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Guo-Tian Ruan,1– 3,&ast; Ming Yang,1– 3,&ast; Xiao-Wei Zhang,1– 3,&ast; Meng-Meng Song,1– 3 Chun-Lei Hu,1– 3 Yi-Zhong Ge,1– 3 Hai-Lun Xie,1– 3 Tong Liu,1– 3 Meng Tang,1– 3 Qi Zhang,1– 3 Xi Zhang,1– 3 Kang-Ping Zhang,1– 3 Xiang-Rui Li,1– 3 Qin-Qin Li,1– 3 Yong-Bing Chen,1– 3 Kai-Ying Yu,1– 3 Ming-Hua Cong,4 Kun-Hua Wang,5 Han-Ping Shi1– 3 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, People’s Republic of China; 5Department of Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery and Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, People’s Republic of ChinaTel +86-10- 6392 6985Fax +86-10 -6392 6325Email shihp@ccmu.edu.cnBackground: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality.Patients and Methods: This multicenter cohort study included 746 EPCC (age > 65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria.Results: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet–lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (< 25.03) had a worse overall survival (OS) than patients with high ALI (≥ 25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590– 2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups.Conclusion: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.Keywords: ALI, systemic inflammation, cancer cachexia, elderly, overall survival

Xi Zhang,1– 3 Jing-Hua Li,4 Qi Zhang,1,3 Qin-Qin Li,1,3 Kang-Ping Zhang,1,3 Meng Tang,1,3 Yi-Zhong Ge,1,3 Wei Li,5 Hong-Xia Xu,6 Zeng-Qing Guo,7 Han-Ping Shi1,3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Radiotherapy, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of China; 5Cancer Center of the First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 6Department of Clinical Nutrition, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, 400042, People’s Republic of China; 7Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University, Fujian, 350014, People’s Republic of ChinaCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaTel +86-10-6392 6985Fax +86-10-6392 6325Email shihp@ccmu.edu.cnBackground: Overweight and obese patients with cancer present with chronic inflammation, dysfunctional antitumor immunity and malnutrition risk. Prognostic nutritional index (PNI) is a promising indicator for predicting inflammatory, immunological and nutritional states; however, its prognostic value in overweight and obese patients with cancer has not been explored. Therefore, the aim of the current study was to explore the prognostic value of PNI levels in overweight and obese patients with cancer.Methods: The current large-scale retrospective cohort multicenter study included 3532 patients. Time-dependent receiver operating characteristic (ROC) curve analysis was used to determine the prediction accuracy of PNI levels for mortality of overweight and obese patients with cancer. Restricted cubic splines were used to model the association between PNI levels and mortality. Association between low PNI and overall survival rate was analyzed using the Kaplan–Meier method and Cox regression model.Results: Area under the curve (AUC) of the PNI for all-cause mortality was higher compared with that of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in overweight and obese patients with cancer. There was a significant inverse relationship between PNI levels and all-cause mortality (per SD increment-HR: 0.79; 95% CI: 0.74, 0.85; P< 0.001). Subgroup analysis showed that the risk for mortality significantly decreased with increase in PNI levels in patients at risk of malnutrition (per SD increment-HR: 0.67; 95% CI: 0.57, 0.78; P< 0.001) and elderly patients (per SD increment-HR: 0.74; 95% CI: 0.64, 0.84; P< 0.001). In addition, PNI levels showed an inverse association with mortality in patients without malnutrition risk (per SD increment-HR: 0.81; 95% CI: 0.75, 0.88; P< 0.001). Subgroup analysis based on tumor type showed that low PNI was an independent predictor of poor prognosis for patients with lung cancer, gastric cancer and hepatobiliary and pancreatic cancer.Conclusion: Low PNI levels are associated with an increased risk for all-cause mortality. PNI level is a potential effective inflammation-based prognostic tool for overweight and obese patients with cancer.Keywords: PNI, mortality, overweight or obese, prognosis, cancer patients

The development of effective agents for overcoming platinum chemoresistance in lung carcinoma continues to have high priority. We have demonstrated recently that β-elemene, a novel antitumor compound, enhances cisplatin activity by triggering lung cancer cell death via apoptosis. Here, we investigated whether β-elemene acts synergistically with cisplatin to inhibit non-small cell lung cancer (NSCLC) cell proliferation by blocking cell cycle progression. β-Elemene substantially increased the suppressive effect of cisplatin on cell growth and proliferation in the NSCLC cell lines H460 and A549. Furthermore, β-elemene augmented cisplatin in the cell cycle arrest of NSCLC cells at G(2)/M. This was associated with upregulated checkpoint kinase (CHK2) expression and reduced CDC2 activity (i.e., increased phosphorylation of CDC2 on Tyr-15 and decreased phosphorylation of CDC2 on Thr-161). Moreover, β-elemene and cisplatin in combination clearly decreased the protein levels of cyclin B1 and CDC25C and increased the levels of p21(Cip1/Waf1), p27(Kip1), and GADD45 in these cells, compared with the effects of either agent alone at the same concentration. These results suggest that the β-elemene-enhanced inhibitory effect of cisplatin on lung carcinoma cell proliferation is regulated by a CHK2-mediated CDC25C/CDC2/cyclin B1 signaling pathway and leads to the blockade of cell cycle progression at G(2)/M. A comparison of the cytotoxic efficacies of β-elemene and three synthetic analogs (β-elemenol, β-elemenal, and β-elemene fluoride) in the two lung cancer cell lines revealed that β-elemenol and β-elemene fluoride had the same antitumor efficacy as β-elemene, whereas β-elemenal was appreciably more potent than β-elemene. Thus, although all three synthetic analogs of β-elemene considerably suppressed NSCLC cell growth and proliferation, β-elemenal may have greater potential as an anticancer alternative to β-elemene in treating lung cancer and other tumors. [ABSTRACT FROM AUTHOR]

β-Elemene is a new anticancer compound extracted from the Chinese medicinal herb Rhizoma zedoariae. We have shown previously that β-elemene increases cisplatin cytotoxicity and enhances cisplatin sensitivity via blocking cell cycle progression at G2/M phase in resistant ovarian tumor cells. In the current study, we asked whether β-elemene-augmented cisplatin activity in ovarian carcinoma cells is mediated through the induction of apoptosis. Here, we show that β-elemene triggered apoptotic cell death in chemoresistant human ovarian cancer A2780/CP and MCAS cells in a dose- and time-dependent fashion, as assessed by six different apoptosis assays. Intriguingly, β-elemene was a stronger inducer of apoptosis than cisplatin in this model system, and a synergistic effect on induction of cell death was observed when the tumor cells were treated with both agents. Furthermore, β-elemene plus cisplatin exposure significantly disrupted the mitochondrial transmembrane potential (ΔΨ (m)) and increased the release of cytochrome c from mitochondria into the cytoplasm. The combination treatment with both compounds also induced increases in caspase-3/8/9 activities and caspase-9 cleavage, enhanced protein expression of Bax and phosphorylation of Bcl-2 at Ser-70, and reduced the protein levels of Bcl-2 and Bcl-X(L) in the platinum-resistant ovarian cancer cells. Taken together, these data indicate that β-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced apoptosis and that the augmented effect of β-elemene on cisplatin cytotoxicity and sensitivity in resistant ovarian tumor cells is mediated through a mitochondria- and caspase-dependent cell death pathway. [ABSTRACT FROM AUTHOR]

The retinoic acid receptor-related orphan receptor γt (RORγt) is a key regulator of Th17 cells, associated with autoimmune diseases, making it a significant drug target. Herein, we designed and synthesized 1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinoline derivatives, improving upon GSK2981278 to enhance bioavailability. Of which, D4 exhibited superior bioavailability (F = 48.1 and 32.9% in mice and rats, respectively) compared to GSK2981278 (F = 6.2 and 4.1%, respectively), and effectively treated psoriasis in mice at lower doses. Moreover, for the first time, we report the efficacies of a RORγt inverse agonist in mouse models of rheumatoid arthritis. ( R )-D4 , the eutomer of D4 , matched or exceeded GSK2981278's therapeutic effects at lower doses, with no adverse effects observed after 2 weeks of administration. These results position ( R )-D4 as a promising and orally bioavailable candidate for Th17-mediated autoimmune disease treatment.

Chebulae Fructus (TCF) is a traditional Chinese medicine and Tibetan medicine with high medicinal value, but its quality control indicators still need clarification. In this study, a strategy was proposed to specify the quality markers (Q-markers) of TCF by constructing a multidimensional feature network that includes dimensions of effectiveness, content, traceability, and specificity. Network pharmacology analysis was performed to validate the effectiveness of the chemical constituents in TCF through creating a TCF-component-disease-target-pathway network. By combining fingerprints analysis with UPLC-QTOF-MS, 17 differential components were identified among 19 batches of TCF samples. Serum pharmacochemical analysis on rats identified seven prototype components absorbed into the blood. The scores for the four dimensions were calculated using these identified components as candidates, and a multidimensional feature network based on the "spider-web" model was constructed. Ultimately, chebulinic acid, ellagic acid, chebulagic acid, methyl gallate, gallic acid, chebulic acid, and trigalloylglucose were clarified as Q-markers of TCF. These Q-markers screened out in this study are closely linked to the efficacy of TCF and can serve as indicator components for quality control of TCF., (© 2024 John Wiley & Sons Ltd.)

Mangroves adapt to periodical submergence and constitute resilient ecosystems in coastal environments. The question is whether they can sustain long submergence stress when sea level rises as a consequence of climate change. To address this, seedlings of two representative mangrove species that acclimate to low to mid tide (Avicennia marina) and mid to high tide (Kandelia obovata) conditions were treated with continual submergence for 7 days as extended hypoxia, or semi-diurnal cyclic submergence and reoxygenation for 7 days. At specific time points, leaves were collected to construct RNA-Sequencing libraries for gene expression analysis. Through the lens of transcriptome, the initial response of A. marina to submergence was mild but more dramatic after prolong immersion. However, the initial response of K. obovata was drastic and reduced in latitude later, suggesting distinct species-specific responses. After adapting to diurnal cycles, both species minimized transcriptome fluctuations similarly. Metabolically, during initial response, sucrose and starch were converted into glucose for fermentation to increase glycolytic flux, coupled with regeneration of NAD + . The energy amelioration was accompanied by longer term phytohormone regulations where ethylene signal transduction pathway was enhanced, but abscisic acid biosynthesis was reduced. Notably, gibberellic acids biosynthesis increased in A. marina but decreased in K. obovata as a unique feature. Genomic level analysis indicated that only about 30 % of the conserved plant submergence responsive genes were expressed during submergence in these mangroves. The function of an ethylene responsive gene was validated in transgenic Arabidopsis. This research elucidates distinct molecular mechanisms and metabolic pathways that empower A. marina and K. obovata to endure prolonged submergence and hypoxia. By highlighting their unique adaptive strategies in response to rising sea levels, these findings enhance our understanding of mangrove resilience and provide insights for the conservation and management of these essential coastal ecosystems in the face of climate change., 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.)

The impact of climate change on medicinal plants has significantly altered their suitable environments, thereby affecting the quality of herbal medicines. Notopterygium franchetii (N. franchetii), a medicinal plant intricately linked to its natural habitat, exhibits substantial quality variations influenced by the ecological conditions of its native region. In this study, comprehensive field surveys were conducted to gather occurrence records and samples of N. franchetii. The Maxent model and ArcGIS software were employed to predict the suitable habitats of N. franchetii during different time periods. A high-performance liquid chromatography (HPLC) method was developed to establish the chemical fingerprints of 21 sample batches. Fourteen common peaks were subjected to cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. The findings revealed quality variations correlated with their geographic origins, identifying peaks 10, 1, 14, 3, and 4 as crucial for quality differentiation. The study indicates that precipitation, temperature, and altitude significantly influence the distribution of N. franchetii. Under current climate conditions, the suitable habitat area for N. franchetii is estimated to be approximately 94,637.33 km 2 . However, projections under three future climate scenarios suggest a declining trend in suitable habitat areas. A quality zoning map of N. franchetii was developed, integrating a correlation model between chemical composition and environmental variables with the spatial analysis and visualization capabilities of ArcGIS. The high-quality regions for N. franchetii are predominantly located in the Gannan, Linxia, Dingxi, Longnan, and Wuwei districts. These research outcomes offer a valuable reference for identifying suitable cultivation areas and assessing the quality of N. franchetii in Gansu Province., (© 2024. The Author(s).)

Photo-thermo catalysis that combines photo- and thermo-catalysis has emerged as an attractive approach for effective and economical elimination of pollutants. Herein, we fabricated a robust, highly water stable 2D Co(II)-MOF photo-thermo catalyst towards the decomposition of permanganate anions. It has been demonstrated that Co(II)-MOF exhibits excellent catalytic capacity, good selectivity and incredible reusability for degrading MnO 4 - . The reaction rate of the process was investigated for thermo-photo vs. thermo/photo processes to provide conclusive evidence that Co(II)-MOF shows a strong synergistic use as both an energy source and Lewis acid.

Abstract: Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo . Methods: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture model was used to detect neutrophil migration, neutrophil extracellular traps level, and organ damage. Result: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of neutrophil extracellular traps, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multiorgan damage and lethality resulting from cecal ligation and puncture. Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Chlorinated polyfluorinated ether sulfonic acid (F-53B), a commonly utilized alternative for perfluorooctane sulfonate, was detected in pregnant women and cord blood recently. However, the lack of detailed toxicokinetic information poses a significant challenge in assessing the human risk assessment for F-53B exposure. Our study aimed to develop a physiologically based pharmacokinetic (PBPK) model for pregnant mice, based on toxicokinetic experiments, and extrapolating it to humans. Pregnant mice were administered 80 μg/kg F-53B orally and intravenously on gestational day 13. F-53B concentrations in biological samples were analyzed via ultraperformance liquid chromatography-mass spectrometry. Results showed the highest F-53B accumulation in the brain, followed by the placenta, amniotic fluid, and liver in fetal mice. These toxicokinetic data were applied to F-53B PBPK model development and evaluation, and Monte Carlo simulations were used to characterize the variability and uncertainty in the human population. Most of the predictive values were within a 2-fold range of experimental data (>72%) and had a coefficient of determination (R 2 ) greater than 0.68. The developed mouse model was then extrapolated to the human and evaluated with human biomonitoring data. Our study provides an important step toward improving the understanding of toxicokinetics of F-53B and enhancing the quantitative risk assessments in sensitive populations, particularly in pregnant women and fetuses.

Objective: To comparing the accuracy of pedicle screw placement in posterior surgery for adult degenerative scoliosis (ADS) between robotic-assisted and traditional freehand techniques. Methods: This retrospective study included 92 patients with ADS who underwent posterior spinal surgery at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) between March 2019 and December 2023. There were 19 males and 73 females with a mean age of (63.6±9.8) years. The patients were divided into two groups based on the technique used for pedicle screw placement: robot-assisted group (34 cases) and manual group (58 cases). Operative duration, intraoperative blood loss, facet joint violation, postoperative complications, magnitude of curve correction, visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores preoperatively, 1 week postoperatively, and 1 month postoperatively were compared and analyzed between the two groups. The Gertzbein-Robbins classification criteria was used to assess the accuracy of screw placement. Results: Differences in baseline data, operative duration, intraoperative blood loss, magnitude of curve correction, and VAS and ODI scores preoperatively, 1 week postoperatively, and 1 month postoperatively between the two groups exhibited no statistically significant differences (all P >0.05). The accuracy of pedicle screw placement in the robot-assisted group was significantly higher than that in the manual group [90.9% (416/458) vs 80.1% (697/870), P <0.001]. In terms of surgical segments, in T 1 -T 12 and L 1 -S 1 segments, the accuracy of pedicle screw placement in the robot group were both significantly higher than those in the control group [91.5% (130/142) vs 77.8% (186/239), P =0.001; 90.3% (271/300) vs 80.8% (502/621), P <0.001]. However, no significant differences was observed in the accuracy of S 2 -alar-iliac (S 2 AI) screw placement between the two groups [90.0%(9/10) vs 93.8%(15/16), P =0.727]. Moreover, no significant differences was found in the deviation direction of the cortical screw penetration between both groups ( P =0.133). Significant differences were observed in the accuracy of screw placement between the Nash Moe 2 and 3 vertebral bodies in the robot group compared with those in the control group [88.9% (88/99) vs 71.0% (115/162), P =0.001; 89.2% (83/93) vs 60.2% (68/113), P <0.001]. Additionally, the incidence and grade of facet joint violation in the manual group were both significantly higher than those in the robot-assisted group (both P <0.001). No statistically significant differences was identified in postoperative complications between the two groups ( P =0.841). Conclusion: It suggests that robot-assisted pedicle screw placement in posterior surgery for patients with ADS can significantly improve the accuracy of screw placement and reduce the incidence of facet joint violation.

Alginate is a linear polysaccharide with a modifiable structure and abundant functional groups, offers immense potential for tailoring diverse alginate-based materials to meet the demands of biomedical applications. Given the advancements in modification techniques, it is significant to analyze and summarize the modification of alginate by physical, chemical and biological methods. These approaches provide plentiful information on the preparation, characterization and application of alginate-based materials. Physical modification generally involves blending and physical crosslinking, while chemical modification relies on chemical reactions, mainly including acylation, sulfation, phosphorylation, carbodiimide coupling, nucleophilic substitution, graft copolymerization, terminal modification, and degradation. Chemical modified alginate contains chemically crosslinked alginate, grafted alginate and oligo-alginate. Biological modification associated with various enzymes to realize the hydrolysis or grafting. These diverse modifications hold great promise in fully harnessing the potential of alginate for its burgeoning biomedical applications in the future. In summary, this review provides a comprehensive discussion and summary of different modification methods applied to improve the properties of alginate while expanding its biomedical potentials., 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.)

Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123 . This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC 50 = 2.1 nM) and FLT3-ITD (IC 50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC 50 = 0.98 nM) and MV4-11 (IC 50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC 50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

Under warm temperatures, plants adjust their morphologies for environmental adaption via precise gene expression regulation. However, the function and regulation of alternative polyadenylation (APA), an important fine-tuning of gene expression, remains unknown in plant thermomorphogenesis. In this study, we found that SUMOylation, a critical post-translational modification, is induced by a long-term treatment at warm temperatures via a SUMO ligase SIZ1 in Arabidopsis. Disruption of SIZ1 altered the global usage of polyadenylation signals and affected the APA dynamic of thermomorphogenesis-related genes. CPSF100, a key subunit of the CPSF complex for polyadenylation regulation, is SUMOylated by SIZ1. Importantly, we demonstrated that SUMOylation is essential for the function of CPSF100 in genome-wide polyadenylation site choice during thermomorphogenesis. Further analyses revealed that the SUMO conjugation on CPSF100 attenuates its interaction with two isoforms of its partner CPSF30, increasing the nuclear accumulation of CPSF100 for polyadenylation regulation. In summary, our study uncovers a regulatory mechanism of APA via SIZ1-mediated SUMOylation in plant thermomorphogenesis., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC 50 values of 3.3, 3.2 and 5.8 μM. Further cell assays showed IC 50 values of 0.2, 1.2 and 0.6 μM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible., (© 2024 Wiley-VCH GmbH.)

Background: In recent years, the trichomonosis in raccoon dogs in China had occurred frequently. Pentatrichomonas hominis had been described in raccoon dogs in China in some previous studies. PURPOSE TO REVEAL: whether raccoon dogs can be infected by other trichomonad species besides P. hominis, and clarify the prevalence and species distribution of trichomonad in raccoon dogs., Methods: Herein, the 389 fecal samples were collected from farm-raised raccoon dogs in Hebei Province, all the samples were detected using the microscopic examination and several fecal samples containing trichomonad-like organisms were processed, cultured, stained, and photographed. Meanwhile, all the samples were screened by the species-specific nested PCR based on the small subunit rRNA (SSU rRNA) gene of P. hominis,Tritrichomonas foetus and Tetratrichomonas buttreyi, respectively, and all positive secondary PCR amplications obtained in this study were sequenced, aligned and analysed., Results: 62 fecal samples (15.9%,62/389) were trichomonad-positive under light microscopy, and the trichomonad-like cells were clearly observed in the culture contents. The PCR results showed that 100 samples were trichomonad-positive, including 45 P. hominis-positive samples (11.6%,45/389), 32 T. foetus-positive samples (8.2%,32/389), and 33 T. buttreyi-positive samples (8.5%,33/389), respectively. Double mixed infections were observed in 10 samples. The prevalence of T. foetus and P. hominis were both significantly higher in raccoon dogs with diarrhea (13.9%, and 25.0%) than that in raccoon dogs without diarrhea (7.6%, and 9.3%) (p < 0.05).All samples confirmed as trichomonad-positive under microscopy were also found to be trichomonad-positive by PCR analysis. The sequencing and phylogenetic analysis demonstrated the sequences obtained in this study belonged to P. hominis, T. foetus and T. buttreyi SSU rRNA, respectively. Among them, the T. buttreyi SSU rRNA sequences obtained in this study harbored the new sequence polymorphisms. Based on preliminary morphological and molecular analyses, raccoon dogs are considered as the new host of T. foetus and T. buttreyi., Conclusion: This is the first report about the identifcation and prevalence of T. foetus and T. buttreyi in raccoon dogs in China, and the results increase our knowledge about the host range and prevalence of trichomonad species., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Organophosphate esters (OPEs) serve as significant flame retardants and plasticizers in various petrochemical downstream products. The petrochemical industry could be a potential source of atmospheric OPEs, but their emissions from this industry are poorly understood. The present study revealed the spatial variation, emission, and atmospheric transport of traditional and novel OPEs (TOPEs and NOPEs, respectively) in atmospheric particulate matter (PM) across Hainan and Guangdong petrochemical complexes (HNPC and GDPC, respectively) in southern China. The total concentrations of TOPEs ranged from 232 to 46,002 pg/m 3 and from 200 to 20,347 pg/m 3 in the HNPC and GDPC, respectively, which were substantially higher than those of NOPEs (HNPC: 23.5-147 pg/m 3 , GDPC: 13.9-465 pg/m 3 ). Enterprises involved in the production of downstream petrochemical products presented relatively high concentrations of OPEs, indicating evident emissions of these pollutants in the petrochemical industry. The correlations of PM-bound OPEs in the atmosphere are determined mainly by their coaddition to industrial products or their coexistence in technical mixtures. The annual emissions of TOPEs and NOPEs in the HNPC were 42.6 kg and 0.34 kg, respectively, and those in the GDPC were 116 kg and 1.85 kg, respectively. OPEs from the HNPC can reach Vietnam, Cambodia, and Guangxi Province, China, and those from the GDPC can reach Guangxi Province and Hunan Province via atmospheric transmission after 24 h of emission. The OPE concentrations reaching the receptor regions were generally less than 3.20 pg/m 3 . Risk assessment revealed that OPE inhalation exposure on two petrochemical complexes likely poses minor risks for people living in the study areas, but the risk resulting from two chlorinated OPEs should be noted since they are close to the threshold values. This study has implications for enhancing control measures for OPE emissions to reduce health risks related to the petrochemical industry., 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.)

The objective of this study is to explore whether sodium valproate (VPA) alleviates epileptic seizures via suppressing lysyl oxidase (Lox)-mediated ferroptosis. Epileptic seizure mouse model was prepared via intrahippocampal injection of kainic acid (250 ng/μl). After treatment with kainic acid, VPA was injected intraperitoneally by the dose of 250 mg/kg twice daily for 4 days. Ferroptosis-associated indices including lipid peroxides (LPO) level and Ptgs2 mRNA in hippocampal tissue samples were detected. Additionally, effects of VPA on Lox mRNA and enzymatic activity were assessed by quantitative real-time PCR and a commercial kit, respectively. Neuronal survival was assessed by Nissl staining. In kainic acid-induced epileptic seizure mouse model, VPA significantly suppressed LPO level and Ptgs2 mRNA and the suppression of ferroptosis was positively correlated with its anti-seizure effect. Lox mRNA and enzymatic activity were also found to decrease in hippocampus of epileptic seizure mice after VPA treatment. Furthermore, overexpression of Lox via adeno-associated virus infection remarkably abrogated the inhibitory effect of VPA on ferroptosis and neuronal impairment together with its anti-seizure effect. VPA suppresses Lox-mediated ferroptosis process, which can provide the explanation for its anti-seizure property., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dipterocarpus retusus Blume is an endangered species on the IUCN Red List. In this study, we reported the complete chloroplast (cp) genome of D. retusus (GenBank accession number: OP271853). The cp genome was 154,303 bp long, with a large single-copy (LSC) region of 85,586 bp and a small single-copy (SSC) region of 20,273 bp separated by a pair of inverted repeats (IRs) of 24,222 bp. It encodes 128 genes, including 84 protein-coding genes, 36 tRNA genes, and eight ribosomal RNA genes. We also reconstructed the cp genome phylogeny of Dipterocarpus , which indicated D. retusus was closely related with the sympatric species D. gracilis . This study may contribute valuable information to the phylogenetic relationships within the genus Dipterocarpus ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity., Methods: The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism., Results: The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ , IL-1β , IL-6 , tumor necrosis factor-alpha ( TNF-α ), and nuclear factor kappa B ( NF-κB ) p65 , while concomitantly upregulating the expression of Janus kinase ( JAK ) and signal transducer and activator of transcription 3 ( STAT3 ). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae , while decreasing the abundance of Bacteroidaceae , Rikenellaceae , and Helicobacteraceae ., Conclusion: Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis., 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 Li, Yan, Zhou, Geng and Xiong.)

Vivipary is a prominent feature of mangroves, allowing seeds to complete germination while attached to the mother plant, and equips propagules to endure and flourish in challenging coastal intertidal wetlands. However, vivipary-associated genetic mechanisms remain largely elusive. Genomes of two viviparous mangrove species and a non-viviparous inland relative were sequenced and assembled at the chromosome level. Comparative genomic analyses between viviparous and non-viviparous genomes revealed that DELAY OF GERMINATION 1 (DOG1) family genes (DFGs), the proteins from which are crucial for seed dormancy, germination, and reserve accumulation, are either lost or dysfunctional in the entire lineage of true viviparous mangroves but are present and functional in their inland, non-viviparous relatives. Transcriptome dynamics at key stages of vivipary further highlighted the roles of phytohormonal homeostasis, proteins stored in mature seeds, and proanthocyanidins in vivipary under conditions lacking DFGs. Population genomic analyses elucidate dynamics of syntenic regions surrounding the missing DFGs. Our findings demonstrated the genetic foundation of constitutive vivipary in Rhizophoraceae mangroves., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chlorogenic acid (CGA), a polyphenol compound, exhibits excellent anti-oxidative, anti-hypoxic, antibacterial, antiviral, and anti-inflammatory activities, however the bioactivity of it has not been fully utilized in vivo due to its instability and low bioavailability. To address these issues, we prepared and characterized CGA-TPGS-LP, which is a TPGS-modified liposome loaded with CGA. The pharmacokinetics of CGA-TPGS-LP were studied in rats after oral administration. CGA-TPGS-LP was fabricated using a combination of thin film dispersion and ion-driven methods. The liposomes were observed to be uniformly small and spherical in shape. Their membranes were composed of lecithin, cholesterol, and TPGS lipophilic head with a TPGS hydrophilic tail chain coating on its surface. The loading efficiency and encapsulation efficiency were found to be 11.21% and 83.22%, respectively. The physicochemical characterisation demonstrated that the CGA was present in an amorphous form and retained its original structural state within the liposomal formulation. The stability of CGA was significantly improved by fabricating TPGS-LP. CGA-TPGS-LP exhibited good sustained-release properties in both simulated gastric and intestinal fluids. Following oral administration, ten metabolites were identified in rat plasma using UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis demonstrated that the oral bioavailability of CGA encapsulated in TPGS-modified liposomes was enhanced by 1.52 times. In addition, the three main metabolites of CGA had higher plasma concentrations and slower degradation rate. These results demonstrate that TPGS-modified liposomes could be a feasible strategy to further enhance the oral bioavailability of CGA, facilitating its clinical use., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Colorectal cancer (CRC) is one of the most prevalent malignancies affecting the gastrointestinal tract and is ranked third among cancers with the highest incidence and second-highest mortality rate worldwide. CRC exhibits a slow progression providing a wide treatment window. The currently employed CRC screening methods have shown great potential to prevent CRC and reduce CRC-related morbidity and mortality. The diagnosis of CRC is achieved by colonoscopy and tissue biopsy, with studies showing that liquid biopsy is more effective in detecting and diagnosing early CRC patients. Increasing number of studies have shown that the tumor components shed into circulating blood can be detected in liquid form, and can be applied in the clinical management of CRC. Analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-associated platelets (TEPs) in the blood can be used for early screening and diagnosis of CRC, aid tumor staging, treatment response monitoring, and prediction of CRC recurrence and metastasis in a minimally invasive manner. This chapter provides an updated review of CTCs, ctDNA, and TEPs as novel biomarkers for CRC, highlighting their strengths and limitations., (© 2024. The Author(s).)

We disclosed herein an enantioselective formal siloxycarbene insertion reaction enabled by chiral phosphoric acid and blue LED irradiation. This is the first time the asymmetric siloxycarbene insertion into an sp 3 C-H bond under transition-metal free conditions has been realized. The reaction features good isolated yields (up to 92%), high enantioselectivity (up to 99:1 er ), mild reaction conditions, and good compatibility. Moreover, this method also provides a green and efficient method to construct a chiral quaternary carbon center.

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., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU)., Aim: To investigate the contributions of H . pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases., Methods: Patients with H . pylori infection and either GU or DU, and healthy individuals without H . pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed., Results: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H . pylori -positive patients with GU was dominated by H . pylori , with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H . pylori -positive GU patients, were all derived from H . pylori , particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori -positive DU patients and healthy controls., Conclusion: H . pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Sepsis is a life-threatening condition marked by a severe systemic response to infection, leading to widespread inflammation, cellular signaling disruption, and metabolic dysregulation. The role of lipid and amino acid metabolism in sepsis is not fully understood, but aberrations in this pathway could contribute to the disease's pathophysiology., Methods: To explore the potential of lipid and amino acid compounds as biomarkers for the diagnosis and prognosis of sepsis, a two-sample Mendelian Randomization (MR) study was conducted, examining the relationship between sepsis and 249 serum lipid and amino acid-related markers. Key enzymes involved in synthesis of phosphatidylcholine, including choline/ethanolamine phosphotransferase 1 (CEPT1), choline phosphotransferase 1 (CPT1), and ethanolamine phosphotransferase 1 (EPT1), were also targeted for drug-target Mendelian randomization., Results: The study found that phosphatidylcholines (OR IVW : 0.88, 95%CI: 0.80-0.96, p = 0.005) and phospholipids in medium HDL (OR IVW : 0.86, 95%CI: 0.77-0.96, p = 0.007) potentially exhibit a protective effect against sepsis nominally. However, the potential drug target of CEPT1, CPT1, and EPT1 was found to be unrelated to septic outcomes., Conclusion: Our findings suggest that increasing levels of phosphatidylcholines and medium HDL phospholipids may reduce the incidence of sepsis. This highlights the potential of lipid-based biomarkers in the diagnosis and management of sepsis, opening avenues for new therapeutic strategies., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

For a nonlinear parabolic distributed parameter system (DPS), a fuzzy boundary sampled-data (SD) control method is introduced in this article, where distributed SD measurement and boundary SD measurement are respected. Initially, this nonlinear parabolic DPS is represented precisely by a Takagi-Sugeno (T-S) fuzzy parabolic partial differential equation (PDE) model. Subsequently, under distributed SD measurement and boundary SD measurement, a fuzzy boundary SD control design is obtained via linear matrix inequalities (LMIs) on the basis of the T-S fuzzy parabolic PDE model to guarantee exponential stability for closed-loop parabolic DPS by using inequality techniques and a acrlong LF. Furthermore, respecting the property of membership functions, we present some LMI-based fuzzy boundary SD control design conditions. Finally, the effectiveness of the designed fuzzy boundary SD controller is demonstrated via two simulation examples.

Vascular endothelial cells (VECs) are key players in the formation of neovessels and tumor metastasis, the ultimate cause of the majority of cancer-related human death. However, the crosstalk between VECs and metastasis remain greatly elusive. Based on our finding that tumor-associated VECs present significant decrease of Nrdp1 protein which is closely correlated with higher metastatic probability, herein we show that the conditional medium from hypoxia-incubated cancer cells induces extensive Nrdp1 downregulation in human and mouse VECs by vascular endothelial growth factor (VEGF), which activates CHIP, followed by Nrdp1 degradation in ubiquitin-proteasome-dependent way. More importantly, lung metastases of cancer cells significantly increase in conditional VECs Nrdp1 knockout mice. Mechanically, Nrdp1 promotes degradation of Fam20C, a secretory kinase involved in phosphorylating numerous secreted proteins. Reciprocally, deficiency of Nrdp1 in VECs (ecNrdp1) results in increased secretion of Fam20C, which induces degradation of extracellular matrix and disrupts integrity of vascular basement membrane, thus driving tumor metastatic dissemination. In addition, specific overexpression of ecNrdp1 by Nrdp1-carrying adeno-associated virus or chemical Nrdp1 activator ABPN efficiently mitigates tumor metastasis in mice. Collectively, we explore a new mechanism for VEGF to enhance metastasis and role of Nrdp1 in maintaining the integrity of vascular endothelium, suggesting that ecNrdp1-mediated signaling pathways might become potential target for anti-metastatic therapies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Parental or ancestral environments can induce heritable phenotypic changes, but whether such environment-induced heritable changes are a common phenomenon remains unexplored. Here, we subject 14 genotypes of Arabidopsis thaliana to 10 different environmental treatments and observe phenotypic and genome-wide gene expression changes over four successive generations. We find that all treatments caused heritable phenotypic and gene expression changes, with a substantial proportion stably transmitted over all observed generations. Intriguingly, the susceptibility of a genotype to environmental inductions could be predicted based on the transposon abundance in the genome. Our study thus challenges the classic view that the environment only participates in the selection of heritable variation and suggests that the environment can play a significant role in generating of heritable variations., (© 2024. The Author(s).)

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM., 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 Masson SAS. All rights reserved.)

Trachinotus ovatus is an economically important fish and has been recommended as a high-quality aquaculture fish breed for the high-quality development of sea ranches in the South China Sea. However, T. ovatus shows intolerance to low temperature, greatly limiting the extension of farming scale, reducing production efficiency in winter, and increasing farming risks. In this study, liver transcriptome analysis was investigated in T. ovatus under acute low temperature conditions (20 and 15 °C) using RNA sequencing (RNA-Seq) technology. Inter-groups differential expression analysis and trend analysis screened 1219 DEGs and four significant profiles (profiles 0, 3, 4, and 7), respectively. GO enrichment analysis showed that these DEGs were mainly related to metabolic process and cell growth and death process. KEGG enrichment analysis found that DEGs were mainly associated with lipid metabolism, carbohydrate metabolism, and cell growth and death, such as gluconeogenesis, glycolysis, fatty acid oxidation, cholesterol biosynthesis, p53 signaling pathway, cell cycle arrest, and apoptotic cell death. Moreover, protein-protein interaction networks identified two hub genes (FOS and JUNB) and some important genes related to metabolic process and cell growth and death process, that corresponding to enrichment analysis. Overall, gluconeogenesis, lipid mobilization, and fatty acid oxidation in metabolic process and cell cycle arrest and apoptotic cell death in cell growth and death process were enhanced, while glycolysis, liver glycogen synthesis and cholesterol biosynthesis in metabolic process were inhibited. The enhancement or attenuatment of metabolic process and cell growth and death process is conducive to maintain energy balance, normal fluidity of cell membrane, normal physiological functions of liver cell, enhancing the tolerance of T. ovatus to cold stress. These results suggested that metabolic process and cell growth and death process play important roles in response to acute cold stress in the liver of T. ovatus. Gene expreesion level analysis showed that acute cold stress at 15 °C was identified as a critical temperature point for T. ovatus in term of cellular metabolism alteration and apoptosis inducement, and rewarming intervention should be timely implemented above 15 °C. Our study can provide theoretical support for breeding cold-tolerant cultivars of T. ovatus, which is contributed to high-quality productions fish production., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The genus Argentina Hill belongs to the tribe Potentilleae Sweet and contains approximately 75 species predominantly distributed in the Sino-Himalayan region and the Malesian archipelago. So far we have less knowledge on the phylogenetic relationships within Argentina owing to limited sampling of Argentina taxa or gene fragments in previous studies. Moreover, to date there is no phylogenetic study on Argentina from the perspective of comparative chloroplast (cp) genomics. Here we performed comparative genomic analyses on the cp genomes of 39 accessions representing 18 taxa of Argentina . The Argentina cp genomes presented the typical quadripartite structure, with the sizes ranging from 155 096 bp to 157 166 bp. The 39 Argentina cp genomes contained a set of 112 unique genes, comprising four ribosomal RNA (rRNA) genes, 30 transfer RNA (tRNA) genes, as well as 78 protein-coding genes (PCGs). The cp genome organization, gene content and order in Argentina were highly conserved, but some visible divergences were present in IR/SC boundary regions. Ten regions ( trnH-GUG-psbA, trnG-GCC-trnfM-CAU, trnD-GUC-trnY-GUA, rpl32-trnL-UAG, atpH-atpI, rps16-trnQ-UUG, trnS-GCU-trnG-UCC, ndhF-rpl32, trnR-UCU-atpA, and accD-psaI ) were identified as excellent candidate DNA markers for future studies on species identification, population genetics and phylogeny of Argentina . Our results indicated that Argentina is monophyletic. In the current sampling, the A. smithiana - A. anserina clade was sister to the remainder of Argentina . Our results corroborated the previous taxonomic treatments to transfer A. phanerophlebia and A. micropetala from the genus Sibbaldia L. to Argentina . Our results showed close relationships among A. stenophylla , A. microphylla , A. taliensis , and A. tatsienluensis , congruent with previous studies based on the morphology of these species. Twenty-six genes ( rps3, rps15, rps16, rps19, rpl16, rpl20, rpl22, rpoA, rpoB, rpoC1, rpoC2, atpA, atpF, psbB, psbF, ndhA, ndhB, ndhC, ndhD, ndhF, rbcL, accD, ccsA, matK, ycf1, ycf2 ) were with sites under positive selection, and adaptive evolution of these genes might have played crucial roles in Argentina species adaptation to the harsh mountain environment. This study will facilitate future work on taxonomy, phylogenetics, and adaptive evolution of Argentina ., 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 Li, Zhang, Aogan and Wen.)

Decapterus maruadsi is a typical representative of small pelagic fish characterized by fast growth rate, small body size, and high fecundity. It is a high-quality marine commercial fish with high nutritional value. However, the underlying genetics and genomics research focused on D. maruadsi is not comprehensive. Herein, a high-quality chromosome-level genome of a male D. maruadsi was assembled. The assembled genome length was 716.13 Mb with contig N50 of 19.70 Mb. Notably, we successfully anchored 95.73% contig sequences into 23 chromosomes with a total length of 685.54 Mb and a scaffold N50 of 30.77 Mb. A total of 22,716 protein-coding genes, 274.90 Mb repeat sequences, and 10,060 ncRNAs were predicted, among which 22,037 (97%) genes were successfully functionally annotated. The comparative genome analysis identified 459 unique, 73 expanded, and 52 contracted gene families. Moreover, 2804 genes were identified as candidates for positive selection, of which some that were related to the growth and development of bone, muscle, cardioid, and ovaries, such as some members of the TGF-β superfamily, were likely involved in the evolution of typical biological features in D. maruadsi . The study provides an accurate and complete chromosome-level reference genome for further genetic conservation, genomic-assisted breeding, and adaptive evolution research for D. maruadsi .

Background: Allergen immunotherapy (AIT)-associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti-IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety., Objective: To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases., Methods: The MEDLINE/PubMed, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random-effect model was established to estimate outcomes with a 95% confidence interval (CI)., Results: A total of 11 eligible RCTs (involving 901 patients) were screened out for the meta-analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio [OR] = 2.43; 95% CI: 1.33-4.44; p = 0.004; I 2  = 35%, and OR = 6.77; 95% CI: 2.10-21.80; p = 0.001; I 2  = 36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR = 0.32; 95% CI: 0.18-0.59; p = 0.0003; I 2  = 0%). Meanwhile, the improvements in symptom severity score (mean difference [MD] = -0.26), rescue medication daily means score (MD = -0.14), and number of patients consuming epinephrine in AIT (OR = 0.20) were all more evident than those in AIT alone., Conclusion: Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic AEs., (© 2023 ARS‐AAOA, LLC.)