Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus

The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP-competitive mitotic kinesin KIF18A inhibitor BTB-1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB-1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran-binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB-1 greatly improved the viability of IAV-infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.     

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX^promotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX^promotor‐AIM2 adenoviruses (Ad‐CAIX^promotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIX^promotor, Ad‐CAIX^promotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIX^promotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIX^promotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIX^promotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIX^promotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.     

Heterotopic ossification of tendon and ligament

Much of the similarities of the tissue characteristics, pathologies and mechanisms of heterotopic ossification (HO) formation are shared between HO of tendon and ligament (HOTL). Unmet need and no effective treatment has been developed for HOTL, primarily attributable to poor understanding of cellular and molecular mechanisms. HOTL forms via endochondral ossification, a common process of most kinds of HO. HOTL is a dynamic pathologic process that includes trauma/injury, inflammation, mesenchymal stromal cell (MSC) recruitment, chondrogenic differentiation and, finally, ossification. A variety of signal pathways involve HOTL with multiple roles in different stages of HO formation, and here in this review, we summarize the progress and provide an up-to-date understanding of HOTL.     

Two New Abietane Diterpenoids from Selaginella moellendorffii Hieron.

Two new abietane diterpenoids, (3S,5R,10S)‐3‐hydroxy‐12‐O‐demethyl‐11‐deoxy‐19(4→3)‐abeo‐cryptojaponol, 12,19‐dihydroxyabieta‐8,11,13‐trien‐7‐one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D‐ and 2D‐NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non‐small‐cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA‐MB‐231 and MCF‐7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC₅₀ values ranging from 16.28 to 40.67 μM.     

Caesalpanins A–C,Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.

Three dimeric cassane diterpenoids, caesalpanins A–C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D‐, 2D‐NMR, and HR‐ESI‐MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen‐containing cassane diterpenoid dimer linked through one ether bond between C‐19 and C‐20′. Caesalpanin B exhibited moderate cytotoxic activity against MCF‐7 cell lines with IC₅₀ value of 29.98 μm . Caesalpanins A and B had weak inhibitory effects against LPS‐induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 μm with inhibitory rate of 36.01 % and 32.93 %, respectively.     

Retarded Charge–Carrier Recombination in Photoelectrochemical Cells from Plasmon‐Induced Resonance Energy Transfer

N‐type metal oxides such as hematite (α‐Fe₂O₃) and bismuth vanadate (BiVO₄) are promising candidate materials for efficient photoelectrochemical water splitting; however, their short minority carrier diffusion length and restricted carrier lifetime result in undesired rapid charge recombination. Herein, a 2D arranged globular Au nanosphere (NS) monolayer array with a highly ordered hexagonal hole pattern (hereafter, Au array) is introduced onto the surface of photoanodes comprised of metal oxide films via a facile drying and transfer‐printing process. Through plasmon‐induced resonance energy transfer, the Au array provides a strong electromagnetic field in the near‐surface area of the metal oxide film. The near‐field coupling interaction and amplification of the electromagnetic field suppress the charge recombination with long‐lived photogenerated holes and simultaneously enhance the light harvesting and charge transfer efficiencies. Consequently, an over 3.3‐fold higher photocurrent density at 1.23 V versus reversible hydrogen electrode (RHE) is achieved for the Au array/α‐Fe₂O₃. Furthermore, the high versatility of this transfer printing of Au arrays is demonstrated by introducing it on the molybdenum‐doped BiVO₄ film, resulting in 1.5‐fold higher photocurrent density at 1.23 V versus RHE. The tailored metal film design can provide a potential strategy for the versatile application in various light‐mediated energy conversion and optoelectronic devices.     

Ultrafine Co3Se4 Nanoparticles in Nitrogen‐Doped 3D Carbon Matrix for High‐Stable and Long‐Cycle‐Life Lithium Sulfur Batteries

Lithium–sulfur batteries are a promising high energy output solution for substitution of traditional lithium ion batteries. In recent times research in this field has stepped into the exploration of practical applications. However, their applications are impeded by cycling stability and short life‐span mainly due to the notorious polysulfide shuttle effect. In this work, a multifunctional sulfur host fabricated by grafting highly conductive Co₃Se₄ nanoparticles onto the surface of an N‐doped 3D carbon matrix to inhibit the polysulfide shuttle and improve the sulfur utilization is proposed. By regulating the carbon matrix and the Co₃Se₄ distribution, N‐CN‐750@Co₃Se₄‐0.1 m with abundant polar sites is experimentally and theoretically shown to be a good LiPSs absorbent and a sulfur conversion accelerator. The S/N‐CN‐750@Co₃Se₄‐0.1 m cathode shows excellent sulfur utilization, rate performance, and cyclic durability. A prolonged cycling test of the as‐fabricated S/N‐CN‐750@Co₃Se₄‐0.1 m cathode is carried out at 0.2 C for more than 5 months which delivers a high initial capacity of 1150.3 mAh g^?1 and retains 531.0 mAh g^?1 after 800 cycles with an ultralow capacity reduction of 0.067% per cycle, maintaining Coulombic efficiency of more than 99.3%. The reaction details are characterized and analyzed by ex situ measurements. This work highly emphasizes the potential capabilities of transition‐metal selenides in lithium–sulfur batteries.     

Influence of Polymer Aggregation and Liquid Immiscibility on Morphology Tuning by Varying Composition in PffBT4T‐2DT/Nonfullerene Organic Solar Cells

The temperature‐dependent aggregation behavior of PffBT4T polymers used in organic solar cells plays a critical role in the formation of a favorable morphology in fullerene‐based devices. However, there is little investigation into the impact of donor/acceptor ratio on morphology tuning, especially for nonfullerene acceptors (NFAs). Herein, the influence of composition on morphology is reported for blends of PffBT4T‐2DT with two NFAs, O‐IDTBR and O‐IDFBR. The monotectic phase behavior inferred from differential scanning calorimetry provides qualitative insight into the interplay between solid–liquid and liquid–liquid demixing. Transient absorption spectroscopy suggests that geminate recombination dominates charge decay and that the decay rate is insensitive to composition, corroborated by negligible changes in open‐circuit voltage. Exciton lifetimes are also insensitive to composition, which is attributed to the signal being dominated by acceptor excitons which are formed and decay in domains of similar size and purity irrespective of composition. A hierarchical morphology is observed, where the composition dependence of size scales and scattering intensity from resonant soft X‐ray scattering (R‐SoXS) is dominated by variations in volume fractions of polymer/polymer‐rich domains. Results suggest an optimal morphology where polymer crystallite size and connectivity are balanced, ensuring a high probability of hole extraction via such domains.     

Phosphorene as Cathode Material for High‐Voltage,Anti‐Self‐Discharge Zinc Ion Hybrid Capacitors

Output voltage and self‐discharge rate are two important performance indices for supercapacitors, which have long been overlooked, though these play a very significant role in their practical application. Here, a zinc anode is used to construct a zinc ion hybrid capacitor. Expanded operating voltage of the hybrid capacitor is obtained with novel electrolytes. In addition, significantly improved anti‐self‐discharge ability is achieved. The phosphorene‐based zinc ion capacitor exploiting a “water in salt” electrolyte with a working potential can reach 2.2 V, delivering 214.3 F g^?1 after 5000 cycles. The operating voltage is further extended to 2.5 V through the use of an organic solvent as the electrolyte; the solvent is prepared by adding 0.2 m ZnCl₂ into the tetraethylammonium tetrafluoroborate in propylene carbonate (Et₄NBF₄/PC) solvent, and it exhibits 105.9 F g^?1 even after 9500 cycles. More importantly, the phosphorene‐based capacitors possess excellent anti‐self‐discharge performance. The capacitors retain 76.16% of capacitance after resting for 300 h. The practical application of the zinc ion capacitor is demonstrated through a flexible paper‐based printed microcapacitor. It is believed that the developed zinc ion capacitor can effectively resolve the severe self‐discharge problem of supercapacitors. Moreover, high‐voltage zinc ion capacitors provide more opportunities for the application of supercapacitors.     

Rational Design of Core@shell Structured CoSx@Cu2MoS4 Hybridized MoS2/N,S‐Codoped Graphene as Advanced Electrocatalyst for Water Splitting and Zn‐Air Battery

A novel hybrid of small core@shell structured CoS_x@Cu₂MoS₄ uniformly hybridizing with a molybdenum dichalcogenide/N,S‐codoped graphene hetero‐network (CoS_x@Cu₂MoS₄‐MoS₂/NSG) is prepared by a facile route. It shows excellent performance toward the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) in alkaline medium. The hybrid exhibits rapid kinetics for ORR with high electron transfer number of ≈3.97 and exciting durability superior to commercial Pt/C. It also demonstrates great potential with remarkable stability for HER and OER, requiring low overpotential of 118.1 and 351.4 mV, respectively, to reach a current density of 10 mA cm^?2. An electrolyzer based on CoS_x@Cu₂MoS₄‐MoS₂/NSG produces low cell voltage of 1.60 V and long‐term stability, surpassing a device of Pt/C + RuO₂/C. In addition, a Zn‐air battery using cathodic CoS_x@Cu₂MoS₄‐MoS₂/NSG catalyst delivers a high cell voltage of ≈1.44 V and a power density of 40 mW cm^?2 at 58 mA cm^?2, better than the state‐of‐the‐art Pt/C catalyst. These achievements are due to the rational combination of highly active core@shell CoS_x@Cu₂MoS₄ with large‐area and high‐porosity MoS₂/NSG to produce unique physicochemical properties with multi‐integrated active centers and synergistic effects. The outperformances of such catalyst suggest an advanced candidate for multielectrocatalysis applications in metal‐air batteries and hydrogen production.