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Background: The number of multigene‐modified donor pigs for xenotransplantation is increasing with the advent of gene‐editing technologies. However, it remains unclear which gene combination is suitable for specific organ transplantation. Methods: In this study, we utilized CRISPR/Cas9 gene editing technology, piggyBac transposon system, and somatic cell cloning to construct GTKO/hCD55/hTBM/hCD39 four‐gene‐edited cloned (GEC) pigs and performed kidney transplantation from pig to rhesus monkey to evaluate the effectiveness of these GEC pigs. Results: First, 107 cell colonies were obtained through drug selection, of which seven were 4‐GE colonies. Two colonies were selected for somatic cell nuclear transfer (SCNT), resulting in seven fetuses, of which four were GGTA1 biallelic knockout. Out of these four, two fetuses had higher expression of hCD55, hTBM, and hCD39. Therefore, these two fetuses were selected for two consecutive rounds of cloning, resulting in 97 live piglets. After phenotype identification, the GGTA1 gene of these pigs was inactivated, and hCD55, hTBM, and hCD39 were expressed in cells and multiple tissues. Furthermore, the numbers of monkey IgM and IgG binding to the peripheral blood mononuclear cells (PBMCs) of the 4‐GEC pigs were markedly reduced. Moreover, 4‐GEC porcine PBMCs had greater survival rates than those from wild‐type pigs through complement‐mediated cytolysis assays. In pig‐to‐monkey kidney xenotransplantation, the kidney xenograft successfully survived for 11 days. All physiological and biochemical indicators were normal, and no hyperacute rejection or coagulation abnormalities were found after transplantation. Conclusion: These results indicate that the GTKO/hCD55/hTBM/hCD39 four‐gene modification effectively alleviates immune rejection, and the pig kidney can functionally support the recipient monkey's life. [ABSTRACT FROM AUTHOR]

Although there have been significant advances in cancer treatment, the urgent need to inhibit breast cancer metastasis remained unmet. Bruceine A (BA) is a natural compound extracted from Bruceae Fructus and has long been recognized to have antitumor effects with high safety and biocompatibility. However, the mechanisms and/or targets of BA for metastatic breast cancer treatment are still not fully elucidated. In this study, we systematically investigated the effects of BA on inhibition of breast cancer metastasis and its underlying mechanisms. We found that, in addition to its cytotoxic effects, BA significantly inhibited the invasion and migration capabilities of two types of breast cancer cell lines (MDA‐MB‐231 and MCF‐7) while concurrently promoting apoptosis in these cells. Further mechanistic studies revealed that, by targeting the canonical PI3K‐AKT signaling pathway, BA initiated autophagy of both types of breast cancer cell lines in vitro. In vivo results further confirmed the in vitro findings, manifested by shrinkage of size and weight of breast tumor as well as initiation of autophagy (indicated by upregulation of LC3I/II) through targeting PI3K‐AKT pathway on mice model. These data collectively demonstrated the potential of BA in antimetastasis of breast cancer cells, suggesting its future clinical transformation in metastatic breast cancer therapy. [ABSTRACT FROM AUTHOR]

Interspecies somatic cell nuclear transfer (iSCNT) has an immense potential to rescue endangered animals and extinct species like mammoths. In this study, we successfully established an Asian elephant's fibroblast cell lines from ear tissues, performed iSCNT with porcine oocytes and evaluated the in vitro and in vivo development of reconstructed embryos. A total of 7780 elephant–pig iSCNT embryos were successfully reconstructed and showed in vitro development with cleavage rate, 4-cell, 8-cell and blastocyst rate of 73.01, 30.48, 5.64, and 4.73%, respectively. The total number of elephant–pig blastocyte cells and diameter of hatched blastocyte was 38.67 and 252.75 μm, respectively. Next, we designed species-specific markers targeting EDNRB, AGRP and TYR genes to verify the genome of reconstructed embryos with donor nucleus/species. The results indicated that 53.2, 60.8, and 60.8% of reconstructed embryos (n = 235) contained elephant genome at 1-cell, 2-cell and 4-cell stages, respectively. However, the percentages decreased to 32.3 and 32.7% at 8-cell and blastocyst stages, respectively. Furthermore, we also evaluated the in vivo development of elephant–pig iSCNT cloned embryos and transferred 2260 reconstructed embryos into two surrogate gilts that successfully became pregnant and a total of 11 (1 and 10) fetuses were surgically recovered after 17 and 19 days of gestation, respectively. The crown-rump length and width of elephant–pig cloned fetuses were smaller than the control group. Unfortunately, none of these fetuses contained elephant genomes, which suggested that elephant embryos failed to develop in vivo. In conclusion, we successfully obtained elephant–pig reconstructed embryos for the first time and these embryos are able to develop to blastocyst, but the in vivo developmental failure needs further investigated. [ABSTRACT FROM AUTHOR]

[Objective] The research aimed to understand the levels of indoor air particles of PM10 and PM2.5 in public places in Chaoyang District of Beijing City, which wiil provide scientific basis for making health standards and policies and regulations of indoor air particulate matter in public places. [ Method] In order to characterize indoor air quality of public places, shopping mall near the walking street, shopping mall near arterial traffic, barbecue style restaurant and eat hutch unicom Chinese restaurant were selected for this study. LD-3C laser measuring dust detector and Sidepak AM-510 artificial intelligence anti-explosion dust detector were used to test the levels of PM10 and PM2.5 in the air of the shopping malls and restaurants. The number of smoking customers and if smelling the smoke were recorded simultaneously. [Result] The average densities of PM10 and PM2.5 in the shopping mall near the walking street were noticeably lower than that near arterial traffic (P< 0.05). The highest level of PM2.5 at the barbecue style restaurant and eating hutch unicom Chinese restaurants were 1 090 and 666 g/m3. The average levels of PM10 at the barbecue style restaurant and eating hutch unicom restaurants were 286 and 399 g/m³ (P<0.05). [Conclusion] The indoor PM10 and PM2.5 concentrations were high in public places, especially in shopping mall near arterial traffic and restaurant. It should be enhanced to supervise indoor air in public places and establish the risk rating of indoor air quality to protect public health. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive disengagement syndrome (CDS) is a psychological disorder characterized by daydreaming, mental fogginess, and slow thinking, while learning burnout (LB) is characterized by a passive and inattentive attitude toward learning. These two disorders are closely related but can be challenging to differentiate from one another. The present study aimed to identify shared and distinct cognitive control deficits between CDS and LB., Methods: We recruited 136 adolescents (aged 14 to 17 years) from an initial screening of CDS and LB (N = 476) and divided them into four groups: CDS, LB, CDS + LB, and typically developing control. After a second screening, 129 adolescents completed two tasks to assess their attentional networks and cognitive control capacity (CCC)., Results: Adolescents with high CDS symptoms (both CDS group and CDS+LB group) exhibited impaired disengaging effect of attention and lower CCC, indicating deficits in orienting attention and the upper limit of information processing for cognitive control specifically. Furthermore, support vector machine modeling identified CCC as the most significant parameter differentiating the CDS and LB groups., Discussion: Our findings suggest that while adolescents with high CDS and high LB symptoms have similar outward manifestations in the adolescent's school life, deficits in attention and cognitive control, particularly in the CCC, may distinguish between the two groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Weng, Wu, Wei, Chen, Liu, Cai and Chen.)

Traditional Chinese Medicine, known for its minimal side effects and significant clinical efficacy, has attracted considerable interest for its potential in cancer therapy. In particular, Inula helenium L. has demonstrated effectiveness in inhibiting a variety of cancers. This study focuses on alantolactone (ALT), a prominent compound from Inula helenium L., recognized for its anti-cancer capabilities across multiple cancer types. The primary objective of this study is to examine the influence of ALT on the proliferation, apoptosis, cell cycle, and tumor growth of cervical cancer (CC) cells, along with its associated signaling pathways. To determine protein expression alterations, Western blot analysis was conducted. Furthermore, an in vivo model was created by subcutaneously injecting HeLa cells into nude mice to assess the impact of ALT on cervical cancer. Our research thoroughly investigates the anti-tumor potential of ALT in the context of CC. ALT was found to inhibit cell proliferation and induce apoptosis in SiHa and HeLa cell lines, particularly targeting ataxia-telangiectasia mutated (ATM) proteins associated with DNA damage. The suppression of DNA damage and apoptosis induction when ATM was inhibited underscores the crucial role of the ATM/cell cycle checkpoint kinase 2 (CHK2) axis in ALT's anti-tumor effects. In vivo studies with a xenograft mouse model further validated ALT's effectiveness in reducing CC tumor growth and promoting apoptosis. This study offers new insights into how ALT combats CC, highlighting its promise as an effective anti-cervical cancer agent and providing hope for improved treatment outcomes for CC patients.

Objective: To develop a comprehensive method for simultaneous analysis of sulfonamides and their metabolites in drinking water by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS)., Methods: Different solid-phase extraction columns were compared with respect to the recovery of target drugs from drinking water. The drinking water samples were adjusted to 3 by HCl and purified by a mix mode cation-ion exchange solid-phase extraction (SPE), following determination using LG-MS/MS. A total of 21 sulfonamides were separated by a C15 column (2.1 mm x 100 mm, 1.7 µm) and analyzed under positive ion mode with multi-reaction monitoring. The matrix-matched external standard calibration was used for quantification., Results: The method quantification limits for 21 analytes were 0.03-0.63 ng/L with overall recoveries of 50.1%-114.9%, and the relative standard deviations less than 20%. The method was finally used to analyze sulfonamides in drinking water in Beijing, and 5 target compounds (sulfadiazine, sulfathiazole, sulfapyridine, trimethoprim and sulfamethazine) were detected at a concentration range of 0.08-32.54 ng/L., Conclusion: This method could be applied in simultaneous analysis of sulfonamides and their metabolites in drinking water samples.