Mutation-induced shift of the photosystem II active site reveals insight into conserved water channels.

Photosystem II (PSII) is the water-plastoquinone photo-oxidoreductase central to oxygenic photosynthesis. PSII has been extensively studied for its ability to catalyze light-driven water oxidation at a Mn4CaO5 cluster called the oxygen-evolving complex (OEC). Despite these efforts, the complete reaction mechanism for water oxidation by PSII is still heavily debated. Previous mutagenesis studies have investigated the roles of conserved amino acids, but these studies have lacked a direct structural basis that would allow for a more meaningful interpretation. Here, we report a 2.14-Å resolution cryo-EM structure of a PSII complex containing the substitution Asp170Glu on the D1 subunit. This mutation directly perturbs a bridging carboxylate ligand of the OEC, which alters the spectroscopic properties of the OEC without fully abolishing water oxidation. The structure reveals that the mutation shifts the position of the OEC within the active site without markedly distorting the Mn4CaO5 cluster metal-metal geometry, instead shifting the OEC as a rigid body. This shift disturbs the hydrogen-bonding network of structured waters near the OEC, causing disorder in the conserved water channels. This mutation-induced disorder appears consistent with previous FTIR spectroscopic data. We further show using quantum mechanics/molecular mechanics methods that the mutation-induced structural changes can affect the magnetic properties of the OEC by altering the axes of the Jahn-Teller distortion of the Mn(III) ion coordinated to D1-170. These results offer new perspectives on the conserved water channels, the rigid body property of the OEC, and the role of D1-Asp170 in the enzymatic water oxidation mechanism.

Water Ligands Regulate the Redox Leveling Mechanism of the Oxygen-Evolving Complex of the Photosystem II.

Understanding how water ligands regulate the conformational changes and functionality of the oxygen-evolving complex (OEC) in photosystem II (PSII) throughout the catalytic cycle of oxygen evolution remains a highly intriguing and unresolved challenge. In this study, we investigate the effect of water insertion (WI) on the redox state of the OEC by using the molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) hybrid methods. We find that water binding significantly reduces the free energy change for proton-coupled electron transfer (PCET) from Mn to YZ•, underscoring the important regulatory role of water binding, which is essential for enabling the OEC redox-leveling mechanism along the catalytic cycle. We propose a water binding mechanism in which WI is thermodynamically favored by the closed-cubane form of the OEC, with water delivery mediated by Ca2+ ligand exchange. Isomerization from the closed- to open-cubane conformation at three post-WI states highlights the importance of the location of the MnIII center in the OEC and the orientation of its Jahn-Teller axis to conformational changes of the OEC, which might be critical for the formation of the O-O bond. These findings reveal a complex interplay between conformational changes in the OEC and the ligand environment during the activation of the OEC by YZ•. Analogous regulatory effects due to water ligand binding are expected to be important for a wide range of catalysts activated by redox state transitions in aqueous environments.

Anti-diabetic effect of quercetin in type 2 diabetes mellitus by regulating the microRNA-92b-3p/EGR1 axis.

Insulin resistance (IR) is predominantly causal for type 2 diabetes mellitus (T2DM). To solve this problem, this study particularly determined the role of quercetin (Que) in controlling IR in T2DM mice. The T2DM mouse model was established, and given 20 mg/kg/d Que by gavage for 6 weeks, and the lentiviral vector that interfered with microRNA-92b-3p (miR-92b-3p) or early growth response 1 (EGR1) expression was injected into the tail vein of T2DM mice. Blood glucose homeostasis and histopathological changes in the pancreas were observed after the corresponding treatment. miR-92b-3p and EGR1 expressions were assessed in T2DM mice, as well as their interlink. In results we found that Que could improve IR and pancreatic histopathological changes in T2DM mice. Low miR-92b-3p and high EGR1 were expressed in T2DM mice, while Que could upregulate miR-92b-3p to target EGR1. Enhancing miR-92b-3p or reducing EGR1 could further improve IR and pancreatic histopathological changes in T2DM mice after Que administration. Nevertheless, silencing miR-92b-3p or overexpressing EGR1 contributed to the opposite results. We concluded that Que exerted anti-diabetic effects in T2DM mice by regulating the miR-92b-3p/EGR1 axis.

[Significance of soluble PD-L1 in patients with chronic hepatitis B and hepatitis C].

Objective: The programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) pathway can negatively regulate the immune response of the body, and serum soluble PD-L1 (sPD-L1) can reflect the expression level of PD-L1. This study aims to compare the expressional differences of sPD-L1 in serum between patients with chronic hepatitis B (CHB) and C (CHC) and further explore the factors influencing the clinical cure of CHB. Methods: 60 cases with CHB, 40 cases with CHC, and 60 healthy controls were selected. Serum levels of sPD-L1 were detected using an ELISA kit. The relationship between sPD-L1 levels and viral load, liver injury indicators, and others was analyzed in CHB and CHC patients. According to the distribution type of the data, a one-way ANOVA or Kruskal Wallis test as well as Pearson's correlation or Spearman's rank correlation analysis were performed. A difference of P<0.05 was considered statistically significant. Results: The serum sPD-L1 levels were significantly higher in CHB patients (414.6 ± 214.9) pg/ml than those in CHC patients (58.9 ± 122.1) pg/ml and the healthy control group (66.27 ± 24.43) pg/ml, and there was no statistically significant difference in serum sPD-L1 between CHC patients and the healthy control group. Further grouping and correlation analysis showed that the level of serum sPD-L1 was positively correlated with the content of HBsAg in CHB patients but not with HBV DNA, alanine transaminase, albumin, and other liver injury indicators. Additionally, there was no correlation between serum sPD-L1 levels, HCV RNA, and liver injury indicators in CHC patients. Conclusion: The serum sPD-L1 levels are significantly higher in CHB patients than those in the healthy control group and the CHC group, and there is a positive correlation between sPD-L1 levels and HBsAg. The persistent presence of HBsAg is an important mechanism for the activity of the PD-1/PD-L1 pathway, indicating that the activity of the PD-1/PD-L1 pathway may be an important factor that cannot be clinically cured in CHB as in CHC.

Pt nanoclusters on GaN nanowires for solar-asssisted seawater hydrogen evolution.

Seawater electrolysis provides a viable method to produce clean hydrogen fuel. To date, however, the realization of high performance photocathodes for seawater hydrogen evolution reaction has remained challenging. Here, we introduce n+-p Si photocathodes with dramatically improved activity and stability for hydrogen evolution reaction in seawater, modified by Pt nanoclusters anchored on GaN nanowires. We find that Pt-Ga sites at the Pt/GaN interface promote the dissociation of water molecules and spilling H* over to neighboring Pt atoms for efficient H2 production. Pt/GaN/Si photocathodes achieve a current density of -10 mA/cm2 at 0.15 and 0.39 V vs. RHE and high applied bias photon-to-current efficiency of 1.7% and 7.9% in seawater (pH = 8.2) and phosphate-buffered seawater (pH = 7.4), respectively. We further demonstrate a record-high photocurrent density of ~169 mA/cm2 under concentrated solar light (9 suns). Moreover, Pt/GaN/Si can continuously produce H2 even under dark conditions by simply switching the electrical contact. This work provides valuable guidelines to design an efficient, stable, and energy-saving electrode for H2 generation by seawater splitting.

Amine Hole Scavengers Facilitate Both Electron and Hole Transfer in a Nanocrystal/Molecular Hybrid Photocatalyst.

A well-known catalyst, fac-Re(4,4'-R2-bpy)(CO)3Cl (bpy = bipyridine; R = COOH) (ReC0A), has been widely studied for CO2 reduction; however, its photocatalytic performance is limited due to its narrow absorption range. Quantum dots (QDs) are efficient light harvesters that offer several advantages, including size tunability and broad absorption in the solar spectrum. Therefore, photoinduced CO2 reduction over a broad range of the solar spectrum could be enabled by ReC0A catalysts heterogenized on QDs. Here, we investigate interfacial electron transfer from Cd3P2 QDs to ReC0A complexes covalently bound on the QD surface, induced by photoexcitation of the QD. We explore the effect of triethylamine, a sacrificial hole scavenger incorporated to replenish the QD with electrons. Through combined transient absorption spectroscopic and computational studies, we demonstrate that electron transfer from Cd3P2 to ReC0A can be enhanced by a factor of ∼4 upon addition of triethylamine. We hypothesize that the rate enhancement is a result of triethylamine possibly altering the energetics of the Cd3P2-ReC0A system by interacting with the quantum dot surface, deprotonation of the quantum dot, and preferential solvation, resulting in a shift of the conduction band edge to more negative potentials. We also observe the rate enhancement in other QD-electron acceptor systems. Our findings provide mechanistic insights into hole scavenger-quantum dot interactions and how they may influence photoinduced interfacial electron transfer processes.

Highly stable preferential carbon monoxide oxidation by dinuclear heterogeneous catalysts.

Atomically dispersed catalysts have been shown highly active for preferential oxidation of carbon monoxide in the presence of excess hydrogen (PROX). However, their stability has been less than ideal. We show here that the introduction of a structural component to minimize diffusion of the active metal center can greatly improve the stability without compromising the activity. Using an Ir dinuclear heterogeneous catalyst (DHC) as a study platform, we identify two types of oxygen species, interfacial and bridge, that work in concert to enable both activity and stability. The work sheds important light on the synergistic effect between the active metal center and the supporting substrate and may find broad applications for the use of atomically dispersed catalysts.

The landscape of computational approaches for artificial photosynthesis.

Artificial photosynthesis is an attractive strategy for converting solar energy into fuels, largely because the Earth receives enough solar energy in one hour to meet humanity's energy needs for an entire year. However, developing devices for artificial photosynthesis remains difficult and requires computational approaches to guide and assist the interpretation of experiments. In this Perspective, we discuss current and future computational approaches, as well as the challenges of designing and characterizing molecular assemblies that absorb solar light, transfer electrons between interfaces, and catalyze water-splitting and fuel-forming reactions.

Integrated 2D beam emission spectroscopy diagnostic at the Huan-Liuqi-2A (HL-2A) tokamak.

Two newly developed, eight-channel, integrated Beam Emission Spectroscopy (BES) detectors have been installed at Huan-Liuqi-2A tokamak, which extends the existing 16 single-channel modular BES system with additional 16 spatial channels. The BES collects the Doppler-shifted Balmer Dα emission with a spatial resolution of 1 cm (radial) × 1.5 cm (poloidal) and a temporal resolution of 0.5 µs to measure long-wavelength (k⊥ρi < 1) density fluctuations. Compared to the modular BES, the dark noise of the integrated BES is reduced by 50%-60% on average. The signal-to-noise ratio of the integrated BES system is optimized by the high light throughput front-end optics, high quantum efficiency photodiodes, high-gain, low-noise preamplifiers, and sufficient cooling capacity provided by the thermoelectric cooling (TEC) units that maintain the detectors at -20 °C. Crosstalk between channels that share the same optical system is found to be negligible. High-quality density fluctuation data enables 2D (radial-poloidal) imaging of turbulence, which allows for multi-channel spectral analysis, multi-channel cross-correlation analysis and velocimetry analysis. Preliminary results show that BES successfully captures the spatiotemporal features of the local turbulence and obtains statistically consistent turbulence characterization results.

Glycerol binding at the narrow channel of photosystem II stabilizes the low-spin S2 state of the oxygen-evolving complex.

The oxygen-evolving complex (OEC) of photosystem II (PSII) cycles through redox intermediate states Si (i = 0-4) during the photochemical oxidation of water. The S2 state involves an equilibrium of two isomers including the low-spin S2 (LS-S2) state with its characteristic electron paramagnetic resonance (EPR) multiline signal centered at g = 2.0, and a high-spin S2 (HS-S2) state with its g = 4.1 EPR signal. The relative intensities of the two EPR signals change under experimental conditions that shift the HS-S2/LS-S2 state equilibrium. Here, we analyze the effect of glycerol on the relative stability of the LS-S2 and HS-S2 states when bound at the narrow channel of PSII, as reported in an X-ray crystal structure of cyanobacterial PSII. Our quantum mechanics/molecular mechanics (QM/MM) hybrid models of cyanobacterial PSII show that the glycerol molecule perturbs the hydrogen-bond network in the narrow channel, increasing the pKa of D1-Asp61 and stabilizing the LS-S2 state relative to the HS-S2 state. The reported results are consistent with the absence of the HS-S2 state EPR signal in native cyanobacterial PSII EPR spectra and suggest that the narrow water channel hydrogen-bond network regulates the relative stability of OEC catalytic intermediates during water oxidation.

High-resolution cryo-electron microscopy structure of photosystem II from the mesophilic cyanobacterium, Synechocystis sp. PCC 6803.

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a high-resolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the D1 subunit is flexible, some waters near the active site are partially occupied, and differences in the PsbV subunit block the Large (O1) water channel. These features strongly influence the structural picture of PSII, especially as it pertains to the mechanism of water oxidation.

Development of an Enantioselective Synthesis of (-)-Euonyminol.

We detail the development of the first enantioselective synthetic route to euonyminol (1), the most heavily oxidized member of the dihydro-ß-agarofuran sesquiterpenes and the nucleus of the macrocyclic alkaloids known as the cathedulins. Key steps in the synthetic sequence include a novel, formal oxyalkylation reaction of an allylic alcohol by [3 + 2] cycloaddition; a tandem lactonization-epoxide opening reaction to form the trans-C2-C3 vicinal diol residue; and a late-stage diastereoselective trimethylaluminum-mediated α-ketol rearrangement. We report an improved synthesis of the advanced unsaturated ketone intermediate 64 by means of a 6-endo-dig radical cyclization of the enyne 42. This strategy nearly doubled the yield through the intermediate steps in the synthesis and avoided a problematic inversion of stereochemistry required in the first-generation approach. Computational studies suggest that the mechanism of this transformation proceeds via a direct 6-endo-trig cyclization, although a competing 5-exo-trig cyclization, followed by a rearrangement, is also energetically viable. We also detail the challenges associated with manipulating the oxidation state of late-stage intermediates, which may inform efforts to access other derivatives such as 9-epi-euonyminol or 8-epi-euonyminol. Our successful synthetic strategy provides a foundation to synthesize the more complex cathedulins.

Is Deprotonation of the Oxygen-Evolving Complex of Photosystem II during the S1 → S2 Transition Suppressed by Proton Quantum Delocalization?

We address the protonation state of the water-derived ligands in the oxygen-evolving complex (OEC) of photosystem II (PSII), prepared in the S2 state of the Kok cycle. We perform quantum mechanics/molecular mechanics calculations of isotropic proton hyperfine coupling constants, with direct comparisons to experimental data from two-dimensional hyperfine sublevel correlation (HYSCORE) spectroscopy and extended X-ray absorption fine structure (EXAFS). We find a low-barrier hydrogen bond with significant delocalization of the proton shared by the water-derived ligand, W1, and the aspartic acid residue D1-D61 of the D1 polypeptide. The lowering of the zero-point energy of a shared proton due to quantum delocalization precludes its release to the lumen during the S1→ S2 transition. Retention of the proton facilitates the shuttling of a proton during the isomerization of the tetranuclear manganese-calcium-oxo (Mn4Ca-oxo) cluster, from the "open" to "closed" conformation, a step suggested to be necessary for oxygen evolution from previous studies. Our findings suggest that quantum-delocalized protons, stabilized by low-barrier hydrogen bonds in model catalytic systems, can facilitate the accumulation of multiple oxidizing equivalents at low overpotentials.

Doppler coherence imaging of scrape-off-layer impurity flows in the HL-2A tokamak.

A new Doppler coherence imaging spectroscopy interferometer has been developed on the HL-2A tokamak for the scrape-off-layer impurity flow measurement. Its spatial resolution is estimated to be up to ∼0.8 mm in the horizontal direction and ∼9 mm in the vertical direction, with a field of view of ∼34°. Its typical temporal resolution is about 1 ms. This salient feature allows for time-resolved 2D measurements in short-time phenomena on HL-2A, such as edge localized modes. Group delay and interference fringe pattern were calibrated with a dedicated calibration system. The robustness of group delay calibration and the feasibility of the extrapolation model for fringe pattern calibration are demonstrated. In this paper, we report the details of the optical instruments, calibration, and the initial experimental results of this Doppler coherence imaging spectroscopy interferometer.

In Situ Identification of Reaction Intermediates and Mechanistic Understandings of Methane Oxidation over Hematite: A Combined Experimental and Theoretical Study.

Effective methane utilization for either clean power generation or value-added chemical production has been a subject of growing attention worldwide for decades, yet challenges persist mostly in relation to methane activation under mild conditions. Here, we report hematite, an earth-abundant material, to be highly effective and thermally stable to catalyze methane combustion at low temperatures (<500 °C) with a low light-off temperature of 230 °C and 100% selectivity to CO2. The reported performance is impressive and comparable to those of precious-metal-based catalysts, with a low apparent activation energy of 17.60 kcal·mol-1. Our theoretical analysis shows that the excellent performance stems from a tetra-iron center with an antiferromagnetically coupled iron dimer on the hematite (110) surface, analogous to that of the methanotroph enzyme methane monooxygenase that activates methane at ambient conditions in nature. Isotopic oxygen tracer experiments support a Mars van Krevelen redox mechanism where CH4 is activated by reaction with a hematite surface oxygen first, followed by a catalytic cycle through a molecular-dioxygen-assisted pathway. Surface studies with in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations reveal the evolution of reaction intermediates from a methoxy CH3-O-Fe, to a bridging bidentate formate b-HCOO-Fe, to a monodentate formate m-HCOO-Fe, before CO2 is eventually formed via a combination of thermal hydrogen-atom transfer (HAT) and proton-coupled electron transfer (PCET) processes. The elucidation of the reaction mechanism and the intermediate evolutionary profile may allow future development of catalytic syntheses of oxygenated products from CH4 in gas-phase heterogeneous catalysis.

Development of a multi-color gas puff imaging diagnostic on HL-2A tokamak.

A Multi-Color (MC) gas puff imaging diagnostic has been developed on HL-2A tokamak. This diagnostic can simultaneously measure two-dimensional (2D, radial, and poloidal) electron density and temperature distributions with a good spatial resolution of 2.5 × 2.5 mm2 and a temporal resolution of about 100 µs at best in edge plasmas. The 2D electron density and temperature distributions are inferred from the ratios of intensities of three different neutral helium emission lines; therefore, it is also referred to as helium beam probe or beam emission spectroscopy on thermal helium. A compact light splitter is used to split the inlet visible emission beam into four channels, and the specific neutral helium lines of the wavelengths λ1 = 587.6 nm, λ2 = 667.8 nm, λ3 = 706.5 nm, and λ4 = 728.1 nm are measured, respectively. This MC diagnostic has been experimentally tested and calibrated on a linear magnetic confinement device Peking University Plasma Test device, and the measured 2D electron density and temperature distributions are compared with the Langmuir probe measurements.

Semiconductor-to-conductor transition in 2D copper(ii) oxide nanosheets through surface sulfur-functionalization.

Functionalization is a widely-used strategy to modulate and optimize the properties of materials towards various applications, including sensing, catalysis, and energy generation. While the influence of sulfur-functionalization of carbon materials and oxides like ZnO and TiO2 has been studied, far less research has been devoted to analyzing sulfur-functionalization of CuO and other transition metal oxide nanomaterials. Here, we report sulfur-functionalization of copper(ii) oxide nanosheets synthesized by using a soft-templating procedure, with sulfur-addition based on hydrogen sulfide gas as a source. The resulting sulfur-functionalization does not change the overall crystal structure and morphology of the CuO nanosheets, but leads to a decrease in surface hydroxyl groups. Sulfur induces a semiconductor-to-conductor state transition of the CuO nanosheets, which is supported by computational modeling. The metallic transition results from shifting of the Fermi level into the valence band due to formation of Cu-S bonds on the surface of the CuO nanosheets.

Multihole water oxidation catalysis on haematite photoanodes revealed by operando spectroelectrochemistry and DFT.

Water oxidation is the key kinetic bottleneck of photoelectrochemical devices for fuel synthesis. Despite advances in the identification of intermediates, elucidating the catalytic mechanism of this multi-redox reaction on metal-oxide photoanodes remains a significant experimental and theoretical challenge. Here, we report an experimental analysis of water oxidation kinetics on four widely studied metal oxides, focusing particularly on haematite. We observe that haematite is able to access a reaction mechanism that is third order in surface-hole density, which is assigned to equilibration between three surface holes and M(OH)-O-M(OH) sites. This reaction exhibits low activation energy (Ea ≈ 60 meV). Density functional theory is used to determine the energetics of charge accumulation and O-O bond formation on a model haematite (110) surface. The proposed mechanism shows parallels with the function of the oxygen evolving complex of photosystem II, and provides new insights into the mechanism of heterogeneous water oxidation on a metal oxide surface.

A case of intracranial molluscum contagiosum virus infection diagnosed by metagenomic sequencing of cerebrospinal fluid.

Molluscum contagiosum is a common, self-limiting infectious disease of the skin caused by molluscum contagiosum virus (MCV). The disease primarily affects children, sexually active adults, and immunocompromised individuals. Transmission of the virus occurs by direct skin contact. Therefore, the virus is usually detected in the skin and genitals of patients. However, the diagnosis of intracranial infection by the virus is difficult if the skin/mucosa lessons are atypical or absent, and the presence of the virus in the cerebrospinal fluid has not been reported. We report a very rare case of intracranial infection by molluscum contagiosum virus. A 25-year-old girl was admitted to our hospital due to severe headache but no fever or other symptoms. Upon examination, some small flesh-colored flattened papules on both arms were noticed. Blood tests showed slightly reduced levels of CD3 and CD4 T lymphocytes. Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and head magnetic resonance (MR) were both normal. Lumbar puncture was performed, and metagenomic sequencing was applied to the spinal fluid. The unique sequences of the molluscum contagiosum virus were identified in the fluid. The patient was then diagnosed with intracranial molluscum contagiosum virus infection. No special treatment was given. The headache gradually disappeared, and the patient was discharged. During our quarterly follow-up, the girl appeared normal, and her skin lesions disappeared. However, her CD3 and CD4 T lymphocyte counts were still slightly lower than the normal level. Our case shows that the application of metagenomic sequencing to cerebrospinal fluid is a sensitive and powerful means to detect pathogens causing intracranial infection. Keywords: Molluscum contagiosum; intracranial infection; metagenomics sequencing.

Thermodynamics of the S2-to-S3 state transition of the oxygen-evolving complex of photosystem II.

The room temperature pump-probe X-ray free electron laser (XFEL) measurements used for serial femtosecond crystallography provide remarkable information about the structures of the catalytic (S-state) intermediates of the oxygen-evolution reaction of photosystem II. However, mixed populations of these intermediates and moderate resolution limit the interpretation of the data from current experiments. The S3 XFEL structures show extra density near the OEC that may correspond to a water/hydroxide molecule. However, in the latest structure, this additional oxygen is 2.08 Šfrom the Oε2 of D1-E189, which is closer than the sum of the van der Waals radii of the two oxygens. Here, we use Boltzmann statistics and Monte Carlo sampling to provide a model for the S2-to-S3 state transition, allowing structural changes and the insertion of an additional water/hydroxide. Based on our model, water/hydroxide addition to the oxygen-evolving complex (OEC) is not thermodynamically favorable in the S2g = 2 state, but it is in the S2g = 4.1 redox isomer. Thus, formation of the S3 state starts by a transition from the S2g = 2 to the S2g = 4.1 structure. Then, electrostatic interactions support protonation of D1-H190 and deprotonation of the Ca2+-ligated water (W3) with proton loss to the lumen. The W3 hydroxide moves toward Mn4, completing the coordination shell of Mn4 and favoring its oxidation to Mn(iv) in the S3 state. In addition, binding an additional hydroxide to Mn1 leads to a conformational change of D1-E189 in the S2g = 4.1 and S3 structures. In the S3 state a fraction of D1-E189 release from Mn1 and bind a proton.