Catalytic Intermolecular Deoxygenative Coupling of Carbonyl Compounds with Alkynes by a Cp*Mo(II)-Catalyst.

Carbonyl is highly accessible and acts as an essential functional group in chemical synthesis. However, the direct catalytic deoxygenative functionalization of carbonyl compounds via a putative metal carbene intermediate is a formidable challenge due to the requirement of a high activation energy for the cleavage of strong C═O double bonds. Here, we report a class of bench stable and readily available Cp*Mo(II)-complexes as efficient deoxygenation catalysts that could catalyze the direct intermolecular deoxygenative coupling of carbonyl compounds with alkynes. Enabled by this powerful Cp*Mo(II)-catalyst, various valuable heteroarenes (10 different classes) were obtained in generally good yields and remarkable chemo- and regioselectivities. Mechanistic studies suggested that this reaction might proceed via a sequence of C═O double bonds cleavage, carbene-alkyne metathesis, cyclization, and aromatization processes. This strategy not only provided a general catalytic platform for the rapid preparation of heteroarenes but also opened a new window for the applications of Cp*Mo(II)-catalysts in organic synthesis.

The expression profiles of cyp19a1, sf-1, esrs and gths in the brain-pituitary during gonadal sex differentiation in juvenile Japanese eels.

Eels are gonochoristic species whose gonadal differentiation initiates at the yellow eel stage and is influenced by environmental factors. We revealed some sex-related genes were sex dimorphically expressed in gonads during gonadal sex differentiation of Japanese eel (Anguilla japonica); however, the expression of sex-related genes in the brain-pituitary during gonadal sex differentiation in eels is still unclear. This study aimed to investigate the sex-related gene expressions in the brain-pituitary and tried to clarify their roles in the brain and gonads during gonadal sex differentiation. Based on our previous histological study, the control eels developed as males, and estradiol-17ß (E2) was used for feminization. Our results showed that during testicular differentiation, the brain cyp19a1 transcripts and aromatase proteins were increased significantly; moreover, the cyp19a1, sf-1, foxl2s, and esrs (except gperb) transcripts in the midbrain/pituitary also were increased significantly. Forebrain gnrh1 transcripts increased slightly during gonadal differentiation of both sexes, but the gnrhr1b and gnrhr2 transcripts in the midbrain/pituitary were stable during gonadal differentiation. The expression levels of gths and gh in the midbrain/pituitary were significantly increased during testicular differentiation and were much higher in males than in E2-feminized females. These results implied that endogenous estrogens might play essential roles in the brain/pituitary during testicular differentiation, sf-1, foxl2s, and esrs may have roles in cyp19a1 regulation in the midbrain/pituitary of Japanese eels. For the GnRH-GTH axis, gths, especially fshb, may be regulated by esrs and involved in regulating testicular differentiation and development in Japanese eels.

The effect of gonadal hormones on the gene expression of brain-pituitary in protandrous black porgy, Acanthopagrus schlegelii.

In black porgy (Acanthopagrus schlegelii), the brain-pituitary-testis (Gnrh-Gths-Dmrt1) axis plays a vital role in male fate determination and maintenance, and then inhibiting female development in further (puberty). However, the feedback of gonadal hormones on regulating brain signaling remains unclear. In this study, we conducted short-term sex steroid treatment and surgery of gonadectomy to evaluate the feedback regulation between the gonads and the brain. The qPCR results show that male phase had the highest gths transcripts; treatment with estradiol-17ß (E2) or 17α-methyltestosterone (MT) resulted in the increased pituitary lhb transcripts. After surgery, apart from gnrh1, there is no difference in brain signaling genes between gonadectomy and sham fish. In the diencephalon/mesencephalon transcriptome, de novo assembly generated 283,528 unigenes; however, only 443 (0.16%) genes showed differentially expressed between sham and gonadectomy fish. In the present study, we found that exogenous sex steroids affect the gths transcription; this feedback control is related to the gonadal stage. Furthermore, gonadectomy may not affect gene expression of brain signaling (Gnrh-Gths axis). Our results support the communication between ovotestis and brain signaling (Gnrh-Gths-testicular Dmrt1) for the male fate.

Fixation technique of biodegradable magnesium alloy suture anchor in the rotator cuff repair of the shoulder in a goat model: a technical note.

BACKGROUND: Shoulder disorders, particularly rotator cuff tears, are prevalent musculoskeletal conditions related to aging. Although the widely used suture anchor technique provides strong mechanical support to the tendon, it is associated with a risk of postoperative tendon retearing. The conventionally used titanium alloys can affect the interpretation of magnetic resonance imaging. Degradable magnesium alloys possess excellent biocompatibility, similar mechanical property to the bone, and stimulating bone formation ability from Mg2+. The purpose of this experiment was to develop innovative magnesium-based suture anchors to enhance rotator cuff repair by improving fixation materials, and to evaluate their feasibility in a goat model. METHODS: We developed fluoridized ZK60 suture anchors as the implantation material for two goats, who underwent rotator cuff repair surgery on both shoulders. Computed tomography (CT) and histological analysis were performed at 12 weeks postoperatively, and the results were compared between the magnesium and titanium alloy groups. Additionally, a hematological examination was conducted, which included assessments of red blood cells, white blood cells, platelets, coagulation function, liver function, kidney function, and magnesium ion concentration. RESULTS: The 12-week postoperative CT images showed intact MgF2 ZK60 suture anchors, effectively reconnecting the infraspinatus tendon to the humeral head. The anchors became less visible on CT scans, indicating absorption by surrounding tissues. New bone formation in the MgF2 group surpassed that in the Ti group, demonstrating superior osseointegration. The similarity between cortical bone and magnesium reduced stress-shielding and promoted bone regeneration. Histological analysis revealed successful tendon healing with MgF2 anchors, while the Ti group showed discontinuous interfaces and reduced collagen secretion. Hematological examination showed stable liver, renal function, and magnesium ion levels. CONCLUSIONS: The findings indicate that MgF2-coated suture anchors are feasible for rotator cuff repair and potentially other orthopedic applications. We hope that magnesium alloy anchors can become the solution for rotator cuff tendon repair surgery.

High-Sensitivity Self-Powered Photodetector Fibers Using Hierarchical Heterojunction Photoelectrodes Enable Wearable Amphibious Optoelectronic Textiles.

Fiber-shaped photodetectors (FPDs) with multidirectional light absorption properties offer exciting opportunities for intelligent optoelectronic textiles. However, achieving FPDs capable of working in ampule environments, especially with high sensitivity, remains a fundamental challenge. Here, quasi-solid-state twisted-fiber photoelectrochemical photodetectors (FPPDs) consisting of photoanode, gel electrolyte, and counter electrode are successfully assembled. In situ decorated n-type one-dimensional (1D) TiO2 nanowire arrays with 2D Ni-Fe metal-organic framework (NiFeMOF) nanosheets serve as hierarchical heterojunction photoanodes, thereby optimizing carrier transfer dynamics at the photoanode/electrolyte interface. As expected, the resulting self-powered FPPD exhibits 88.6 mA W-1 high responsiveness and a < 30 ms fast response time. Significantly, our FPPD can operate in both terrestrial and aquatic environments thanks to its intrinsic ionic properties, making it a versatile tool for detecting ultraviolet light on land and facilitating optical communication underwater. These high-sensitivity self-powered FPPDs with hierarchical heterojunction photoelectrodes hold promise for the development of wearable amphibious optoelectronic textiles.

Radiation exposure in augmented fluoroscopic bronchoscopy procedures: a comprehensive analysis for patients and physicians.

Cancer is a major health challenge and causes millions of deaths worldwide each year, and the incidence of lung cancer has increased. Augmented fluoroscopic bronchoscopy (AFB) procedures, which combine bronchoscopy and fluoroscopy, are crucial for diagnosing and treating lung cancer. However, fluoroscopy exposes patients and physicians to radiation, and therefore, the procedure requires careful monitoring. The National Council on Radiation Protection and Measurement and the International Commission on Radiological Protection have emphasised the importance of monitoring patient doses and ensuring occupational radiation safety. The present study evaluated radiation doses during AFB procedures, focusing on patient skin doses, the effective dose, and the personal dose equivalent to the eye lens for physicians. Skin doses were measured using thermoluminescent dosimeters. Peak skin doses were observed on the sides of the patients' arms, particularly on the side closest to the x-ray tube. Differences in the procedures and experience of physicians between the two hospitals involved in this study were investigated. AFB procedures were conducted more efficiently at Hospital A than at Hospital B, resulting in lower effective doses. Cone-beam computed tomography (CT) contributes significantly to patient effective doses because it has higher radiographic parameters. Despite their higher radiographic parameters, AFB procedures resulted in smaller skin doses than did image-guided interventional and CT fluoroscopy procedures. The effective doses differed between the two hospitals of this study due to workflow differences, with cone-beam CT playing a dominant role. No significant differences in left and right eyeHp(3) values were observed between the hospitals. For both hospitals, theHp(3) values were below the recommended limits, indicating that radiation monitoring may not be required for AFB procedures. This study provides insights into radiation exposure during AFB procedures, concerning radiation dosimetry, and safety for patients and physicians.

Interfacially Ordered NiCoMoS Nanosheets Arrays on Hierarchical Ti3C2Tx MXene for High-energy-density Fiber-Shaped Supercapacitors with Accelerated Pseudocapacitive Kinetics.

Balancing electrochemical activity and structural reversibility of fibrous electrodes with accelerated Faradaic charge transfer kinetics and pseudocapacitive storage are highly crucial for fiber-shaped supercapacitors (FSCs). Herein, we report novel core-shell hierarchical fibers for high-performance FSCs, in which the ordered NiCoMoS nanosheets arrays are chemically anchored on Ti3C2Tx fiber. Beneficial from architecting stable polymetallic sulfide arrays and conductive networks, the NiCoMoS-Ti3C2Tx fiber maintains fast charge transfer, low diffusion and OH- adsorption barrier, and stabilized multi-electronic reaction kinetics of polymetallic sulfide. Consequently, the NiCoMoS-Ti3C2Tx fiber exhibits a large volumetric capacitance (2472.3 F cm-3) and reversible cycling performance (20,000 cycles). In addition, the solid-state symmetric FSCs deliver a high energy density of 50.6 mWh cm-3 and bending stability, which can significantly power electronic devices and offer sensitive detection for dopamine.

exo-6b2-Methyl-Substituted Pentabenzocorannulene: Synthesis, Structural Analysis, and Properties.

exo-6b2-Methyl-substituted pentabenzocorannulene (exoPBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π···π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

Cellular mechanisms underlying extraordinary sulfide tolerance in a crustacean holobiont from hydrothermal vents.

The shallow-water hydrothermal vent system of Kueishan Island has been described as one of the world's most acidic and sulfide-rich marine habitats. The only recorded metazoan species living in the direct vicinity of the vents is Xenograpsus testudinatus, a brachyuran crab endemic to marine sulfide-rich vent systems. Despite the toxicity of hydrogen sulfide, X. testudinatus occupies an ecological niche in a sulfide-rich habitat, with the underlying detoxification mechanism remaining unknown. Using laboratory and field-based experiments, we characterized the gills of X. testudinatus that are the major site of sulfide detoxification. Here sulfide is oxidized to thiosulfate or bound to hypotaurine to generate the less toxic thiotaurine. Biochemical and molecular analyses demonstrated that the accumulation of thiosulfate and hypotaurine is mediated by the sodium-independent sulfate anion transporter (SLC26A11) and taurine transporter (Taut), which are expressed in gill epithelia. Histological and metagenomic analyses of gill tissues demonstrated a distinct bacterial signature dominated by Epsilonproteobacteria. Our results suggest that thiotaurine synthesized in gills is used by sulfide-oxidizing endo-symbiotic bacteria, creating an effective sulfide-buffering system. This work identified physiological mechanisms involving host-microbe interactions that support life of a metazoan in one of the most extreme environments on our planet.

Targeting influenza A virus by splicing inhibitor herboxidiene reveals the importance of subtype-specific signatures around splice sites.

BACKGROUND: The association between M segment splicing and pathogenicity remains ambiguous in human influenza A viruses. In this study, we aimed to investigate M splicing in various human influenza A viruses and characterize its physiological roles by applying the splicing inhibitor, herboxidiene. METHODS: We examined the M splicing of human H1N1 and H3N2 viruses by comparing three H1N1 and H3N2 strains, respectively, through reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. We randomly selected M sequences of human H1N1, H2N2, and H3N2 viruses isolated from 1933 to 2020 and examined their phylogenetic relationships. Next, we determined the effects of single nucleotide variations on M splicing by generating mutant viruses harboring the 55C/T variant through reverse genetics. To confirm the importance of M2 splicing in the replication of H1N1 and H3N2, we treated infected cells with splicing inhibitor herboxidiene and analyzed the viral growth using plaque assay. To explore the physiological role of the various levels of M2 protein in pathogenicity, we challenged C57BL/6 mice with the H1N1 WSN wild-type strain, mutant H1N1 (55T), and chimeric viruses including H1N1 + H3wt and H1N1 + H3mut. One-tailed paired t-test was used for virus titer calculation and multiple comparisons between groups were performed using two-way analysis of variance. RESULTS: M sequence splice site analysis revealed an evolutionarily conserved single nucleotide variant C55T in H3N2, which impaired M2 expression and was accompanied by collinear M1 and mRNA3 production. Aberrant M2 splicing resulted from splice-site selection rather than a general defect in the splicing process. The C55T substitution significantly reduced both M2 mRNA and protein levels regardless of the virus subtype. Consequently, herboxidiene treatment dramatically decreased both the H1N1 and H3N2 virus titers. However, a lower M2 expression only attenuated H1N1 virus replication and in vivo pathogenicity. This attenuated phenotype was restored by M replacement of H3N2 M in a chimeric H1N1 virus, despite low M2 levels. CONCLUSIONS: The discrepancy in M2-dependence emphasizes the importance of M2 in human influenza A virus pathogenicity, which leads to subtype-specific evolution. Our findings provide insights into virus adaptation processes in humans and highlights splicing regulation as a potential antiviral target.

Mechanisms of cancer cell killing by metformin: a review on different cell death pathways.

Cancer resistance to anti-tumour agents has been one of the serious challenges in different types of cancer treatment. Usually, an increase in the cell death markers can predict a higher rate of survival among patients diagnosed with cancer. By increasing the regulation of survival genes, cancer cells can display a higher resistance to therapy through the suppression of anti-tumour immunity and inhibition of cell death signalling pathways. Administration of certain adjuvants may be useful in order to increase the therapeutic efficiency of anti-cancer therapy through the stimulation of different cell death pathways. Several studies have demonstrated that metformin, an antidiabetic drug with anti-cancer properties, amplifies cell death mechanisms, especially apoptosis in a broad-spectrum of cancer cells. Stimulation of the immune system by metformin has been shown to play a key role in the induction of cell death. It seems that the induction or suppression of different cell death mechanisms has a pivotal role in either sensitization or resistance of cancer cells to therapy. This review explains the cellular and molecular mechanisms of cell death following anticancer therapy. Then, we discuss the modulatory roles of metformin on different cancer cell death pathways including apoptosis, mitotic catastrophe, senescence, autophagy, ferroptosis and pyroptosis.

Third-generation sequencing-selected Scardovia wiggsiae promotes periodontitis progression in mice.

BACKGROUNDS: Periodontitis is an oral-bacteria-directed disease that occurs worldwide. Currently, periodontal pathogens are mostly determined using traditional culture techniques, next-generation sequencing, and microbiological screening system. In addition to the well-known and cultivatable periodontal bacteria, we aimed to discover a novel periodontal pathogen by using DNA sequencing and investigate its role in the progression of periodontitis. OBJECTIVE: This study identified pathogens from subgingival dental plaque in patients with periodontitis by using the Oxford Nanopore Technology (ONT) third-generation sequencing system and validated the impact of selected pathogen in periodontitis progression by ligature-implanted mice. METHODS: Twenty-five patients with periodontitis and 25 healthy controls were recruited in this study. Subgingival plaque samples were collected for metagenomic analysis. The ONT third-generation sequencing system was used to confirm the dominant bacteria. A mouse model with ligature implantation and bacterial injection verified the pathogenesis of periodontitis. Neutrophil infiltration and osteoclast activity were evaluated using immunohistochemistry and tartrate-resistant acid phosphatase assays in periodontal tissue. Gingival inflammation was evaluated using pro-inflammatory cytokines in gingival crevicular fluids. Alveolar bone destruction in the mice was evaluated using micro-computed tomography and hematoxylin and eosin staining. RESULTS: Scardovia wiggsiae (S. wiggsiae) was dominant in the subgingival plaque of the patients with periodontitis. S. wiggsiae significantly deteriorated ligature-induced neutrophil infiltration, osteoclast activation, alveolar bone destruction, and the secretion of interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α in the mouse model. CONCLUSION: Our metagenome results suggested that S. wiggsiae is a dominant flora in patients with periodontitis. In mice, the induction of neutrophil infiltration, proinflammatory cytokine secretion, osteoclast activation, and alveolar bone destruction further verified the pathogenic role of S. wiggsiae in the progress of periodontitis. Future studies investigating the metabolic interactions between S. wiggsiae and other periodontopathic bacteria are warranted.

Interface-Anchored Covalent Organic Frameworks@Amino-Modified Ti3 C2 Tx MXene on Nylon 6 Film for High-Performance Deformable Supercapacitors.

Designing deformable supercapacitors (D-SCs) that have robust skeleton and smoothly active channels for charges kinetic migration and faradic storage are highly crucial for wearable systems. Here, we develop the high-performance D-SCs made of the covalent organic frameworks(COF)@amino-modified Ti3 C2 Tx deposited on decorated nylon 6 (DPA) film (COF@N-Ti3 C2 Tx /DPA) via layer-by-layer fabrication. The hierarchical COF@N-Ti3 C2 Tx /DPA exhibits admirable specific capacitance, rate performance and cycling stability in three-electrode system due to the superior H+ storage property and large interfacial charge transfer clarified by density functional theory calculations. Additionally, the solid-state D-SCs deliver favourable energy density and practical energy-supply applications. Particularly, the solid-state D-SCs present high deformable stabilities, with regard to 80.7, 80.6 and 83.4 % capacitance retention after 5000 bending cycles, 2000 stretching cycles and 5000 folding cycles, separately.

Multiscale Dot-Wire-Sheet Heterostructured Nitrogen-Doped Carbon Dots-Ti3 C2 Tx /Silk Nanofibers for High-Performance Fiber-Shaped Supercapacitors.

Fiber-shaped supercapacitors (FSCs) have become one of the significantly strategical flexible energy-storage materials towards future wearable textile electronics and metaverse technologies. Here, we develop the high-performance FSCs based on multiscale dot-wire-sheet heterostructure microfiber of nitrogen-doped carbon dots-Ti3 C2 Tx /silk nanofibers (NCDs-Ti3 C2 Tx /SNFs) hybrids via microfluidic fabrication. Due to the enlarged interlayer spacing, plentiful porous channels, accelerated H+ ion transport dynamics, large electrical conductivity and excellent mechanical strength/flexibility, the NCDs-Ti3 C2 Tx /SNFs possesses high volumetric capacitance (2218.7 F cm-3 ) and reversible charge-discharge stability in 1 M H2 SO4 electrolyte. Furthermore, the solid-state FSCs present high energy density (57.9 mWh cm-3 ), good capacitance (1157 F cm-3 ), long-life cycles (82.3 % capacitance retention after 40000 cycles), which realize the actual energy-supply applications (powering lamp, watch and toy car).

Localized Ligands Assist Ultrafast Multivalent-Cation Intercalation Pseudocapacitance.

Rechargeable batteries based on multivalent cation (Mvn+ , n>1) carriers are considered potentially low-cost alternatives to lithium-ion batteries. However, the high charge-density Mvn+ carriers generally lead to sluggish kinetics and poor structural stability in cathode materials. Herein, we report an Mvn+ storage via intercalation pseudocapacitance mechanism in a 2D bivalve-like organic framework featured with localized ligands. By switching from conventional intercalation to localized ligand-assisted-intercalation pseudocapacitance, the organic cathode exhibits unprecedented fast kinetics with little structural change upon intercalation. It thus enables an excellent power density of 57 kW kg-1 over 20000 cycles for Ca2+ storage and a power density of 14 kW kg-1 with a long cycling life over 45000 cycles for Zn2+ storage. This work may provide a largely unexploited route toward constructing a local dynamic coordination microstructure for ultrafast Mvn+ storage.

Long noncoding RNA Gas5 induces cell apoptosis and inhibits tumor growth via activating the CHOP-dependent endoplasmic reticulum stress pathway in human hepatoblastoma HepG2 cells.

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor-associated regulatory factors. LncRNA growth arrest-specific transcript 5 (Gas5) acts as an anti-oncogene in most cancers. Whether Gas5 acts as an oncogene or anti-oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription-polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull-down experiments and analyzed by mass spectrometry. A series of novel Gas5-interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose-regulated protein (GRP78) was identified as a direct target of Gas5 by Rip-qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5-mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.

Role of the Chaperone Protein 14-3-3ε in the Regulation of Influenza A Virus-Activated Beta Interferon.

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in retinoic acid-inducible gene I (RIG-I) translocation to mitochondrial antiviral-signaling protein (MAVS) to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-ß promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-ß expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C terminus-truncated NS1 with a T49A mutation dramatically increases IFN-ß mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-ß expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in retinoic acid-inducible gene I (RIG-I) translocation that induces type I interferon (IFN) expression, and that NS1 protein prevents RIG-I translocation to the mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-ß suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

Asymmetric Catalytic Assembly of Triple-Columned and Multilayered Chiral Folding Polymers Showing Aggregation-Induced Emission (AIE).

Unprecedented chiral multilayer folding 3D polymers have been assembled and regulated by uniform and differentiated aromatic chromophore units between naphthyl piers. Screening catalysts, catalytic systems and monomers were proven to be crucial for asymmetric catalytic Suzuki-Miyaura polycouplings for this assembly. X-ray crystallography of the corresponding dimers and trimers revealed the absolute configuration and the intermolecular packing pattern. Up to 61 960 Mw /41 900 Mn and m/z 4317 for polymers and oligomers, as confirmed by gel permeation chromatography (GPC) and MALDI-TOF MS, indicated that these frameworks were composed of multiple stacked layers. The resulting multiple π-assemblies exhibited remarkable optical properties in aggregated states (photoluminescence in solids and aggregation-induced emission in solutions), as well as reversible redox properties in electrochemical performance.

Asymmetric Catalytic Assembly of Triple-Columned and Multilayered Chiral Folding Polymers Showing Aggregation-Induced Emission (AIE).

Invited for the cover of this issue are Guigen Li's groups at Texas Tech University and Nanjing University. The cover artwork shows that chirality patterns exist from universal to molecular levels showing light emission properties. Read the full story of multilayer 3D chirality and its asymmetric catalytic synthesis at 10.1002/chem.202104102.

Functional and structural properties of cardiotoxin isomers produced by blocking negatively charged groups.

In this study, we investigated the functional roles of Asp40, Asp57, and C-terminal Asn60 in Naja atra cardiotoxin 3 (CTX3) structure and function by modifying these three carboxyl groups with semicarbazide. The conjugation of the carboxyl groups with semicarbazide produced two conformational isomers whose gross and fine structures were different from those of CTX3. The blocking of the carboxyl groups increased the structural flexibility of CTX3 in response to trifluoroethanol-induced effect. Despite presenting modest to no effect on decreasing the induction of permeability in zwitterionic phospholipid vesicles, the carboxyl group-modified CTX3 showed a marked reduction in its permeabilizing effect on anionic phospholipid vesicles in comparison to that of the native protein. Compared with native CTX3, carboxyl group-modified CTX3 exhibited lower activity in inducing membrane leakage in U937 cells. The CD spectra of lipid-bound toxins and the color transition of polydiacetylene/lipid assay showed that the membrane interaction mode of CTX3 was distinctly changed by the modification in the carboxyl groups. Given that the selective modification of Asp40 does not cause the conformational isomerization of CTX3, our data indicate that the carboxyl groups in Asp57 and Asn60 are essential in maintaining the structural topology of CTX3. Furthermore, modification of carboxyl groups changes the interdependence between the infrastructure and the global conformation of CTX3 in modulating membrane permeabilizing activity.