Infections caused by Pseudomonas aeruginosa (P. aeruginosa) pose a severe threat to public health due to high antibiotic resistance and robust biofilm formation, which collectively hinder the penetration and efficacy of antibiotics and antibodies. To address this issue, we developed a chemo-bio-hybrid delivery system, termed EcN@TGG, by chemically engineering the probiotic strain Escherichia coli Nissle 1917 (EcN). Leveraging its intrinsic swimming capability, EcN was harnessed as an active penetration vehicle against established biofilms. Via a simple co-incubation process, EcN is functionalized with tannic acid (TA), gallium (Ga3+), and a bispecific monoclonal antibody Gremubamab (MEDI3902) targeting P. aeruginosa. EcN@TGG actively penetrates biofilm matrix, enabling deep delivery of therapeutic payloads (Ga3+ and MEDI3902) thereby achieving effective biofilm disruption and potent bactericidal activity. The robust antimicrobial efficacy and biocompatibility of EcN@TGG confer potent antibiofilm activity against P. aeruginosa, as demonstrated both in vitro and in vivo. This platform not only provides a promising strategy for treating refractory infections caused by P. aeruginosa, but also establishes a versatile chemo-bio-hybrid strategy for combating diverse biofilm-associated diseases.

Bacillus cereus threatens food preservation owing to its robust biofilm-forming capacity and antibiotic resistance. This study demonstrates that Sophora flavescens Aiton, a traditional Chinese medicine and functional food ingredient, can inhibit B. cereus and its drug-resistant strains. Using UPLC-ESI-MS/MS, 367 known constituents were identified from S. flavescens, among which several showed antibacterial activity against B. cereus, with totarol exhibiting the strongest effect. The MICs of totarol against B. cereus and its drug-resistant strains was 1.5625-3.125 μg/mL, with MBCs of 7.8125-15.625 μg/mL. Scanning electron microscopy, live/dead cell staining, genomic DNA and proteins profile electrophoresis confirmed the growth-inhibitory effect of totarol. Notably, totarol suppressed B. cereus biofilm formation by 92.99% at the concentration of 1 MIC. Transcriptomic analysis revealed that totarol downregulated genes related to carbon metabolism, protein synthesis and peptide transport. Additionally, totarol showed excellent antibacterial ability against B. cereus in cooked rice model. These results validate the first evidence of totarol against B. cereus and its potential in food application.

Bacterial-based materials, leveraging their inherent hypoxia and immunosuppressive microenvironment-targeting capabilities, immunomodulatory effects, and drug delivery advantages, have emerged as promising strategies to modulate the tumor microenvironment (TME) for converting immunologically "cold" tumors into "hot" ones. This study innovatively functionalizes Lactobacillus reuteri (L. reuteri) using metal-phenolic networks (MPNs) to co-deliver αPD-L1 antibodies and gallium ions (Ga3 +) for synergistic anti-tumor therapy. The MPN coating materials enable pH-responsive drug release, whereby αPD-L1 reverses immunosuppression and Ga3 + disrupts tumor iron metabolism, mimicking Fe3 + to induce selective ferroptosis. In vivo evaluations in B16 and LLC tumor-bearing mouse models revealed that functionalized L. reuteri had the potential to reprogram the tumor immune microenvironment and significantly enhanced tumor regression. This system achieved multifunctional tumor regression in vivo, integrating bacterial hypoxia-driven chemotaxis, MPN-mediated ferroptosis, and immune checkpoint inhibitors (ICIs)-driven immune activation. Thus, the multifunctional materials offer a novel strategy for treating refractory or immunologically "cold" tumors.

With advancements in renewable energy and the swift expansion of the electric vehicle sector, lithium-ion capacitors (LICs) are recognized as energy storage devices that merge the high power density of supercapacitors with the high energy density of lithium-ion batteries, offering broad application potential across various fields. This paper initially presents an overview of the developmental history, energy storage mechanisms, and classifications of LICs. It then concentrates on the latest advancements in anode and cathode materials for LICs, systematically reviewing strategies for optimizing electrochemical performance through microstructure adjustment, elemental doping, and the use of composite materials. Furthermore, it delves into the recent progress in the electrolyte system of LICs and prelithiation technologies, examining the features of different electrolyte systems and detailing various prelithiation approaches along with their merits and drawbacks. In conclusion, this paper summarizes and anticipates the current research trends in LICs, offering new perspectives and directions for future investigations.

The orthopoxvirus genus, particularly the monkeypox virus (MPXV), continues to pose a significant global public health threat. Therefore, the development of novel anti-orthopoxvirus agents remains an urgent priority. Machine learning has proven to be an effective approach for identifying potential drug candidates. In this study, we implemented a dual-view deep learning model that combines BERT and a graph neural network to analyze molecular sequences and structural graphs. The model was trained following a pre-training-then-fine-tuning paradigm and was subsequently applied to identify new molecules with potential anti-orthopoxvirus activity. Notably, a cinnamoyl anthranilic acid derivative (compound 6) was successfully predicted and demonstrated potent anti-orthopoxvirus effects both in vitro and in vivo. Furthermore, integrin subunit beta 3 (ITGB3) has been validated as one of the direct target protein of 6. In conclusion, we established a robust dual-view deep learning model for the discovery of novel anti-orthopoxvirus agents, and compound 6 is a promising candidate for orthopoxvirus treatment via ITGB3 targeting.

Silicon (Si) exhibits significant potential as a high-capacity anode material for lithium-ion batteries. However, its commercial viability is hindered by challenges such as volumetric expansion during charge and discharge cycles, inadequate electrical conductivity, and a limited cycle life. To address these issues, the combination of Si with transition metal oxides and carbon coatings has proven to be an effective strategy for enhancing cycling performance. This paper presents a straightforward and cost-effective one-pot method for synthesizing Si@AMOA (Silicon composite carbon-coated amorphous manganese oxides) composites. The pores between the cross-linked nanorods can provide a large volume expansion space, and the embedded nanorods have strong Si-C bonding, which can buffer the volume change of the Si active material, while the use of phenolic resin to form an amorphous carbon layer encapsulated with Si-composite amorphous MnO2 improves electrical conductivity and stability, and the Si@AMOA anode material is loose and porous, with a large specific surface area, which is conducive to the ionic and electronic transport. The absence of the MnO2 lattice leads to the presence of oxygen vacancies thus enabling the electrode material to have a better wettability with the electrolyte, which reduces the polarisation and improves the material's electrical conductivity, thus enabling the lithium to be rapidly intercalated/decalcified through the thin wall, thus improving its cycling stability performance. The Si@AMOA anode demonstrates a specific discharge capacity of 972.6 mAh g- 1 after more than 600 cycles at a current density of 0.5 A g- 1, while exhibiting excellent electrochemical stability across varying current densities.

Zinc-ion batteries (ZIBs) offer safe, low-cost, high-capacity energy storage, but dendrite growth, hydrogen evolution, and corrosion limit their use. This paper reviews stability strategies and research directions.

Background: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. Purpose: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. Methods: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determi- nation, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. Results: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 mu g/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. Conclusions: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo . These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.

The development of resistance against most of the available antibiotics has made Acinetobacter baumannii (A. baumannii) a pathogen of high risk. In this study, thirty novel berberine derivatives are rationally designed, synthesized, and evaluated for their synergistic antibacterial activities against A. baumannii. Among them, compound 2d shows the most potent synergetic effect to aztreonam against A. baumannii, including carbapenem-resistant and extended-spectrum β-lactamases-producing strains. Moreover, synergistic effects were observed for the combinations of 2d and different antibacterial used in clinical practices, indicating its potent broad-spectrum antibiotic-sensitizing effects against A. baumannii. The combination of 2d and aztreonam significantly improves the survival rates of G. mellonella larvae compared with aztreonam treatment alone. Mechanism studies indicate that 2d inhibits the drug efflux and iron acquisition of the bacteria by targeting the AdeB transporter protein, thus achieving a synergistic antimicrobial efficacy with different antibacterials. Therefore, berberine derivatives represent a new family of antimicrobial adjuvants against A. baumannii, with the advantage of dual-function antibacterial effect, and are worthy of further investigation.

Accurate detection of saliva glucose levels is crucail for diagnosing diabetes and oral diseases. However, the complex bacterial environment in the oral cavity presents challenges, particularly in reducing sensor sensitivity due to bacterial adhesion. The excellent self-cleaning capabilities of super-hydrophilic materials make them one of the top choices. To surpass the limitations of traditional super-hydrophilic materials, a Spin coating-Plasma treatment-Coprecipitation treatment (SPC) strategy was implemented to develop a super-hydrophilic gel saliva glucose sensor. Surface-initiated polymerization was used to form phenylboric acid hydrogels for glucose binding. A spin-coated transition layer protects the hydrogel, while plasma treatment and co-precipitation methods create a super-hydrophilic surface, providing antibacterial properties. The sensor demonstrated a remarkable ability to reduced bacterial adhesion of the five oral pathogenic bacteria by over 95 %, and significantly inhibited biofilm formation of Streptococcus pneumoniae and Streptococcus mitis by 95.7 % and 96.7 %, respectively. Its detection limit of 3.04 mg/L meets the requirements for saliva glucose detection. Overall, the development of this super-hydrophilic gel sensor holds great promise for wearable oral monitoring devices, offering new opportunities in healthcare managing and monitoring.

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25–0.5 μg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.

Metal–organic frameworks (MOFs) are regarded as potential candidate materials for the cathodes of aqueous zinc-ion batteries. This review presents the applications of MOFs and their derivatives in the cathodes of aqueous zinc-ion batteries.

Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C–H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and scalability. Of them, compound 6b displayed a moderate anti-human coronavirus OC43 (HCoV-OC43) potency and blocked the viral entry stage through a host mechanism of action. Using chemoproteomic techniques, both transmembrane serine protease 2 (TMPRSS2) and scavenger receptor class B type 1 (SR-B1) proteins, which act as host cofactors of viral entry, were identified to be the direct targets of 6b against HCoV-OC43. Furthermore, 6b may deactivate the TMPRSS2 by inducing a change in protein conformation, rather than binding to its catalytic center, thus suppressing the viral membrane fusion. Accordingly, our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against human β-coronavirus, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) infection, currently lacks specific preventive and therapeutic interventions. Here, we demonstrated that Pien Tze Huang (PZH) could dose-dependently inhibit EV-A71 replication at the cellular level, resulting in significant reductions in EV-A71 virus protein 1 (VP1) expression and viral yields in Vero and human rhabdomyosarcoma cells. More importantly, we confirmed that PZH could protect mice from EV-A71 infection for the first time, with Ribavirin serving as a positive control. PZH treatment reduced EV-A71 VP1 protein expression, viral yields in infected muscles, and improved muscle pathology. Additionally, we conducted a preliminary mechanism study using quantitative proteomics. The results suggested that the suppression of the PI3K/AKT/mTOR and NF-κB signaling pathways may contribute to the anti-EV-A71 activity of PZH. These findings provide strong evidence supporting the potential therapeutic application of PZH for EV-A71 infection management.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a（IMBZ18G） is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant（MDR） Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4—512folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly,preclinical studies of 33a alone and 33a-avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

A series of new tricyclic matrinane derivatives were continuously synthesized and evaluated for their inhibitory effects on genes and proteins related to hepatic fibrosis at the cellular level, including collagen type I α1 chain (COL1A1), α smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and matrix metalloprotein 2 (MMP-2). Among them, compound 6k exerted an appealing potency and significantly reduced liver injury and fibrosis in both bile duct ligation (BDL) rats and Mdr2 knockout mice. An activity-based protein profiling (ABPP) assay indicated that 6k might directly bind to Ewing sarcoma breakpoint region 1 (EWSR1) to inhibit its function and affect the expression of downstream liver fibrosis-related genes and thus regulate liver fibrosis. These results provided a potential novel target for the treatment of liver fibrosis and powerful information for the development of tricyclic matrinanes into promising anti-hepatic fibrosis agents.

Pseudomonas aeruginosa is one of the multipledrug-resistant (MDR) Gram-negative pathogens with few drugs available for treatment. Antibiotic adjuvant approach provides an alternative and complementary strategy. In this study, the stereo-structure-activity relationship of monobactams against MDR Gram-negative organisms was extended. Meanwhile, a series of novel peptidemimetic derivatives as antibiotic adjuvants was synthesized and evaluated for their synergistic effects with aztreonam (AZT) against P. aeruginosa, using dipeptide PAβN as the lead. Among the analogues, compound 22j showed a significant synergistic effect against MDR P. aeruginosa in vitro and in vivo, presumably through the mechanism of affecting the permeability of outer membrane. Thus, we identified 22j as a novel peptidemimetic lead compound to potentiate the activity of AZT against MDR P. aeruginosa, which is worthy of further development as antibiotic adjuvant candidates.

The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. ABSTRACT Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen. This study investigated the antibacterial and anti-biofilm activity of celastrol (CEL), a natural product originating from Tripterygium wilfordii Hook F, against enterococci, and its adjuvant capacity of restoring the susceptibility of VRE to vancomycin in vitro and in vivo. CEL inhibited all enterococcus strains tested, with MICs ranging from 0.5 to 4 μg/mL. More than 50% of biofilm was eliminated by CEL at 16 μg/mL after 24 h of exposure. The combination of CEL and vancomycin showed a synergistic effect against all 23 strains tested in checkerboard assays. The combination of sub-MIC levels of CEL and vancomycin showed a synergistic effect in a time-kill assay and exhibited significant protective efficacy in Galleria mellonella larval infection model compared with either drug used alone. The underlying mechanisms of CEL were explored by conducting biomolecular binding interactions and an enzyme inhibition assay of CEL on bacterial cell-division protein FtsZ. CEL presented strong binding and suppression ability to FtsZ, with Kd and IC50 values of 2.454 μM and 1.04 ± 0.17 μg/mL, respectively. CEL exhibits a significant antibacterial and synergic activity against VRE in vitro and in vivo and has the potential to be a new antibacterial agent or adjuvant to vancomycin as a therapeutic option in combating VRE. IMPORTANCE The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. In the present study, CEL exhibited antibacterial activity against enterococci, including VRE strains, and restored the activity of vancomycin against VRE in vitro and in vivo. Hence, CEL has the potential to be a new antibacterial adjuvant to vancomycin and could provide a promising therapeutic option in combating VRE.

The COVID-19 pandemic highlights the urgent need to develop effective small-molecule antivirals. Thirty-three novel biaryl amide derivatives were synthesized and evaluated for anti-coronaviral activity. Some significant SARs were uncovered and the intensive structure modifications led to the most active compounds 8b and 8h. The broad-spectrum anti-coronaviral effects of 8h were validated at RNA and protein levels. 8h inhibits coronavirus replication at multiple stages, from virus entry to virus dsRNA synthesis. The mechanism of action showed that 8h may simultaneously act on 3CLpro and TMPRSS2 to display anti-coronaviral effects. 8h combined with RdRp inhibitor showed synergistic inhibitory activity against coronavirus. This study confirmed that biaryl amide derivatives may be a new class of potential therapeutic agents against coronavirus with multiple target effect, worthy of further investigation.