Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity.

The CD4(+) and CD8(+) T cell dichotomy is essential for effective cellular immunity. How individual T cell identity is established remains poorly understood. Here we show that the high-mobility group (HMG) transcription factors Tcf1 and Lef1 are essential for repressing CD4(+) lineage-associated genes including Cd4, Foxp3 and Rorc in CD8(+) T cells. Tcf1- and Lef1-deficient CD8(+) T cells exhibit histone hyperacetylation, which can be ascribed to intrinsic histone deacetylase (HDAC) activity in Tcf1 and Lef1. Mutation of five conserved amino acids in the Tcf1 HDAC domain diminishes HDAC activity and the ability to suppress CD4(+) lineage genes in CD8(+) T cells. These findings reveal that sequence-specific transcription factors can utilize intrinsic HDAC activity to guard cell identity by repressing lineage-inappropriate genes.

RNet: a network strategy to predict RNA binding preferences.

Determining the RNA binding preferences remains challenging because of the bottleneck of the binding interactions accompanied by subtle RNA flexibility. Typically, designing RNA inhibitors involves screening thousands of potential candidates for binding. Accurate binding site information can increase the number of successful hits even with few candidates. There are two main issues regarding RNA binding preference: binding site prediction and binding dynamical behavior prediction. Here, we propose one interpretable network-based approach, RNet, to acquire precise binding site and binding dynamical behavior information. RNetsite employs a machine learning-based network decomposition algorithm to predict RNA binding sites by analyzing the local and global network properties. Our research focuses on large RNAs with 3D structures without considering smaller regulatory RNAs, which are too small and dynamic. Our study shows that RNetsite outperforms existing methods, achieving precision values as high as 0.701 on TE18 and 0.788 on RB9 tests. In addition, RNetsite demonstrates remarkable robustness regarding perturbations in RNA structures. We also developed RNetdyn, a distance-based dynamical graph algorithm, to characterize the interface dynamical behavior consequences upon inhibitor binding. The simulation testing of competitive inhibitors indicates that RNetdyn outperforms the traditional method by 30%. The benchmark testing results demonstrate that RNet is highly accurate and robust. Our interpretable network algorithms can assist in predicting RNA binding preferences and accelerating RNA inhibitor design, providing valuable insights to the RNA research community.

LectoScape: A Highly Multiplexed Imaging Platform for Glycome Analysis and Biomedical Diagnosis.

Glycosylation, a fundamental biological process, involves the attachment of glycans to proteins, lipids, and RNA, and it plays a crucial role in various biological pathways. It is of great significance to obtain the precise spatial distribution of glycosylation modifications at the cellular and tissue levels. Here, we introduce LectoScape, an innovative method enabling detailed imaging of tissue glycomes with up to 1 µm resolution through image mass cytometry (IMC). This method utilizes 12 distinct, nonoverlapping lectins selected via microarray technology, enabling the multiplexed detection of a wide array of glycans. Furthermore, we developed an efficient labeling strategy for these lectins. Crucially, our approach facilitates the concurrent imaging of diverse glycan motifs, including N-glycan and O-glycan, surpassing the capabilities of existing technologies. Using LectoScape, we have successfully delineated unique glycan structures in various cell types, enhancing our understanding of the glycan distribution across human tissues. Our method has identified specific glycan markers, such as α2,3-sialylated Galß1, 3GalNAc in O-glycan, and terminal GalNAc, as diagnostic indicators for cervical intraepithelial neoplasia. This highlights the potential of LectoScape in cancer diagnostics through the detection of abnormal glycosylation patterns.

Prediction of allosteric druggable pockets of cyclin-dependent kinases.

Cyclin-dependent kinase (Cdk) proteins play crucial roles in the cell cycle progression and are thus attractive drug targets for therapy against such aberrant cell cycle processes as cancer. Since most of the available Cdk inhibitors target the highly conserved catalytic ATP pocket and their lack of specificity often lead to side effects, it is imperative to identify and characterize less conserved non-catalytic pockets capable of interfering with the kinase activity allosterically. However, a systematic analysis of these allosteric druggable pockets is still in its infancy. Here, we summarize the existing Cdk pockets and their selectivity. Then, we outline a network-based pocket prediction approach (NetPocket) and illustrate its utility for systematically identifying the allosteric druggable pockets with case studies. Finally, we discuss potential future directions and their challenges.

Constructing Innovative Covalent and Noncovalent Compound Libraries: Insights from 3D Protein-Ligand Interactions.

Noncovalent interactions between small-molecule drugs and protein targets assume a pivotal role in drug design. Moreover, the design of covalent inhibitors, forming covalent bonds with amino acid residues, requires rational reactivity for their covalent warheads, presenting a key challenge as well. Understanding the intricacies of these interactions provides a more comprehensive understanding of molecular binding mechanisms, thereby guiding the rational design of potent inhibitors. In this study, we adopted the fragment-based drug design approach, introducing a novel methodology to extract noncovalent and covalent fragments according to distinct three-dimensional (3D) interaction modes from noncovalent and covalent compound libraries. Additionally, we systematically replaced existing ligands with rational fragment substitutions, based on the spatial orientation of fragments in 3D space. Furthermore, we adopted a molecular generation approach to create innovative covalent inhibitors. This process resulted in the recombination of a noncovalent compound library and several covalent compound libraries, constructed by two commonly encountered covalent amino acids: cysteine and serine. We utilized noncovalent ligands in KLIFS and covalent ligands in CovBinderInPDB as examples to recombine noncovalent and covalent libraries. These recombined compound libraries cover a substantial portion of the chemical space present in the original compound libraries and exhibit superior performance in terms of molecular scaffold diversity compared to the original compound libraries and other 11 commercial libraries. We also recombined BTK-focused libraries, and 23 compounds within our libraries have been validated by former researchers to possess potential biological activity. The establishment of these compound libraries provides valuable resources for virtual screening of covalent and noncovalent drugs targeting similar molecular targets.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

Metal-Metal Charge Transfer Properties of a Series of Trinuclear Fe2 Ru and Corresponding Pentanuclear Fe2 Ru2 Ag Cyanido-Bridged Complexes.

A series of trimetallic cyanidometal-bridged compounds [Men Cp(dppe)FeII -(µ-NC)-RuII (MeOpy)4 -(µ-CN)-FeII (dppe)CpMen ] - [PF6 ]2 (N[PF6 ]2 , n=0, N =1; n=1, N=2; n=3, N=3; Cp=cyclopentadiene, dppe=1,2-bis(diphenylphosphino)ethane, MeOpy=4-methoxypyridine) and their one- and two-electron oxidized compounds N3+ and N4+ were synthesized and characterized. Meanwhile, a series of corresponding linear cyanido-bridged pentanuclear compounds [Men Cp(dppe)FeIII -(µ-NC)-RuII (MeOpy)4 -(µ-NC)-AgI -(µ-CN)-RuII (MeOpy)4 -(µ-CN)-FeIII (dppe)CpMen ][BF4 ]5 (M[BF4 ]5 , n=0, M=4; n=1, M=5; n=3, M=6) were also obtained and well characterized. The investigations suggest that in the trinuclear system there exists remote interaction between the two Fe centers, but no significant interactions exist across the central silver unit between the metals on the two sides of the silver center in the pentanuclear system. In both the trinuclear N4+ and the pentanuclear M5+ complexes, there exists the neighboring RuII →FeIII MM'CT transitions, and the MM'CT energy in the corresponding trinuclear system is higher than those in the pentanuclear system in which no remote metal-metal interaction occurs. Meanwhile, as the substituted methyl groups on the cyclopentadiene increases, the redox potential of the ruthenium in the trinuclear N4+ series increases, but that in the pentanuclear M5+ complexes decreases.

Protective effects of MiR-146b in cerebral infarction via targeting SIRT1/FOXO1 signaling pathway.

To observe the therapeutic effect of micro ribonucleic acid (miR)-146b on brain tissue injury in rats with cerebral infarction (CI) by regulating the Sirtuin 1 (SIRT1)/forkhead box protein O1 (FOXO1) signaling pathway, a rat model of CI was established. Lentiviral cells were used to transfect and silence or overexpress miR-146b. The rats were divided into the miR-146b inhibitor group (Inhibitors), miR-146b mimic group (Mimics) and normal group (Control). Then quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the transfection rate of miR-146b in rat brain tissues in each group. The improved method was adopted to score the nerves of rats, and the infarction volume of rats in each group was determined. Subsequently, the levels of superoxide dismutase (SOD) and reactive oxygen species (ROS) in the brain tissues in each group were measured via enzyme-linked immunosorbent assay (ELISA), the apoptosis of nerve cells in the brain tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and glial fibrillary acidic protein (GFAP), S100ß gene and SIRT1/FOXO1 pathway-related genes and proteins in the brain tissues were determined through qRT-PCR and Western blotting. MiR-146b exhibited a high expression in Mimics and an extremely low expression in Inhibitors. Rats in Mimics were normal in movement, and their neurological scores were close to those in Control. Rats in Inhibitors could walk normally, and their neurological scores were notably higher than those in other groups (P<0.05). In addition, Inhibitors had a remarkably larger CI volume (P<0.05), a remarkably increased ROS level and a significantly reduced SOD level compared with those in other groups. Moreover, TUNEL staining results manifested that apoptotic cells, especially glial cells, were notably increased in Inhibitors compared with those in Mimics. Besides, the messenger RNA (mRNA) expression levels of S100ß and GFAP in Inhibitors were higher than those in other groups (P<0.05). SIRT1 and FOXO1 genes were increased in Mimics, which were close to those in Control. According to Western blotting results, the protein expression levels of SIRT1 and FOXO1 in Mimics were notably higher than those in Inhibitors. MiR-146b can play a protective role in CI rats by activating the SIRT1/FOXO1 signaling pathway, lowering the oxidative stress level and reducing brain tissue apoptosis.

MiR-182 promotes apoptosis of neural cells in cerebral infarction rats by PI3K/AKT signaling pathway.

To explore the effects of micro ribonucleic acid (miR)-182 on the proliferation and apoptosis of neural cells in cerebral infarction rats and its underlying mechanism. The rat model of cerebral infarction was established, and neural cells were extracted accordingly. The cell proliferation ability was detected via cell counting kit-8 (CCK8) assay. In addition, the apoptosis rate was determined through flow cytometry and the activity of active caspase-3. Furthermore, the interaction between miR-182 and PI3K was explored via dual luciferase reporter assay, and the protein expression levels were observed via Western blotting. The neural cells in mouse brain tissues significantly decreased in the model group compared with that in the control group via HE stain. Additionally, the expression level of miR-182 was significantly increased in the model group compared with that in the control group. Furthermore, overexpression of miR-182 could inhibit the proliferation of neural cells through inducing cell apoptosis. Besides, the results of the luciferase reporter assay showed that the relative luciferase activity in neural cells could be inhibited by the transfection with miR-182 (P<0.05). Overexpression of miR-182 significantly reduced the protein expression levels of phosphatidylinositol 3-hydroxy kinase (PI3K) and p-AKT. MiR-182 induces apoptosis of neural cells through inhibiting the PI3K/AKT signaling pathway, which plays an important regulatory role in the apoptosis of neural cells in cerebral infarction rats.

Evaluation of DNA-protein complex structures using the deep learning method.

Biological processes such as transcription, repair, and regulation require interactions between DNA and proteins. To unravel their functions, it is imperative to determine the high-resolution structures of DNA-protein complexes. However, experimental methods for this purpose are costly and technically demanding. Consequently, there is an urgent need for computational techniques to identify the structures of DNA-protein complexes. Despite technological advancements, accurately identifying DNA-protein complexes through computational methods still poses a challenge. Our team has developed a cutting-edge deep-learning approach called DDPScore that assesses DNA-protein complex structures. DDPScore utilizes a 4D convolutional neural network to overcome limited training data. This approach effectively captures local and global features while comprehensively considering the conformational changes arising from the flexibility during the DNA-protein docking process. DDPScore consistently outperformed the available methods in comprehensive DNA-protein complex docking evaluations, even for the flexible docking challenges. DDPScore has a wide range of applications in predicting and designing structures of DNA-protein complexes.

Dynamic geometry design of cyclic peptide architectures for RNA structure.

Designing inhibitors for RNA is still challenging due to the bottleneck of maintaining the binding interaction of inhibitor-RNA accompanied by subtle RNA flexibility. Thus, the current approach usually needs to screen thousands of candidate inhibitors for binding. Here, we propose a dynamic geometry design approach to enrich the hits with only a tiny pool of designed geometrically compatible scaffold candidates. First, our method uses graph-based tree decomposition to explore the complementarity rigid binding cyclic peptide and design the amino acid side chain length and charge to fit the RNA pocket. Then, we perform an energy-based dynamical network algorithm to optimize the inhibitor-RNA hydrogen bonds. Dynamic geometry-guided design yields successful inhibitors with low micromolar binding affinity scaffolds and experimentally competes with the natural RNA chaperone. The results indicate that the dynamic geometry method yields higher efficiency and accuracy than traditional methods. The strategy could be further optimized to design the length and chirality by adopting nonstandard amino acids and facilitating RNA engineering for biological or medical applications.

Atmospheric wet deposition of trace elements in Bangladesh: A new insight into spatiotemporal variability and source apportionment.

The interaction between water vapor and natural/anthropogenic airborne particles deposits a massive amount of trace elements in the ecosystem. As the principal source region of the Indian monsoon originated from the Bay of Bengal, atmospheric trace elements in Bangladesh have impacted atmospheric wet deposition along the pathway, even reaching the headwaters in the Asian water tower. However, no study reports the atmospheric wet deposition of trace elements at the spatiotemporal scale. Thus, this study investigated the concentration, sources, and deposition of eighteen trace elements (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Rb, Sr, Mo, Cd, Sn, Sb, Ba, and Pb) from 232 precipitation samples at four sites in Bangladesh. Results showed that the VWM concentrations of the eighteen measured trace elements ranged from 0.03 to 535.6 µg L-1. Zn, Fe, and Al were the principal elements of the atmosphere at four sites with mean values of 207.9 ± 227.8, 18.2 ± 9.3, and 16.3 ± 6.8 µg L-1, respectively. Besides, the eighteen trace elements showed significant variation in spatial scale with distinct seasonality. Enrichment factors of Zn, Sb, and Cd indicated serious anthropogenic influences. The major sources of trace elements were fossil fuel combustion, brick kilns, crustal dust, fugitive Pb, metal smelters, and battery recycling. Both the concentration and precipitation amount played a pivotal role in the deposition. Most of the air masses during the monsoon season came from marine sources passing over southern India and Sri Lanka. Meanwhile, the air masses during the non-monsoon season were from West Asia and the northwestern Indian subcontinent. The air masses are transported over a long range and deposit massive amounts of particulate matter in the Third Pole Himalayan region. This first-hand work on spatiotemporal variation provides a reference dataset for future targeting of the scientific community and policymakers for the development of strategies and action plans.

Comparison of 3 CT Perfusion Software Packages in Estimation of Ischemic Lesions in Acute Ischemic Stroke Patients.

OBJECTIVE: The aim of this study was to compare 3 computed tomography perfusion (CTP) software packages in the estimation of infarct core volumes, hypoperfusion volumes, and mismatch volumes. METHODS: Forty-three patients with large vessel occlusion in the anterior circulation who underwent CTP imaging were postprocessed by 3 software packages: RAPID, advantage workstation (AW), and NovoStroke Kit (NSK). Infarct core volumes and hypoperfusion volumes were generated by RAPID with default settings. The AW and NSK threshold settings were the following: infarct core (cerebral blood flow [CBF] <8 mL/min/100 g, CBF <10 mL/min/100 g, CBF <12 mL/min/100 g, and cerebral blood volume [CBV] <1 mL/100 g) and hypoperfusion (T max >6 seconds). Mismatch volumes were then obtained for all the combinations of the settings. Bland-Altman, intraclass correlation coefficient (ICC), and Spearman ρ or Pearson correlation coefficient were applied for statistical analysis. RESULTS: In the estimation of infarct core volumes, good agreement was observed between AW and RAPID when CBV <1 mL/100 g (ICC, 0.767; P < 0.001). For hypoperfusion volumes, good agreement (ICC, 0.811; P < 0.001) and strong correlation ( r = 0.856; P < 0.001) were observed between NSK and RAPID. For mismatch volumes, the setting of CBF <10 mL/min/100 g combined with hypoperfusion with NSK resulted in moderate agreement (ICC, 0.699; P < 0.001) with RAPID, which was the best among all other settings. CONCLUSIONS: The estimation results varied among different software packages. Advantage workstation had the best agreement with RAPID in the estimation of infarct core volumes when CBV <1 mL/100 g. NovoStroke Kit had better agreement and correlation with RAPID in the estimation of hypoperfusion volumes. NovoStroke Kit also had moderate agreement with RAPID in estimating mismatch volumes.

First Report of Alternaria alternata Causing White Leaf Spot on Allium tuberosum in China.

Puding County is the major Allium tuberosum growing area in Guizhou Province of China. In 2019, white leaf spots were observed on Allium tuberosum in Puding County (26.31°N, 105.64°E). The white spots, ranging from elliptic to irregular in shape, first appeared on leaf tips. With disease aggravation, spots gradually coalesced, forming necrotic patches with yellow margins causing leaf necrosis; sometimes there was gray mold on dead leaves. The incidence of the diseased leaf rate was estimated to be 27-48%. To identify the pathogenic agent, 150 leaf tissues (5 mm × 5 mm) were obtained from disease-healthy junctions of 50 diseased leaves. Leaf tissues were disinfected in 75% ethanol for 30 s, soaked in 0.5% sodium hypochlorite for 5 min, and flushed three times with sterile water, before being placed on potato dextrose agar (PDA) in the dark at 25 °C. When colonies appeared, the mycelial tips were picked and placed on new PDA. Purified fungus was obtained after repeating this last step several times. The colonies were grayish-green with white round margins. Conidiophores (2.7-4.5 µm × 27-81 µm) were brown, straight, or flexuous with branches and septa. Conidia (8-34 µm × 5-16 µm) were brown, with 0-5 transverse septa and 0-4 longitudinal septa. The 18S nuclear ribosomal DNA (nrDNA; SSU), 28S nrDNA (LSU), RNA polymerase II second largest subunit (RPB2), internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and translation elongation factor 1-alpha (TEF-α) (Woudenberg et al. 2013) were amplified and sequenced. The sequences were deposited in GenBank (ITS: OP703616, LSU: OP860684, SSU: OP860685, GAPDH: OP902372, RPB2: OP902373, TEF1-α: OP902374). According to BLAST analysis, the ITS, LSU, GAPDH, RPB2, SSU, and TEF1-α of the straishowed 100% (689 of 731 base pairs; bp), 100% (916 of 938 bp), 100% (579 of 600 bp), 100% (946 of 985 bp), 100% (1093 of 1134 bp), and 100% (240 of 240 bp) sequence identity to those of Alternaria alternata (ITS: LC440581.1, LSU: KX609781.1, GAPDH: MT109295.1, RPB2: MK605900.1, SSU: ON055699.1 and TEF1-α: OM220081.1). A phylogenetic tree was constructed using PAUP4 and the maximum parsimony method with 1000 replicas of bootstrapping for all datasets. According to morphological characteristics and phylogenetic analysis, FJ-1 was identified as Alternaria alternata (Simmons 2007, Woudenberg et al. 2015). The strain was preserved in the Agricultural Culture Collection of China (preservation number: ACC39969). To determine the pathogenicity of Alternaria alternata against Allium tuberosum, wounded healthy leaves were inoculated with a conidial suspension (106 conidial/mL) and round mycelial plugs (4mm). Sterile agar PDA plugs with no mycelium or sterile water were inoculated as negative controls. Three days later, white spots appeared on the wounded leaves inoculated with mycelial plugs or conidial suspension. However, the symptoms caused by conidial suspensions were weaker than those caused by mycelial plugs. No symptoms were observed in the control group. The experimental symptoms were consistent with the phenomena observed in the field. The same fungus was reisolated from necrotic lesions and identified as Alternaria alternata using the method described above. To our knowledge, this is the first report of Alternaria alternata causing white leaf spots on Allium tuberosum in China, a disease seriously affected the yield and quality of Allium tuberosum and caused economic losses to farmers. Reference: Simmons EG (2007) Alternaria: an identification manual. CBS Fungal Biodiversity Centre, Utrecht, the Netherlands. Woudenberg JHC, Groenewald JZ, Binder M, Crous PW ( 2013) Alternaria redefined. Stud Mycol, 75: 171-212. https://doi.org/10.3114/sim0015. Woudenberg JHC, Seidl MF, Groenewald JZ, Vries M de, Stielow JB, Thomma BPHJ, Crous PW (2015) Alternaria section Alternaria: Species, formae speciales or pathotypes? Stud Mycol, 82:1-21. https://doi.org/10.1016/j.simyco.2015.07.001.

[Physicochemical properties and anti-inflammatory and immunomodulatory effects of Shengfupian polysaccharides].

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 µg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 µg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 µg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1ß and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

Effects of cis/trans-Configuration and Ligand Substitution of the Cyanidometal Bridge on Metal to Metal Charge Transfer Properties in Mixed Valence Complexes.

To investigate the effects of cis/trans-configuration of the cyanidometal bridge and the electron donating ability of the auxiliary ligand on the cyanidometal bridge on metal to metal charge transfer (MMCT) in cyanidometal-bridged mixed valence compounds, two groups of trinuclear cyanidometal-bridged compounds cis/trans-[Cp(dppe)Fe(µ-NC)Ru(4,4'-dmbpy)2 (µ-CN)Fe(dppe)Cp][PF6 ]n (n=2 (cis/trans-1[PF6 ]2 ), 3 (cis/trans-1[PF6 ]3 ), 4 (cis/trans-1[PF6 ]4 )) and cis/trans-[Cp(dppe)Fe(µ-NC)Ru(bpy)2 (µ-CN)Fe(dppe)Cp][PF6 ]3 (cis/trans-2[PF6 ]3 ) were synthesized and fully characterized. The experimental results indicate that for these one- and two-electron oxidation mixed valence compounds, the trans-configuration compounds are more beneficial for MMCT than the cis-configuration compounds, and increasing the electron donating ability of the auxiliary ligand on the cyanidometal bridge is also conductive to MMCT. Moreover, compounds cis/trans-1[PF6 ]n (n=3, 4) and cis/trans-2[PF6 ]3 belong to localized compounds by analyzing the experimental characterization results, supported by the TDDFT calculations.

Predation capacity of Bradymonabacteria, a recently discovered group in the order Bradymonadales, isolated from marine sediments.

Bacterial predation is a vital feeding behavior that affects community structure and maintains biodiversity. However, predatory bacterial species in coastal sediments are comparatively poorly described. In this study, the predation capacity of all nine culturable Bradymonabacteria strains belonging to the recently discovered order Bradymonadales was determined against different types of prey. The predatory efficiency of Bradymonabacteria increased as the initial prey proportion in a mixed culture decreased. When the initial prey proportion was 0.5, the number of surviving prey bacterial cells significantly decreased after 4 h of predation with the Bradymonabacteria strains TMQ1, SEH01, B210 and FA350. However, growth of the prey strain occurred in the presence of the Bradymonabacteria strains TMQ4, TMQ2, TMQ3, V1718 and YN101. When the initial prey proportion decreased to 0.1 or 0.01, most of the Bradymonabacteria strains preyed efficiently. Furthermore, established neighboring colonies of prey were destroyed by Bradymonabacteria. This invading predation capacity was determined by the predation ability of the strain and its motility on the agar surface. Our findings provide new insights into the potential ecological significance of predatory Bradymonabacteria, which may serve as a potential probiotic for use in the aquaculture.

AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner.

Targeting autophagy might be a promising anticancer strategy; however, the dual roles of autophagy in cancer development and malignancy remain unclear. NSCLC (non-small cell lung cancer) cells harbour high levels of SQSTM1 (sequestosome 1), the autophagy receptor that is critical for the dual roles of autophagy. Therefore, mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC. Herein, we used multiple autophagy flux models and autophagy readouts to show that aldo-keto reductase family 1 member C1 (AKR1C1), which is highly expressed in NSCLC, promotes autophagy by directly binding to SQSTM1 in a catalytic-independent manner. This interaction may be strengthened by reactive oxygen species (ROS), important autophagy inducers. Further mechanistic research demonstrated that AKR1C1 interacts with SQSTM1 to augment SQSTM1 oligomerization, contributing to the SQSTM1 affinity for binding cargo. Collectively, our data reveal a catalytic-independent role of AKR1C1 for interacting with SQSTM1 and promoting autophagy. All these findings not only reveal a novel functional role of AKR1C1 in the autophagy process but also indicate that modulation of the AKR1C1-SQSTM1 interaction may be a new strategy for targeting autophagy.

Development of magnetic resonance imaging of brachial plexus neuralgia.

As the incidence of peripheral neurological diseases increases, the precise display of nerves becomes important in imaging examinations. Among them, the pain caused by brachial plexus neuropathy is very prominent, and the magnetic resonance imaging of nerve is quite complex and messy. This paper will systematically elaborate from the aspects of brachial plexus neuropathy, morphological and functional imaging, and post-processing.

Travel changes and equitable access to urban parks in the post COVID-19 pandemic period: Evidence from Wuhan, China.

COVID-19 has spread worldwide, leading to a significant impact on daily life. Numerous studies have confirmed that people have changed their travel to urban green spaces during the COVID-19 pandemic. However, in China, where COVID-19 has been effectively controlled, how the travel behavior of visitors to urban parks has changed under different risk levels (RLs) of COVID-19 is unclear. Faced with these gaps, we took a highly developed city, Wuhan, as a case study and a questionnaire survey was conducted with 3276 respondents to analyze the changes in park visitors' travel behaviors under different COVID-19 RLs. Using a stated preference (SP) survey method, four RLs were assigned: new cases in other provinces (RL1), Hubei province (RL2), Wuhan (RL3), and in the district of the park (RL4). The results indicated that visitors reduced their willingness to visit urban parks, with 78.39%, 37.97%, and 13.34% of visitors remaining under RL2, RL3, and RL4, respectively. Furthermore, the service radius of urban parks also shrank from 4230 m under no new cases of COVID-19 to approximately 3000 m under RL3. A higher impact was found for visitors using public transport, those with a higher income and higher education, and female visitors. Based on the modified travel behaviors, the Gaussian-based two-step floating catchment area (2SFCA) method was used to evaluate the accessibility and the Gini coefficient was calculated to represent the equality of the urban parks. A higher RL led to lower accessibility and greater inequitable access. The results should help the government guide residents' travel behaviors after COVID-19.