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"Zhang, Ni"
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Metal nanoparticles as a promising technology in targeted cancer treatment
Traditional anticancer treatments have several limitations, but cancer is still one of the deadliest diseases. As a result, new anticancer drugs are required for the treatment of cancer. The use of metal nanoparticles (NPs) as alternative chemotherapeutic drugs is on the rise in cancer research. Metal NPs have the potential for use in a wide range of applications. Natural or surface-induced anticancer effects can be found in metals. The focus of this review is on the therapeutic potential of metal-based NPs. The potential of various types of metal NPs for tumor targeting will be discussed for cancer treatment. The in vivo application of metal NPs for solid tumors will be reviewed. Risk factors involved in the clinical application of metal NPs will also be summarized.
Journal Article
An omics-based framework for assessing the health risk of antimicrobial resistance genes
Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.
Antibiotic resistance genes are common but not all are of high risk to human health. Here, the authors develop an omics-based framework for ranking genes by risk that incorporates level of enrichment in human associated environments, gene mobility, and host pathogenicity.
Journal Article
The SARS‐CoV‐2 main protease (Mpro): Structure, function, and emerging therapies for COVID‐19
The main proteases (Mpro), also termed 3‐chymotrypsin‐like proteases (3CLpro), are a class of highly conserved cysteine hydrolases in β‐coronaviruses. Increasing evidence has demonstrated that 3CLpros play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus‐caused infectious diseases, including COVID‐19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) main protease Mpro (also known as 3CLpro), as well as recent advances in discovering and developing SARS‐CoV‐2 3CLpro inhibitors. To better understand the characteristics of SARS‐CoV‐2 3CLpro inhibitors, the inhibition activities, inhibitory mechanisms, and key structural features of various 3CLpro inhibitors (including marketed drugs, peptidomimetic, and non‐peptidomimetic synthetic compounds, as well as natural compounds and their derivatives) are summarized comprehensively. Meanwhile, the challenges in this field are highlighted, while future directions for designing and developing efficacious 3CLpro inhibitors as novel anti‐coronavirus therapies are also proposed. Collectively, all information and knowledge presented here are very helpful for understanding the structural features and inhibitory mechanisms of SARS‐CoV‐2 3CLpro inhibitors, which offers new insights or inspiration to medicinal chemists for designing and developing more efficacious 3CLpro inhibitors as novel anti‐coronavirus agents.
A comprehensive summary of recent advances in SARS‐CoV‐2 3CLpro inhibitors (including marketed drugs, peptidomimetic, and non‐peptidomimetic synthetic compounds, as well as natural compounds and their derivatives), including the inhibitory activities, inhibitory mechanisms, and key structural features, provides new insights for designing and developing more efficacious 3CLpro inhibitors as broad‐spectrum anti‐coronavirus agents.
Journal Article
Effect of platelet-derived bone enhancers used as adjuncts to deproteinized bovine bone matrix in maxillary sinus floor elevation: a systematic review and meta-analysis
Background
The success of dental implant restoration is significantly influenced by the volume and density of alveolar bone in the surgical area. Maxillary sinus floor elevation (MSFE) surgery is a reliable method to increase residual bone height (RBH) before implantation. This study aimed to evaluate the impact of platelet-derived bone enhancers, namely platelet-rich plasma (PRP), platelet-rich fibrin (PRF) and platelet-rich growth factor (PRGF), when used as adjuncts to deproteinized bovine bone matrix (DBBM) in MSFE on bone neoformation, implant stability, and implant survival.
Methods
A systematic review and meta-analysis were conducted following the PRISMA guideline. Electronic databases, including PubMed, Embase, CENTRAL, Web of Science, Scopus, and Google Scholar, were searched up to February 2025. Randomized controlled trials (RCTs), and case-control studies assessing the effect of PRP/PRF/PRGF as an adjuvant to DBBM in MSFE were included. Mean difference (MD) or risk ratio (RR) was selected as the effect size to perform the meta analysis.
Results
Sixteen studies met the inclusion criteria, involving 372 patients and 455 surgical procedures. The meta-analysis revealed a significant enhancement of bone neoformation (MD = 5.92, 95%CI: 2.17 ~ 9.67,
p
= 0.002) and reduced residual graft volume (MD = -1.93, 95%CI: -2.25 ~ -1.61,
p
< 0.001) when PRP/PRF/PRGF was added to DBBM. However, there was no significant difference in graft resorption rate, percentage of fibrous tissue, immediate implant stability, and implant survival rate, between the two groups. Subgroup analyses showed that PRF subgroup, and subgroups with 4 m or 6 m healing intervals and with DBBM particles of 0.25-1 mm are related to significantly enhanced bone neoformation; all subgroups except for the PRP subgroup are related to significantly decreased residual graft.
Conclusions
The addition of PRF or PRGF to DBBM in the first stage of MSFE significantly enhances new bone formation and reduces residual graft volume, providing a more reliable alveolar bone matrix for subsequent implant placement. No evidence support the application of PRP as an effective enhancer to DBBM in MSFE procedure. In addition, PRP/PRF/PRGF does not significantly affect the immediate stability or survival of implants in the second stage.
Journal Article
X-Mapper: fast and accurate sequence alignment via gapped x-mers
Sequence alignment is foundational to many bioinformatic analyses. Many aligners start by splitting sequences into contiguous, fixed-length seeds, called k-mers. Alignment is faster with longer, unique seeds, but more accurate with shorter seeds avoiding mutations. Here, we introduce X-Mapper, aiming to offer high speed and accuracy via dynamic-length seeds containing gaps, called gapped x-mers. We observe 11–24-fold fewer suboptimal alignments analyzing a human reference and 3–579-fold lower inconsistency across bacterial references than other aligners, improving on 53% and 30% of reads aligned to non-target strains and species, respectively. Other seed-based analysis algorithms might benefit from gapped x-mers too.
Journal Article
Effects of Adding Transversus Abdominis Plane Block on Intravenous Nalbuphine and Dexmedetomidine for Severely Pre‐Eclamptic Parturients After Cesarean Delivery
ABSTRACT
The use of opioids is frequently associated with the occurrence of adverse effects during cesarean delivery, especially for primiparous women with severe preeclampsia, creating a critical need for investigation of alternative analgesic strategies. The study aims to determine the effects of adding transversus abdominis plane block (TAPB) on patient‐controlled intravenous analgesia (PCIA) of nalbuphine (Nal) and dexmedetomidine (Dex) on severely pre‐eclamptic parturients after cesarean delivery. This is a randomized controlled trial. Severely pre‐eclamptic parturients who were scheduled for elective cesarean delivery with spinal anesthesia were randomly assigned into the TAPB group (TAPB combined with PCIA with Nal and Dex; n = 49) and the PCIA group (same block procedures with normal saline followed by PCIA with Nal and Dex; n = 51). Results showed that adding TAPB to PCIA with Nal and Dex significantly lowered visual analog scale (VAS) scores at rest at 2 and 6 h, at mobilization at 2, 6, and 12 h after surgery, reduced press time of PCIA, shortened time for first feeding and out‐of‐bed movement, enhanced maternal satisfaction with pain control, and lowered plasma levels of cortisone and norepinephrine. The findings of the study suggest that adding TAPB to PCIA with Nal and Dex could enhance acute recovery with fewer stress responses for severely pre‐eclamptic parturients after cesarean delivery.
Journal Article
Trajectories of depressive symptoms in middle-aged and older Chinese adults: identifying subgroups, core symptoms and predictors
Background
Depressive symptoms among middle-aged and older adults are a significant public health concern, with varying symptom trajectories over time. Understanding these trajectories and their predictors can inform targeted interventions.
Objectives
To identify subgroups of depressive symptom trajectories, determine predictors of these subgroups, and explore the core symptoms and their predictive relationships.
Methods
This study analyzed 7,166 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study across four waves (2011, 2013, 2015, 2018). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale. Group-based trajectory modeling (GBTM) identified depressive symptom trajectories. Multivariate logistic regression explored influencing factors, while Cross-lagged panel network models (CLPN) were used to identify core symptoms.
Results
Three distinct trajectory groups were identified: “
stable low
” (66.4%), “
decline followed by an increase
” (27.8%), and “
continuously rising
” (5.8%). Females, those with lower education, poor self-reported health, unmarried status and rural residents were associated with worsening symptoms. CLPN analysis revealed “
depressive mood
” as the core symptom, with “
feeling lonely
” and “
could not get going
” predicting “
depressive mood
.”
Conclusion
This study identifies distinct trajectories of depressive symptoms in older adults and pinpoints “depressive mood” as a core symptom, which is dynamically predicted by loneliness and a lack of behavioral activation. Therefore, an effective public health strategy should involve not only identifying at-risk individuals based on their trajectory profiles but also targeting these specific precursor symptoms to prevent escalation.
Journal Article
In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy
Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (
Gi-F-CAA
). Under the acidic microenvironment of the tumor, the
Gi-F-CAA
self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (
AEB
) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with
AEB
effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.
The poor tumour delivery efficacy of GPX4 inhibitor has dampened its in vivo therapeutic value. Here the authors report a peptide ferriporphyrin conjugate to improve tumour penetration, endocytosis and GPX4 inhibition, synergistically enhancing its anticancer activity by ferroptosis.
Journal Article
Hydrogen sulfide is a crucial element of the antioxidant defense system in Glycine max–Sinorhizobium fredii symbiotic root nodules
Aim
H
2
S is emerging as a signaling molecule involved in the regulation of many physiological processes in plants. Here, we investigated the potential antioxidant role of H
2
S in soybean (
Glycine max
)-rhizobia (
Sinorhizobium fredii
) symbiotic root nodules.
Method
An endogenous H
2
S production deficit rhizobia mutant ∆
CSE
was constructed to study the effect of decreased content of H
2
S in soybean nodules. Fluorescent probes and confocal microscope were used to observe the production and accumulation of H
2
S and reactive oxygen species. Transmission electronic microscopy was conducted to study the structural changes in ∆
CSE
soybean nodules. Finally, qRT-PCR, enzymatic activity, and oxidative damage parameters were measured.
Result
The results demonstrated that abundant H
2
S was generated in the nitrogen-fixing zone of soybean nodules. The deletion of the cystathionine γ-lyase (
CSE
) gene in
S. fredii
(
∆CSE
) caused a sharp decrease in H
2
S production in both free-living rhizobia and soybean nodules. We found that decrease in the H
2
S level in nodule cells inhibited nitrogenase activity. In addition, to elevated H
2
O
2
and malondialdehyde accumulation, increased protein carbonyl content and decreased O
2
−
scavenging ability was observed in ∆CSE root nodules. Transmission electron microscopy revealed that an H
2
S deficit caused the deformation of bacteroids and damage of peribacteroid membranes in nodule cells. Moreover, the expression of some rhizobial and soybean genes related to antioxidant defense was up-regulated in
∆CSE
nodules.
Conclusion
H
2
S is crucial for the nitrogen-fixation ability of soybean nodules by acting as an antioxidant element that protects nodule cells and bacteroids from oxidative damage.
Journal Article