Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

Theoretical Study on Ion Diffusion Mechanism in W-Doped K3SbS4 as Solid-State Electrolyte for K-Ion Batteries.

The development of a solid-state electrolyte (SSE) is crucial for overcoming the side reactions of metal potassium anodes and advancing the progress of K-ion batteries (KIBs). Exploring the diffusion mechanism of the K ion in SSE is important for deepening our understanding and promoting its development. In this study, we conducted static calculations and utilized deep potential molecular dynamics (DeepMD) to investigate the behavior of cubic K3SbS4. The original K3SbS4 exhibited poor ionic conductivity, but we discovered that introducing heterovalent tungsten doping created vacancies, which significantly reduced the activation energy to 0.12 eV and enhanced the ionic conductivity to 1.80 × 10-2 S/cm. The diffusion of K-ions in K3SbS4 primarily occurs through the exchange of positions with K vacancies. This research provides insights into the design of SSE with high ionic conductivity. Furthermore, it highlights the effectiveness of DeepMD as a powerful tool for studying the SSE.

CSCD2: an integrated interactional database of cancer-specific circular RNAs.

The significant function of circRNAs in cancer was recognized in recent work, so a well-organized resource is required for characterizing the interactions between circRNAs and other functional molecules (such as microRNA and RNA-binding protein) in cancer. We previously developed cancer-specific circRNA database (CSCD), a comprehensive database for cancer-specific circRNAs, which is widely used in circRNA research. Here, we updated CSCD to CSCD2 (http://geneyun.net/CSCD2 or http://gb.whu.edu.cn/CSCD2), which includes significantly more cancer-specific circRNAs identified from a large number of human cancer and normal tissues/cell lines. CSCD2 contains >1000 samples (825 tissues and 288 cell lines) and identifies a large number of circRNAs: 1 013 461 cancer-specific circRNAs, 1 533 704 circRNAs from only normal samples and 354 422 circRNAs from both cancer and normal samples. In addition, CSCD2 predicts potential miRNA-circRNA and RBP-circRNA interactions using binding motifs from >200 RBPs and 2000 microRNAs. Furthermore, the potential full-length and open reading frame sequence of these circRNAs were also predicted. Collectively, CSCD2 provides a significantly enhanced resource for exploring the function and regulation of circRNAs in cancer.

Construction of floating photothermal-assisted S-scheme heterojunction with enhanced photocatalytic degradation of tetracycline: Insights into mechanisms, degradation pathways and toxicity assessment.

Inspired by ecological floating beds to treat water pollution through photosynthesis, we employed a combination of calcination and hydrothermal methods to construct a photothermal-assisted photocatalysis system based on a floating monolithic porous mesh of g-C3N4 (MPMCN) loaded with the excellent photothermal material Bi2MoO6 (BMO), forming a BMO/MPMCN S-scheme heterojunction. This approach improved the utilization efficiency of solar light by BMO/MPMCN, minimized heat loss, and enhanced the overall temperature of the material during the reaction process, thereby accelerating interfacial electron transfer. The unique floating structure confers a larger specific surface area to BMO/MPMCN, providing more reaction sites for TC pollutants and efficiently removing TC contamination from water. BMO/MPMCN degradated 99.3% of TC after 90 min of photothermal reaction, and exhibited good recyclability and reusability. Structural and performance characterizations of the material were carried out using techniques such as XRD, TEM, electrochemical testing, and ESR. Furthermore, the corresponding band structure and S-scheme electron transfer mechanism of the BMO/MPMCN heterojunction were deduced through the combination of in-situ XPS and UPS. The possible degradation pathways of TC and the ecological toxicity changes of intermediate products were analyzed. Finally, a mechanistic model for the photothermal-assisted photocatalytic degradation of TC in water by the BMO/MPMCN S-scheme heterojunction was established, providing a novel approach for the practical application of photocatalysis technology.

Molecule and Microstructure Modulations of Cyano-Containing Electrodes for High-Performance Fully Organic Batteries.

Cyano-containing electrodes usually promise high theoretical potentials while suffering from uncontrollable self-dissolution and sluggish reaction kinetics. Herein, to remedy their limitations, an unprecedented core-shell heterostructured electrode of carbon nanotubes encapsulated in poly(1,4-dicyanoperfluorobenzene sulfide) (CNT@PFDCB) is rationally crafted via molecule and microstructure modulations. Specifically, the linkage of sulfide bridges of PFDCB prevents the active cyano groups from dissolving, resulting in a robust structure. The fluorinations modulate the electronic configurations in frontier orbitals, allowing higher electrical conductivity and elevated output voltage. Combined with the core-shell architecture to unlock the sluggish diffusion kinetics for both electrons and guest ions, the CNT@PFDCB exhibits an impressive capacity (203.5 mAh g-1), remarkable rate ability (127.6 mAh g-1 at 3.0 A g-1), and exceptional cycling stability (retaining 81.1 % capacity after 3000 cycles at 1.0 A g-1). Additionally, the Li-storage mechanisms regarding PFDCB are thoroughly revealed by in situ attenuated total reflection infrared spectroscopy, in situ Raman spectroscopy, and theoretical simulations, which involve the coordination interaction between Li ions and cyano groups and the electron delocalization along the conjugated skeleton. More importantly, a practical fully organic cell based on the CNT@PFDCB is well-validated that demonstrates a tremendous potential of cyanopolymer as the cathode to replace its inorganic counterparts.

Identification of the gossypol derivatives as androgen receptor inhibitor.

Prostate cancer (PCa) is the most frequently diagnosed male malignant tumor and remains the second leading cause of male cancer mortality in western countries. The development of novel antiandrogens to circumvent the drug resistance in anti-PCa treatment is highly demanded. Herein, we identified that gossypol (GOS) specificly inhibited the AR signaling. Further optimization of GOS derivatives led to the discovery of compound XY-32. XY-32 efficiently inhibits AR signaling with the IC50 of 1.23 µM. XY-32 downregulates both the full-length AR and the AR variable splice AR-V7 via suppressing the mRNA expression. It inhibits the proliferation of CRPC cells such as the LNCaP cells, the PC-3 cells, and enzalutamide resistance 22Rv1 cells. The work demonstrates the GOS derivatives represent a novel series of anti-androgen to conquer the acquired AR mutations or AR splice variants induced drug resistance of mCRPC.

Development of novel androgen receptor antagonists based on the structure of darolutamide.

Androgen signaling pathway plays an important role in the occurrence and development of prostate cancer (PCa), and anti-androgen drugs are one of the most effective therapies for PCa. Darolutamide 4 (ODM-201) is a promising second- generation antiandrogen because of its unique chemical structure and good activity against androgen receptor (AR). Herein, the structure-activity relationship of ODM-201 was studied, and 37 analogues were synthesized. Half of them exhibited similar or better anti-AR transcriptional activity compared to ODM-201. In addition, the inhibitory activity of compound 28t against the two resistant mutants (AR-F876L and AR-T877A) was superior to that of ODM-201. This study provides a new clue for the further optimization of ODM-201 and the development of anti-CRPC drugs.

Graphene/Amorphous Carbon Restriction Structure for Stable and Long-Lifespan Antimony Anode in Potassium-Ion Batteries.

Sb-based materials have attracted much attention owing to their ability to undergo a multi-electron alloy reaction with K+ . However, there are still the serious problems of volume change and aggregation of particles, which lead to rapid capacity fading and a limited lifespan. In this work, a graphene/amorphous carbon restriction structure is proposed, in which the amorphous carbon layer on the surface of Sb nanoparticles can protect the particles from pulverization, and the graphene can buffer the volume change of the material. In addition, the conductive network formed by the dual carbon structure effectively improves the rate performance of the material. Thus, the material delivers a high capacity of 550 mA h g-1 at 100 mA g-1 , a rate capability of 370 mA h g-1 at 2000 mA g-1 , and a long lifespan of 350 cycles without significant capacity fading. The dual carbon strategy proposed offers a reference for the design of high-performance anode materials.

Effects of Structure and Magnetism on the Electrochemistry of the Layered Li1+x(Ni0.5Mn0.5)1-xO2 Cathode Material.

We have synthesized a series of Li1+x(Ni0.5Mn0.5)1-xO2 (LNMO) materials to study the influence of excess lithium ions on the structure and electrochemical behaviors of nickel-manganese-based layered compounds. The increasing content of Li+ ions in the transition-metal (TM) layer leads to the departure of the follower-like clusters to Ni-rich and Mn-rich clusters. The Ni2+ ions in the Li layer couple with adjacent transition-metal ions via strong 180° exchange interactions and moderate the local structure, which leads to magnetic clusters with finite size. Electrochemical performance shows that appropriate Ni2+ ions could improve the cycle stability without decreasing the rate capability. Among them, Li1.1Ni0.45Mn0.45O2 shows a rate capability of 76 mAh g-1 at 1000 mA g-1 and a lifespan of 300 cycles at 200 mA g-1. This work shows that structure moderation has an essential impact on its electrochemical performance. Besides this, the crystal and magnetic combined methods we use could offer a better way of studying cathode materials.

A kinetics study on intercalation pseudocapacitance of layered TiS2 in K-ion batteries.

The boundary between a capacitor and a battery is vague for layered transition metal sulfides, especially when it comes to TiS2 with a multi-phase transition process. In this work we analyzed both the quasi-static process and dynamic process of K+ storage in TiS2 with carbonate based electrolytes, which proved to be an intercalation pseudocapacitive behavior.

Assembly of SnSe Nanoparticles Confined in Graphene for Enhanced Sodium-Ion Storage Performance.

Sodium-ion batteries (SIBs) have attracted much interest as a low-cost and environmentally benign energy storage system, but more attention is justifiably required to address the major technical issues relating to the anode materials to deliver high reversible capacity, superior rate capability, and stable cyclability. A SnSe/reduced graphene oxide (RGO) nanocomposite has been prepared by a facile ball-milling method, and its structural, morphological, and electrochemical properties have been characterized and compared with those of the bare SnSe material. Although the redox behavior of SnSe remains nearly unchanged upon the incorporation of RGO, its electrochemical performance is significantly enhanced, as reflected by a high specific capacity of 590 mA h g(-1) at 0.050 A g(-1) , a rate capability of 260 mA h g(-1) at 10 A g(-1) , and long-term stability over 120 cycles. This improvement may be attributed to the high electronic conductivity of RGO, which also serves as a matrix to buffer changes in volume and maintain the mechanical integrity of the electrode during (de)sodiation processes. In view of its excellent Na(+) storage performance, this SnSe/RGO nanocomposite has potential as an anode material for SIBs.

Inducing or enhancing protein-protein interaction to develop drugs: Molecular glues with various biological activity.

Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders.

Efficacy and safety of novel immune checkpoint inhibitor-based combinations versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer: A network meta-analysis.

BACKGROUND: Patients with extensive-stage small cell lung cancer (ES-SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide-platinum is recommended as standard first-line therapy. However, which combination pattern is the best still remains unknown. This network meta-analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients. METHODS: Hazard ratios (HRs) and odds ratios (ORs) were generated using R software. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (grade ≥ 3 adverse events [AEs]) were analyzed. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 5544 patients were included for analysis. Drug combination patterns included adebrelimab, atezolizumab, durvalumab, durvalumab plus tremelimumab, ipilimumab, pembrolizumab, serplulimab, benmelstobart plus anlotinib, tislelizumab, tiragolumab plus atezolizumab and toripalimab in combination with chemotherapy. The novel antiangiogenic agent containing regimen benmelstobart + anlotinib + chemotherapy showed the highest possibility to present the best PFS and OS versus chemotherapy. Compared with ICI plus chemotherapy, it also achieved significantly better PFS and presented a tendency of OS benefit. As for safety and toxicity, patients treated with benmelstobart + anlotinib + chemotherapy and durvalumab + tremelimumab + chemotherapy suffered a higher likelihood of more grade ≥ 3 AEs without unexpected AEs. CONCLUSION: PD-1/PD-L1 inhibitors-based combinations are associated with significant improvement in both PFS and OS for treatment-naïve ES-SCLC patients. Benmelstobart plus anlotinib with chemotherapy (CT) yielded better survival benefit versus CT alone or other ICIs + CT with caution for more adverse effects along with the addition of an antiangiogenic agent.

Lattice-Confined Single-Atom Catalyst: Preparation, Application and Electron Regulation Mechanism.

Lattice-confined single-atom catalyst (LC SAC), featuring exceptional activity, intriguing stability and prominent selectivity, has attracted extensive attention in the fields of various reactions (e.g., hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), etc.). To design a "smart" LC SAC for catalytic applications, one must systematically comprehend updated advances in the preparation, the application, and especially the peculiar electron regulation mechanism of LC SAC. In this review, the specific preparation methods of LC SAC based on general coordination strategy are updated, and its applications in HER, OER, ORR, N2 reduction reaction (NRR), advanced oxidation processes (AOPs) and so forth are summarized to display outstanding activity, stability and selectivity. Uniquely, the electron regulation mechanisms are first and deeply discussed and can be primarily categorized as electron transfer bridge with monometallic active sites, novel catalytic centers with polymetallic active sites, and positive influence by surrounding environments. In the end, the existing issues and future development directions are put forward with a view to further optimize the performance of LC SAC. This review is expected to contribute to the in-depth understanding and practical application of highly efficient LC SAC.

METTL3 inhibitor suppresses the progression of prostate cancer via IGFBP3/AKT pathway and synergizes with PARP inhibitor.

The RNA N6-methyladenosine (m6A) regulator METTL3 is an important regulatory gene in various progressive processes of prostate cancer (PCa). METTL3 inhibitors have been reported to possess potent tumor suppression capacity in some cancer types. Nevertheless, the detailed influence and mechanism of METTL3 inhibitors on PCa progression and their potential synergy with other drugs are poorly understood. In this study, we demonstrated that METTL3 was overexpressed and associated with poor survival in most PCa patients. METTL3 inhibitor STM2457 reduced m6A levels of PCa cells, thus inhibiting their proliferation, colony formation, migration, invasion, and stemness in vitro. Furthermore, STM2457 suppressed PCa progression in both the CDX and PDX models in vivo. MeRIP-seq analysis coupled with biological validation revealed that STM2457 influenced multiple biological processes in PCa cells, mainly through the IGFBP3/AKT pathway. We also proved that STM2457 induced DNA damage and showed synergistic anti-PCa effects with the PARP inhibitor olaparib both in vitro and in vivo. All in all, this work provides a novel therapeutic strategy for targeting RNA m6A modifications for the treatment of PCa and provides a meaningful reference for further clinical trials.

Efficacy and patient-reported outcomes in advanced non-small cell lung cancer patients receiving aumolertinib as first-line therapy: a real-world study.

Background: Aumolertinib demonstrated superior progression-free survival (PFS) and a well-tolerated toxicity profile compared to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, patient-reported outcomes (PROs) of aumolertinib have not been published. Methods: In this real-world study, the efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC Quality of Life lung cancer-specific module (QLQ-LC13) in advanced NSCLC patients receiving aumolertinib as initial therapy. Pre-specified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling in hands or feet, chest pain, arm or shoulder pain, and pain at other sites. Results: A total of 33 patients were included, 23 of whom had efficacy information up to January 2024. The median follow-up time was 264 days (interval: 36-491 days). The objective response rate and disease control rate were 65.2% and 91.3%, respectively. The EORTC QLQ-LC30 general health status scale showed that functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by the EORTC QLQ-LC13 showed that improvements in cough, sore mouth or tongue, tingling in hands or feet, chest pain, arm or shoulder pain, and other pain sites were both clinically and statistically significant after 6 months of aumolertinib treatment (p < 0.05). Conclusion: In this real-world study, aumolertinib showed comparable disease control and objective response rates as reported in the AENEAS trial for advanced NSCLC patients with EGFR-sensitizing mutations. Aumolertinib treatment improved PROs, further supporting it in first-line clinical practice.

Ethanol as Solvent Additives with Competitive Effect for High-Stable Aqueous Zinc Batteries.

Aqueous zinc-ion batteries are emerging as promising sustainable energy-storage devices. However, their cyclic stability is still a great challenge due to the inevitable parasitic reaction and dendrite growth induced by water. Herein, a cosolvent strategy based on competitive effect is proposed to address the aforementioned challenges. Ethanol with a higher Gutmann donor number demonstrates lower polarity and better wettability on the Zn surface compared with water, which endows ethanol with the ability of minimizing water activity by weakening H bonds and preferentially adsorbing on the Zn electrode. The above competitive advantages synergistically contribute to inhibiting the decomposition of free water and dendrite growth. Besides, an organic-inorganic hybrid solid-electrolyte interphase layer is in situ built based on ethanol additives, where organic matrix suppresses water corrosion while inorganic fillers promote fast Zn2+ diffusion. Consequently, the electrolyte with ethanol additives boosts a high reversibility of Zn deposition, long-term durability, as well as superior Zn2+ diffusibility in both Zn half-cells (Zn||Cu and Zn||Zn batteries) and Zn full cells (Zn||PTCDA and Zn||VO2 batteries). This work sheds light on a universal strategy to design a high-reversible and dendrite-free Zn anode for stable aqueous batteries.

Design and Synthesis of Dual-Target Inhibitors Targeting Androgen Receptors and Glucocorticoid Receptors to Overcome Antiandrogen Resistance in Castration-Resistant Prostate Cancer.

Androgen receptor (AR) antagonists play important roles in the treatment of castration-resistant prostate cancer (CRPC). The glucocorticoid receptor (GR) upregulation leads to drug resistance for clinically used antiandrogens. Therefore, blocking AR/GR signaling simultaneously has become an efficient strategy to overcome the drug resistance of CRPC. Our previous work indicated that Z19 could inhibit the activity of both AR and GR. Herein, we optimized the structure of Z19 and identified GA32 as a potent AR/GR dual inhibitor. GA32 efficiently reduced the mRNA and protein levels of AR/GR downstream genes. GA32 efficiently inhibited the proliferation of enzalutamide resistance CRPC both in vitro and in vivo. GA32 could directly bind to AR and GR, and the predicted binding modes for GA32 with AR/GR suggested that GA32 binds to the AR or GR hormone binding pocket. This work provides a potential lead compound with dual AR/GR inhibitory activity to conquer the drug resistance of CRPC.

Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer.

Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.