Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.

Comparison of Ophiopogon japonicus and Liriope spicata var. prolifera from Different Origins Based on Multi-Component Quantification and Anticancer Activity.

The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.

The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis.

BACKGROUND AND AIMS: The exosomal long noncoding RNAs (lncRNAs) have been reported to have cardioprotective effects on ischemia-reperfusion (I/R) injury by hindering ferroptosis, but the role of lncRNA Mir9-3 host gene (Mir9-3hg) in cardiac I/R injury remains unclear. METHODS AND RESULTS: Exosomes were extracted from mouse bone marrow mesenchymal stem cells (BMSCs) and identified by detecting the exosome specific marker levels, and the results showed that Mir9-3hg was highly expressed in BMSCs-Exo. Hypoxia/reoxygenation (H/R)-treated HL-1 mouse cardiomyocytes were incubated with exosomes extracted from BMSCs transfected with Mir9-3hg siRNA. BMSCs-Exo incubation observably facilitated cell proliferation, increased glutathione (GSH) content, and reduced iron ion concentration, reactive oxygen species (ROS) level and ferroptosis marker protein levels in H/R-treated cells, while interfering Mir9-3hg reversed these effects. RNA binding protein immunoprecipitation assay was found that Mir9-3hg bound with pumilio RNA binding family member 2 (Pum2) protein and downregulated Pum2 expression. Silence of Pum2 reversed the effects of Mir9-3hg inhibition on cell functions. Chromatin immunoprecipitation assay was revealed that Pum2 bound with peroxiredoxin 6 (PRDX6) promoter and restrained PRDX6 expression. Silence of PRDX6 reversed the improved effects of Pum2 downregulation on cell functions. Additionally, BMSCs-Exo treatment ameliorated cardiac function in I/R-treated mice by inhibiting cardiomyocyte ferroptosis. CONCLUSIONS: BMSCs-Exo treatment attenuates I/R-induced cardiac injury by inhibiting cardiomyocyte ferroptosis through modulating the Pum2/PRDX6 axis, thereby ameliorating cardiac function.

Rapid Screening of Lipase Inhibitors from Ophiopogonis Radix Using High-Performance Thin Layer Chromatography by Two Step Gradient Elution Combined with Bioautographic Method.

In this study, a high-performance thin layer chromatography (HPTLC) method by two step gradient elution with two mobile phases was developed for the simultaneous analysis of seven constituents in Ophiopogonis Radix. The chromatography was performed on silica gel 60 F254 plate with dichloromethane-methanol-ethyl acetate-water (70:25:12:3, v/v/v/v) and dichloromethane-methanol (300:1, v/v) as the mobile phase for two step gradient elution. Then, the HPTLC profiles were observed after derivatization with 10% sulfuric acid in ethanol solution. The obtained HPTLC images were further analyzed by chemometric approaches and the samples could be clustered based on regions and/or growth years, which were two important factors affecting the constituents in Ophiopogonis Radix. Furthermore, five compounds including ophiopogonin D, ophiopojaponin C, ophiopogonin D', ophiopogonin C' and methylophiopogonanone B were screened as potential lipase inhibitors from Ophiopogonis Radix by the HPTLC-bioautographic method. The binding modes and interactions between the five compounds and lipase were further explored by molecular docking analysis. The developed HPTLC method could be used for quality control of Ophiopogonis Radix and screening of the potential lipase inhibitors.

Enhancement of thermoelectric performance across the topological phase transition in dense lead selenide.

Alternative technologies are required in order to meet a worldwide demand for clean non-polluting energy sources. Thermoelectric generators, which generate electricity from heat in a compact and reliable manner, are potential devices for waste heat recovery. However, thermoelectric performance, as encapsulated by the figure of merit ZT, has remained at around 1.0 at room temperature, which has limited practical applications. Here, we study the effects of pressure on ZT in Cr-doped PbSe, which has a maximum ZT of less than 1.0 at a temperature of about 700 K. By applying external pressure using a diamond anvil cell, we obtained a room-temperature ZT value of about 1.7. From thermoelectric, magnetoresistance and Raman measurements, as well as density functional theory calculations, a pressure-driven topological phase transition is found to enable this enhancement. Experiments also support the appearance of a topological crystalline insulator after the transition. These findings point to the possibility of using compression to increase not just ZT in existing thermoelectric materials, but also the possibility of realizing topological crystalline insulators.

A Triazine-Based Analogue of Graphyne: Scalable Synthesis and Applications in Photocatalytic Dye Degradation and Bacterial Inactivation.

Graphyne, a theorized carbon allotrope possessing only sp- and sp2 -hybridized carbon atoms, holds great potentials in many fields, especially in catalysis and energy-transfer/storage devices. Using a bottom-up strategy, we synthesized a new N-doped graphyne analogue, triazine- and 1,4-diethynylbenzene-based graphyne TA-BGY, in solution in gram-scale. The unique sp/sp2 carbon-conjugated TA-BGY possesses an extended porous network structure with a BET surface area of approximately 300 m2 g-1 . Owing to its low optical band gap (1.44 eV), TA-BGY was expected to have many applications, which were exemplified by the photodegradation of methyl orange and photocatalytic bacterial inactivation.

Order-disorder transition in p-oligophenyls.

Poly(para-phenylene) has been recognized as one important family of conducting polymers upon doping with donors or acceptors. This system possesses a chain-like structure with infinite benzene rings linked with a single C-C bond. Oligophenyls as models of poly(para-phenylene) with short chains in the para position were found to exhibit superconductivity at transition temperatures ranging from 3 K to 123 K upon doping. Structural studies have revealed that there exist order-disorder transitions in many p-oligophenyls with almost doubled lattice constants in the b and c directions at low temperatures. Such a transition is of relevance to the understanding of the emergence of novel quantum functionality where unconventional polaronic interactions are relevant for the new emerging theory of superconductivity in this system. However, the accurate temperatures for the order-disorder transitions amongst these p-oligophenyls are still needed to be determined. The chain length effects on the order-disorder transitions in this system remain unknown. Here we report the systematic investigation of the evolution of the vibrational properties of the crystalline p-oligophenyls over a wide temperature range. The order-disorder transition is identified by three indicators, the lowest energy peak together with the intensity ratios between the 1280 cm-1 and 1220 cm-1 modes and between the two modes at around 1600 cm-1. A phase diagram of the order-disorder transition temperature and the melting curve for p-oligophenyls are thus established. The former is found to increase with the chain length and saturates at around 350 K for poly(para-phenylene).

Superconductivity in an organometallic compound.

Organometallic compounds constitute a very large group of substances that contain at least one metal-to-carbon bond in which the carbon is part of an organic group. They have played a major role in the development of the science of chemistry. These compounds are used to a large extent as catalysts (substances that increase the rate of reactions without themselves being consumed) and as intermediates in the laboratory and in industry. Recently, novel quantum phenomena such as topological insulators and superconductors were also suggested in these materials. However, there has been no report on the experimental exploration of the topological state. Evidence for superconductivity from the zero-resistivity state in any organometallic compound has not been achieved yet, though much effort has been made. Here we report the experimental realization of superconductivity with a critical temperature of 3.6 K in a potassium-doped organometallic compound, i.e. tri-o-tolylbismuthine, with evidence of both the Meissner effect and the zero-resistivity state through dc and ac magnetic susceptibility measurements. The obtained superconducting parameters classify this compound as a type-II superconductor. The benzene ring is identified to be the essential superconducting unit in such a phenyl organometallic compound. The superconducting phase and its composition are determined by combined studies of X-ray diffraction and theoretical calculations as well as Raman spectroscopy measurements. These findings enrich the applications of organometallic compounds in superconductivity and add a new electron-acceptor family of organic superconductors. This work also points to a large pool for finding superconductors from organometallic compounds.

Crossover from metal to insulator in dense lithium-rich compound CLi4.

At room environment, all materials can be classified as insulators or metals or in-between semiconductors, by judging whether they are capable of conducting the flow of electrons. One can expect an insulator to convert into a metal and to remain in this state upon further compression, i.e., pressure-induced metallization. Some exceptions were reported recently in elementary metals such as all of the alkali metals and heavy alkaline earth metals (Ca, Sr, and Ba). Here we show that a compound of CLi4 becomes progressively less conductive and eventually insulating upon compression based on ab initio density-functional theory calculations. An unusual path with pressure is found for the phase transition from metal to semimetal, to semiconductor, and eventually to insulator. The Fermi surface filling parameter is used to describe such an antimetallization process.

Unusual Pressure-Induced Periodic Lattice Distortion in SnSe_{2}.

We performed high-pressure x-ray diffraction (XRD), Raman, and transport measurements combined with first-principles calculations to investigate the behavior of tin diselenide (SnSe_{2}) under compression. The obtained single-crystal XRD data indicate the formation of a (1/3,1/3,0)-type superlattice above 17 GPa. According to our density functional theory results, the pressure-induced transition to the commensurate periodic lattice distortion (PLD) phase is due to the combined effect of strong Fermi surface nesting and electron-phonon coupling at a momentum wave vector q=(1/3,1/3,0). In contrast, similar PLD transitions associated with charge density wave (CDW) orderings in transition metal dichalcogenides (TMDs) do not involve significant Fermi surface nesting. The discovered pressure-induced PLD is quite remarkable, as pressure usually suppresses CDW phases in related materials. Our findings, therefore, provide new playgrounds to study the intricate mechanisms governing the emergence of PLD in TMD-related materials.

Superconductivity and phase stability of potassium-doped biphenyl.

Phenyl molecules are proposed as potential high-temperature superconductors due to exhibiting interesting properties. Here, we report the discovery of superconductivity with the critical temperature (Tc) of ∼7.2 Kelvin in potassium (K)-doped biphenyl (C12H10). The dc magnetic susceptibility measurements provide solid evidence for the presence of the Meissner effect in KxC12H10. The Raman spectra detected bipolaronic characteristics in this superconducting state, which are proposed to account for the electron pairing. Theoretical simulations provided the information of the crystal structure of KxC12H10. Combining XRD data with formation energy, we suggest that the superconducting phase corresponds to K2C12H10 or with a small charge fluctuation in a layered structure. The discovery of superconductivity in K-doped biphenyl vastly expands the potential applications in the superconducting field.

Vibrational Properties of p-Terphenyl.

Vibrational properties associated with the intra- and intermolecular terms of pristine p-terphenyl at low temperatures are analyzed in detail by Raman spectroscopy. Nearly all of the vibrational modes exhibit anomalous behaviors at the transition temperature of about 193 K on the frequencies, widths, and intensities. Meanwhile, the drastic drops of the spectrum weight result in the splits of many peaks like the lattice vibrational peaks and the peaks located at around 1220, 1280, and 1600 cm-1. All the anomalies result from the drastic decrease of the vibrational anharmonic coupling effects in the crystalline p-terphenyl after entering into the ordered state. The rapidly declining anharmonicity also makes contributions to the anomalous behaviors of the intensity ratios of the 1220, 1280, and 1600 cm-1 modes, as well as the energy separations between the combination bands and the fundamental bands. Our work is of great significance to understand the internal vibrational properties of p-terphenyl.

Re-emerging superconductivity at 48 kelvin in iron chalcogenides.

Pressure has an essential role in the production and control of superconductivity in iron-based superconductors. Substitution of a large cation by a smaller rare-earth ion to simulate the pressure effect has raised the superconducting transition temperature T(c) to a record high of 55 K in these materials. In the same way as T(c) exhibits a bell-shaped curve of dependence on chemical doping, pressure-tuned T(c) typically drops monotonically after passing the optimal pressure. Here we report that in the superconducting iron chalcogenides, a second superconducting phase suddenly re-emerges above 11.5 GPa, after the T(c) drops from the first maximum of 32 K at 1 GPa. The T(c) of the re-emerging superconducting phase is considerably higher than the first maximum, reaching 48.0-48.7 K for Tl(0.6)Rb(0.4)Fe(1.67)Se(2), K(0.8)Fe(1.7)Se(2) and K(0.8)Fe(1.78)Se(2).

Structures of lithium-zinc compounds at high pressures.

Intermetallic lithium compounds have found a wide range of applications owing to their light mass and desirable electronic and mechanical properties. Here, by compressing pure lithium and zinc mixtures in a diamond-anvil cell, we observe a direct reaction forming the stoichiometric compound LiZn, at pressures below 1 GPa. On further compression above 10 GPa, we observe the formation of Li2Zn, which is the highest lithium content compound to be discovered in the Li-Zn system. Our results constrain the structures of these compounds and their evolution with pressure, furthering our understanding of potentially useful light volume-efficient energy storage materials.

Superconductivity at 3.5 K and/or 7.2 K in potassium-doped triphenylbismuth.

We develop a two-step synthesis method-ultrasound treatment and low temperature annealing to explore superconductivity in potassium-doped triphenylbismuth, which is composed of one bismuth atom and three phenyl rings. The combination of dc and ac magnetic measurements reveals that one hundred percent of synthesized samples exhibit superconductivity at 3.5 K and/or 7.2 K at ambient pressure. The magnetization hysteresis loops provide a strong piece of evidence of type-II superconductors. It is found that the doped materials crystallize into the triclinic P1 structure, with a mole ratio of 4:1 between potassium and triphenylbismuth. Both the calculated electronic structure and measured Raman spectra indicate that superconductivity is realized by transferring electrons from the K-4s to C-2p orbital. Our study opens an encouraging window for the search of organic superconductors in organometallic molecules.

Synthesis and Raman spectroscopy of a layered SiS2 phase at high pressures.

Dichalcogenides are known to exhibit layered solid phases, at ambient and high pressures, where 2D layers of chemically bonded formula units are held together by van der Waals forces. These materials are of great interest for solid-state sciences and technology, along with other 2D systems such as graphene and phosphorene. SiS2 is an archetypal model system of the most fundamental interest within this ensemble. Recently, high pressure (GPa) phases with Si in octahedral coordination by S have been theoretically predicted and also experimentally found to occur in this compound. At variance with stishovite in SiO2, which is a 3D network of SiO6 octahedra, the phases with octahedral coordination in SiS2 are 2D layered. Very importantly, this type of semiconducting material was theoretically predicted to exhibit continuous bandgap closing with pressure to a poor metallic state at tens of GPa. We synthesized layered SiS2 with octahedral coordination in a diamond anvil cell at 7.5-9 GPa, by laser heating together elemental S and Si at 1300-1700 K. Indeed, Raman spectroscopy up to 64.4 GPa is compatible with continuous bandgap closing in this material with the onset of either weak metallicity or of a narrow bandgap semiconductor state with a large density of defect-induced, intra-gap energy levels, at about 57 GPa. Importantly, our investigation adds up to the fundamental knowledge of layered dichalcogenides.

Raman Characterization on Two-Dimensional Materials-Based Thermoelectricity.

The emergence and development of two-dimensional (2D) materials has provided a new direction for enhancing the thermoelectric (TE) performance due to their unique structural, physical and chemical properties. However, the TE performance measurement of 2D materials is a long-standing challenge owing to the experimental difficulties of precise control in samples and high demand in apparatus. Until now, there is no universal methodology for measuring the dimensionless TE figure of merit (ZT) (the core parameter for evaluating TE performance) of 2D materials systematically in experiments. Raman spectroscopy, with its rapid and nondestructive properties for probing samples, is undoubtedly a powerful tool for characterizing 2D materials as it is known as a spectroscopic 'Swiss-Army Knife'. Raman spectroscopy can be employed to measure the thermal conductivity of 2D materials and expected to be a systematic method in evaluating TE performance, boosting the development of thermoelectricity. In this review, thermoelectricity, 2D materials, and Raman techniques, as well as thermal conductivity measurements of 2D materials by Raman spectroscopy are introduced. The prospects of obtaining ZT and testing the TE performance of 2D materials by Raman spectroscopy in the future are also discussed.

High-Pressure Behavior of Hydrogen and Deuterium at Low Temperatures.

In situ high-pressure low-temperature high-quality Raman data for hydrogen and deuterium demonstrate the presence of a novel phase, phase II^{'}, unique to deuterium and distinct from the known phase II. Phase II^{'} of D_{2} is not observed in hydrogen, making it the only phase that does not exist in both isotopes and occupies a significant part of P-T space from ∼25 to 110 GPa and below 125 K. For H_{2}, the data show that below 30 K the transition to phase II happens at as low as 73 GPa. The transformation from phase II to III commences at around ∼155 GPa and is completed by 170 GPa with the average pressure of ∼160 GPa being slightly higher than previously thought. The updated phase diagrams of H_{2} and D_{2} demonstrate the difference between the isotopes at low temperatures and moderate pressures, providing new information on the phase diagrams of both elements.

Enhancement of superconductivity by pressure-driven competition in electronic order.

Finding ways to achieve higher values of the transition temperature, T(c), in superconductors remains a great challenge. The superconducting phase is often one of several competing types of electronic order, including antiferromagnetism and charge density waves. An emerging trend documented in heavy-fermion and organic conductors is that the maximum T(c) for superconductivity occurs under external conditions that cause the critical temperature for a competing order to go to zero. Recently, such competition has been found in multilayer copper oxide high-temperature superconductors (HTSCs) that possess two crystallographically inequivalent CuO(2) planes in the unit cell. However, whether the competing electronic state can be suppressed to enhance T(c) in HTSCs remains an open question. Here we show that pressure-driven phase competition leads to an unusual two-step enhancement of T(c) in optimally doped trilayer Bi(2)Sr(2)Ca(2)Cu(3)O(10+delta) (Bi2223). We find that T(c) first increases with pressure and then decreases after passing through a maximum. Unexpectedly, T(c) increases again when the pressure is further raised above a critical value of around 24 GPa, surpassing the first maximum. The presence of this critical pressure is a manifestation of the crossover from the competing order to superconductivity in the inner of the three CuO(2) planes. We suggest that the increase at higher pressures occurs as a result of competition between pairing and phase ordering in different CuO(2) planes.

Saponins from Chinese Medicines as Anticancer Agents.

Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.