Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

OBJECTIVES: The diagnostic value of ultrasonographic quantitative indicators of umbilical cord coiling, such as the umbilical coiling index (UCI) and pitch value, in identifying hypercoiling and predicting adverse pregnancy outcomes remains controversial. This study aims to evaluate the predictive value of UCI, pitch value, and the cerebroplacental ratio in pregnancies complicated by umbilical cord hypercoiling. METHODS: Pregnant women with densely coiled umbilical cords identified by routine obstetric ultrasound at Changsha Maternal and Child Health Hospital between November 2022 and November 2024 were enrolled. Complete clinical data, including UCI, pitch value, and cerebroplacental ratio (CPR), were collected. Pregnancy outcome scores were calculated, and newborns were categorized into the normal outcome group (n=177) and adverse outcome group (n=85), with the latter further subdivided into mild (n=51), moderate (n=19), and severe (n=15) subgroups. Differences in baseline data, UCI, pitch value, and incidence of CRP<1 were compared between groups and among subgroups. Correlations between UCI, pitch value, and adverse pregnancy outcomes were analyzed. Receiver operating characteristic (ROC) curve were used to assess the predictive performance of UCI, pitch value, CPR<1, and their combinations. RESULTS: Compared with the normal outcome group, the adverse outcome group had higher age, parity, parity, incidence of CPR<1, and UCI, while gestational age at delivery and pitch values were lower (all P<0.05). The incidence of obesity, gestational diabetes mellitus, and hypertensive disorders of pregnancy did not differ significantly between the 2 groups (all P>0.05). The normal outcome group showed lower UCI and higher pitch values than all 3 adverse outcome subgroups (all P<0.05), while differences among the 3 adverse subgroups were not significant (all P>0.05). UCI was positively correlated with adverse pregnancy outcomes (r_s=0.350, P<0.05), whereas pitch value was negatively correlated (r_s=-0.286, P<0.05). ROC curve analysis showed that the area under the curve (AUC) values for predicting adverse outcomes were 0.837 for UCI, 0.886 for pitch value, and 0.610 for CPR<1, with sensitivities of 77.6%, 82.4%, and 27.1% and specificities of 78.5%, 83.6%, and 94.9%, respectively. The combined UCI+CPR<1 and pitch value+CPR<1 models yielded AUCs of 0.841 and 0.886, with sensitivities of 78.8% and 81.2% and specificities of 78.5% and 84.2%, respectively. No significant differences were found between the AUCs of UCI and pitch value (P>0.05), but both outperformed CPR<1 alone (both P<0.001). The combined models showed no significant improvement over UCI or pitch value alone (both P>0.05), though both were superior to CPR<1 alone (both P<0.001). CONCLUSIONS Most umbilical cord hypercoiling cases had favorable outcomes, with UCI, pitch value, CPR<1 and their combinations demonstrating significant predictive value for adverse pregnancy outcomes.
Humans ; Female ; Pregnancy ; Pregnancy Outcome ; Adult ; Ultrasonography, Prenatal/methods* ; Umbilical Cord/diagnostic imaging* ; Hemodynamics ; Predictive Value of Tests ; Infant, Newborn ; ROC Curve

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Echocardiography is an important imaging technique in mithal valve transcatheter edge-to-edge repair (TEER). During the operation, mitral leaflets capture and clamping have the highest requirements for ultrasound image quality and should be performed under the guidance of high-quality commissural view. However, standard commissural view cannot be obtained in some patients due to cardiac enlargement, transposition or limited esophageal acoustic window. In this condition, the optimal view can be obtained by Multivue technology. This paper reports a male patient aged 67 years with successful mitral valve TEER under the real-time guidance of Multivue technology, and summarizes the key points of this technology.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.