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Abstract Background Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components. Case presentation A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences. Conclusions This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.

Abstract Sepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients. Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively. Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes. Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes. In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients.

Abstract Background Mutations in the SLC5A7 gene cause congenital myasthenia, a rare genetic disorder. Mutation points in the SLC5A7 gene differ among individuals and encompass various genetic variations; however, exon deletion variants have yet to be reported in related cases. This study aims to explore the clinical phenotype and genetic traits of a patient with congenital myasthenic syndrome due to SLC5A7 gene variation and those of their family members. Case presentation We describe a case of a Chinese male with congenital myasthenic syndrome presenting fluctuating limb weakness. Genetic testing revealed a heterozygous deletion mutation spanning exons 1–9 in the SLC5A7 gene. QPCR confirmed a deletion in exon 9 of the SLC5A7 gene in the patient’s mother and brother. Clinical symptoms of myasthenia improved following treatment with pyridostigmine. Conclusion Exons 1, 5, and 9 of the SLC5A7 gene encode the choline transporter’s transmembrane region. Mutations in these exons can impact the stability and plasma membrane levels of the choline transporter. Thus, a heterozygous deletion in exons 1–9 of the SLC5A7 gene could be the pathogenic cause for this patient. In patients exhibiting fluctuating weakness, positive RNS, and seronegativity for myasthenia gravis antibodies, a detailed family history should be considered, and enhanced genetic testing is recommended to determine the cause.

IntroductionTo investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms.Methods56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR.Results654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI.DiscussionThis study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock.

Acinic cell carcinoma (AciCC) of the breast is a rare malignant epithelial neoplasm, with approximately 60 cases reported in the literature. It predominantly affects women and exhibits significant histological heterogeneity. The diagnosis of breast AciCC is primarily based on the presence of eosinophilic and/or basophilic granular cytoplasm and markers of serous acinar differentiation. Despite being considered a low-grade variant of conventional triple-negative breast cancer (TNBC), over 25% of patients with breast AciCC have adverse clinical outcomes. Additionally, in early research, microglandular adenosis (MGA) and atypical MGA were considered potential precursors for various breast cancers, including intraductal carcinoma, invasive ductal carcinoma, adenoid cystic carcinoma, metaplastic carcinoma, and AciCC. Similarly, some studies have proposed that breast AciCC should be considered a type of carcinoma developing in MGA with acinic cell differentiation rather than a distinct entity. Therefore, the pathogenesis of breast AciCC has not yet been clarified. Moreover, to the best of our knowledge, the literature has not summarized the latest prognosis and treatment of breast AciCC. In this review, we synthesized the current literature and the latest developments, aiming at exploring the clinicopathology, histological origin, molecular features, prognosis, and treatment of breast AciCC from a novel perspective.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Abstract Loess owns the characteristics of collapsibility, disintegration and solubility, which pose a challenge to engineering construction. To examine the shear strength of basalt fiber-reinforced (BFR) loess, consolidated undrained (CU) triaxial tests were conducted to explore the impacts of water content (w), fiber length (FL), fiber content (FC) and cell pressure (σ 3) on the shear strength. According to the results, the shear strength model was established taken into account the impacts of FL, FC, and fiber diameter (d). The results showed that the peak strength of BFR soils enhanced as FL, FC, and σ 3 increasing, whereas it decreased with increasing of w. Compared to unreinforced soil, the peak strength of BFR loess improved 64.60% when FC was 0.2% and FL was 16 mm. The optimum reinforcement condition for experimental loess was that of FL was 16 mm and FC was 0.8%. The reinforcing mechanism of fibers was divided into a single tensile effect and spatial mesh effect. The experimental and calculated results agreed well, which suggested the model is suitable for predicting the shear strength of BFR loess. The research results can offer a guideline for the application of BFR loess in the subgrade and slope engineering.

Chang’e-6 (CE-6) is the first sample-return mission from the lunar farside and will be launched in May of 2024. The landing area is in the south of the Apollo basin inside the South Pole Aitken basin. Statistics and analyses of impact craters in the landing area are essential to support safe landing and geologic studies. In particular, the crater size–frequency distribution information of the landing area is critical to understanding the provenance of the CE-6 lunar samples to be returned and can be used to verify and refine the lunar chronology model by combining with the radioisotope ages of the relevant samples. In this research, a digital orthophoto map (DOM) mosaic with resolution of 3 m/pixel of the CE-6 landing area was generated from the 743 Narrow Angle Camera of the Lunar Reconnaissance Orbiter Camera. Based on the DOM, craters were extracted by an automated method and checked manually. A total of 770,731 craters were extracted in the whole area of 246 km × 135 km, 511,484 craters of which were within the mare area. Systematic analyses of the crater distribution, completeness, spatial density, and depth-to-diameter ratio were conducted. Geologic model age estimation was carried out in the mare area that was divided into three geologic units according to the TiO2 abundance. The result showed that the east part of the mare had the oldest model age of μ3.27−0.045+0.036 Ga, and the middle part of the mare had the youngest model age of μ2.49−0.073+0.072 Ga. The crater catalogue and the surface model age analysis results were used to support topographic and geologic analyses of the pre-selected landing area of the CE-6 mission before the launch and will contribute to further scientific researches after the lunar samples are returned to Earth.

The content of protein and oil in soybeans is an important trait for evaluating quality and is regulated by genetic and environmental factors, lacking comprehensive identification under a variety of ecological conditions. Therefore, evaluating the stability of soybean quality traits under different environmental conditions has great significance for various applications. In this study, we compare 150 soybean varieties from Northeast China (Group A and Group B) and the Huang-Huai-Hai region (Group C). As the release time progressed, the oil content in the soybean varieties showed an upward trend in both Northeast China and the Huang-Huai-Hai region, while the protein content showed a downward trend. Additionally, the oil contents were negatively correlated with the protein contents and the sum of protein and oil contents, while the protein contents were positively correlated with the sum of protein and oil contents, with the correlation becoming stronger as the latitude decreased. Moreover, there were obvious variations in quality stability among different varieties. Hefeng 45, Jilinxiaolidou 4, and Zhonghuang 19 had relatively high protein contents and exhibited good stability across different environments, while Kenjiandou 25, Changnong 17, Dongnong 46, Kennong 17, Liaodou 14, and GR8836 had relatively high oil contents with good stability performance in varying environments.