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CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Galloway-Mowat syndrome-4 (GAMOS4) is a very rare renal-neurological disease caused by gene mutations. GAMOS4 is characterized by early-onset nephrotic syndrome, microcephaly, and brain anomalies. To date, only nine GAMOS4 cases with detailed clinical data (caused by eight deleterious variants in ) have been reported. This study aimed to examine the clinical and genetic characteristics of three unrelated GAMOS4 patients with gene compound heterozygous mutations. Whole-exome sequencing (WES) was used to identify four novel variants in three unrelated Chinese children. Clinical characteristics such as biochemical parameters and image findings of patients were also evaluated. Furthermore, four studies of GAMOS4 patients with variants were reviewed. In addition, clinical and genetic features were described after a retrospective analysis of clinical symptoms, laboratory data, and genetic test results. The three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. Furthermore, patient 1 had slight proteinuria, while patient 2 had epilepsy. However, none of the individuals had nephrotic syndrome, and all were alive for more than 3 years of age. This is the first study to assess four variants in the gene (NM_033550.4: c.15_16dup/p.A6Efs*29, c.745A > G/p.R249G, c.185G > A/p.R62H, and c.335A > G/p.Y112C). The clinical characteristics of the three children with mutations are significantly different from the known GAMOS4 traits, including early nephrotic syndrome and mortality mainly occurring in the first year of life. This study provides insights into the pathogenic gene mutation spectrum and clinical phenotypes of GAMOS4.

An experiment was performed to study the influence of polymer binders on the physical properties,and stability against a simulated rainfall,of a slope consisting of engineering spoil.Results showed that low polymer binder concentrations（≤500g/m3） could enhance the air permeability and moisture-retaining capacity of the engineering spoil;however,adding more polymer binder made the hardness of the engineering spoil increase and then decline.With the increase of polymer binder concentrations,the surface（0-5cm） permeability of the engineering spoil decreased but the permeability of the lower layers（5-10cm） increased.Polymer binders might reduce runoff and sediment,but the effect becomes weaker with the increase of rainfall.The results of this study have significance for engineering practices.Further experiments are needed to study the effects of binders under other conditions,such as natural rainfall,different slopes,different rock types,different degrees and spoil weathering and different added material,and the chemical interaction between soil and polymer binders.

Four new sesquiterpene hydroquinones, xishaeleganins A–D (6–9), along with eleven known related ones (12 and 14–23) were isolated from the Xisha marine sponge Dactylospongia elegans (family Thorectida). Their structures were determined by extensive spectroscopic analysis, ECD calculations, and by comparison with the spectral data reported in the literature. Compounds 7, 15, 20, and 21 showed significant antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentration values of 1.5, 2.9, 5.6, and 5.6 µg/mL, which are comparable with those obtained for the positive control vancomycin (MIC: 1.0 µg/mL).

Inflammation plays an important role during sepsis, and excessive inflammation can result in organ damage, chronic inflammation, fibrosis, and scarring. The study aimed to investigate the specific mechanism of emodin by constructing in vivo and in vitro septic lung injury models via inhibition and reduction of NF‐kB and high mobility group box 1 (HMGB1) pathways. A cecal ligation and puncture (CLP) model was built for adult male Sprague–Dawley rats. Concentrations of TNF‐α, IL‐1β, and IL‐6 in bronchoalveolar lavage fluid were determined using commercially available ELISA kits. Hematoxylin and eosin staining was used for the right lung inferior lobes. Myeloperoxidase (MPO) activity of the lung tissue was detected by using the MPO kit. Murine alveolar epithelial cell line (MLE‐12) cells were used for flow cytometry and Western blot to analyze the apoptosis rate and protein expression. Emodin significantly decreased CLP‐induced cell apoptosis, upregulated expression of sirtuin 1 (SIRT1), and inhibited p‐p65/p65 and HMGB1. In lipopolysaccharide (LPS) treated cell model, emodin treatment markedly decreased LPS‐induced release of IL‐1, IL‐6, and tumor necrosis factor (TNF)‐α, inhibited LPS‐induced cell apoptosis and suppressed protein levels of P‐P65/P65 and HMGB1. However, science of SIRT1 reversed the above effects by treatment of emodin. In summarize, this study found that emodin can alleviate sepsis‐induced lung injury in vivo and in vitro through regulation of SIRT1.

Fifteen new diterpenoids, namely xishaklyanes A-O (1–15), along with three known related ones (16–18), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher’s method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 μg/mL against Lactococcus garvieae.

Marine organisms often produce a variety of metabolites with unique structures and diverse biological activities that enable them to survive and struggle in the extremely challenging environment. During the last two decades, our group devoted great effort to the discovery of pharmaceutically interesting lead compounds from South China Sea marine plants and invertebrates. We discovered numerous marine secondary metabolites spanning a wide range of structural classes, various biosynthetic origins and various aspects of biological activities. In a series of reviews, we have summarized the bioactive natural products isolated from Chinese marine flora and fauna found during 2000–2012. The present review provides an updated summary covering our latest research progress and development in the last decade (2012–2022) highlighting the discovery of over 400 novel marine secondary metabolites with promising bioactivities from South China Sea marine organisms.

A new prenyleudesmane type diterpene, sinupol (8), and a new capnosane type diterpenoid, sinulacetate (9), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4–7 and 10). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds (8 and 9) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity.

Malus sieversii , a Tertiary relict and primary progenitor of the cultivated apple, is experiencing severe habitat degradation in China’s Tianshan Mountains. To understand how soil ecosystem functions respond to tree vigor decline, we monitored surface soils beneath the canopy of wild apple trees monthly from April to October. Trees were classified into three vigor classes based on the percentage of dead branches: Vigor Class I (<20%), Vigor Class II (40–60%), and Vigor Class III (>80%). Soil multifunctionality (SMF) and temporal variability of nutrients (TVN) were derived from seven key nutrient indicators. Soils under Vigor Class II trees exhibited the lowest SMF and highest TVN, indicating maximal functional instability during intermediate degradation. While SMF peaked and TVN reached its seasonal minimum in October, Vigor Class II showed a consistent decline in TVN over time, unlike the irregular fluctuations in Vigor Classes I and III. A significant negative SMF–TVN correlation in Vigor Classes II and III suggests a trade-off between functionality and stability. Partial least squares path modeling revealed that soil organic carbon, total nitrogen, and total phosphorus were the dominant direct driver of both SMF and TVN, with climate exerting no significant direct effects once tree vigor and soil conditions were accounted for. These results suggest that Vigor Class II represents a critical early-warning stage: soil functional capacity begins to deteriorate before visible signs of severe tree decline or mortality. Targeted ecological restoration of Vigor Class II trees is essential to prevent irreversible ecosystem degradation. Therefore, while continued protection of healthy Vigor Class I trees remains essential, conservation efforts should place greater emphasis on restoring Vigor Class II trees to disrupt degradation feedbacks before irreversible ecosystem decline occurs.

The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53, conferring tumor development and survival. Antagonists targeting the p53-binding domains of MDM2 and MDMX kill tumor cells both in vitro and in vivo by reactivating the p53 pathway, promising a class of antitumor agents for cancer therapy. Aided by native chemical ligation and mirror image phage display, we recently identified a D-peptide inhibitor of the p53-MDM2 interaction termed D PMI-α (TNWYANLEKLLR) that competes with p53 for MDM2 binding at an affinity of 219 nM. Increased selection stringency resulted in a distinct D-peptide inhibitor termed D PMI-γ (DWWPLAFEALLR) that binds MDM2 at an affinity of 53 nM. Structural studies coupled with mutational analysis verified the mode of action of these D-peptides as MDM2-dependent p53 activators. Despite being resistant to proteolysis, both d PMI-α and d PMI-γ failed to actively traverse the cell membrane and, when conjugated to a cationic cell-penetrating peptide, were indiscriminately cytotoxic independently of p53 status. When encapsulated in liposomes decorated with an integrin-targeting cyclic-RGD peptide, however, d PMI-α exerted potent p53-dependent growth inhibitory activity against human glioblastoma in cell cultures and nude mouse xenograft models. Our findings validate D-peptide antagonists of MDM2 as a class of p53 activators for targeted molecular therapy of malignant neoplasms harboring WT p53 and elevated levels of MDM2.