither detected in the mandibular central (16.0% [male] vs 14.3% [female]; p = 0.862), nor in the mandibular lateral incisors (26.9% [male] vs 33.3% [female]; p = 0.611). Age group difference was also not detected in the mandibular central (p = 0.717) and lateral incisors (p = 0.521). The incidence of double root canals was 15.1% (8/53) in the central incisors, and 30.2% (16/53) in the lateral incisors, but the difference did not reach statistical significance (p = 0.063). The most frequent non-single canal type was the type III (1-2-1) (18.9% [20/106]), and the other types identified included 1 case of type II (2-1) and 3 cases of type V (1-2). The incidence of accessory canals was 17.9% (19/106), with a mean level of 1.92 ± 1.19 mm from the apex. The frequency of long-oval (2 ≤ D/d < 4) and flattened canals (D/d ≥ 4), as well as the mean value of D, d and D/d ratio increased from the apical 1 mm to the apical 4 mm level (the D/d ratio increased from 1.9 to 2.9 for the single canals, from 1.4 to 3.3 for the buccal canals and from 1.2 to 2.3 for the lingual canals), and the D/d ratio reached the peak at the mid-root level. Double curvatures were detected in 33.3% (8/24) of the buccal canals and 37.5% (9/24) of the lingual canals, and the difference has no statistical significance (p = 0.063). The degrees of the primary curvatures were 21.5 ± 7.1 degrees for the buccal and 30.1 ± 9.2 degrees for the lingual canals, and the degrees of secondary curvatures were 27.0 ± 11.4 degrees for the buccal and 30.5 ± 12.5 degrees for the lingual canals in the double curvatures. The degrees of the single curvatures were 14.2 ± 6.3 degrees for the buccal and 15.6 ± 6.0 degrees for the lingual canals. Significant difference was detected among above 6 groups of canal curvatures (p = 0.000), and severe curvatures (≥ 20 degrees) were more frequently detected in the double curved canals. CONCLUSIONS: Double-canaled mandibular incisors were not uncommon in the Chinese population, and type 1-2-1 was the most frequent non-single canal type. Gender and age did not significantly impact the occurrence of a second canal in mandibular incisors. Long-oval and flattened canals were very common at different root levels and their incidence increased from apex to the mid-root level. Severe curvatures were frequently detected in the double canal systems, especially in those canals with double curvatures.

[Research progress on anti-tumor effects by traditional Chinese medicine based on "soothing" or "blockage" regulation of tumor vessels].

Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.

[Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea].

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.

[Q-marker prediction of resin ethanol extract of Gegen Qinlian Decoction based on characteristic spectrum and network pharmacology].

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.

NeuroGen: Activation optimized image synthesis for discovery neuroscience.

Functional MRI (fMRI) is a powerful technique that has allowed us to characterize visual cortex responses to stimuli, yet such experiments are by nature constructed based on a priori hypotheses, limited to the set of images presented to the individual while they are in the scanner, are subject to noise in the observed brain responses, and may vary widely across individuals. In this work, we propose a novel computational strategy, which we call NeuroGen, to overcome these limitations and develop a powerful tool for human vision neuroscience discovery. NeuroGen combines an fMRI-trained neural encoding model of human vision with a deep generative network to synthesize images predicted to achieve a target pattern of macro-scale brain activation. We demonstrate that the reduction of noise that the encoding model provides, coupled with the generative network's ability to produce images of high fidelity, results in a robust discovery architecture for visual neuroscience. By using only a small number of synthetic images created by NeuroGen, we demonstrate that we can detect and amplify differences in regional and individual human brain response patterns to visual stimuli. We then verify that these discoveries are reflected in the several thousand observed image responses measured with fMRI. We further demonstrate that NeuroGen can create synthetic images predicted to achieve regional response patterns not achievable by the best-matching natural images. The NeuroGen framework extends the utility of brain encoding models and opens up a new avenue for exploring, and possibly precisely controlling, the human visual system.

Shedding Light on Luminescent Janus Nanoparticles: From Synthesis to Photoluminescence and Applications.

Luminescent Janus nanoparticles refer to a special category of Janus-based nanomaterials that not only exhibit dual-asymmetric surface nature but also attractive optical properties. The introduction of luminescence has endowed conventional Janus nanoparticles with many alluring light-responsive functionalities and broadens their applications in imaging, sensing, nanomotors, photo-based therapy, etc. The past few decades have witnessed significant achievements in this field. This review first summarizes well-established strategies to design and prepare luminescent Janus nanoparticles and then discusses optical properties of luminescent Janus nanoparticles based on downconversion and upconversion photoluminescence mechanisms. Various emerging applications of luminescent Janus nanoparticles are also introduced. Finally, opportunities and future challenges are highlighted with respect to the development of next-generation luminescent Janus nanoparticles with diverse applications.

Toxoplasma gondii glutathione S-transferase 2 plays an important role in partial secretory protein transport.

Toxoplasma gondii is an apicomplexan parasite, which has three unique secretory organelles: micronemes, rhoptries, and dense granules. Almost all the secreted proteins are transported through the endoplasmic reticulum (ER) and Golgi system to function in their respective destination by accurate targeting and packaging. Glutathione S-transferase (GST) is a supergene family enzyme that has multiple functions, which include regulation of cell proliferation and death signaling pathways, and participation in transportation and metabolism in mammal cells. However, the role of GST in Toxoplasma gondii has not been explained. In this study, we identified three GST proteins in T gondii, of which GST2 acts as a membrane protein that localizes to the Golgi-endosomal system and colocalizes with proteins involved in vesicle transport as well, including synaptobrevin, putative sortilin (VPS10), Rab5 and Rab6, which function as vesicle transport factors. Moreover, the loss of TgGST2 leads to Rab5 and Rab6 distribution of discrete puncta, and incorrect localization and decreased expression of several secretory proteins, and to significantly reduced invasion capacity and virulence to mice. Consistent with its relation to vesicle transport proteins, the distribution of TgGST2 relies on post-Golgi trafficking. Overall, our findings demonstrated that TgGST2 contributes to vesicle trafficking and plays a critical role in parasite lytic cycle.