Regulating Cu Oxidation State for Electrocatalytic CO2 Conversion into CO with Near-Unity Selectivity via Oxygen Spillover.

Cu-based catalysts are the most intensively studied in the field of electrocatalytic CO2 reduction reaction (CO2RR), demonstrating the capacity to yield diverse C1 and C2+ products albeit with unsatisfactory selectivity. Manipulation of the oxidation state of Cu sites during CO2RR process proves advantageous in modulating the selectivity of productions, but poses a formidable challenge. Here, an oxygen spillover strategy is proposed to enhance the oxidation state of Cu during CO2RR by incorporating the oxygen donor Sb2O4. The Cu-Sb bimetallic oxide catalyst attains a remarkable CO2-to-CO selectivity approaching unity, in stark contrast to the diverse product distribution observed with bare CuO. The exceptional Faradaic efficiency of CO can be maintained across a wide range of potential windows of ≈700 mV in 1 m KOH, and remains independent of the Cu/Sb ratio (ranging from 0.1:1 to 10:1). Correlative calculations and experimental results reveal that oxygen spillover from Sb2O4 to Cu sites maintains the relatively high valence state of Cu during CO2RR, which diminishes the binding strength of *CO, thereby achieving heightened selectivity in CO production. These findings propose the role of oxygen spillover in CO2RR over Cu-based catalysts, and shed light on the rational design of highly selective CO2 reduction catalysts.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Tunable Optical Activity in Twisted Anisotropic Two-Dimensional Materials.

Twisted van der Waals structures exhibit a variety of unusual electrical and optical phenomena and could provide a powerful means for designing nanodevices with tunable chiral properties. However, programming intrinsic chiral properties of the film on the atomic scale remains a great challenge due to the limitations of fabrication and measurement techniques. Here, we report a highly tunable large optical activity of twisted anisotropic two-dimensional (2D) materials, including black phosphorus (BP), ReS2, PdSe2, and α-MoO3, by varying the twist angle between the stacked layers. The chirality can be deliberately tailored through the engineering of the symmetry, band structure, and anisotropy of 2D materials, demonstrating the high tunability of the chirality. The results show the highest thickness-normalized ellipticity value (13.8 deg µm-1, twisted ReS2) and ellipticity value (1581 mdeg, twisted BP) among the systems based on 2D materials. It is also shown that the chiroptical response exists in an extremely large spectral range from the visible to the infrared. Furthermore, the twisted ReS2 enabled spin-selective control of the information transformation. These results show that highly controllable chirality in twisted 2D anisotropic materials has considerable potential in on-chip polarization optics, nano-optoelectronics, and biology.

PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote TNFα-mediated cell death.

Activation of TNFR1 by TNFα induces the formation of a membrane-associated, intracellular complex termed complex I. Complex I orchestrates a complex pattern of modifications on key regulators of TNF signaling that collectively determines the cell fate by activating pro-survival or executing cell death programs. However, the regulatory mechanism of complex I in cell-fate decision is not fully understood. Here we identify protein phosphatase-6 (PP6) as a previously unidentified component of complex I. Loss of PP6 protects cells from TNFα-mediated cell death. The role of PP6 in regulating cell death requires its phosphatase activity and regulatory subunits. Further mechanistic studies show that PP6 modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote RIPK1 activation and c-FLIPL degradation. We also show that melanoma-associated PP6 inactivating mutants offer resistance to cell death due to the loss of sensitivity to TNFα. Thus, our study provides a potential mechanism by which melanoma-related PP6 inactivating mutations promote cancer progression.

SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.

Thickness-dependent ultrafast charge-carrier dynamics and coherent acoustic phonon oscillations in mechanically exfoliated PdSe2 flakes.

Recently, palladium diselenide (PdSe2) has emerged as a promising material with potential applications in electronic and optoelectronic devices due to its intriguing electronic and optical properties. The performance of the device is strongly dependent on the charge-carrier dynamics and the related hot phonon behavior. Here, we investigate the photoexcited-carrier dynamics and coherent acoustic phonon (CAP) oscillations in mechanically exfoliated PdSe2 flakes with a thickness ranging from 10.6 nm to 54 nm using time-resolved non-degenerate pump-probe transient reflection (TR) spectroscopy. The results imply that the CAP frequency is thickness-dependent. Polarization-resolved transient reflection (PRTR) measurements reveal the isotropic charge-carrier relaxation dynamics and the CAP frequency in the 10.6 nm region. In addition, the deformation potential (DP) mechanism dominates the generation of the CAP. Moreover, a sound velocity of 6.78 × 103 m s-1 is extracted from the variation of the oscillation period with the flake thickness and the delay time of the acoustic echo. These results provide insight into the ultrafast optical coherent acoustic phonon and optoelectronic properties of PdSe2 and may open new possibilities for PdSe2 applications in THz-frequency mechanical resonators.

Discovery of a cooperative mode of inhibiting RIPK1 kinase.

RIPK1, a death domain-containing kinase, has been recognized as an important therapeutic target for inhibiting apoptosis, necroptosis, and inflammation under pathological conditions. RIPK1 kinase inhibitors have been advanced into clinical studies for the treatment of various human diseases. One of the current bottlenecks in developing RIPK1 inhibitors is to discover new approaches to inhibit this kinase as only limited chemotypes have been developed. Here we describe Necrostatin-34 (Nec-34), a small molecule that inhibits RIPK1 kinase with a mechanism distinct from known RIPK1 inhibitors such as Nec-1s. Mechanistic studies suggest that Nec-34 stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain. Furthermore, we show that Nec-34 series of compounds can synergize with Nec-1s to inhibit RIPK1 in vitro and in vivo. Thus, Nec-34 defines a new strategy to target RIPK1 kinase and provides a potential option of combinatorial therapy for RIPK1-mediated diseases.

Laser Writable Multifunctional van der Waals Heterostructures.

Achieving multifunctional van der Waals nanoelectronic devices on one structure is essential for the integration of 2D materials; however, it involves complex architectural designs and manufacturing processes. Herein, a facile, fast, and versatile laser direct write micro/nanoprocessing to fabricate diode, NPN (PNP) bipolar junction transistor (BJT) simultaneously based on a pre-fabricated black phosphorus/molybdenum disulfide heterostructure is demonstrated. The PN junctions exhibit good diode rectification behavior. Due to different carrier concentrations of BP and MoS2 , the NPN BJT, with a narrower base width, renders better performance than the PNP BJT. Furthermore, the current gain can be modulated efficiently through laser writing tunable base width WB , which is consistent with the theoretical results. The maximum gain for NPN and PNP is found to be ≈41 (@WB ≈600 nm) and ≈12 (@WB ≈600 nm), respectively. In addition, this laser write processing technique also can be utilized to realize multifunctional WSe2 /MoS2 heterostructure device. The current work demonstrates a novel, cost-effective, and universal method to fabricate multifunctional nanoelectronic devices. The proposed approach exhibits promise for large-scale integrated circuits based on 2D heterostructures.

An enzyme-free and substrate-free electrochemical biosensor with robust porphyrin-based covalent-linked nanomaterial as nanoelectrocatalyst and efficient support for sensitive detection of uracil-DNA glycosylase.

We developed a novel electrochemical biosensor for uracil-DNA glycosylase (UDG) detection based on enzyme-free and substrate-free electrocatalytic signal amplification by porphyrin-based covalent-linked nanomaterial (OAPS-Por). This OAPS-Por could not only absorb much Thionine (Thi), but also possess obvious electrocatalytic activity toward the reduction of Thi without involvement of H2O2. Sequentially, the functionalized OAPS-Por with Thi, Au nanoparticles and single-stranded DNA (OAPS-Por/Thi@AuNPs-ssDNA) was ingeniously designed as the signal probe. Meantime, the hairpin DNA (hDNA) with four uracil bases was immobilized on AuNPs/GCE via an Au-S bond. When UDG was present, the uracil in hDNA was removed and hairpin structure was unfolded. Next, the signal probes binded with the unfolded hDNA by DNA hybridization. The Thi in signal probes could generated an original electrochemical signal, which could be further amplified and output due to the robust electrocatalytic activities of OAPS-Por toward Thi. As a result, the as-constructed electrochemical biosensor had a broad linear range from 0.005 to 1 U mL-1. It also exhibited a low detection limit of 6.97 × 10-4 U mL-1. Moreover, this biosensor could be used to assay the inhibition of UDG (UGI) and the UDG activity in real samples (HeLa cell lysates and human blood serums), and demonstrated great prospect in clinical diagnostics and biomedical research.

Bacterial Detection and Elimination Using a Dual-Functional Porphyrin-Based Porous Organic Polymer with Peroxidase-Like and High Near-Infrared-Light-Enhanced Antibacterial Activity.

The efficient fabrication of multifunctional nanoplatforms for bacterial detection and elimination is of great importance in nanobiotechnology. A new porphyrin-based porous organic polymer, FePPOPBFPB, was synthesized via the reaction between pyrrole and 4-{2,2-bis[(4-formylphenoxy)methyl]-3-(4-formylphenoxy) propoxy} benzaldehyde (BFPB). The C-centric tetrahedral structure of BFPB promoted the formation of FePPOPBFPB with a 3D interconnected porous structure, high specific surface area, and plentiful surface catalytic active sites. The adjustable structural alkyl chain also enhanced the absorption capability of FePPOPBFPB in the long-wavelength visible and near-infrared regions (NIR). FePPOPBFPB exhibited excellent peroxidase-like activity toward a representative peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2. Utilizing these features, a rapid and visual detection of Staphylococcus aureus (S. aureus) based on FePPOPBFPB was established and exhibited high sensitivity and stability. Combining the catalysis with near-infrared-light (NIR) absorption, FePPOPBFPB can effectively catalyze the decomposition of biologically relevant concentrations of H2O2 to produce vast amounts of •OH radicals via the photo-Fenton reaction, which avoids the utilization of high toxic concentrations of H2O2. On the basis of these satisfactory features, FePPOPBFPB had a conspicuous bactericidal performance against S. aureus under NIR irradiation. To our knowledge, this is the first example of a porphyrin-based porous organic polymer antibacterial agent. The main reactive oxygen species (ROS) produced in this system and the possible antibacterial mechanism of FePPOPBFPB was also proposed through a series of experiments.

A gate-tunable symmetric bipolar junction transistor fabricated via femtosecond laser processing.

Two-dimensional (2D) bipolar junction transistors (BJTs) with van der Waals heterostructures play an important role in the development of future nanoelectronics. Herein, a convenient method is introduced for fabricating a symmetric bipolar junction transistor (SBJT), constructed from black phosphorus and MoS2, with femtosecond laser processing. This SBJT exhibits good bidirectional current amplification owing to its symmetric structure. We placed a top gate on one side of the SBJT to change the difference in the major carrier concentration between the emitter and collector in order to further investigate the effects of electrostatic doping on the device performance. The SBJT can also act as a gate-tunable phototransistor with good photodetectivity and photocurrent gain of ß = ∼21. Scanning photocurrent images were used to determine the mechanism governing photocurrent amplification in the phototransistor. These results promote the development of the applications of multifunctional nanoelectronics based on 2D materials.

Increased LGALS3 expression independently predicts shorter overall survival in patients with the proneural subtype of glioblastoma.

In the current study, we tried to study the expression of LGALS3 and LGALS3BP, their potential as prognostic markers and the possible genetic/epigenetic mechanisms underlying their dysregulation in different subtypes of glioblastoma (GBM). An in silico retrospective study was performed using large online databases. Results showed that LGALS3 and LGALS3BP were upregulated at both RNA and protein levels in GBM tissue and were generally associated with shorter overall survival (OS) in GBM patients. However, in subgroup analysis, we only found the association in proneural subtype. The copy number alterations did not necessarily lead to LGALS3/LGALS3BP dysregulation. In the proneural subtype of GBM patients, hypermethylation of the two CpG sites (cg19099850 and cg17403875) was associated with significantly lower expression of LGALS3. In univariate and multivariate analysis, LGALS3 expression independently predicted shorter OS in the proneural subtype of GBM (HR: 1.487, 95% CI: 1.229-1.798, P < 0.001), after adjustment of age, gender, IDH1 mutations, temozolomide chemotherapy, radiotherapy and LGALS3BP expression. In comparison, LGALS3BP lost the prognostic value in multivariate analysis. Based on these findings, we infer that LGALS3 expression serves as an independent biomarker of shorter OS in the proneural subtype of GBM, the expression of which might be regulated in an epigenetic manner.

Molybdenum-Based Co-catalysts in Photocatalytic Hydrogen Production: Categories, Structures, and Roles.

Photocatalytic hydrogen production by using solar energy has attracted great interest around the world. The main challenges are the high costs of the photocatalysts and the low efficiency of photocatalytic hydrogen production. Co-catalysts, as crucial components of photocatalysts, are usually used to stimulate photoexcited electron transfer from the light absorber to the surface, and they also catalyze the proton-reduction reaction to form H2 in water. However, most co-catalysts used in photocatalytic hydrogen production are noble metals, which are expensive and contradict the low-costs demanded by industry. Therefore, the development of earth-abundant and cheap co-catalysts to replace noble metals is necessary for photocatalytic H2 production. This account highlights the performance and roles of molybdenum-based non-noble metal co-catalysts in photocatalytic hydrogen production. We developed a series of inexpensive and efficient molybdenum-based co-catalysts. We demonstrated that more H2 could be produced by loading Mo-based co-catalysts on CdS by using the co-precipitation method than by using traditional Pt/CdS same under the same photocatalytic conditions. The molybdenum-based co-catalysts were able to form heterojunctions, which served as bridges to facilitate the transport and separation of photogenerated charges; moreover, the molybdenum-based co-catalysts were able to accept and store photoexcited electrons owing to their large specific capacitance. The stored photoelectrons could then be released according to proton-reduction processes to form H2 . Furthermore, the molybdenum-based co-catalysts were found to have metastable state structures and multiple valence states, which provided more active sites and effectively catalyzed the production of H2 and inhibited the reverse reaction. The discovery of Mo-based co-catalysts with superior properties will provide guidance for the design of new co-catalysts.

Carrier Engineering in Polarization-Sensitive Black Phosphorus van der Waals Junctions.

van der Waals p-n heterostructures based on p-type black phosphorus (BP) integrated with other two-dimensional (2D) layered materials have shown potential applications in electronic and optoelectronic devices, including logic rectifiers and polarization-sensitive photodetectors. However, the engineering of carriers transport anisotropy, which is related to the linear dichroism, have not yet been investigated. Here, we demonstrate a novel van der Waals device of orientation-perpendicular BP homojunction based on the anisotropic band structures between the armchair and zigzag directions. The structure exhibits good gate-tunable diode-like rectification characteristics caused by the barrier between the two perpendicular crystal orientations. Moreover, we demonstrate that the unique mechanisms of the polarization-sensitivity properties of this junction are involved with the linear dichroism and the anisotropic carriers transport engineering. These results were verified by the scanning photocurrent images experiments. This work paves the way for 2D anisotropic layered materials for next-generation electronic and optoelectronic devices.

Modulation of photothermal anisotropy using black phosphorus/rhenium diselenide heterostructures.

Manipulating the polarization of an incident beam using two-dimensional materials has become an important research direction towards the development of nano-optical devices. Black phosphorus (BP) and rhenium diselenide (ReSe2) possess excellent in-plane optical anisotropy with optical birefringence in the visible region, which has led to novel applications in polarizing optics and optoelectronics. Herein, the polarization-dependent absorption of BP and ReSe2 and a modulated pump beam is utilized to obtain the photothermal signal from them. The photothermal anisotropy of BP and ReSe2 has been explored using photothermal detection. Then we have defined the photothermal contrast using the ratio of the maximum to the minimum of the photothermal signal. The photothermal contrast of BP and ReSe2 can be obtained accurately by the relationship between the polarization angle of the pump light and the photothermal signal. We demonstrate that a layered BP with different thicknesses can remarkably change the photothermal contrast. In contrast, the photothermal contrast of ReSe2 does not change with the different thicknesses of the samples. Further, the photothermal anisotropies of BP/ReSe2 heterostructures were also explored. The photothermal contrasts of samples were observed to change with different stacking angles indicating that the photothermal anisotropy of heterostructures is dependent on the stacking angle. Our findings provide new prospects for designing novel optical devices based on two-dimensional anisotropic materials, with potential applications in electronics, photonics, and optoelectronics.

Fast and safe synthesis of micron germanium in an ammonia atmosphere using Mo2N as catalyst.

Here, we reported a new method for fast and safe synthesis of a micron germanium (Ge) semiconductor. The Ge was successfully prepared from mixed GeO2 with a low amount of MoO3 by the NH3 reduction method at 800 °C for an ultra-short time of 10 min. XRD patterns show that the Ge has a tetragonal structure. SEM images show that the size of the Ge particles is from 5 µm to 10 µm, and so it is on the micron scale. UV-visible diffuse reflectance spectroscopy shows that the Ge has good light absorption both in the ultraviolet and visible regions. The formation of Ge mainly goes through a two-step conversion in the NH3 flow. Firstly, GeO2 is converted to Ge3N4, and then Ge3N4 is decomposed to generate Ge. The comparison experiments of MoO3 and Mo2N demonstrate that Mo2N is the catalyst for the Ge synthesis which improves the Ge3N4 decomposition. The presented fast and safe synthesis method of Ge has great potential for industrialization and the proposed Mo2N boosting the Ge3N4 decomposition has provided significant guidance for other nitride decomposition systems.