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HIV-1 envelope glycoproteins (Env) from primary HIV-1 isolates typically adopt a pretriggered "closed" conformation that resists to CD4-induced (CD4i) non-neutralizing antibodies (nnAbs) mediating antibody-dependent cellular cytotoxicity (ADCC). CD4-mimetic compounds (CD4mcs) "open-up" Env allowing binding of CD4i nnAbs, thereby sensitizing HIV-1-infected cells to ADCC. Two families of CD4i nnAbs, the anti-cluster A and anti-coreceptor binding site (CoRBS) Abs, are required to mediate ADCC in combination with the indane CD4mc BNM-III-170. Recently, new indoline CD4mcs with improved potency and breadth have been described. Here, we show that the lead indoline CD4mc, CJF-III-288, sensitizes HIV-1-infected cells to ADCC mediated by anti-CoRBS Abs alone, contributing to improved ADCC activity. Structural and conformational analyses reveal that CJF-III-288, in combination with anti-CoRBS Abs, potently stabilizes an asymmetric "open" State-3 Env conformation, This Env conformation orients the anti-CoRBS Ab to improve ADCC activity and therapeutic potential.

Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm ) into a supramolecular cage formed by duad semicage p - tert -butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.

Peritoneal metastasis is one of the common site of colorectal cancer metastasis and associated with a poor prognosis. The core strategy for colorectal cancer peritoneal metastasis primarily revolves around a comprehensive treatment approach with cytoreductive surgery and systemic chemotherapy as the mainstay, supplemented by intraperitoneal chemotherapy. As an important supplement to treatment, intraperitoneal chemotherapy has broad application prospects. The main modalities are hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), early postoperative intraperitoneal chemotherapy (EPIC), sequential postoperative intraperitoneal chemotherapy (SPIC), normothermic intraperitoneal chemotherapy (NIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). To promote the standardized application of intraperitoneal chemotherapy, further research on the mechanisms underlying peritoneal metastasis of colorectal cancer, selection of effective intraperitoneal chemotherapy agents, determination of optimal timing and administration protocols, exploration of the feasibility of sequential intraperitoneal chemotherapy and conduction of valuable basic and clinical research are currently needed. This paper will review the development and origins of intraperitoneal chemotherapy, treatment modalities, as well as the current application status and prospects of various treatment approaches in the context of peritoneal metastasis of colorectal cancer.

It is still a great challenge to achieve high selectivity of ethanol in CO 2 electroreduction reactions (CO 2 RR) because of the similar reduction potentials and lower energy barrier of possible other C 2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5 % at -1.0 V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66 mA cm -2 . By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO 2 -to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO 2 -to-EtOH., (© 2024 Wiley-VCH GmbH.)

In [Mn(5-MeOsalen)(Cl)] 2 (dibenzo[24]crown-8), dibenzo[24]crown-8 formed a supramolecule via multi-point interactions with the [Mn(5-MeOsalen)(Cl)] dimer. The dimer was magnetically isolated with S T = 4 and weak interdimer magnetic interactions. The crystal exhibited single-molecule magnet behaviour with an anisotropic barrier of 26(1) K, which is the highest among the Mn-salen series reported to date.

Background: Cancer screening and early detection greatly increase the chances of successful treatment. However, most cancer types lack effective early screening biomarkers. In recent years, natural language processing (NLP)-based text-mining methods have proven effective in searching the scientific literature and identifying promising associations between potential biomarkers and disease, but unfortunately few are widely used., Methods: In this study, we used an NLP-enabled text-mining system, MarkerGenie, to identify potential stool bacterial markers for early detection and screening of colorectal cancer. After filtering markers based on text-mining results, we validated bacterial markers using multiplex digital droplet polymerase chain reaction (ddPCR). Classifiers were built based on ddPCR results, and sensitivity, specificity, and area under the curve (AUC) were used to evaluate the performance., Results: A total of 7 of the 14 bacterial markers showed significantly increased abundance in the stools of colorectal cancer patients. A five-bacteria classifier for colorectal cancer diagnosis was built, and achieved an AUC of 0.852, with a sensitivity of 0.692 and specificity of 0.935. When combined with the fecal immunochemical test (FIT), our classifier achieved an AUC of 0.959 and increased the sensitivity of FIT (0.929 vs. 0.872) at a specificity of 0.900., Conclusions: Our study provides a valuable case example of the use of NLP-based marker mining for biomarker identification., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The HIV-1 entry inhibitor temsavir prevents the viral receptor CD4 (cluster of differentiation 4) from interacting with the envelope glycoprotein (Env) and blocks its conformational changes. To do this, temsavir relies on the presence of a residue with small side chain at position 375 in Env and is unable to neutralize viral strains like CRF01_AE carrying His375. Here we investigate the mechanism of temsavir resistance and show that residue 375 is not the sole determinant of resistance. At least six additional residues within the gp120 inner domain layers, including five distant from the drug-binding pocket, contribute to resistance. A detailed structure-function analysis using engineered viruses and soluble trimer variants reveals that the molecular basis of resistance is mediated by crosstalk between His375 and the inner domain layers. Furthermore, our data confirm that temsavir can adjust its binding mode to accommodate changes in Env conformation, a property that likely contributes to its broad antiviral activity., (© 2023. Springer Nature Limited.)

Rationale : Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor thrombus (PVTT) in HCC remains unclear. As a consequence of myeloid cell developmental arrest, CD71 + erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells play important roles in HCC; however, their roles in PVTT remain unclear. Methods: The role of CD71 + EPCs in the HCC tumor microenvironment (TME) was evaluated via morphological, RNA-sequencing, enzyme-linked immunosorbent assay, and flow cytometric analyses. Co-culture techniques were employed to assess the CD45 + EPCs and their vascular compromising effect. Additionally, the PVTT-promoting function of CD45 + EPCs was explored in vivo in a murine model. Results: The CD45 + EPCs in HCC tissues exhibited increased myeloid cell features, including morphology, surface markers, transforming growth factor (TGF)-β generation, and gene expression, compared with those in circulation. Hence, a large proportion of CD45 + EPCs, particularly those in TMEs, comprise erythroid-transdifferentiated myeloid cells (EDMCs). Additionally, the expression of C-C chemokine receptor type 2 (CCR2) mRNA was upregulated in CD45 + EPCs within the TME. Tumor macrophages from HCC tissues induced substantial migration of CD45 + EPCs in a dose-dependent manner. Meanwhile, results from immunofluorescence analyses revealed that these two cell types are positively associated in the TME and circulation. That is, EDMCs are chemoattracted by HCC macrophages mainly via CCR2 from CD45 + EPCs in the circulation. Additionally, the expressions of FX, FVII, FGB, C4b, CFB, and CFH were elevated in CD45 + EPCs within the TME compared with those in the spleen. The CD45 + EPCs from the HCC TME promoted vessel endothelial cell migration and compromised tube formation through TGF-β and FGB, respectively. Additionally, CD45 + EPCs from the TME induced HCC cell migration. HCC macrophage-induced CD45 + EPCs to exhibit higher levels of FX, FVII, FGB, and TGF-β. Meanwhile, upregulation of CCAAT/enhancer binding protein beta expression induced FGB and TGF-β generation in CD45 + EPCs in the TME. WTAP, a major RNA m 6 A writer, stabilized FX and FVII mRNA and enhanced their nuclear export in CD45 + EPCs from the TME. CD45 + EPCs from the TME were positively associated with PVTT and poor prognosis. Splenectomy reduced the level of CD45 + EPCs in the circulation and TME, as well as the incidence of microvascular invasion. The incidence of microvascular invasion increased following the transfer of HCC tissue CD45 + EPCs to splenectomized HCC-bearing mice. Conclusions: The CD45 + EPCs enriched in the HCC microenvironment are EDMCs, which are induced by HCC macrophages to migrate from the circulation to the TME. Subsequently, EDMCs promote PVTT by compromising the blood vessel endothelium, aggravating coagulation, and promoting HCC cell migration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The key to designing and fabricating highly efficient mixed protonic-electronic conductors materials (MPECs) is to integrate the mixed conductive active sites into a single structure, to break through the shortcomings of traditional physical blending. Herein, based on the host-guest interaction, an MPEC is consisted of 2D metal-organic layers and hydrogen-bonded inorganic layers by the assembly methods of layered intercalation. Noticeably, the 2D intercalated materials (≈1.3 nm) exhibit the proton conductivity and electron conductivity, which are 2.02 × 10 -5 and 3.84 × 10 -4 S cm -1 at 100 °C and 99% relative humidity, much higher than these of pure 2D metal-organic layers (>>1.0 × 10 -10 and 2.01×10 -8 S cm -1 ), respectively. Furthermore, combining accurate structural information and theoretical calculations reveals that the inserted hydrogen-bonded inorganic layers provide the proton source and a networks of hydrogen-bonds leading to efficient proton transport, meanwhile reducing the bandgap of hybrid architecture and increasing the band electron delocalization of the metal-organic layer to greatly elevate the electron transport of intrinsic 2D metal-organic frameworks., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

HBsAg seroclearance, the ideal aim of anti-hepatitis B virus (HBV) treatment, cannot be achieved easily. Anemia is another common issue for chronic hepatitis B (CHB) patients, which leads to elevation of erythroid progenitor cells (EPCs) and immune suppression in cancer. This study investigated the role of EPCs in HBsAg seroclearance following pegylated interferon-α (PEG-IFN) treatment. CD45 + EPC accumulation in CHB patients and an AAV/HBV mice model was found in the circulation and liver by flow cytometry and immunofluorescence tests. Wright-Giemsa staining showed that these pathological CD45 + EPCs presented elevated erythroid cells with relative immature morphologies and atypical cells compared with the control cells. CD45 + EPCs were associated with immune tolerance and decreased HBsAg seroclearance during finite PEG-IFN treatment. CD45 + EPCs suppressed antigen non-specific T cell activation and HBV-specific CD8 + T cells, partially through transforming growth factor β (TGF-β). RNA-seq revealed that CD45 + EPCs in patients with CHB presented a distinct gene expression profile compared with CD45 - EPCs and CD45 + EPCs from cord blood. Notably, CD45 + EPCs from patients with CHB expressed high level of Lymphocyte-activation gene 3 (LAG3), an immune checkpoint molecule, and were then defined as LAG3 + EPCs. LAG3 + EPCs diminished the function of antigen presenting cells through LAG3, which was another mechanism by which LAG3 + EPCs' suppressed HBV-specific CD8 + T cells. Anti-LAG3 and anti-TGF-β combination treatment decreased serum HBeAg, HBV DNA levels and HBsAg level, as well as HBsAg-expression in hepatocytes during PEG-IFN treatment in the AAV/HBV mice model. Conclusions: LAG3 + EPCs inhibited the efficacy of PEG-IFN treatment on HBsAg seroclearance induced by LAG3 and TGF-β. Anti-LAG3, anti-TGF-β and PEG-IFN combination treatment might facilitate HBV clearance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro . Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients., Competing Interests: A.F. has filed a provisional patent application on the following monoclonal antibodies: CV3-1 and CV3-25. A.F., J.P., V.L. M.A.S., V.-P.L., and E.H. have filed a provisional patent application on the following monoclonal antibodies: EH3 and EH8., (© 2022 The Author(s).)

A rigid hydrogen-bonded organic framework (HOF) was constructed from a C 3 -symmetric hexatopic carboxylic acid with a hydrophilic 18-crown-6-ether (18C6) component. Despite the flexible macrocyclic structure with many conformations, the derivative with three 4,4'-dicarboxy-o-terphenyl moieties in the periphery yielded a rigid layered porous framework through directional intermolecular hydrogen bonding. Interestingly, the HOF possesses 1D channels with bottleneck composed of 18C6 rings. The HOF shows proton conductivity (1.12×10 -7  S cm -1 ) through Grotthuss mechanism (E a =0.27 eV) under 98 %RH. The present unique water channel structure provides an inspiration to create molecular porous materials., (© 2022 Wiley-VCH GmbH.)

Modulating the transport route of photogenerated carriers on hollow cadmium sulfide without changing its intrinsic structure remains fascinating and challenging. In this work, a series of well-defined heterogeneous hollow structural materials consisting of CdS hollow nanocubes (CdS NCs) and graphitic C 3 N 4 nanoparticles (CN NPs) were strategically designed and fabricated according to an electrostatic interaction approach. It was found that such CN NPs/CdS NCs still retained the hollow structure after CN NP adorning and demonstrated versatile and remarkably boosted photoreduction performance. Specifically, under visible light irradiation (λ ≥ 420 nm), the hydrogenation ratio over 2CN NPs/CdS NCs (the mass ratio of CN NPs to CdS NCs is controlled to be 2%) toward nitrobenzene, p -nitroaniline, p -nitrotoluene, p -nitrophenol, and p -nitrochlorobenzene can be increased to 100%, 99.9%, 83.2%, 93.6%, and 98.2%, respectively. In addition, based on the results of photoelectrochemical performances, the 2CN NPs/CdS NCs reach a 0.46% applied bias photo-to-current efficiency, indicating that the combination with CN NPs can indeed improve the migration and motion behavior of photogenerated carriers, besides ameliorating the photocorrosion and prolonging the lifetime of CdS NCs.

The flexibility and guest-responsive behavior of some metal-organic frameworks (MOFs) indicate their potential in the fields of sensors and molecular recognition. As a subfamily of MOFs, the flexible zeolitic imidazolate frameworks (ZIFs) typically feature a small displacive transition due to the rigid zeolite topology. Herein, an atypical reversible displacive transition (6.4 Å) is observed for the sodalite (SOD) cage in flexible ZIF-65(Zn), which represents an unusually large breathing effect compared to other ZIFs. ZIF-65(Zn) exhibits a stepwise II → III → I expansion between an unusual ellipsoidal SOD cage (8.6 Å × 15.9 Å for II) and a spherical SOD cage (15.0 Å for I). The breathing behavior of ZIF-65(Zn) varies depending on the nature of the guest molecules (polarity and shape). Computational simulations are employed to rationalize the differences in the breathing behavior depending on the structure of the ZIF-65(Zn) cage and the nature of the guest-associated host-guest and guest-guest interactions., (© 2022. The Author(s).)

Using Na-encapsulated benzo[18]crown-6 (Na)(B18C6) as a counter cation, we successfully magnetically isolated a fluoride-bridging Dy dinuclear complex {[(PW 11 O 39 )Dy(H 2 O) 2 ] 2 F} (Dy 2 POM) with lacunary Keggin ligands. (Na)(B18C6) formed two types of tetramers through C-H⋯O, π⋯π and C-H⋯π interactions, and each tetramer aligned in one dimension along the c -axis to form two types of channels. One channel was partially penetrated by a supramolecular cation from the ± a -axis direction, dividing the channel in the form of a "bamboo node". Dy 2 POM was spatially divided by this "bamboo node," which magnetically isolated one portion from the other. The temperature dependence of the magnetic susceptibility indicated a weak ferromagnetic interaction between the Dy ions bridged by fluoride. Dy 2 POM exhibited the magnetic relaxation characteristics of a single-molecule magnet, including the dependence of AC magnetic susceptibility on temperature and frequency. Magnetic relaxation can be described by the combination of thermally active Orbach and temperature-independent quantum tunneling processes. The application of a static magnetic field effectively suppressed the relaxation due to quantum tunneling., Competing Interests: We have no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

[MnCr(oxalate) 3 ] - possesses a two-dimensional ferromagnetic network that is an ideal system for the construction of multifunctional molecular materials based on ferromagnetism. This is because additional functions, such as ferroelectricity, can be hybridised by incorporating functional cations between the layers. However, the majority of [MnCr(oxalate) 3 ] - networks readily incorporate solvent molecules upon crystallisation, and it is sometimes difficult to measure the crystal physical properties because of the collapse associated with desolvation. Upon desolvation, the polar crystal (CBA + )([18]crown-6)[MnCr(oxalate) 3 ] - (CH 3 OH) (1·CH 3 OH) (CBA + = 4-carboxybutan-1-aminium) underwent a crystal-to-crystal transformation to form (CBA + )([18]crown-6)[MnCr(oxalate) 3 ] - , 1. Furthermore, this change was accompanied by hydrogen bond reorganisation in the (CBA + )([18]crown-6) supramolecular assembly. Both crystals exhibited ferromagnetic ordering at approximately 5 K. In crystal 1, a "merry-go-round" motion of [18]crown-6 was observed, with an activation energy of 41.41 kJ mol -1 , which resulted in dielectric relaxation. This crystal-to-crystal structural transformation provides a strategy for designing multifunctional hybrid materials, in which an additional function arises from molecular motion.

Background: Systemic acquired resistance (SAR) protects plants against a wide variety of pathogens. In recent decades, numerous studies have focused on the induction of SAR, but its molecular mechanisms remain largely unknown., Methods: We used a metabolomics approach based on ultra-high-performance liquid chromatographic (UPLC) and mass spectrometric (MS) techniques to identify SAR-related lipid metabolites in an Arabidopsis thaliana model. Multiple statistical analyses were used to identify the differentially regulated metabolites., Results: Numerous lipids were implicated as potential factors in both plant basal resistance and SAR; these include species of phosphatidic acid (PA), monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG)., Conclusions: Our findings indicate that lipids accumulated in both local and systemic leaves, while other lipids only accumulated in local leaves or in systemic leaves. PA (16:0_18:2), PE (34:5) and PE (16:0_18:2) had higher levels in both local leaves inoculated with Psm ES4326 or Psm avrRpm1 and systemic leaves of the plants locally infected with Psm avrRpm1 or Psm ES4326 . PC (32:5) had high levels in leaves inoculated with Psm ES4326 . Other differentially regulated metabolites, including PA (18:2_18:2), PA (16:0_18:3), PA (18:3_18:2), PE (16:0_18:3), PE (16:1_16:1), PE (34:4) and TGs showed higher levels in systemic leaves of the plants locally infected with Psm avrRpm1 or Psm ES4326 . These findings will help direct future studies on the molecular mechanisms of SAR., Competing Interests: The authors declare there are no competing interests., (©2022 Song et al.)

In recent years, molecular perovskite energetic materials have attracted more attention because of their simple synthesis processes, high thermal stabilities, excellent performances, and great significance as a design platform for energetic materials. To explore the possibility of the application of molecular perovskite energetic materials in heat-resistant explosives, four silver(I)-based molecular perovskite energetic compounds, (H 2 A)[Ag(ClO 4 ) 3 ], where H 2 A = piperazine-1,4-diium (H 2 pz 2+ ) for PAP-5, 1-methyl-piperazine-1,4-diium (H 2 mpz 2+ ) for PAP-M5, homopiperazine-1,4-diium (H 2 hpz 2+ ) for PAP-H5, and 1,4-diazabicyclo[2.2.2]octane-1,4-diium (H 2 dabco 2+ ) for DAP-5, were synthesized by a one-pot self-assembly strategy and structurally characterized. The single-crystal structures indicated that PAP-5, PAP-M5, and DAP-5 possess cubic perovskite structures while PAP-H5 possesses a hexagonal perovskite structure. Differential thermal analyses showed that their onset decomposition temperatures are >308.3 °C. For PAP-5 and DAP-5, they have not only exceptional calculated detonation parameters ( D values of 8.961 and 8.534 km s -1 and P values of 42.4 and 37.9 GPa, respectively) but also the proper mechanical sensitivity (impact sensitivities of ≤10 J for PAP-5 and 3 J for DAP-5 and friction sensitivities of ≤5N for both PAP-5 and DAP-5) and thus are of interest as potential heat-resistant primary explosive components.

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here, we elucidate the structural basis and mode of action for two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 and CV3-25, which remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggers potent shedding of the S1 subunit. In contrast, CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in the RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

The coexistence of multiferroic orders has attracted increasing attention for its potential applications in multiple-state memory, switches, and computing, but it is still challenging to design single-phase crystalline materials hosting multiferroic orders at above room temperature. By utilizing versatile ABX 3 -type perovskites as a structural model, we judiciously introduced a polar organic cation with easily changeable conformations into a tetrafluoroborate-based perovskite system, and successfully obtained an unprecedented molecular perovskite, (homopiperazine-1,4-diium)[K(BF 4 ) 3 ], hosting both ferroelectricity and ferroelasticity at above room temperature. By using the combined techniques of variable-temperature single-crystal X-ray structural analyses, differential scanning calorimetry, and dielectric, second harmonic generation, and piezoresponse force microscopy measurements, we demonstrated the domain structures for ferroelectric and ferroelastic orders, and furthermore disclosed how the delicate interplay between stepwise changed dynamics of organic cations and cooperative deformation of the inorganic framework induces ferroelectric and ferroelastic phase transitions at 311 K and 455 K, respectively. This instance, together with the underlying mechanism of ferroic transitions, provides important clues for designing advanced multiferroic materials based on organic-inorganic hybrid crystals., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Surgical-site infection (SSI) was one of the most common post-operative morbidities of ileostomy reversal. Although several skin-closure procedures had been developed to reduce the rate of SSI, the optimal procedure remains unclear. In this study, we compared the effect of two surgical techniques for wound closure following ileostomy reversal: gunsight suture (GS) and linear suture (LS)., Methods: A total of 233 patients who underwent loop ileostomy at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2017 were enrolled into our study. These patients were divided into two groups: the LS group and the GS group. We compared the clinical characteristics between the two groups and analyzed the data using IBM SPSS to identify risk factors for SSI., Results: Both groups successfully underwent surgery. The rate of SSI was significantly lower in the GS group ( n  = 2, 0.02%) than in the LS group ( n  = 16, 12.00%, P  = 0.007). The length of hospital stay after the operation in the GS group was significantly shorter than that in the LS group (8.1 ± 3.2 vs 10.8 ± 5.4 days, P  < 0.001). Multivariate analysis showed that GS was an independent protective risk factor for SSI (odds ratio = 0.212, P  = 0.048)., Conclusions: Compared with the LS technique, the GS technique can significantly decrease the rate of SSI and shorten the length of hospital stay after surgery. The GS technique may be recommended for wound closure following ileostomy reversal., (© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

The 26S proteasome is specialized for regulated protein degradation and formed by a dynamic regulatory particle (RP) that caps a hollow cylindrical core particle (CP) where substrates are proteolyzed. Its diverse substrates unify as proteasome targets by ubiquitination. We used cryogenic electron microscopy (cryo-EM) to study how human 26S proteasome interacts with M1-linked hexaubiquitin (M1-Ub 6 ) unanchored to a substrate and E3 ubiquitin ligase E6AP/UBE3A. Proteasome structures are available with model substrates extending through the RP ATPase ring and substrate-conjugated K63-linked ubiquitin chains present at inhibited deubiquitinating enzyme hRpn11 and the nearby ATPase hRpt4/hRpt5 coiled coil. In this study, we find M1-Ub 6 at the hRpn11 site despite the absence of conjugated substrate, indicating that ubiquitin binding at this location does not require substrate interaction with the RP. Moreover, unanchored M1-Ub 6 binds to this hRpn11 site of the proteasome with the CP gating residues in both the closed and opened conformational states., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Ltd.)

The human GABA B receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction 1 . A unique GPCR that is known to require heterodimerization for function 2-6 , the GABA B receptor has two subunits, GABA B1 and GABA B2 , that are structurally homologous but perform distinct and complementary functions. GABA B1 recognizes orthosteric ligands 7,8 , while GABA B2 couples with G proteins 9-14 . Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail 15 . Although the VFT heterodimer structure has been resolved 16 , the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABA B receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.

We present a new hybrid compound, namely (Me2NH2)[KFe(CN)5(NO)], possessing a unique nitroprusside-based inorganic host framework in 4-connected sra topology encapsulating organic guest cations. The flexible host-guest hydrogen bonds and synchronously deformed inorganic framework give rise to thermal-responsive switching behaviours on both thermal expansion and nonlinear optical properties during the phase transition at around room temperature.

Two new compounds were obtained by assembling the [(2-methoxy-5-nitro-anilinium)(18-crown-6)]+ cation with non-polar PF6- and polar SO3CF3- anions, respectively. Benefiting from its polar anion, the SO3CF3- compound reveals a more significant dielectric switching behaviour during phase transition, demonstrating an effective strategy to enhance the dielectric property by adding polar components.

mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Molecular sieving can lead to ultrahigh selectivity and low regeneration energy because it completely excludes all larger molecules via a size restriction mechanism. However, it allows adsorption of all molecules smaller than the pore aperture and so separations of complicated mixtures can be hindered. Here, we report an intermediate-sized molecular sieving (iSMS) effect in a metal-organic framework (MAF-41) designed with restricted flexibility, which also exhibits superhydrophobicity and ultrahigh thermal/chemical stabilities. Single-component isotherms and computational simulations show adsorption of styrene but complete exclusion of the larger analogue ethylbenzene (because it exceeds the maximal aperture size) and smaller toluene/benzene molecules that have insufficient adsorption energy to open the cavity. Mixture adsorption experiments show a high styrene selectivity of 1,250 for an ethylbenzene/styrene mixture and 3,300 for an ethylbenzene/styrene/toluene/benzene mixture (orders of magnitude higher than previous reports). This produces styrene with a purity of 99.9%+ in a single adsorption-desorption cycle. Controlling/restricting flexibility is the key for iSMS and can be a promising strategy for discovering other exceptional properties.

The rotational dynamics, dielectric response and phase transitions of a unique crystalline supramolecular rotor are controlled by the existence/absence of guest water molecules causing prominent effects on the supramolecular interactions. Such an unprecedented rotationally bistable rotor can promote the understanding of precise control of molecular rotors in crystals.

Efficient adsorptive separation of propylene/propane (C 3 H 6 /C 3 H 8 ) is highly desired and challenging. Known strategies focus on either the thermodynamic or the kinetic mechanism. Here, we report an interesting reactivity of a metal-organic framework that improves thermodynamic and kinetic adsorption selectivity simultaneously. When the metal-organic framework is heated under oxygen flow, half of the soft methylene bridges of the organic ligands are selectively oxidized to form the more polar and rigid carbonyl bridges. Mixture breakthrough experiments showed drastic increase of C 3 H 6 /C 3 H 8 selectivity from 1.5 to 15. For comparison, the C 3 H 6 /C 3 H 8 selectivities of the best-performing metal-organic frameworks Co-MOF-74 and KAUST-7 were experimentally determined to be 6.5 and 12, respectively. Gas adsorption isotherms/kinetics, single-crystal X-ray diffraction, and computational simulations revealed that the oxidation gives additional guest recognition sites, which improve thermodynamic selectivity, and reduces the framework flexibility, which generate kinetic selectivity., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The dynamic behaviors of a new type of three-dimensional (3D) water framework symbiotic with 1D stacking organic guests, including an order-disorder transition of hydrogen atoms, a supercooling phenomenon during phase transition, and a dipole-glass-like relaxation behavior due to locally trapped water molecules, are presented. This extremely scarce 3D water framework, together with the rich dynamic behaviors it exhibits, provides new clues to design new ice-like models for promoting the fundamental understanding of the dynamic behavior of water in diverse solid-states.

Solvothermal reactions of 3-methyl-5-trifluoromethyl-1,2,4-triazole (Hfmtz) with Cu(CH 3 COO) 2 at 120 °C in the presence of Cl - generate two partially fluorinated coordination polymers: i.e., [Cu 4 Cl(fmtz) 3 ] (1 or MAF-51) and [Cu 7 Cl(fmtz) 6 ] (2 or MAF-52). Single-crystal X-ray diffraction revealed 1 to have a three-dimensional (3D) nonporous structure with pcu topology consisting of 6-connected Cu 4 (μ 4 -Cl) clusters and 2 to possess a highly porous (void ratio 48%) 3D bnn network consisting of 5-connected Cu 5 (μ 5 -Cl) clusters. Benefiting from the hydrophobic pendant groups, complete coordination of the ligand N atoms, and strong M-N coordination bonds, 1 and 2 possess high water stability (exposed to water for at least 1 year) and hydrophobicity (water contact angles of 141° and 148°, respectively). The N 2 sorption isotherm of activated 2 gave Langmuir/BET surface areas of 1023/848 m 2 g -1 and a pore volume of 0.365 cm 3 g -1 . Moreover, 2 can adsorb large amounts of benzene and methanol but barely adsorb water. Both 1 and 2 show phosphorescence of Cu(I) complexes, but only that of porous 2 is sensitive to O 2 , showing a linear Stern-Volmer response below 1 mbar with an ultrahigh K sv value of 5234 bar -1 and ultralow limit of detection of 1.9 ppm.

Mutations in the retinal protein retinoschisin (RS1) cause progressive loss of vision in young males, a form of macular degeneration called X-linked retinoschisis (XLRS). We previously solved the structure of RS1, a 16-mer composed of paired back-to-back octameric rings. Here, we show by cryo-electron microscopy that RS1 16-mers can assemble into extensive branched networks. We classified the different configurations, finding four types of interaction between the RS1 molecules. The predominant configuration is a linear strand with a wavy appearance. Three less frequent types constitute the branch points of the network. In all cases, the "spikes" around the periphery of the double rings are involved in these interactions. In the linear strand, a loop (usually referred to as spike 1) occurs on both sides of the interface between neighboring molecules. Mutations in this loop suppress secretion, indicating the possibility of intracellular higher-order assembly. These observations suggest that branched networks of RS1 may play a stabilizing role in maintaining the integrity of the retina., (© 2019 Heymann et al.)

Cobalt imidazolate frameworks are classical electrocatalysts for the oxygen evolution reaction (OER) but suffer from the relatively low activity. Here, a non-3d metal modulation strategy is presented for enhancing the OER activity of cobalt imidazolate frameworks. Two isomorphous frameworks [Co 4 (MO 4 )(eim) 6 ] (M=Mo or W, Heim=2-ethylimidazole) having Co(eim) 3 (MO 4 ) units and high water stabilities were designed and synthesized. In different neutral media, the Mo-modulated framework coated on a glassy carbon electrode shows the best OER performances (1 mA cm -2 at an overpotential of 210 mV in CO 2 -saturated 0.5 m KHCO 3 electrolyte and 2/10/22 mA cm -2 at overpotential of 388/490/570 mV in phosphate buffer solution) among non-precious metal catalysts and even outperforms RuO 2 . Spectroscopic measurements and computational simulations revealed that the non-3d metals modulate the electronic structure of Co for optimum reactant/product adsorption and tailor the energy of rate-determining step to a more moderate value., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Spin-reorientation-induced magnetodielectric coupling effects were discovered in two layered perovskite magnets, [C 6 H 5 CH 2 CH 2 NH 3 ] 2 [MCl 4 ] (M = Mn 2+ and Cu 2+ ), via isothermal magnetodielectric measurements on single-crystal samples. Specifically, peak-like dielectric anomalies and spin-flop transitions appeared simultaneously at around ±34 kOe for the canted antiferromagnet (M = Mn 2+ ) at below 44.3 K, while a low-field (1 kOe) controlled magnetodielectric effect was observed in the "soft" ferromagnet (M = Cu 2+ ) at below 9.5 K. These isothermal magnetodielectric effects are highly reproducible and synchronous with the field-induced magnetization at different temperatures, well confirming the essential role of spin reorientation on inducing magnetodielectric coupling effects. These findings strongly imply that the layered perovskite magnets are new promising organic-inorganic hybrid systems to host magnetodielectric coupling effects.

We report the near atomic resolution (3.3 Å) of the human polycystic kidney disease 2-like 1 (polycystin 2-l1) ion channel. Encoded by PKD2L1, polycystin 2-l1 is a calcium and monovalent cation-permeant ion channel in primary cilia and plasma membranes. The related primary cilium-specific polycystin-2 protein, encoded by PKD2, shares a high degree of sequence similarity, yet has distinct permeability characteristics. Here we show that these differences are reflected in the architecture of polycystin 2-l1., Competing Interests: RH, ZL, RH, JZ, DC No competing interests declared, (© 2018, Hulse et al.)

Plasmodium vivax is the most widely distributed malaria parasite that infects humans 1 . P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. vivax reticulocyte-binding protein 2b (PvRBP2b) and transferrin receptor 1 (TfR1) 2 . TfR1-deficient erythroid cells are refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies inhibit reticulocyte binding and block P. vivax invasion in field isolates 2 . Here we report a high-resolution cryo-electron microscopy structure of a ternary complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 Å resolution. Mutational analyses show that PvRBP2b residues involved in complex formation are conserved; this suggests that antigens could be designed that act across P. vivax strains. Functional analyses of TfR1 highlight how P. vivax hijacks TfR1, an essential housekeeping protein, by binding to sites that govern host specificity, without affecting its cellular function of transporting iron. Crystal and solution structures of PvRBP2b in complex with antibody fragments characterize the inhibitory epitopes. Our results establish a structural framework for understanding how P. vivax reticulocyte-binding protein engages its receptor and the molecular mechanism of inhibitory monoclonal antibodies, providing important information for the design of novel vaccine candidates.

Two-dimensional (2D) materials and ultrathin nanosheets are advantageous for elevating the catalysis performance and elucidating the catalysis mechanism of heterogeneous catalysts, but they are mostly restricted to inorganic or organic materials based on covalent bonds. We report an electrochemical/chemical exfoliation strategy for synthesizing metal-organic 2D materials based on coordination bonds. A catechol functionalized ligand is used as the redox active pillar to construct a pillared-layer framework. When the 3D pillared-layer MOF serves as an electrocatalyst for water oxidation (pH 13), the pillar ligands can be oxidized in situ and removed. The remaining ultrathin (2 nm) nanosheets of the metal-organic layers are an efficient catalyst with overpotentials as low as 211 mV at 10 mA cm -2 and a turnover frequency as high as 30 s -1 at an overpotential of 300 mV., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.

Background: To examine the safety and efficacy of Masquelet's technique as a surgical method for treating the first metatarsophalangeal joint in cases of gout accompanied by a massive bone defect., Methods: From January 2010 to January 2016, eleven patients (7 males and 4 females; mean age 33.1 years; range, 23-43 years) received surgical treatment for a first metatarsophalangeal joint tophus which caused a serious bone defect. The first metatarsophalangeal bone defects ranged from 3-6cm, or nearly 50% of the length of normal bone. During the first stage of Masquelet's technique, we removed the tophus and infused that area with bone cement that contained antibiotics. Two months later, we performed the second stage, in which the prosthesis was replaced with iliac cancellous bone, and the operated area was stabilized via locking plate fixation., Results: All of the surgeries were successful, and the 11 patients were followed up for an average of 10.9 months. Postoperative evaluations showed that 10 of the 11 patients healed between 9 and 14 days after the initial surgery. Bone fusion occurred between 2.3 and 3.6 months after the operation, and the average healing time was 3.0 months. One foot wound became infected, but healed after vacuum aspiration. When the American Association of Foot and Ankle Surgery Maryland Foot scoring system was used to evaluate the foot function of the 11 patients prior to surgery, all 11 patients were graded as "failures." Following surgery, 2 patients were graded excellent, 5 were good, 3 were fair, and only 1 patient failed. The total combined excellent and good rate was 63.6%. The total mean Maryland scores pre- and post-surgery were 27.8 points and 74.1 points, respectively; thus the average patient score increased by 46.3 points., Conclusions: Joints with advanced tophus nodules develop segmental bone defects. Masquelet's technique is an effective method for treating such nodules and their associated bone defects., (Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

In bacteria, the activation of gene transcription at many promoters is simple and only involves a single activator. The cyclic adenosine 3',5'-monophosphate receptor protein (CAP), a classic activator, is able to activate transcription independently through two different mechanisms. Understanding the class I mechanism requires an intact transcription activation complex (TAC) structure at a high resolution. Here we report a high-resolution cryo-electron microscopy structure of an intact Escherichia coli class I TAC containing a CAP dimer, a σ 70 -RNA polymerase (RNAP) holoenzyme, a complete class I CAP-dependent promoter DNA, and a de novo synthesized RNA oligonucleotide. The structure shows how CAP wraps the upstream DNA and how the interactions recruit RNAP. Our study provides a structural basis for understanding how activators activate transcription through the class I recruitment mechanism., (Copyright © 2017, American Association for the Advancement of Science.)

Bacterial sporulation allows starving cells to differentiate into metabolically dormant spores that can survive extreme conditions. Following asymmetric division, the mother cell engulfs the forespore, surrounding it with two bilayer membranes. During the engulfment process, an essential channel, the so-called feeding tube apparatus, is thought to cross both membranes to create a direct conduit between the mother cell and the forespore. At least nine proteins are required to create this channel, including SpoIIQ and SpoIIIAA-AH. Here, we present the near-atomic resolution structure of one of these proteins, SpoIIIAG, determined by single-particle cryo-EM. A 3D reconstruction revealed that SpoIIIAG assembles into a large and stable 30-fold symmetric complex with a unique mushroom-like architecture. The complex is collectively composed of three distinctive circular structures: a 60-stranded vertical β-barrel that forms a large inner channel encircled by two concentric rings, one β-mediated and the other formed by repeats of a ring-building motif (RBM) common to the architecture of various dual membrane secretion systems of distinct function. Our near-atomic resolution structure clearly shows that SpoIIIAG exhibits a unique and dramatic adaptation of the RBM fold with a unique β-triangle insertion that assembles into the prominent channel, the dimensions of which suggest the potential passage of large macromolecules between the mother cell and forespore during the feeding process. Indeed, mutation of residues located at key interfaces between monomers of this RBM resulted in severe defects both in vivo and in vitro, providing additional support for this unprecedented structure., Competing Interests: The authors declare no conflict of interest.

Two new double perovskite-like azido coordination polymers with trimethylammonium as the guest cation, namely, (Me 3 NH) 2 [CrNa(N 3 ) 6 ] and (Me 3 NH) 2 [CrK(N 3 ) 6 ], have been prepared. The molecular dynamics for both compounds are investigated and are clearly uncovered by the first-principles molecular dynamics simulation and the significant dielectric relaxation. Structural analyses of these compounds in combination with their analogue (Me 3 NH)[Mn(N 3 ) 3 ] reveal that the guest trimethylammonium has flexible structural adaptability, especially with a variety of disordered distributions, to match the different symmetries of varied metal-azido frameworks. Interestingly, the replacement of the divalent metal ion by mixed monovalent/trivalent metal ions can change the symmetry, shape, and charge distribution of the host cage unit; thus it may influence and regulate the arrangement of the guest inclusion and its molecular dynamics as well as the structural phase transition.

Aim: The aim was to evaluate the association of neoadjuvant therapy with increases in the incidence of anastomotic leakage (AL) after middle and low rectal anterior resection., Method: The electronic databases of PubMed, Web of Science, Scopus and Ovid were searched between 1980 and 2015. The random effects model was used to model the pooled data to determine the odds ratio with 95% confidence interval. Heterogeneity was evaluated using the Q test and I 2 statistics. Subgroup, sensitivity and meta-regression analysis was conducted to explore heterogeneity., Results: Neoadjuvant therapy was not shown to increase the incidence of postoperative AL as demonstrated by an OR of 1.16 [95% CI 0.99-1.36; P = 0.07 (random effects model)]. The subgroup analysis of neoadjuvant radiotherapy using the random effects model suggested that it did not increase the rate of postoperative AL (OR = 1.24, 95% CI 0.97-1.58; P = 0.08). The subgroup analysis of neoadjuvant chemoradiotherapy indicated that the rate of postoperative AL again did not increase with an OR = 1.06 [95% CI 0.86-1.30; P = 0.59 (random effects model)]. The interval to surgery after neoadjuvant therapy and preoperative radiotherapy (short or long course) was not associated with an increased incidence of postoperative AL., Conclusion: Neoadjuvant therapy does not appear to increase the incidence of postoperative AL after anterior resection for mid and low rectal cancer. In addition, neither the interval to surgery after neoadjuvant therapy nor the radiotherapy regimen increases the rate of postoperative AL., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

The type III secretion (T3S) injectisome is a specialized protein nanomachine that is critical for the pathogenicity of many Gram-negative bacteria, including purveyors of plague, typhoid fever, whooping cough, sexually transmitted infections and major nosocomial infections. This syringe-shaped 3.5-MDa macromolecular assembly spans both bacterial membranes and that of the infected host cell. The internal channel formed by the injectisome allows for the direct delivery of partially unfolded virulence effectors into the host cytoplasm. The structural foundation of the injectisome is the basal body, a molecular lock-nut structure composed predominantly of three proteins that form highly oligomerized concentric rings spanning the inner and outer membranes. Here we present the structure of the prototypical Salmonella enterica serovar Typhimurium pathogenicity island 1 basal body, determined using single-particle cryo-electron microscopy, with the inner-membrane-ring and outer-membrane-ring oligomers defined at 4.3 Å and 3.6 Å resolution, respectively. This work presents the first, to our knowledge, high-resolution structural characterization of the major components of the basal body in the assembled state, including that of the widespread class of outer-membrane portals known as secretins.

Using bulky amides as the structure-directing agents (SDAs) is an alternative synthetic strategy for the exploration of crystalline large pore (≥12-membered ring) zeolitic imidazolate frameworks (ZIFs). Specifically, by using the bulky amides, dibutylformamide (DBF) and dipropylformamide (DPF) as solvent and imidazole (Im) as a ligand, two ZIFs mimicking the CAN and AlPO-5 (AFI) zeotypes with 12-membered ring (MR) pore openings were synthesized, and denoted as CAN-[Zn(Im) 2 ] and AFI-[Zn(Im) 2 ], respectively. These two materials are the first known examples of Zn(Im) 2 polymorphs with 12-MR pores and AFI-[Zn(Im) 2 ] has the largest pore apertures reported to date for ZIF materials. The concept that the bulky amides used were not simply acting as the solvent, but were in fact acting as SDAs or templates during the synthesis of the large pore ZIFs, was suggested by the closeness of the geometrical fit between the guest DBF and the can cages (composite building units) of the CAN-[Zn(Im) 2 ].

The changeable molecular dynamics of flexible polar cations in the variable confined space between inorganic chains brings about a new type of two-step nonlinear optical (NLO) switch with genuine "off-on-off" second harmonic generation (SHG) conversion between one NLO-active state and two NLO-inactive states., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)