Immune checkpoint therapy-elicited sialylation of IgG antibodies impairs antitumorigenic type I interferon responses in hepatocellular carcinoma.

The reinvigoration of anti-tumor T cells in response to immune checkpoint blockade (ICB) therapy is well established. Whether and how ICB therapy manipulates antibody-mediated immune response in cancer environments, however, remains elusive. Using tandem mass spectrometric analysis of modification of immunoglobulin G (IgG) from hepatoma tissues, we identified a role of ICB therapy in catalyzing IgG sialylation in the Fc region. Effector T cells triggered sialylation of IgG via an interferon (IFN)-γ-ST6Gal-I-dependent pathway. DC-SIGN+ macrophages represented the main target cells of sialylated IgG. Upon interacting with sialylated IgG, DC-SIGN stimulated Raf-1-elicited elevation of ATF3, which inactivated cGAS-STING pathway and eliminated subsequent type-I-IFN-triggered antitumorigenic immunity. Although enhanced IgG sialylation in tumors predicted improved therapeutic outcomes for patients receiving ICB therapy, impeding IgG sialylation augmented antitumorigenic T cell immunity after ICB therapy. Thus, targeting antibody-based negative feedback action of ICB therapy has potential for improving efficacy of cancer immunotherapies.

Cholinergic macrophages promote the resolution of peritoneal inflammation.

The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using Chat-GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal Mϕs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, Chat deficiency in Mϕs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, Chat deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of Mϕ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.

Intracellular bottlenecking permits no more than three tomato yellow leaf curl virus genomes to initiate replication in a single cell.

Viruses are constantly subject to natural selection to enrich beneficial mutations and weed out deleterious ones. However, it remains unresolved as to how the phenotypic gains or losses brought about by these mutations cause the viral genomes carrying the very mutations to become more or less numerous. Previous investigations by us and others suggest that viruses with plus strand (+) RNA genomes may compel such selection by bottlenecking the replicating genome copies in each cell to low single digits. Nevertheless, it is unclear if similarly stringent reproductive bottlenecks also occur in cells invaded by DNA viruses. Here we investigated whether tomato yellow leaf curl virus (TYLCV), a small virus with a single-stranded DNA genome, underwent population bottlenecking in cells of its host plants. We engineered a TYLCV genome to produce two replicons that express green fluorescent protein and mCherry, respectively, in a replication-dependent manner. We found that among the cells entered by both replicons, less than 65% replicated both, whereas at least 35% replicated either of them alone. Further probability computation concluded that replication in an average cell was unlikely to have been initiated with more than three replicon genome copies. Furthermore, sequential inoculations unveiled strong mutual exclusions of these two replicons at the intracellular level. In conclusion, the intracellular population of the small DNA virus TYLCV is actively bottlenecked, and such bottlenecking may be a virus-encoded, evolutionarily conserved trait that assures timely selection of new mutations emerging through error-prone replication.

Parallel Proteomic Comparison of Mutants With Altered Carbon Metabolism Reveals Hik8 Regulation of PII Phosphorylation and Glycogen Accumulation in a Cyanobacterium.

Carbon metabolism is central to photosynthetic organisms and involves the coordinated operation and regulation of numerous proteins. In cyanobacteria, proteins involved in carbon metabolism are regulated by multiple regulators including the RNA polymerase sigma factor SigE, the histidine kinases Hik8, Hik31 and its plasmid-borne paralog Slr6041, and the response regulator Rre37. To understand the specificity and the cross-talk of such regulations, we simultaneously and quantitatively compared the proteomes of the gene knockout mutants for the regulators. A number of proteins showing differential expression in one or more mutants were identified, including four proteins that are unanimously upregulated or downregulated in all five mutants. These represent the important nodes of the intricate and elegant regulatory network for carbon metabolism. Moreover, serine phosphorylation of PII, a key signaling protein sensing and regulating in vivo carbon/nitrogen (C/N) homeostasis through reversible phosphorylation, is massively increased with a concomitant significant decrease in glycogen content only in the hik8-knockout mutant, which also displays impaired dark viability. An unphosphorylatable PII S49A substitution restored the glycogen content and rescued the dark viability of the mutant. Together, our study not only establishes the quantitative relationship between the targets and the corresponding regulators and elucidated their specificity and cross-talk but also unveils that Hik8 regulates glycogen accumulation through negative regulation of PII phosphorylation, providing the first line of evidence that links the two-component system with PII-mediated signal transduction and implicates them in the regulation of carbon metabolism.

Proximity Labeling Facilitates Defining the Proteome Neighborhood of Photosystem II Oxygen Evolution Complex in a Model Cyanobacterium.

Ascorbate peroxidase (APEX)-based proximity labeling coupled with mass spectrometry has a great potential for spatiotemporal identification of proteins proximal to a protein complex of interest. Using this approach is feasible to define the proteome neighborhood of important protein complexes in a popular photosynthetic model cyanobacterium Synechocystis sp. PCC6803 (hereafter named as Synechocystis). To this end, we developed a robust workflow for APEX2-based proximity labeling in Synechocystis and used the workflow to identify proteins proximal to the photosystem II (PS II) oxygen evolution complex (OEC) through fusion APEX2 with a luminal OEC subunit, PsbO. In total, 38 integral membrane proteins (IMPs) and 93 luminal proteins were identified as proximal to the OEC. A significant portion of these proteins are involved in PS II assembly, maturation, and repair, while the majority of the rest were not previously implicated with PS II. The IMPs include subunits of PS II and cytochrome b6/f, but not of photosystem I (except for PsaL) and ATP synthases, suggesting that the latter two complexes are spatially separated from the OEC with a distance longer than the APEX2 labeling radius. Besides, the topologies of six IMPs were successfully predicted because their lumen-facing regions exclusively contain potential APEX2 labeling sites. The luminal proteins include 66 proteins with a predicted signal peptide and 57 proteins localized also in periplasm, providing important targets to study the regulation and selectivity of protein translocation. Together, we not only developed a robust workflow for the application of APEX2-based proximity labeling in Synechocystis and showcased the feasibility to define the neighborhood proteome of an important protein complex with a short radius but also discovered a set of the proteins that potentially interact with and regulate PS II structure and function.

Spatial Proteome Reorganization of a Photosynthetic Model Cyanobacterium in Response to Abiotic Stresses.

Spatial proteome reorganization in response to a changing environment represents a different layer of adaptation mechanism in addition to differential expression of a subset of stress responsive genes in photosynthetic organisms. Profiling such reorganization events is critically important to extend our understanding how photosynthetic organisms adapt to adverse environments. Thus, we treated a unicellular photosynthetic model cyanobacterium, Synechocystis sp. PCC 6803 (hereafter referred to as Synechocystis), with five different types of abiotic stresses including nitrogen starvation, iron deficiency, cold, heat, and darkness, and systematically identified proteins showing stress-induced differential expression and/or redistribution between the membrane and the soluble fractions using a quantitative proteomics approach. A number of proteins showing such a redistribution in response to a single or multiple types of abiotic stresses were identified. These include 12 ribosomal proteins displaying unanimous cold-induced redistribution to the membrane and the protein FurA, a master regulator of iron acquisition, displaying iron deficiency- and nitrogen starvation-induced redistribution to the membrane. Such findings shed light on a novel regulatory mechanism underlying the corresponding stress responses, and establish the results in the present study as an important resource for future studies intended to understand how photosynthetic organisms cope with adverse environments.

Macroscopic Helical Assembly of One-Dimensional Coordination Polymers: Helicity Inversion Triggered by Solvent Isomerism.

Assembling macroscopic helices with controllable chirality and understanding their formation mechanism are highly desirable but challenging tasks for artificial systems, especially coordination polymers. Here, we utilize solvents as an effective tool to induce the formation of macroscopic helices of chiral coordination polymers (CPs) and manipulate their helical sense. We chose the Ni/R-,S-BrpempH2 system with a one-dimensional tubular structure, where R-,S-BrpempH2 stands for R-,S-(1-(4-bromophenyl)ethylaminomethylphosphonic acid). The morphology of the self-assemblies can be controlled by varying the cosolvent in water, resulting in the formation of twisted ribbons of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-2T) in pure H2O; needle-like crystals of R-,S-Ni(Brpemp)(H2O)2·1/3CH3CN (R-,S-1C) in 20 vol % CH3CN/H2O; nanofibers of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-3F) in 20-40 vol % methanol/H2O or ethanol/H2O; and superhelices of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-4H or 5H) in 40 vol % propanol/H2O. Interestingly, the helicity of the superhelix can be controlled by using a propanol isomer in water. For the Ni/R-BrpempH2 system, a left-handed superhelix of R-4H(M) was obtained in 40 vol % NPA/H2O, while a right-handed superhelix of R-5H(P) was isolated in 40 vol % IPA/H2O. These results were rationalized by theoretical calculations. Adsorption studies revealed the chiral recognition behavior of these compounds. This work may contribute to the development of chiral CPs with a macroscopic helical morphology and interesting functionalities.

Quorum Sensing Is Required for the Colony Establishment of a Plant Phyllosphere Bacterium Rhodopseudomonas palustris Strain GJ-22.

The phyllosphere presents a hostile environment for many biocontrol agents; however, it is as significant as is the rhizosphere for plant health. Deploying biocontrol bacteria into the phyllosphere can efficiently suppress diseases; however, the lack of knowledge on the phyllosphere adaptive traits of biocontrol bacteria poses challenges. In this study, we demonstrated that Rhodopseudomonas palustris GJ-22 colonizes the phyllosphere by forming cell aggregates. The formation of cell aggregates required the production of exopolysaccharides (EPS), which depended on the function of the rpaI-rpaR quorum sensing (QS) mechanism, mediated by the signaling molecule p-coumaroyl-HSL (pC-HSL). The mutation of the EPS biosynthesis gene Exop1 or the signaling molecule biosynthesis gene rpaI compromised the ability of GJ-22 to tolerate reactive oxygen intermediates (ROIs), such as H2O2, in vitro and to form cell aggregates in vivo. Collectively, the results revealed that QS mediates EPS production and consequently leads to bacterial cell aggregation. IMPORTANCE Quorum sensing is used by various bacteria for coordinating the multiplication of bacterial cells in a group and for modulating the behaviors of surrounding microbial species. Host plants can benefit from this interspecies modulation, as it can disrupt the QS circuits of pathogenic bacteria. Some N-acyl homoserine lactone- (AHL-) producing bacteria that were introduced into the phyllosphere as biocontrol agents may establish AHL-based crosstalk with indigenous microbes to steer the nutritional and microecological conditions toward their own and the host plant's benefit. Here, we showed that biocontrol bacteria introduced into the phyllosphere require a functioning QS circuit to establish colonies and suppress pathogens. Furthermore, our findings provoked a broader investigation into the role of the QS circuit in beneficial microorganism-plant interactions.

Gut microbiota characteristics of Mongolian and Han populations in anti-tuberculosis drug-induced liver injury: a population-based case-control study.

BACKGROUND: The pathogenesis of anti-tuberculosis (TB) drug-induced liver injury (ADLI) is complicated and remains unclear. We aimed to analyse the relationship between the characteristics of gut microbiota and ADLI in Mongolian and Han patients with pulmonary TB and identify the most notable bacteria related to the occurrence of liver injury in those populations. METHODS: Patients with concurrent liver injury (LI) and no liver injury (ULI) before receiving first-line anti-TB drug treatment (T1) from the Han population in Tangshan and the Mongolian population in Inner Mongolia were selected as research subjects. At the time of liver injury (T2), stool samples were measured by bacterial 16S rRNA gene high-throughput sequencing to analyse and compare the differences in the gut microbiota of the LI and ULI Mongolian and Han patients at T1 and T2 and identify the differences between those patients. RESULTS: A total of 45 Mongolian and 37 Han patients were enrolled in our study. A dynamic comparison from T1 to T2 showed that the microbiota of the LI and ULI groups changed significantly from T1 to T2 in both the Mongolian and Han populations. However, there were commonalities and personality changes in the microbiota of the two ethnic groups. CONCLUSION: Differences in gut microbes in ADLI were found among the Han and Mongolian patients in our study. Ekmania and Stenotrophomonas were related to the occurrence of ADLI in Mongolian patients, while Ekmania and Ruminococcus__gnavus_group were related to the occurrence of ADLI in the Han population.

X-Ray Triggered Coordination-Bond Breakage in Dysprosium-Organic Framework and its Impact on Magnetic Properties.

Photosensitive lanthanide-based single-molecule magnets (Ln-SMM) are very attractive for their potential applications in information storage, switching, and sensors. However, the light-driven structural transformation in Ln-SMMs hardly changes the coordination number of the lanthanide ion. Herein, for the first time it is reported that X-ray (λ=0.71073 Å) irradiation can break the coordination bond of Dy-OH2 in the three-dimensional (3D) metal-organic framework Dy2 (amp2 H2 )3 (H2 O)6 ⋅ 4H2 O (MDAF-5), in which the {Dy2 (OPO)2 } dimers are cross-linked by dianthracene-phosphonate ligands. The structural transformation proceeds in a single-crystal-to-single-crystal (SC-SC) fashion, forming the new phase Dy2 (amp2 H2 )3 (H2 O)4 ⋅ 4H2 O (MDAF-5-X). The phase transition is accompanied by a significant change in magnetic properties due to the alteration in coordination geometry of the DyIII ion from a distorted pentagonal bipyramid in MDAF-5 to a distorted octahedron in MDAF-5-X.

Photocontrollable Magnetism and Photoluminescence in a Binuclear Dysprosium Anthracene Complex.

By incorporating photoreactive anthracene moieties into binuclear Dy2O2 motifs, we obtain two new compounds with the formulas [Dy2(SCN)4(L)2(dmpma)4] (1) and [Dy2(SCN)4(L)2(dmpma)2(CH3CN)2] (2), where HL is 4-methyl-2,6-dimethoxyphenol and dmpma is dimethylphosphonomethylanthracene. Compound 1 contains face-to-face π-π interacted anthracene groups that meet the Schmidt rule for a [4 + 4] photocycloaddition reaction, while stacking of the anthracene groups in compound 2 does not meet the Schmidt rule. Compound 1 undergoes a reversible single-crystal-to-single-crystal structural transformation upon UV-light irradiation and thermal annealing, forming a one-dimensional coordination polymer of [Dy2(SCN)4(L)2(dmpma)2(dmpma2)]n (1UV). The process is concomitant with changes in the magnetic dynamics and photoluminescent properties. The spin-reversal energy barrier is significantly increased from 1 (55.9 K) to 1UV (116 K), and the emission color is changed from bright yellow for 1 to weak blue for 1UV. This is the first binuclear lanthanide complex that exhibits synergistic photocontrollable magnetic dynamics and photoluminescence. Ab initio calculations are conducted to understand the magnetostructural relationships of compounds 1, 1UV, and 2.

Enhancing the Circularly Polarized Luminescence of Europium Coordination Polymers by Doping a Chromophore Ligand into Superhelices.

Lanthanide-based molecular materials showing efficient circularly polarized luminescence (CPL) activity with a high quantum yield are attractive due to their potential applications in data storage, optical sensors, and 3D displays. Herein we present an innovative method to achieve enhanced CPL activity and a high quantum yield by doping a chromophore ligand into a coordination polymer superhelix. A series of homochiral europium(III) phosphonates with a helical morphology were prepared with the molecular formula S-, R-[Eu(cyampH)3-3n(nempH)3n]·3H2O (S/R-Eu-n, n = 0-5%). The doping of chromophore ligand S- or R-nempH2 into superhelices of S/R-Eu-0% not only turned on the CPL activity with the dissymmetry factor |glum| on the order of 10-3 but also increased the quantum yield by about 14-fold. This work may shed light on the development of efficient CPL-active lanthanide-based coordination polymers for applications.

Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma.

Macrophages constitute a major component in human hepatocellular carcinoma (HCC) and perform various functions to facilitate disease progression. Reprogramming or reconstituting the tumor surveillance phenotypes of macrophages represents an attractive immunotherapeutic strategy in cancer treatments. The current study identified CD169 as a potential target for macrophage repolarization since it signified a population of macrophages positively correlated with an activated immune signature and better prognosis of patients with HCC. In vitro experiments revealed that a low dose of type I interferon (IFN) could effectively reprogram human monocyte-derived macrophages to upregulate CD169 expression, and such induced CD169+ macrophages exhibited significantly enhanced phagocytotic and CD8+ T cell-activating capacities compared to controls. A low dose of IFNα also inhibited hepatoma growth in mice in vivo, presumably through polarizing the CD169+ macrophage population and enhancing CD8+ T cell activities. Notably, IFNα also induced substantial PD-L1 expression on macrophages in vivo, and thus blockade of PD-L1 could further increase the anti-tumor efficacy of IFNα in the treatment of HCC. We propose a low dose of IFNα in combination with a PD-L1 blocking agent as a potential anti-tumor therapeutic strategy via its effects on macrophage polarization.

A Systematic Survey of the Light/Dark-dependent Protein Degradation Events in a Model Cyanobacterium.

Light is essential for photosynthetic organisms and is involved in the regulation of protein synthesis and degradation. The significance of light-regulated protein degradation is exemplified by the well-established light-induced degradation and repair of the photosystem II reaction center D1 protein in higher plants and cyanobacteria. However, systematic studies of light-regulated protein degradation events in photosynthetic organisms are lacking. Thus, we conducted a large-scale survey of protein degradation under light or dark conditions in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter referred to as Synechocystis) using the isobaric labeling-based quantitative proteomics technique. The results revealed that 79 proteins showed light-regulated degradation, including proteins involved in photosystem II structure or function, quinone binding, and NADH dehydrogenase. Among these, 25 proteins were strongly dependent on light for degradation. Moreover, the light-dependent degradation of several proteins was sensitive to photosynthetic electron transport inhibitors (DCMU and DBMIB), suggesting that they are influenced by the redox state of the plastoquinone (PQ) pool. Together, our study comprehensively cataloged light-regulated protein degradation events, and the results serve as an important resource for future studies aimed at understanding light-regulated processes and protein quality control mechanisms in cyanobacteria.

Does vertical supervision promote regional green transformation? Evidence from Central Environmental Protection Inspection.

Vertical supervision is an important institutional arrangement designed to overcome the challenges of environmental governance and promotion of green development in the region. Based on the panel data of 278 cities in China from 2010 to 2018, we use Central Environmental Protection Inspection (CEPI) as an exogenous policy and the multi-period Difference-in-Differences method to test the role of vertical supervision in promoting regional green transformation. Our findings indicate that CEPI, a typical vertical supervision policy, effectively promotes green transformation regionally by reducing local pollution emissions and improving total factor productivity. The analysis of mechanism shows that local governments mainly promote regional green transformation by increasing the investment in pollutant governance, research and development in green technologies, and updating fixed assets. Our study provides a valuable reference for the implementation of vertical supervision policies and effective governance of local governments by the central government.

Photo-responsive Single-Molecule Magnet Showing 0D to 1D Single-Crystal-to-Single-Crystal Structural Transition and Hysteresis Modulation.

Photo-responsive lanthanide-based single-molecule magnets (SMM) hold great promise for future switching and memory devices. Herein, we report a dysprosium phosphonate [DyIII (SCN)2 (NO3 )(depma)2 (4-hpy)2 ] (1Dy), which features a supramolecular framework containing layers of hydrogen-bonding network and pillars of π-π interacted anthracene units. The photocycloaddition reaction of anthracene pairs led to a rapid and reversible single-crystal-to-single-crystal (SC-SC) structural transition to form the 1D coordination polymer [DyIII (SCN)2 (NO3 )(depma2 )(4-hpy)2 ]n (2Dy), accompanied by photoswitchable SMM properties with the reduction of effective energy barrier by half and the narrowing of the butterfly-like hysteresis loop. The diluted sample showed a photo-induced switch of the blocking temperature (TB ) from 3.8 K for 1Dy@Y to 2.6 K for 2Dy@Y. This work may inspire the construction of lanthanide-based molecular materials with targeted photo-responsive magnetic properties.

Replication-Dependent Biogenesis of Turnip Crinkle Virus Long Noncoding RNAs.

Long noncoding RNAs (lncRNAs) of virus origin accumulate in cells infected by many positive-strand (+) RNA viruses to bolster viral infectivity. Their biogenesis mostly utilizes exoribonucleases of host cells that degrade viral genomic or subgenomic RNAs in the 5'-to-3' direction until being stalled by well-defined RNA structures. Here, we report a viral lncRNA that is produced by a novel replication-dependent mechanism. This lncRNA corresponds to the last 283 nucleotides of the turnip crinkle virus (TCV) genome and hence is designated tiny TCV subgenomic RNA (ttsgR). ttsgR accumulated to high levels in TCV-infected Nicotiana benthamiana cells when the TCV-encoded RNA-dependent RNA polymerase (RdRp), also known as p88, was overexpressed. Both (+) and (-) strand forms of ttsgR were produced in a manner dependent on the RdRp functionality. Strikingly, templates as short as ttsgR itself were sufficient to program ttsgR amplification, as long as the TCV-encoded replication proteins p28 and p88 were provided in trans. Consistent with its replicational origin, ttsgR accumulation required a 5' terminal carmovirus consensus sequence (CCS), a sequence motif shared by genomic and subgenomic RNAs of many viruses phylogenetically related to TCV. More importantly, introducing a new CCS motif elsewhere in the TCV genome was alone sufficient to cause the emergence of another lncRNA. Finally, abolishing ttsgR by mutating its 5' CCS gave rise to a TCV mutant that failed to compete with wild-type TCV in Arabidopsis. Collectively, our results unveil a replication-dependent mechanism for the biogenesis of viral lncRNAs, thus suggesting that multiple mechanisms, individually or in combination, may be responsible for viral lncRNA production. IMPORTANCE Many positive-strand (+) RNA viruses produce long noncoding RNAs (lncRNAs) during the process of cellular infections and mobilize these lncRNAs to counteract antiviral defenses, as well as coordinate the translation of viral proteins. Most viral lncRNAs arise from 5'-to-3' degradation of longer viral RNAs being stalled at stable secondary structures. Here, we report a viral lncRNA that is produced by the replication machinery of turnip crinkle virus (TCV). This lncRNA, designated ttsgR, shares the terminal characteristics with TCV genomic and subgenomic RNAs and overaccumulates in the presence of moderately overexpressed TCV RNA-dependent RNA polymerase (RdRp). Furthermore, templates that are of similar sizes as ttsgR are readily replicated by TCV replication proteins (p28 and RdRp) provided from nonviral sources. In summary, this study establishes an approach for uncovering low abundance viral lncRNAs, and characterizes a replicating TCV lncRNA. Similar investigations on human-pathogenic (+) RNA viruses could yield novel therapeutic targets.

Layered Uranyl Phosphonates Encapsulating Co(II)/Mn(II)/Zn(II) Ions: Exfoliation into Nanosheets and Its Impact on Magnetic and Luminescent Properties.

Layered heterometallic 5f-3d uranyl phosphonates can exhibit unique luminescent and/or magnetic properties, but the fabrication and properties of their 2D counterparts have not been investigated. Herein we report three heterobimetallic uranyl phosphonates, namely, [(UO2 )3 M(2-pmbH)4 (H2 O)4 ] ⋅ 2H2 O [MU, M=Co(II), CoU; Mn(II), MnU; Zn(II), ZnU; 2-pmbH3 =2-(phosphonomethyl)benzoic acid]. They are isostructural and display two-dimensional layered structures where the M(II) centers are encapsulated inside the windows generated by the diamagnetic uranyl phosphonate layer. Each M(II) has an octahedral geometry filled with four water molecules in the equatorial positions and two phosphonate oxygen atoms in the axial positions. The uranium atoms adopt UO7 pentagonal bipyramidal and UO6 square bipyramidal geometries. The lattice and coordination water molecules can be released by thermal treatment and reabsorbed in a reversible manner, accompanied with changes of magnetic dynamics. Interestingly, the bulk samples of MU can be exfoliated in acetone via freezing and thawing processes forming nanosheets with single-layer or two-layer thickness (MU-ns). Magnetic studies revealed that the CoU and MnU systems exhibited field-induced slow magnetization relaxation at low temperature. Compared with crystalline CoU, the magnetic relaxation of the CoU-ns aggregates is significantly accelerated. Moreover, photoluminescence measured at 77 K showed slight red-shift of the five characteristic uranyl emission bands for ZnU-ns in comparison with those of the crystalline ZnU. This work gives the first examples of 2D materials based on 5f-3d heterometallic uranyl phosphonates and illustrates the impact of dimension reduction on their magnetic/optical properties.

Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors.

PD-1/PD-L1 axis represents an important target for renormalizing and resetting anti-tumor immunity in cancer patients. Currently, anti-PD-1/PD-L1 therapy has been applied in a broad spectrum of tumors and has yielded durable remission in patients. However, how to further broaden the application, guide personalized therapeutic strategies, and improve clinical responses remains a vital task. At present, PD-L1 expression is an important parameter of clinical indications for immune checkpoint blockade in many types of cancers, a strategy based on the supposition that positive PD-L1 expression reflects local T cell response. Recent studies have revealed that PD-L1 expression is regulated by multiple layers of complicated factors, during which the host immune microenvironment exerts a pivotal role and determines the clinical efficacy of the therapy. In this review, we will summarize recent findings on PD-1/PD-L1 in cancer, focusing on how local immune landscape participates in the regulation of PD-L1 expression and modification. Importantly, we will also discuss these topics in the context of clinical treatment and analyze how these fundamental principles might inspire our efforts to develop more precise and effective immune therapeutics for cancer.

pH and Salt-Assisted Macroscopic Chirality Inversion of Gadolinium Coordination Polymer.

The precise adjustment of handedness of helical architectures is important to regulate their functions. Macroscopic chirality inversion has been achieved in organic supramolecular systems by pH, metal ions, solvents, chiral and non-chiral additives, temperature, and light, but rarely in coordination polymers (CPs). In particular, salt-assisted macroscopic chirality inversion has not been reported. In this work, we carried out a systematic investigation on the role of pH and salt in regulating the morphology of CPs based on Gd(NO3)3 and R-(1-phenylethylamino)methylphosphonic acid (R-pempH2). Without extra NO3-, the chirality inversion from the left-handed superhelix R-M to the right-handed superhelix R-P can be achieved by pH modulation from 3.2 to 3.8. The addition of NaNO3 (2.0 eq) at pH 3.8 results in an inversion of chiral sense from R-P to R-M as a pure phase. To our knowledge, this is the first example of salt-assisted macroscopic helical inversion in artificial systems.