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Objective: The purpose of this study is to explore the relationship between Life's Essential 8 (LE8) and the risk of gestational diabetes among US adults., Method: We used National Health and Nutrition Examination Surveys 2007-2018 data to perform this study. LE8 scores comprised 4 health behaviors (diet, physical activity, nicotine exposure, and sleep duration) and 4 health factors (BMI, non-high-density lipoprotein [HDL] cholesterol, blood glucose, and blood pressure). Then, LE8 were categorized into low CVH (0 to 49 scores), moderated CVH (50 to 79 scores), and high CVH (80 to 100 scores). Weighted multivariate Logistic regression analysis model were used to estimate the relationship between LE8 and gestational diabetes., Result: A total of 3,189 participants were included, and the portion of gestational diabetes was 15.33%, 11.46%, 7.71% in low CVH, moderate CVH, and high CVH, respectively. Adjustment for covariates, we found that high CVH (OR: 0.49, 95%CI: 0.29-0.83, p  = 0.01) was associated with decreased of gestational diabetes, not moderate CVH (OR: 0.78, 95%CI: 0.50-1.20, p  = 0.25). This inverse associations were dose-response dependent ( p -nonlinear = 0.982). This inverse associations were significant in subgroup. Significant interaction between CVH and family diabetes with the risk of gestational diabetes was found ( P for interaction = 0.04). High CVH (OR: 0.357, 95%CI: 0.176-0.724, p  = 0.005) could significantly decrease the risk of gestational diabetes in the population with family diabetes. The results were generally robust in sensitivity analyses after excluding of ASCVD participants., Conclusion: The high CVH could decrease the risk of gestational diabetes, especially in the population of family diabetes.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Tuberculosis is the leading cause of death from an infectious disease, and is caused by Mycobacterium tuberculosis (M.tb). More than 1 billion people worldwide are thought to harbor an M.tb infection. The multidrug therapy that represents the current standard of care requires a minimum of four months of dosing and drug resistant Mycobacterium tuberculosis treatment regimens are significantly longer. Inosine-5'-monophosphate dehydrogenase (GuaB) is the enzyme that performs the rate-limiting step in de novo guanine nucleotide biosynthesis that is critical for growth and viability of bacteria including M.tb. The development of a novel antibiotic that inhibits GuaB could combine with existing therapies in novel ways and thereby contribute to effective therapeutic regimens for the treatment of tuberculosis. Here we describe the discovery of structurally distinct small molecule GuaB inhibitors that are potent against M.tb H37Ra and H37Rv strains and have desirable safety and AMDE profiles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y.Z., I. A., S. W., C. B., D. J. B., K. C., T.D., J. F., A. G., H. G., E. H., S. F. H., C. H., S. K., M. K., J. L., X. L., F. M., J. M., J. N., J. S., S. U., G. W., P. W., Y. X., C. W. Y., T. F. E., M. W. T., E. M. K., T. D. C., are either current or former employees of Genentech or Roche and may hold stock in Roche Holding AG. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aims: "Astringent seed" is a type of abortive seed frequently observed in Chinese fir ( Cunninghamia lanceolata ). It is widely recognized but poorly understood for its underlying causes. This study investigates the potential of astringent seeds to alleviate the toxic effects of active aluminum ions., Methods: This study involved treating seeds and seedlings with two distinct concentrations of astringent seeds water extracts under the aluminum ion stress. Then the germination of seeds and growth of seedlings were evaluated and compared., Results: Under aluminum stress, both seed germination and seedling growth were notably inhibited. Treatment with a low-concentration of the extract significantly alleviated this inhibition. Root elongation in the seedlings increased by 36.95% compared to the control group, and the aluminum ion accumulation at the root tips was reduced by 38.89% relative to the aluminum-stressed group. This treatment also normalized the levels of malondialdehyde (MDA) in the roots and leaves, enhanced the activities of antioxidative enzymes such as superoxide dismutase (SOD) and catalase (CAT), and restored the levels of endogenous hormones including gibberellin (GA 3 ), indole-3-acetic acid (IAA), methyl jasmonate (Ja-ME), and abscisic acid (ABA). Furthermore, the low-concentration of the extract positively impacted the disorganized chloroplast structures. In contrast, a high-concentration of the extract failed to revert most of these stress indicators., Conclusion: Low concentrations of astringent seed water extract effectively alleviate the inhibitory effects of aluminum ions on seed and seedling. This implies that in natural environments, the proximity of healthy seeds to astringent seeds could potentially enhance their growth., 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 Mu, Yang, Qu, Wang, Ma, Ding, Ye, Zhang, Zhang, Lyu, Li, Cao, Wu, Ding and Chen.)

Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes. In the present study, to determine its function of TMEM232 in testes, we constructed a Tmem232-null mouse model using CRISPR-Cas9 technology. Tmem232 knockout (KO) male mice was completely infertile, and their sperm were immotile, with morphological defects of the flagellum. Electron microscopy revealed an aberrant midpiece-principal junction and the loss of the fourth outer microtubule doublet in the sperm of Tmem232 -/- mice. Sperm cells presented an 8 + 2 conformation and an irregular arrangement of the mitochondrial sheath. Proteomic analysis revealed altered expression of proteins related to flagellar motility, sperm capacitation, the integrity and stability of sperm structure, especially an upregulated expression of multiple ribosome components in TMEM232-deficient spermatids. Additionally, TMEM232 was observed to be involved in autophagy by interacting with autophagy-related proteins, such as ATG14, to regulate ribosome homeostasis during spermiogenesis. These results suggest that TMEM232, as a potential scaffold protein involving in the correct assembly, distribution, and stability maintenance of certain functional complexes by recruiting key intracellular proteins, is essential for the formation of a highly structured flagellum and plays an important role in the autophagic elimination of cytosolic ribosomes to provide energy for sperm motility., (© 2024. The Author(s).)

Saline-alkali stress is a widely distributed abiotic stress that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report a MYB-like protein, I-box binding factor (SlMYBI), which positively regulates saline-alkali tolerance through induced GABA accumulation by directly modulating the glutamate decarboxylase (GAD) gene SlGAD1 in tomato (Solanum lycopersicum L.). Overexpression of SlGAD1 increased GABA levels and decreased reactive oxygen species accumulation under saline-alkali stress, while silencing of SlGAD1 further suggested that SlGAD1 plays an active role in GABA synthesis and saline-alkali tolerance of tomato. In addition, we found that SlMYBI activates SlGAD1 transcription. Both overexpression of SlMYBI and editing of SlMYBI using CRISPR-Cas9 showed that SlMYBI regulates GABA synthesis by modulating SlGAD1 expression. Furthermore, the interaction of SlNF-YC1 with SlMYBI enhanced the transcriptional activity of SlMYBI on SlGAD1 to further improve saline-alkali tolerance in tomato. Interestingly, we found that ethylene signaling was involved in the GABA response to saline-alkali stress by RNA-seq analysis of SlGAD1-overexpressing lines. This study elucidates the involvement of SlMYBI in GABA synthesis regulation. Specifically, the SlMYBI-SlNF-YC1 module is involved in GABA accumulation in response to saline-alkali stress., Competing Interests: Conflict of interest statement: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A soy protein isolate (SPI) - sea buckthorn flavonoid emulsion was developed to study its effects on roasted lamb quality and heterocyclic amine (HAAs) precursors. The emulsion was stable with uniformly dispersed, well-encapsulated droplets averaging 0.1 to 10 μm. CLSM confirmed its good physical stability, small particle size, and uniform dispersion. FTIR the existence of hydrogen bond, hydrophobic interaction and physical adhesion between SPI and sea-buckthorn flavonoids. The emulsion improved lamb pellet texture by reducing chewiness and hardness, increasing adhesion, and decreasing browning. The emulsion-treated roasted mutton showed a 47.95-53.56 % increase in DPPH scavenging activity and MDA content reduction from 60.78 to 17.80 nmol/mg, indicating strong antioxidant activity and lipid oxidation inhibition. For both precursors and HAAs, there was a significant intensity of inhibition, where creatine decreased by about 44.91-68.34 %, glucose by 84.47 %-97.74 %, and the seven HAAs, Norharman, Harman, IQ, MeIQ, MeIQx, AαC, and PhIP, were inhibited by 79.64 %, respectively, 88.76 %, 65.07 %, 87.27 %, 96.16 %, 89.30 % and 49.44 %, respectively. This study aimed to develop a novel soy protein isolate-sea buckthorn flavonoid emulsion and evaluate its potential to improve roasted lamb quality while inhibiting the formation of harmful HAAs., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m 6 A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m 6 A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Chronic heart failure has become a serious threat to the health of the global population, and self-management is key to treating chronic heart failure. The emergence of mobile health (mHealth) provides new ideas for the self-management of chronic heart failure in which the informal caregiver plays an important role. Current research has mainly studied the experiences with using mHealth among patients with chronic heart failure from the perspective of individual patients, and there is a lack of research from the dichotomous perspective., Objective: The aim of this study was to explore the experiences with mHealth use among patients with chronic heart failure and their informal caregivers from a dichotomous perspective., Methods: This descriptive phenomenological study from a post-positivist perspective used a dyadic interview method, and face-to-face semistructured interviews were conducted with patients with chronic heart failure and their informal caregivers. Data were collected and managed using NVivo 12 software, and data analysis used thematic analysis to identify and interpret participants' experiences and perspectives. The thematic analysis included familiarizing ourselves with the data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report., Results: A total of 14 dyads of patients with chronic heart failure and their informal caregivers (13 men and 15 women) participated in this study, including 3 couples and 11 parent-child pairs. We constructed 4 key themes and their subthemes related to the experiences with mHealth use: (1) opposing experiences with mHealth as human interaction or trauma (great experience with mHealth use; trauma), (2) supplement instead of replacement (it is useful but better as a reference; offline is unavoidable sometimes), (3) both agreement and disagreement over who should be the adopter of mHealth (achieving consensus regarding who should adopt mHealth; conflict occurs when considering patients as the adopter of mHealth), (4) for better mHealth (applying mHealth with caution; suggestions for improved mHealth)., Conclusions: This study reported that the experiences with mHealth use among patients with chronic heart failure and their informal caregivers were mixed, and it highlighted the human touch of mHealth and the importance of network security. These results featured mHealth as a complement to offline hospitals rather than a replacement. In the context of modern or changing Chinese culture, we encourage patients to use mHealth by themselves and their informal caregivers to provide help when necessary. In addition, we need to use mHealth carefully, and future mHealth designs should focus more on ease of use and be oriented more toward older adults., (©Xiaorong Jin, Yimei Zhang, Min Zhou, Xiong Zhang, Qian Mei, Yangjuan Bai, Wei Wei, Fang Ma. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.10.2024.)

Aim: The aim of this review is to evaluate and summarize the evidence for preoperative visit-care of transcatheter aortic valve replacement (TAVR) and to provide evidence-based support for clinical intervention., Design: The review presents an evidence summary report, following the standard of the Fudan University Center for Evidence-based Nursing., Methods: Literature related to preoperative visit-care for transcatheter aortic valve replacement have been retrieved based on the "6S" pyramid model of evidence. The types of literature included systematic reviews, expert consensus, evidence summary, and guidelines., Data Sources: Up To Date, Cochrane Library, Joanna Briggs Institute, National Institute for Health and Care Excellence, Medlive, American Heart Association, Registered Nurses Association of Ontario, Scottish Intercollegiate Guidelines Network, European Society of Cardiology, American College of Cardiology, PubMed, CINAHL, Wanfang database, VIP database, Chinese biomedical literature database, CNKI. The search period is limited to the time when each database was established until February 2024., Results: A total of 18 articles were included in this review, consisting of 1 systematic review, 1 evidence summary, 3 guidelines and 13 expert consensuses. This review summarized 30 pieces of the best evidence for preoperative visit-care for transcatheter aortic valve replacement, encompassing three evidence themes: multidisciplinary team collaboration, preoperative assessment, and preoperative education., Conclusion: The study has established an ideal foundation of evidence for preoperative visit-care in TAVR. However, throughout the particular application process, it was crucial to assess the feasibility and relevance of the evidence in clinical practice by taking into account elements such as the application setting, recommendations from experts with diverse expertise, and the preferences of the patients., (© 2024. The Author(s).)

Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in de novo guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether in vivo inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacy in vivo against Acinetobacter baumannii mouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures of A. baumannii, Staphylococcus aureus , and Escherichia coli GuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clear in vivo efficacy of these small molecule GuaB inhibitors in a model of A. baumannii infection validates GuaB as an essential antibiotic target., Importance: The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of de novo guanine biosynthesis is bactericidal in a mouse model of Acinetobacter baumannii infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections., Competing Interests: All authors were employed by Genentech, Inc., a member of the Roche Group.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southeast Asia, and in the Guangxi and Guangdong provinces of China. The spermatogenic transcription factor zip 1 (SPZ1) is a member of bHLH zip family, and promotes tumorigenesis in the liver, colon and breast tissues. However, the role of SPZ1 in the progression of NPC is unclear. In this study, we found that SPZ1 mRNA and protein levels were significantly upregulated in NPC tissues compared to the normal nasopharyngeal tissues. Furthermore, SPZ1 knockdown in NPC cell lines inhibited proliferation, epithelial-mesenchymal transition, migration, and invasion in vitro , and suppressed tumorigenesis in an in vivo model. On the other hand, SPZ1 overexpression facilitated the growth of NPC cells. Mechanistically, SPZ1-driven progression of NPC is dependent on the Wnt5a/interleukin-6 (IL-6) signaling pathway. Consistent with this, IL-6 levels were significantly increased in NPC tissues and correlated positively with SPZ1 expression. Taken together, our findings suggest that SPZ1 mediates NPC progression through Wnt5a/IL-6 signaling, and the SPZ1/Wnt5a/IL-6 axis is a potential therapeutic target for NPC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Preoperative visit-care for transcatheter aortic valve replacement (TAVR) plays a crucial role in improving the quality of care and patient safety. However, preoperative care for TAVR patients is still in its early stages in China, with the care often being experience-based. The application of relevant evidence in nursing practice is necessary. Little is known regarding the facilitators and barriers to apply and compliance to the evidences about preoperative visit-care for TAVR in nursing., Methods: The Nurse's Compliance Checklist was used to investigate the evidence-based compliance of nurses (n = 21) who worked in the TAVR team in the evidence-based implementation setting. Meanwhile, an Evidence-Based Practice Beliefs Scale, and Influencing Factors Checklist were used to investigate all nurses (n = 66) who work in the same setting. Stakeholders (Middle and senior-level nursing administrators, frontline clinical nurses, and patients) interview was carried out to further disclose the barriers and facilitators in the process of evidence-based practice., Results: The results of this study showed that only 1 evidence implemented fully (100%) by nurses, 3 evidences with 0% implementation rate, and implementation rate of the other evidences were 9.5∼71.4%. The overall score of nurses' evidence-based nursing belief level was (3.52 ± 0.82). Three domains of barriers were identified: the Context Domain included lack of nursing procedures, inadequate health education materials, insufficient training; the Practitioner Domain included insufficient attention, lack of relevant knowledge, high work pressure and uncertainty of expected results, and Patient Domain included lack of relational knowledge. Facilitating factors included leadership support, nurse' high evidence-based nursing belief, high executive ability and enthusiasm for learning., Conclusion: The study indicated that the nurses' compliance of evidence-based practice in preoperative visit-care for TAVR was in lower level. There were some factors influencing the application of the evidences. The study revealed potential modifiable barriers to the successful implementation of evidence-based preoperative visit-care, including a lack of preoperative visit- care routine, related knowledge and training. Leadership support and nurse training should be considered to improve nurses' compliance with evidence-based practice., (© 2024. The Author(s).)

Background: : Family coping, as an essential part of family management of patients with chronic heart failure (CHF), is an important component of CHF interventions, affecting the health of patients, family members, and the whole family. It is necessary to understand the current situation of family coping in patients with CHF to facilitate the development of family interventions for patients with CHF. This study aims to develop and validate a tool for assessing the family coping scale for patients with CHF., Methods: The semi-structured interviews, expert consensus meetings, expert consultations, and item analysis were used to develop the initial scale. We employed classical test theory and exploratory factor analysis to scrutinize and refine the items in the scale. To validate the scale, we used confirmatory factor analysis to assess structural validity. We assessed internal consistency, and split-half reliability to ensure the scale's robustness and accuracy., Results: The FCS-CHF consisted of 24 items, including six dimensions: strategies for better management of CHF, psychological coping, substantial support by family members, emergency coping, overall heart failure awareness, and patients' health behavior. The results of confirmatory factor analysis showed that the scale fitted the data with well construct validity. The results of the confirmatory factor analysis for the overall goodness of fit indices for the fitted model were found to be acceptable for the scale. The scale demonstrates good reliability and validity, meeting the requirements of psychometrics., Conclusions: The FCS-CHF developed in this study is considered reliable and valid, which can measure family coping in patients with CHF and provide a basis for developing family coping enhancement strategies., Competing Interests: We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Zhang et al.)

Studies indicate that the lysine-specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C-C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post-SNT resulted in a higher paw withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV-EGFP-KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV-EGFP-KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV-EGFP-KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP-PCR analysis revealed that increased binding of p-STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV-EGFP-KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Dynamic in vitro absorption systems and mechanistic absorption modeling via PBPK have both shown promise in predicting human oral absorption, although these efforts have been largely separate; this work aimed to integrate knowledge from these approaches to investigate the oral absorption of a RET inhibitor, pralsetinib, with BCS Class II properties. Tiny-TIM (TIM B.V., Weteringbrug​, The Netherlands) is a dynamic in vitro model with close simulation of the successive physiological conditions of the human stomach and small intestine. Tiny-TIM runs with pralsetinib were performed at doses of 200 mg and 400 mg under fasting conditions. Mechanistic modeling of absorption was performed in Simcyp V21 (Certara, Manchester, UK). Pralsetinib fasted bioaccessibility in the Tiny-TIM system was 63% at 200 mg and 53% at 400 mg; a 16% reduction at 400 mg was observed under elevated gastric pH. Maximum pralsetinib solubility from the small intestinal compartment in Tiny-TIM directly informed the supersaturation/precipitation model parameters. The PBPK model predicted a similar fraction absorbed at 200 mg and 400 mg, consistent with the dose proportional increases in observed pralsetinib exposure. Integrating dynamic in vitro systems with mechanistic absorption modeling provides a promising approach for understanding and predicting human absorption with challenging low solubility compounds., Competing Interests: Declaration of conflict of interest All authors declare no competing interests for this work. CB, FM, SC, DK, NK, YC JL and P-CC are employees of Genentech Inc, a member of the Roche Group and may hold stock or options. MJD is an employee of Roche Products Pty Ltd, a member of the Roche Group and may hold stock or options., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The characterization of structure of organic salts in complex mixtures has been a difficult problem in analytical chemistry. In the analysis of Scutellariae Radix (SR), the pharmacopoeia of many countries stipulates that the quality control component is baicalin (≥9% by high performance liquid chromatography (HPLC)). The component with highest response in SR was also baicalin detected by liquid chromatography-mass spectrometry (LC-MS). However, in the attenuated total reflection Fourier transform infrared spectroscopy, the carbonyl peak of glucuronic acid of baicalin did not appear in SR. The results of element analysis, time of flight secondary ion mass spectrometry, matrix assisted laser desorption ionization mass spectrometry and solid-state nuclear magnetic resonance all supported the existence of baicalin magnesium salt. Based on this, this study proposes an analysis strategy guided by infrared spectroscopy and combined with multi-spectroscopy techniques to analyze the structure of organic salt components in medicinal plant. It is meaningful for the research of mechanisms, development of new drugs, and quality control., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The investigation into the spatial distribution of living woody (LWD) and coarse woody debris (CWD) within forests represents a fundamental methodology for probing the inherent mechanisms governing coexistence and mortality within forest ecosystems. Here, a complete spatial randomness (CSR) null model was employed to scrutinize the spatial pattern, while canonical correspondence analysis (CCA) and the Torus-translation test (TTT) were utilized to elucidate the distribution patterns of LWD and CWD within warm-temperate deciduous broadleaf secondary forests in Dongling Mountains plot, northern China. The results reveal that both LWD and CWD exhibit an aggregated distribution as the predominant pattern in the Dongling Mountains plot, with the proportion and intensity of aggregation diminishing as spatial scale increases. Specifically, the aggregation intensity g 0-10 demonstrates a significant negative correlation with abundance and maximum diameter at breast height (DBH). Notably, the g 0-10 of LWD manifests a stronger correlation with the maximum DBH, whereas the g 0-10 of CWD exhibits a greater association with the mortality rate. CCA outcomes suggest that elevation, convexity, and aspect significantly impact LWD distribution, whereas CWD distribution shows substantial negative correlations with elevation, convexity, slope, and aspect. TTT findings indicate that ecosystems characterized by a substantial presence of LWD also display a notable prevalence of CWD. Additionally, the majority of species exhibit no habitat preference, displaying neutral habitat connections and low ecological niche differentiation within the sampled plot.

The lack of amino acids triggers the autophagic response. Some studies have shown such starvation conditions also induce mitochondrial fusion, revealing a close correlation between the two processes. Although Mitofusin-2 (MFN2) has been demonstrated to play a role in fusion regulation, its role in the autophagic response and the variables that activate MFN2 under stress remain unknown. In this investigation, we screened and confirmed that forkhead box protein O3 (FOXO3) participates in MFN2's expression during short periods of starvation. Luciferase reporter test proved that FOXO3 facilitates MFN2's transcription by binding to its promoter region, and FOXO3 downregulation directly depresses MFN2's expression. Consequently, inhibiting the FOXO3-MFN2 axis results in the loss of mitochondrial fusion, disrupting the normal morphology of mitochondria, impairing the degradation of substrates, and reducing autophagosome accumulation, ultimately leading to the blockage of the autophagy. In conclusion, our work demonstrates that the FOXO3-MFN2 pathway is essential for adaptive changes in mitochondrial morphology and cellular autophagy response under nutritional constraints., (© 2024 Wiley Periodicals LLC.)

Compensation and intracellular storage of PD-L1 may compromise the efficacy of antibody drugs targeting the conformational blockade of PD1/PD-L1 on the cell surface. Alternative therapies aiming to reduce the overall cellular abundance of PD-L1 thus might overcome resistance to conventional immune checkpoint blockade. Here we show by bioinformatics analysis that colon adenocarcinoma (COAD) with high microsatellite instability (MSI-H) presents the most promising potential for this therapeutic intervention, and that overall PD-L1 abundance could be controlled via HSC70-mediated lysosomal degradation. Proteomic and metabolomic analyses of mice COAD with MSI-H in situ unveil a prominent acidic tumor microenvironment. To harness these properties, an artificial protein, IgP β, is engineered using pH-responsive peptidic foldamers. This features customized peptide patterns and designed molecular function to facilitate interaction between neoplastic PD-L1 and HSC70. IgP β effectively reduces neoplastic PD-L1 levels via HSC70-mediated lysosomal degradation, thereby persistently revitalizing the action of tumor-infiltrating CD8 + T cells. Notably, the anti-tumor effect of lysosomal-degradation-based therapy surpasses that of antibody-based immune checkpoint blockade for MSI-H COAD in multiple mouse models. The presented strategy expands the use of peptidic foldamers in discovering artificial protein drugs for targeted cancer immunotherapy., (© 2024. The Author(s).)

The regiocontrol in constructing benzo-fused five-membered rings by C-H cyclization remains an important challenge. We report a highly general and regioselective methodology to access such heterocycles and indenones, where under the catalysis of CoBr 2 /bipyridine, aryl titanates, alkynes and EX 2 (E = NR, S(O), RP(O), R 2 Si, CO, etc.) were assembled to various heterocycles and indenones in a modular manner. Unprecedented 1,2-Co/Ti heterobimetallic arylene and benzotitanole intermediates have played crucial roles in these syntheses.

Physiologically based pharmacokinetic (PBPK) modeling was used to predict the human pharmacokinetics and drug-drug interaction (DDI) of GDC-2394. PBPK models were developed using in vitro and in vivo data to reflect the oral and intravenous PK profiles of mouse, rat, dog, and monkey. The learnings from preclinical PBPK models were applied to a human PBPK model for prospective human PK predictions. The prospective human PK predictions were within 3-fold of the clinical data from the first-in-human study, which was used to optimize and validate the PBPK model and subsequently used for DDI prediction. Based on the majority of PBPK modeling scenarios using the in vitro CYP3A induction data (mRNA and activity), GDC-2394 was predicted to have no-to-weak induction potential at 900 mg twice daily (BID). Calibration of the induction mRNA and activity data allowed for the convergence of DDI predictions to a narrower range. The plasma concentrations of the 4 β -hydroxycholesterol (4 β -HC) were measured in the multiple ascending dose study to assess the hepatic CYP3A induction risk. There was no change in plasma 4 β -HC concentrations after 7 days of GDC-2394 at 900 mg BID. A dedicated DDI study found that GDC-2394 has no induction effect on midazolam in humans, which was reflected by the totality of predicted DDI scenarios. This work demonstrates the prospective utilization of PBPK for human PK and DDI prediction in early drug development of GDC-2394. PBPK modeling accompanied with CYP3A biomarkers can serve as a strategy to support clinical pharmacology development plans. SIGNIFICANCE STATEMENT: This work presents the application of physiologically based pharmacokinetic modeling for prospective human pharmacokinetic (PK) and drug-drug interaction (DDI) prediction in early drug development. The strategy taken in this report represents a framework to incorporate various approaches including calibration of in vitro induction data and consideration of CYP3A biomarkers to inform on the overall CYP3A-related DDI risk of GDC-2394., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen-induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid-like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA., (© 2024 John Wiley & Sons Ltd.)

Mapping the N-glycome of porcine sperm before and after sperm capacitation is important for understanding the rearrangement of glycoconjugates during capacitation. In this work, we characterized the N-glycome on the membranes of 18 pairs of fresh porcine sperm before capacitation and porcine sperm after capacitation by MALDI-MS (Matrix-assisted laser desorption/ionization-mass spectrometry). A total of 377 N-glycans were detected and a comprehensive N-glycome map of porcine sperm membranes before and after capacitation was generated, which presents the largest N-glycome dataset of porcine sperm cell membranes. Statistical analysis revealed a significantly higher level of high mannose glycosylation and a significantly lower level of fucosylation, galactosylation, and α-2,6-NeuAc after capacitation, which is further verified by flow cytometry and lectin blotting. This research reveals new insights into the relationship between N-glycosylation variations and sperm capacitation, including the underlying mechanisms of the capacitation process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The endometrium is an important part of women's bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity but also to common diseases related to endometrial receptivity. Glycosylation can improve endometrial receptivity, promote embryo localization and trophoblast cell adhesion and invasion, and contribute to successful implantation. Two diseases related to endometrial receptivity include endometriosis and endometrial cancer. As a common benign disease in women, endometriosis is often accompanied by an increased menstrual volume, prolonged menstrual periods, progressive and aggravated dysmenorrhea, and may be accompanied by infertility. Protein glycosylation modification of the endometrial surface indicates the severity of the disease and may be an important pathogenesis of endometriosis. In cancer, glycosylation modifications on the surface of tumor cells can be a marker to distinguish the type and severity of endometrial cancer. This review highlights the role of protein glycosylation in embryo-maternal endometrial dialogue and explores its potential mechanisms in diseases related to endometrial receptivity, which could provide a new clinical approach for their diagnosis and treatment.

Objective: This study aimed to explore the determinants influencing training transfer and evaluate how those factors change over time among nurses who graduated from clinical nurse specialist training to provide a theoretical basis for improving the training transfer of clinical nurse specialists (CNSs)., Methods: A quantitative longitudinal survey with four rounds of data collection was utilized to measure the influencing aspects of training transfer from June 2018 to December 2019. A total of 46 new CNSs participated in this study, including 30 and 16 nurses receiving training programs for CNSs in Infusion, Wound and Ostomy. The factor influencing training transfer (FITT) questionnaire was used to collect data for the first month (time 1), the third month (time 2), the sixth month (time 3), and the first year (time 4) after training. This questionnaire contains 53 items divided into five dimensions, including managerial support (20 items); hindrance in the organization (6 items); the validity of the training program (10 items); organizational and personal facilitators (11 items); and personal attitudes towards training transfer (6 items)., Results: The influencing factors of CNSs transfer decreased over time, with managerial support, hindrance in the organization, the validity of the training program, and personal attitudes towards training transfer changing statistically over time ( P  < 0.05), and no statistical difference in organizational and personal facilitators over time ( P  = 0.229). During early after training (the first month and the third month after training), hindrance in the organization is the biggest obstacle to training transfer. During the later of training (the sixth month and first year after the training), managerial support is the biggest obstacle to training transfer. Overall level of influencing factors of training transfer decreased in three months after training among Infusion nurses ( P  < 0.001), and Wound and Ostomy nurses decreased in the first year after training ( P  < 0.001)., Conclusions: The trend and level of training transfer predictors decreased depending on time. Clarifying the factors influencing transfer and its patterns may help nursing managers enhance the implementation and impact of nurse specialist training., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p  = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p  = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p  = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p  = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Key Message: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

High-temperature stress poses a significant environmental challenge for aquatic organisms, including tsinling lenok trout (Brachymystax lenok tsinlingensis). This study aimed to investigate the role of microRNAs (miRNAs) in inducing liver inflammation in tsinling lenok trout under high-temperature stress. Tsinling lenok trout were exposed to high-temperature conditions (24 °C) for 8 h, and liver samples were collected for analysis. Through small RNA sequencing, we identified differentially expressed miRNAs in the liver of high-temperature-stressed tsinling lenok trout compared to the control group (maintained at 16 °C). Several miRNAs, including novel-m0105-5p and miR-8159-x, showed significant changes in expression levels. Additionally, we conducted bioinformatics analysis to explore the potential target genes of these differentially expressed miRNAs. Our findings revealed that these miRNA target genes are involved in inflammatory response pathways, such as NFKB1 and MAP3K5. The downregulation of novel-m0105-5p and miR-8159-x in the liver of high-temperature-stressed tsinling lenok trout suggests their role in regulating liver inflammatory responses. To validate this, we performed a dual-luciferase reporter assay to confirm the regulatory relationship between miRNAs and target genes. Our results demonstrated that novel-m0105-5p and miR-8159-x enhance the inflammatory response of hepatocytes by promoting the expression of NFKB1 and MAP3K5, respectively. In conclusion, our study provides evidence that high-temperature stress induces liver inflammation in tsinling lenok trout through dysregulation of miRNAs. Understanding the molecular mechanisms underlying the inflammatory response in tsinling lenok trout under high-temperature stress is crucial for developing strategies to mitigate the negative impacts of environmental stressors on fish health and aquaculture production., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the global effort to reduce CO 2 emissions, the concurrent enhancement of pollutant degradation and reductions in fossil fuel consumption are pivotal aspects of microalgae-mediated wastewater treatment. Clarifying the degradation mechanisms of bacteria and microalgae during pollutant treatment, as well as regulatory biolipid production, could enhance process sustainability. The synergistic and inhibitory relationships between microalgae and bacteria are introduced in this paper. The different stimulators that can regulate microalgal biolipid accumulation are also reviewed. Wastewater treatment technologies that utilize microalgae and bacteria in laboratories and open ponds are described to outline their application in treating heavy metal-containing wastewater, animal husbandry wastewater, pharmaceutical wastewater, and textile dye wastewater. Finally, the major requirements to scale up the cascade utilization of biomass and energy recovery are summarized to improve the development of biological wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sodium is one of the essential additives in meat processing, but excessive sodium intake may increase risk of hypertension and cardiovascular disease. However, reducing salt content while preserving its preservative effect, organoleptic properties, and technological characteristics poses challenges. In this review, the mechanism of salt reduction of umami substances was introduced from the perspective of gustation-taste interaction, and the effects of the addition of traditional umami substances (amino acids, nucleotides, organic acids(OAs)) and natural umami ingredients (mushrooms, seaweeds, tomatoes, soybeans, tea, grains) on the sensory properties of the meat with reduced-salt contents were summarized. In addition, the impacts of taste enhancers on eating quality (color, sensory, textural characteristics, and water-holding capacity (WHC)), and processing quality (lipid oxidation, pH) of meat products (MP) and their related mechanisms were also discussed. Among them, natural umami ingredients exhibit distinct advantages over traditional umami substances in terms of enhancing quality and nutritional value. On the basis of salt reduction, natural umami ingredients improve the flavor, texture, WHC and antioxidant capacity. This comprehensive review may provide the food industry with a theoretical foundation for mitigating salt consumption through the utilization of umami substances and natural ingredients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 ., (© 2024. The Author(s).)

The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients., Methods: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias., Results: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001)., Conclusions: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Pseudorabies virus (PRV) is a highly contagious viral disease, which leads to severe financial losses in the breeding industry worldwide. Presently, PRV is mainly controlled using live attenuated and inactivated vaccines. However, these vaccines have an innate tendency to lose their structural conformation upon exposure to environmental and chemical stressors and cannot provide full protection against the emerging prevalent PRV variants. In this work, first, we synthesized aminated ZIF-7/8 nanoparticles (NPs), and then chemical bond-coated alginate dialdehyde (ADA, a type of dioxide alginate saccharide) on their surface via Schiff base reaction to obtain ZIF-7/8-ADA NPs. The as-fabricated ZIF-7/8-ADA NPs exhibited high stability, monodispersity and a high loading ratio of antigen. Furthermore, the ZIF-7/8-ADA NPs showed good biocompatibility in vitro and in vivo . Using ZIF-7/8-ADA NPs as an adjuvant and inactivated PRV as a model antigen, we constructed a PR vaccine through a simple mixture. The immunity studies indicated that ZIF-7/8-ADA induced an enhancement in the Th1/Th2 immune response, which was superior to that of the commercial ISA201, alum adjuvant and ZIF-7/8. Due to the pH-sensitive release of the antigen in lysosomes, the as-prepared PR vaccine subsequently accelerated the antigen presentation and improved the immune responses in vitro and in vivo . The results of PRV challenge using mice as the model demonstrated that ZIF-7/8-ADA achieved the same preventive effect as the commercial ISA201 and was much better than the alum adjuvant, and thus can serve as a promising delivery system and adjuvant to enhance humoral and cellular responses against PRV infection.

Background: To describe and conclude the in vitro fertilization (IVF) results of patients with X chromosome abnormality., Methods: A retrospective case series was conducted. According to the number of normal X, patients were allocated into two groups: Group A (patients with only a normal X, while other X has any types of abnormalities) and Group B (patients have two or more normal X chromosomes). Clinical data, including basic information, fertility information, and IVF outcomes, were collected., Results: Fourteen patients with X chromosome abnormality were included, among which 13 patients underwent a total of 29 cycles. Patients in Group B had five successful pregnancies and three live births, while no patient in Group A had a clinical pregnancy. Furthermore, the blastocyst formation rate and incidence of pregnancy were significantly lower in Group A (Z = -3.135, p = .002; Z = -2.946, p = .003, respectively). When controlled covariates, the karyotype of one normal X was also a risk factor for both blastocyst formation rate and success pregnancy (β = .820, 95% confidence interval [CI] = 0.458-1.116, β = .333, 95% CI = 0.017-0.494, respectively)., Conclusions: Our results revealed that women with only one normal X might suffer from worse IVF outcomes, mainly blastocyst formation rate, compared with those who had two or more normal X, including mosaic Turner syndrome and 47,XXX., (© 2024 Wiley Periodicals LLC.)

Background: The cell endocrine pathway is a critical physiological process composed of the endoplasmic reticulum, Golgi apparatus and associated vesicles. Loss of enzymes or proteins can cause dysfunction of endoplasmic reticulum and Golgi apparatus and affect secretion pathways leading to a variety of human diseases, including cancer., Methods: The single-cell RNA sequencing and single nucleotide variant principal component analysis data of ovarian cancer were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Eighty-four genes from SECRETORY&#95;PATHWAYs were obtained from the gene set enrichment analysis (GSEA) website. Univariate cox regression analyses and ConsensusClusterPlus were used to identify prognostic genes and molecular subtypes, which were validated using the tumor immune dysfunction and exclusion (i.e. TIDE) analysis and gene mutation analysis. A prognosis model was established by randomForestSRC. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ssGSEA, ESTIMATE, MCP-counter and GSEA. The drug sensitive analysis was performed using pRRophetic package. Immunotherapy datasets and pan-carcinoma analysis were used to examine the performance of prognostic model., Results: Eighteen prognostic genes from SECRETORY&#95;PATHWAYs were found in both TCGA and GEO datasets. Next, two clusters (C1 and C2) were determined, for which C1 with a poor prognosis had higher immune infiltration. Tumor-related pathways, such as PATHWAYS&#95;IN&#95;CANCER and B&#95;CELL&#95;RECEPTOR&#95;SIGNALING&#95;PATHWAY, were enriched in C1. Moreover, C2 was suitable for immunotherapy. A four-gene (DNAJA1, NDRG3, LUZP1 and ZCCHC24) signature was developed and successfully validated. RiskScore of higher levels were significantly associated with worse prognoses. An enhanced immune infiltration, increased pathways score and inappropriate immunotherapy were observed in the high RiskScore group. The high- and low-RiskScore groups had different drug sensitivities. Immunotherapy datasets and pan-carcinoma analysis indicated that the low RiskScore group may benefit from immunotherapy., Conclusions: Based on the perspective of the secretory signaling pathway, a robust prognostic signature with great performances was determined, which may provide clues for clinical precision treatment of ovarian cancer., (© 2024 John Wiley & Sons Ltd.)

Synergistic remediation of heavy metal (HM) contaminated soil using beneficial microorganisms (BM) and plants is a common and effective in situ bioremediation method. However, the shortcomings of this approach are the low colonisation of BM under high levels of heavy metal stress (HMS) and the poor state of plant growth. Previous studies have overlooked the potential of biochar to mitigate the above problems and aid in-situ remediation. Therefore, this paper describes the characteristics and physicochemical properties of biochar. It is proposed that biochar enhances plant resistance to HMS and aids in situ bioremediation by increasing colonisation of BM and HM stability. On this basis, the paper focuses on the following possible mechanisms: specific biochar-derived organic matter regulates the transport of HMs in plants and promotes mycorrhizal colonisation via the abscisic acid signalling pathway and the karrikin signalling pathway; promotes the growth-promoting pathway of indole-3-acetic acid and increases expression of the nodule-initiating gene NIN; improvement of soil HM stability by ion exchange, electrostatic adsorption, redox and complex precipitation mechanisms. And this paper summarizes guidelines on how to use biochar-assisted remediation based on current research for reference. Finally, the paper identifies research gaps in biochar in the direction of promoting beneficial microbial symbiotic mechanisms, recognition and function of organic molecules, and factors affecting practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study is to understand and analyze the development history, research hotspots, and research trends in the study of microbial diseases of cultural heritage through bibliometric analyses in order to fill the current gap of no literature review in this research field and to make certain contributions to the research in this field and the protection of cultural heritage. Bibliometric and visual analyses of the literature on cultural heritage microbial diseases in the Web of Science (WoS) core collection were carried out using VOSviewer and R-bibliometrix, choosing the two main literature types of papers and reviews. The emphasis was placed on analyzing and summarizing core research strengths, hotspots, and trends. Six hundred sixty-seven documents (573 articles and 94 reviews) were retrieved. αIn the WoS core collection, the first literature on cultural heritage microbial disease research was published in January 2000, and the annual number of publications from 2000 to 2009 did not exceed one; the annual number of publications from 2010 onwards increased rapidly, and after 2018, the number of publications per year exceeded 60, reaching 94 in 2020, which indicates that cultural heritage microbial disease research is booming. Our research showed that Italy, the USA, and China were the leading research countries, and Univ Milan was the institution with the most publications. International Biodeterioration &Biodegradation was the most published and co-cited journal, and Gu JD was the most prolific author. The research hotspots in the study of microbial diseases of cultural heritage mainly include biological degradation of cultural heritage; identification of diseased microorganisms and disease mechanisms; cultural heritage microbial disease prevention and control methods; monitoring, prevention, and control of diseased microorganisms in indoor air; antibacterial agents, especially essential oils, nanoparticles, and other safe and efficient antibacterial products research and development; and exploration of the mechanisms of biofilm protection of cultural heritage on cultural heritage surfaces. Monitoring and identifying cultural heritage microbial communities, identifying disease mechanisms, and researching safe and efficient bacteriostatic products such as essential oils and nanoparticles will be the main research directions in the field of cultural heritage microbial disease prevention and control in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Food waste and byproducts (FWBP) are a global issue impacting economies, resources, and health. Recycling and utilizing these wastes, due to processing and economic constraints, face various challenges. However, valuable components in food waste inspire efficient solutions like active intelligent packaging. Though research on this is booming, its material selectivity, effectiveness, and commercial viability require further analysis. This paper categorizes FWBP and explores their potential for producing packaging from both animal and plant perspectives. In addition, the preparation/fabrication methods of these films/coatings have also been summarized comprehensively, focusing on the advantages and disadvantages of these methods and their commercial adaptability. Finally, the functions of these films/coatings and their ultimate performance in protecting food (meat, dairy products, fruits, and vegetables) are also reviewed systematically. FWBP provide a variety of methods for the application of edible films, including being made into coatings, films, and fibers for food preservation, or extracting active substances directly or indirectly from them (in the form of encapsulation) and adding them to packaging to endow them with functions such as barrier, antibacterial, antioxidant, and pH response. In addition, the casting method is the most commonly used method for producing edible films, but more film production methods (extrusion, electrospinning, 3D printing) need to be tried to make up for the shortcomings of the current methods. Finally, researchers need to conduct more in-depth research on various active compounds from FWBP to achieve better application effects and commercial adaptability., (© 2024 Institute of Food Technologists®.)

Background: Families of children with congenital heart disease (CHD) face tremendous stressors in the process of coping with the disease, which threatens the health of families of children with CHD. Studies have shown that nursing interventions focusing on family stress management can improve parents' ability to cope with illness and promote family health. At present, there is no measuring tool for family stressors of CHD., Methods: The items of the scale were generated through qualitative interviews and a literature review. Initial items were evaluated by seven experts to determine content validity. Factor analysis and reliability testing were conducted with a convenience sample of 670 family members. The criterion-related validity of the scale was calculated using scores on the Self-Rating Anxiety Scale (SAS)., Results: The CHD Children's Family Stressor Scale consisted of six dimensions and 41 items. In the exploratory factor analysis, the cumulative explained variance of the six factors was 61.085%. In the confirmatory factor analysis, the six factors in the EFA were well validated, indicating that the model fits well. The correlation coefficient between CHD Children's Family Stressor Scale and SAS was r  = 0.504 ( p  < 0.001), which indicated that the criterion-related validity of the scale was good. In the reliability test, Cronbach's α coefficients of six sub-scales were 0.774-0.940, and the scale-level Cronbach's α coefficient value was 0.945., Conclusion: The study indicates that the CHD Children's Family Stressor Scale is valid and reliable, and it is recommended for use in clinical practice to assess CHD children's family stressors., 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 Zhang, Zhou, Bai, Chen, Wang, Hu, Yang, Wei, Ding and Ma.)

Ethnopharmacological Relevance: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and currently there are no specific and effective drugs for its treatment. Podocyte injury is a detrimental feature and the major cause of albuminuria in DN. We previously reported Tangshen Formula (TSF), a Chinese herbal medicine, has shown therapeutic effects on DN. However, the underlying mechanisms remain obscure., Aim of the Study: This study aimed to explore the protective effect of TSF on podocyte apoptosis in DN and elucidate the potential mechanism., Materials and Methods: The effects of TSF were assessed in a murine model using male KKAy diabetic mice, as well as in advanced glycation end products-stimulated primary mice podocytes. Transcription factor EB (TFEB) knockdown primary podocytes were employed for mechanistic studies. In vivo and in vitro studies were performed and results assessed using transmission electron microscopy, immunofluorescence staining, and western blotting., Results: TSF treatment alleviated podocyte apoptosis and structural impairment, decreased albuminuria, and mitigated renal dysfunction in KKAy mice. Notably, TSF extracted twice showed a more significant reduction in proteinuria than TSF extracted three times. Accumulation of autophagic biomarkers p62 and LC3, and aberrant autophagic flux in podocytes of DN mice were significantly altered by TSF therapy. Consistent with the in vivo results, TSF prevented the apoptosis of primary podocytes exposed to AGEs and activated autophagy. However, the anti-apoptosis capacity of TSF was countered by the autophagy-lysosome inhibitor chloroquine. We found that TSF increased the nuclear translocation of TFEB in diabetic podocytes, and thus upregulated transcription of its several autophagic target genes. Pharmacological activation of TFEB by TSF accelerated the conversion of autophagosome to autolysosome and lysosomal biogenesis, further augmented autophagic flux. Conversely, TFEB knockdown negated the favorable effects of TSF on autophagy in AGEs-stimulated primary podocytes., Conclusions: These findings indicate TSF appears to attenuate podocyte apoptosis and promote autophagy in DN via the TFEB-mediated autophagy-lysosome system. Thus, TSF may be a therapeutic candidate for DN., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Urinary tract infections (UTIs) represent a significant challenge in clinical practice, with recurrent forms (rUTIs) posing a continual threat to patient health. Escherichia coli ( E. coli ) is the primary culprit in a vast majority of UTIs, both community-acquired and hospital-acquired, underscoring its clinical importance. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. The type II TA system, prevalent in prokaryotes, emerges as a critical player in stress response, biofilm formation, and cell dormancy. ccdAB , the first identified type II TA module, is renowned for maintaining plasmid stability. This paper aims to unravel the physiological role of the ccdAB in rUTIs caused by E. coli , delving into bacterial characteristics crucial for understanding and managing this disease. We investigated UPEC-induced rUTIs, examining changes in type II TA distribution and number, phylogenetic distribution, and Multi-Locus Sequence Typing (MLST) using polymerase chain reaction (PCR). Furthermore, our findings revealed that the induction of ccdB expression in E. coli BL21 (DE3) inhibited bacterial growth, observed that the expression of both ccdAB and ccdB in E. coli BL21 (DE3) led to an increase in biofilm formation, and confirmed that ccdAB plays a role in the development of persistent bacteria in urinary tract infections. Our findings could pave the way for novel therapeutic approaches targeting these systems, potentially reducing the prevalence of rUTIs. Through this investigation, we hope to contribute significantly to the global effort to combat the persistent challenge of rUTIs., 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 Zhang, Tao, Chen, Fang, Xu, Chen, Ma and Liang.)

Diabetic vascular complications include diabetic macroangiopathy and diabetic microangiopathy. Diabetic microangiopathy is characterised by impaired microvascular endothelial function, basement membrane thickening, and microthrombosis, which may promote renal, ocular, cardiac, and peripheral system damage in diabetic patients. Therefore, new preventive and therapeutic strategies are urgently required. Sirt1, a member of the nicotinamide adenine dinucleotide-dependent histone deacetylase class III family, regulates different organ growth and development, oxidative stress, mitochondrial function, metabolism, inflammation, and aging. Sirt1 is downregulated in vascular injury and microangiopathy. Moreover, its expression and distribution in different organs correlate with age and play critical regulatory roles in oxidative stress and inflammation. This review introduces the background of diabetic microangiopathy and the main functions of Sirt1. Then, the relationship between Sirt1 and different diabetic microangiopathies and the regulatory roles mediated by different cells are described. Finally, we summarize the modulators that target Sirt1 to ameliorate diabetic microangiopathy as an essential preventive and therapeutic measure for diabetic microangiopathy. In conclusion, targeting Sirt1 may be a new therapeutic strategy for diabetic microangiopathy., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Transition issues have been discussed for many decades, yet little is known about successful transition expectations in the context of Chinese culture., Purpose: This article was designed to describe the expectations of newly graduated nurses in China regarding successful transition., Methods: A qualitative, descriptive study design was employed, and a purposive sampling method was used to recruit interviewees. All of the one-to-one conversations were held in a quiet room to ensure privacy. All of the interviews were transcribed and then analyzed using thematic analysis., Results: Nineteen new nurses were recruited from seven tertiary hospitals and participated in the in-depth interview process. Transition success, that is, "professional metamorphosis," was revealed through the four themes of "being competent in nursing work," "establishing a professional identity," "establishing comfortable interpersonal relationships," and "achieving balance between work and life.", Conclusions/implications for Practice: Chinese new nurses expect their successful transition to achieve a professional metamorphosis in many aspects. A successful transition is not only a journey of professionalization but also a process of socialization. New nurses expect to achieve both maturity in their work and wisdom in life. The results of this study provide a greater understanding of transition issues in the context of Chinese culture. Thus, support and strategies cannot be limited to interventions designed to improve working competence but should be individualized to help new nurses achieve a smooth transition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Non-classical secretory proteins are widely found in bacteria and have been extensively studied due to their important physiological roles. However, the relevant non-classical secretory mechanisms remain unclear. In this study, we found that oxalate decarboxylase (Bacm OxDC) from Bacillus mojavensis XH1 belongs to non-classical secretory proteins. Its N-terminus showed high hydrophilicity, which was different from the conventional signal peptide. The truncation test revealed that the deletion of the N-terminus affects the structure resulting in its inability to cross the cell membrane. Further studies verified that the exported peptide YydF played an important role in the secretion process of Bacm OxDC. Experimental results on the secretion mechanism indicated that Bacm OxDC bound to the exported peptide YydF and they are translocated to the cell membrane together, after which Bacm OxDC caused cell membrane relaxation for transmembrane secretion. Thereafter, three recombinant proteins were successfully secreted with certain enzymatic activity by fusing Bacm OxDC as a guide protein with various target proteins. To the best of our knowledge, this was the first time that non-classical secretion mechanism in bacteria has been analyzed. The novel discovery may provide a reference and broaden the horizons of the secretion pathway and expression regulation of proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)