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Since the world’s first in vitro fertilization baby was born in 1978, there have been more than 8 million children conceived through assisted reproductive technologies (ART) worldwide, and a significant proportion of them have reached puberty or young adulthood. Many studies have found that ART increases the risk of adverse perinatal outcomes, including preterm birth, low birth weight, small size for gestational age, perinatal mortality, and congenital anomalies. However, data regarding the long-term outcomes of ART offspring are limited. According to the developmental origins of health and disease theory, adverse environments during early life stages may induce adaptive changes and subsequently result in an increased risk of diseases in later life. Increasing evidence also suggests that ART offspring are predisposed to an increased risk of non-communicable diseases, such as malignancies, asthma, obesity, metabolic syndrome, diabetes, cardiovascular diseases, and neurodevelopmental and psychiatric disorders. In this review, we summarize the risks for long-term health in ART offspring, discuss the underlying mechanisms, including underlying parental infertility, epigenetic alterations, non-physiological hormone levels, and placental dysfunction, and propose potential strategies to optimize the management of ART and health care of parents and children to eliminate the associated risks. Further ongoing follow-up and research are warranted to determine the effects of ART on the long-term health of ART offspring in later life.

The correlation between sound and psychophysiological health is complex. This study explores effects of various sound pressure levels (SPLs) on psychophysiological responses, utilizing dynamic features of neural activity. Two sound types (traffic noise and spring water sound) and five SPLs (40, 45, 50, 55, and 60 dBA) were tested, with no sound serving as the control condition. The electrocardiography (ECG) and electroencephalogram (EEG) of 38 young college students were collected. The results indicate that spring water sound (SWS) significantly enhances sound perception, with sound comfort votes (SCV) and sound pleasure votes (SPV) increasing by 0.10–0.95 and 0.05–1.10, respectively. SWS facilitated parasympathetic nervous system comfort. Compared to the no sound, as SPLs increased, LF/HF decreased (by 0.07–0.41), and SDNN increased (by 8.85–18.56 ms), whereas traffic noise (TN) exhibited the opposite trend. For brain oscillatory activity, α, θ, and β power—associated with stress recovery—initially increased and then decreased with rising SPLs under spring water sound exposure. At 50 dBA SWS, effective delay duration, linked to comfort, peaked at 284.78 ms. Conversely, the α power and τe for TN diminished with increasing SPLs. The left frontal-parietal and right occipital lobes exhibited the highest sensitivity ( p  < 0.01). SWS exposure reduced the avalanche critical index (ACI) by 4.78–17.29% compared to no sound, enhancing brain comfort, while TN increased the ACI by 2.28–29.37%. The 50 dBA SWS showed the greatest improvement in brain comfort, being 1.74 times higher than that of TN. Furthermore, compared to no sound, brain power loss was lower for 52.63–63.16% of participants exposed to 50–60 dBA SWS. This study provides a methodology for soundscape evaluation and enhances understanding of how brain activity changes under sound exposure can improve the indoor acoustic environment.

In sepsis-3, in contrast with sepsis-1, the definition “systemic inflammatory response” has been replaced with “dysregulated host response”, and “systemic inflammatory response syndrome” (SIRS) has been replaced with “sequential organ failure assessment” (SOFA). Although the definition of sepsis has changed, the debate regarding its nature is ongoing. What are the fundamental processes controlling sepsis-induced inflammation, immunosuppression, or organ failure? In this review, we discuss the heterogeneity of sepsis-3 and address the central role of inflammation in the pathogenesis of sepsis. An unbalanced pro- and anti-inflammatory response, inflammatory resolution disorder, and persistent inflammation play important roles in the acute and/or chronic phases of sepsis. Moreover, powerful links exist between inflammation and other host responses (such as the neuroendocrine response, coagulation, and immunosuppression). We suggest that a comprehensive evaluation of the role of the inflammatory response will improve our understanding of the heterogeneity of sepsis.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth.Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy.Conclusions: UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Escalating antibiotic resistance of Klebsiella pneumoniae underscores the urgent need for therapeutic strategies. Whereas gut bacterial dysbiosis exacerbates pulmonary infections, the role of gut fungi in modulating lung immunity remains understudied. Here, we demonstrate that antibiotic-induced gut fungal expansion aggravates pneumonia by enhancing alveolar macrophage-driven inflammation via Dectin-1 signaling. Clinical analyses demonstrated that pneumonia patients receiving ineffective prehospital antibiotic therapy showed gut bacterial depletion accompanied by fungal overgrowth (primarily Candida spp.), with a positive correlation observed between fungal abundance and hospitalization duration. In murine models, antibiotic-induced gut microbiota disruption promoted fungal proliferation, subsequently upregulating Dectin-1 expression in alveolar macrophages. This activation triggered excessive IL-1β secretion and neutrophil recruitment, exacerbating lung injury and mortality. Our results demonstrated that both antifungal intervention and Dectin-1 knockout reversed these pathological effects, resulting in improved survival rates, reduced bacterial dissemination, and attenuated inflammatory cytokine levels. Mechanistically, gut fungi remotely potentiated pulmonary inflammation through the alveolar macrophage “Dectin-1/IL-1β/neutrophil axis”, independent of pathogen clearance. Although recent studies have begun to uncover “mycobiome-lung” disease associations, our findings specifically demonstrate that fungal dysbiosis mediates the “gut-lung axis” during multidrug-resistant K. pneumoniae infections. This study provides mechanistic insights into microbial crosstalk and advances translational approaches for combating antibiotic-exacerbated pneumonias.

Kiwifruit fruit stored at low temperatures are susceptible to chilling injury, leading to rapid softening, which therefore affects storage and marketing. The effect of 150 nM mL−1 of exogenous phytosulfokine α (PSKα) on reactive oxygen species (ROS) metabolism, Ca2+ signaling, and signal-transducing MAPK in kiwifruit, stored at 0 °C for 60 days, was investigated. The results demonstrated that PSKα treatment effectively alleviated chilling injury in kiwifruit, with a 15% reduction in damage compared to the control on day 60. In addition, PSKα enhanced the activities and gene expression levels of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), Ca2+−ATPase, and mitogen−activated protein kinase (MAPK). In contrast, the activities and gene expression levels of NADPH oxidase (NOX) were inhibited, leading to a lower accumulation of O2− and H2O2, which were 47.2% and 42.2% lower than those in the control at the end of storage, respectively. Furthermore, PSKα treatment enhanced the calmodulin (CaM) content of kiwifruit, which was 1.41 times that of the control on day 50. These results indicate that PSKα can mitigate chilling injury and softening of kiwifruit by inhibiting the accumulation of ROS, increasing antioxidant capacity by inducing antioxidant enzymes, activating Ca2+ signaling, and responding to MAPK protein kinase. The present results provide evidence that exogenous PSKα may be taken for a hopeful treatment in alleviating chilling injury and maintaining the quality of kiwifruit.

Background Prolonged and difficult weaning is associated with higher rates of complications and mortality. Therefore, it is important to identify the associated factors. Case presentation We describe our experience with a 37-year-old man diagnosed with severe viral pneumonia (influenza A). He presented with acute respiratory failure type I on admission. During intubation, his blood pressure and heart rate decreased, and epinephrine and norepinephrine were administered. Although his clinical condition improved 8 days after intensive care unit (ICU) admission, he experienced difficulty weaning. He remained conscious but had a poor spontaneous cough with sputum production and weak limb muscle strength. His cough reflex was absent during bronchoscopic sputum suction, and he used abdominal breathing during the T-tube test. Magnetic resonance imaging revealed an Arnold–Chiari malformation type I, posterior dislocation of the odontoid process, and syringomyelia, with compression and deformation of the medulla and high cervical cord. The patient was successfully weaned from the ventilator at 20 days after ICU admission. Conclusions Arnold–Chiari malformation type I and posterior dislocation of the odontoid process, which aggravate medullary compression and increase the risk of cervical nerve injury, might be a rare factor affecting prolonged weaning in critical illness.

Amplification of the 11q13.3 locus has been observed in various tumors. This study sought to determine the correlation of gene amplification at the 11q13.3 locus with the immune status and survival of breast cancer. Amplification of the 11q13.3 locus was characterized by analyzing a publicly available database from the cBioPortal platform (TCGA). The correlation of amplified genes with immune cell infiltration in breast cancer was further analyzed using the TIMER2.0 platform. Immunohistochemical staining was used to determine the expression levels of Cyclin D1 (CCND1), Fas-associated death domain (FADD) and P53 in 156 clinical breast cancer samples. This study revealed that amplification of the 11q13.3 amplicon in breast cancer is likely more frequently detected in luminal B breast cancer. Moreover, high expression or amplification of , fibroblast growth factor 3 ( ), fibroblast growth factor 4 ( ), fibroblast growth factor 19 ( ) and was inversely correlated with the abundance of CD4+ T cells and dendritic cell infiltration in breast cancer ( < 0.05). Data analysis also demonstrated that high expression of and mRNA levels was closely correlated with shorter recurrence-free survival (RFS) in patients with breast cancer ( < 0.05). The results of immunohistochemical staining from clinical samples further confirmed that high expression of CCND1 and FADD was frequently detected in luminal B and high-grade breast cancer with shorter metastasis-free survival times ( < 0.05). This study demonstrated that coamplification of genes located on the 11q13.3 amplicon is frequently detected in luminal B subtype breast cancer and is closely associated with worse survival in patients with breast cancer. Moreover, coamplification of the locus might decrease antitumor immune activity in breast cancer, indicating that coamplification of the 11q13.3 amplicon is likely to be a key determinant of therapeutic resistance and accelerate the aggressive evolution of breast cancer.

Kiwifruit fruit stored at low temperatures are susceptible to chilling injury, leading to rapid softening, which therefore affects storage and marketing. The effect of 150 nM mL[sup.−1] of exogenous phytosulfokine α (PSKα) on reactive oxygen species (ROS) metabolism, Ca[sup.2+] signaling, and signal-transducing MAPK in kiwifruit, stored at 0 °C for 60 days, was investigated. The results demonstrated that PSKα treatment effectively alleviated chilling injury in kiwifruit, with a 15% reduction in damage compared to the control on day 60. In addition, PSKα enhanced the activities and gene expression levels of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), Ca[sup.2+]−ATPase, and mitogen−activated protein kinase (MAPK). In contrast, the activities and gene expression levels of NADPH oxidase (NOX) were inhibited, leading to a lower accumulation of O[sub.2] [sup.−] and H[sub.2]O[sub.2], which were 47.2% and 42.2% lower than those in the control at the end of storage, respectively. Furthermore, PSKα treatment enhanced the calmodulin (CaM) content of kiwifruit, which was 1.41 times that of the control on day 50. These results indicate that PSKα can mitigate chilling injury and softening of kiwifruit by inhibiting the accumulation of ROS, increasing antioxidant capacity by inducing antioxidant enzymes, activating Ca[sup.2+] signaling, and responding to MAPK protein kinase. The present results provide evidence that exogenous PSKα may be taken for a hopeful treatment in alleviating chilling injury and maintaining the quality of kiwifruit.

Up to 50% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) infection, and the surface protein of HBV is essential for the progression of HBV-related HCC. The expression of large HBV surface antigen (LHB) is presented in HBV-associated HCC tissues and is significantly associated with the development of HCC. Gene set enrichment analysis revealed that LHB overexpression regulates the cell cycle process. Excess LHB in HCC cells induced chronic endoplasmic reticulum (ER) stress and was significantly correlated with tumor growth in vivo. Cell cycle analysis showed that cell cycle progression from G1 to S phase was greatly enhanced in vitro. We identified intensive crosstalk between ER stress and cell cycle progression in HCC. As an important regulator of the G1/S checkpoint, p27 was transcriptionally upregulated by transcription factors ATF4 and XBP1s, downstream of the unfolded protein response pathway. Moreover, LHB-induced ER stress promoted internal ribosome-entry-site-mediated selective translation of p27, and E3 ubiquitin ligase HRD1-mediated p27 ubiquitination and degradation. Ultimately, the decrease in p27 protein levels reduced G1/S arrest and promoted the progress of HCC by regulating the cell cycle.