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Lung cancer is the leading factor of cancer-related death in the worldwide. Hexavalent chromium [Cr(VI)] is a potential carcinogen for inducing lung cancers. To understand new mechanism of Cr(VI)-induced tumorigenesis and cancer development, we identified that PDK1 expression levels were greatly increased in chromium-transformed cells (Cr-T) compared to the parental BEAS-2B (B2B) cells by proteomic profiling and Western blotting; PDK1 levels were also induced in lung cancer cell lines and in lung samples of mice exposed to Cr(VI). Cr(VI) increased Warburg effect, cell migration, proliferation and colony formation through PDK1 upregulation. To identify the mechanism of PDK1 induction, we performed miRNA-seq analysis of Cr-T and B2B cells, and found miR-493 levels was significantly suppressed by Cr(VI). PDK1 was induced by miR-493 suppression, and was a direct target of miR-493. Interestingly, we also found HIF-1α was directly targeting by miR-493 and was induced by miR-493 downregulation. HIF-1α expression levels were upregulated in lung samples of mice with Cr(VI)-exposure. PDK1 was induced by HIF-1α, showing miR-493 suppression can directly induce PDK1 as well as through HIF-1α induction. MiR-493 overexpression was sufficient to suppress tumor growth, PDK1 and HIF-1α expression in vivo. We also showed that levels of miR-493 suppression, HIF-1α and PDK1 elevations were strongly correlated with poor prognosis of lung cancer subjects. These results demonstrate both HIF-1α and PDK1 expression are induced by Cr(VI)-mediated miR-493 suppression, and MiR-493/HIF-1α/PDK1 axis is a new pathway in Cr(VI)-inducing carcinogenesis and tumor growth., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Bakuchiol (BAK), a specialized meroterpene, is known for its valuable biological properties and has recently gained prominence in cosmetology for its retinol-like functionality. However, low abundance in natural sources leads to environmentally unfriendly and unsustainable practices associated with crop-based manufacturing and chemical synthesis. Here, we identified a prenyltransferase (PT) from Psoralea corylifolia that catalyzes the reverse geranylation of a nonaromatic carbon in para -coumaric acid ( p -CA), coupled with a decarboxylation step to form BAK. Given that the biosynthesis pathway of BAK is well elucidated, we engineered Saccharomyces cerevisiae to produce BAK, starting from glucose. To enhance the titer of BAK, we employed a multifaceted approach that included increasing the supply of precursors, balancing the fluxes in the two parallel biosynthetic pathways, engineering of prenyltransferase, and fusing enzymes. Consequently, the engineered yeast strains showed a marked improvement of 117.3-fold in BAK production, reaching a titer of 9.28 mg/L from glucose. Our work provides a viable approach for the sustainable microbial production of complex natural meroterpenes.

To gain a deeper understanding of the ACE inhibition effect, the inhibitory effect of ACE-inhibiting peptide (ACEIP) FPPDVA's digestive products on ACE was further investigated. Two novel peptides, PD (IC 50 = 161.1 ± 1.10 μM) and DV (IC 50 = 66.51 ± 0.99 μM) were identified in the digestive products of FPPDVA using LC-MS/MS. The Peptide Mix (FPPDVA, PD, and DV) exhibited a remarkable synergistic effect on ACE inhibition by significantly enhancing it by up to 508% compared to the individual peptides alone. Furthermore, theoretical simulations suggest that the Peptide Mix synergistically inhibits ACE activity by forming more stable complexes with the active site of ACE, facilitated by an increased number of hydrogen bonds. Additionally, Lineweaver-Burk plot analysis and spectroscopic studies further verified the presence of these stable complexes. ITC results show that the combination of Peptides Mix and ACE is a spontaneous exothermic process driven by entropy. The study showed that FPPDVA has a stronger inhibitory effect on ACE after digestion, making it suitable as an antihypertensive peptide in functional foods.

Background: Pea protein isolate (PPI) is gaining increasing popularity in the food industry. It provides a diverse range of health benefits, such as hypoallergenic and gluten-free characteristics. However, the functional performance of PPI is hindered by its low solubility and poor stability. Therefore, in this article, PPI and dextran (DX) of different molecular weights were grafted to investigate the effects of grafting DX with different molecular weights on the interface properties and antioxidant properties of PPI. Additionally, the stability and digestive properties of the glycated PPI nanoemulsion system were explored., Results: The result showed that the grafting degree of PPI-DX conjugates (PPI-DC) decreased with an increase in the molecular weight of DX. Surface hydrophobicity, antioxidant activity and solubility of PPI-DC were significantly improved after grafting compared with PPI and PPI-DX mixtures (PPI-DM). Astaxanthin-loaded emulsions stabilized by grafted conjugates had smaller droplets and higher astaxanthin encapsulation rate compared to PPI emulsions. In vitro digestion demonstrated that the bioavailability of PPI-DC emulsions was higher than of PPI emulsion. Furthermore, after 24 days of storage, retention rate of astaxanthin-loaded emulsions prepared by conjugates remained above 70%, surpassing that of PPI emulsion., Conclusion: These results indicated that DX grafting can improve the emulsion properties of PPI. In addition, the DX with a molecular weight of 5 kDa showed the most significant improvement. This study contributes to the advancement of natural emulsifiers by modifying PPI through glycation, and furnishes a valuable reference for its utilization in functional foods. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Environmental estrogens are currently a significant research topic, and poultry manure serves as a crucial source. This study investigated the degradation characteristics and effect mechanisms of six estrogens (E1, 17α-E2, 17β-E2, E3, 17α-EE2, and DES) during the aerobic composting of chicken manure. An orthogonal test comprising four factors (aeration rate, calcium-magnesium-phosphorus fertilizer (Ca-Mg-P fertilizer), coconut shell biochar, initial moisture content) and three levels of aerobic composting was conducted over a 45-day period to monitor the changes in estrogens and basic parameters. The results indicated that the factors influencing the estrogen degradation rate ranked as: initial moisture content (MC) > Ca-Mg-P fertilizer > aeration rate > coconut shell biochar. These factors significantly influenced the abundance of estrogen-degrading genera. Optimal composting conditions for estrogen degradation were identified as the addition of 10% coconut shell biochar, maintaining an initial moisture content of 60%, and using an aeration rate of 0.08 L min -1 ∙kg -1 DM (dry matter), with an average degradation rate of 86.88% for the six estrogens under these conditions. During the composting process under various treatments, five known estrogen-degrading genera were observed with high relative abundance (max 31.08%), and the predominant genera were Staphylococcus and Brachybacterium for 17α-E2, 17β-E2, E3, 17α-EE2, and DES, and Pusillimonas for E1. The composition of microbial community structure changed significantly, and the dominated environment factors effecting the composition and succession of these genera were carbon to nitrogen ratio (C/N) and MC. The research results can provide both a theoretical basis and practical reference for the effective degradation of estrogens during the composting of chicken manure., 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.)

Progestins are crucial steroid hormones that have attracted wide attention due to their endocrine disrupting effects in fish. The aim of this study is to investigate the effects of long-term exposure to low concentrations of norgestrel (NGT) on the reproductive and thyroid endocrine systems of adult zebrafish. Adult zebrafish were exposed to 7 and 39 ng/L NGT for a duration of 90 days. The results revealed that exposure to 39 ng/L NGT led to a significant up-regulation of 3β-hydroxysteroid dehydrogenase (hsd3b) and 20β-hydroxysteroid dehydrogenase (hsd20b) genes in the ovary of female zebrafish. Additionally, there was a significant up-regulation of 11β-hydroxysteroid dehydrogenase 2 (hsd11b2) gene in the testis of male zebrafish. Furthermore, egg production decreased significantly, accompanied by notable alterations in the proportion of ovarian development stages, as well as reductions of sex hormone levels (E2, 11-KT, and T) in both females and males. However, long-term exposure to low concentrations of NGT did not lead to changes in thyroid hormone levels and thyroid histopathology in adult zebrafish. The overall results imply that environmental concentrations of NGT have a strong endocrine disrupting effect on the reproductive system of zebrafish, while the thyroid system is not sensitive to NGT exposure. The present study underscores the reproductive endocrine impacts of NGT and emphasizes the necessity for prolonged exposure at environmental concentrations., 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.)

Introduction: Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen., Methods: A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates., Results: PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 μmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels., Conclusions: It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen., Competing Interests: Declaration of competing interest I confirm that I have no known conflicts of interest that would influence the results or interpretation the data presented in this manuscript, and I understand that failure to disclose a conflict of interest is ethical and may result in sanctions being imposed on me., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Glycinin basic peptide (GBP) is the basic polypeptide of soybean glycinin that is isolated using cheap and readily available raw materials (soybean meals). GBP can bear high-temperature processing and has good functional properties, such as emulsification and adhesion properties et al. GBP exhibits broad-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria as well as fungi. Beyond that, GBP shows enormous application potential to improve the quality and extend the shelf life of food products. This review will systematically provide information on the purification, physicochemical and functional properties of GBP. Moreover, the antimicrobial activities and multi-target antimicrobial mechanism of GBP as well as the applications of GBP in different food products are also reviewed and discussed in detail. This review aims to offer valuable insights for the applications of GBP in the food industry as a promising natural food additive and preservative., 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.)

Objective: Circular RNAs (circRNAs) are widely involved in the regulation of lipid deposition in animals, but there are few reports on key circRNAs regulating intramuscular adipocyte differentiation in goats. Therefore, this study took an abundantly expressed in goat adipocytes chi-circ_0009659 as the object., Methods: Based on the identification of back splicing site in chi-circ_0009659, its expression level during the goat intramuscular preadipocyte differentiation was detected by qPCR. The chi-circ_0009659 loss-of-function and gain-of-function cell models were obtained by adenovirus and smarter silencer, respectively. and the adipocyte differentiation were explored by Oil Red O staining, Bodipy staining and qPCR. Its major cytoplasmic localization was determined by FISH, nucleocytoplasmic separation and qPCR. The interaction between chi-circ_0009659, miR-3431-5p, and STEAP family member 4 (STEAP4) was verified by bioinformatics, RNA pull down and dual luciferase reporter assay., Results: Silencing chi-circ_0009659 inhibited lipid droplet accumulation and the expression of differentiation-determining genes in goat intramuscular adipocytes, while overexpression of chi-circ_0009659 reversed these results. chi-circ_0009659 was predominantly localized to the cytoplasm and could regulate miR-3431 expression which in turn affects STEAP4. Consistent with expectations, miR-3431-5p acted as a negative regulator of GIMPA differentiation, while STEAP4 promoted differentiation., Conclusion: We demonstrated chi-circ_0009659 positively regulates goat intramuscular preadipocyte differentiation by sponging miR-3431-5p to further regulate the expression of STEAP4. This research provides a new reference for in-depth understanding of the effects of circRNA on adipocyte differentiation.

One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy ( 1 H, 13 C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC 50 value of 0.656 μM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Despite continuous expansion of the RNA binding protein (RBP) world, there is a lack of systematic understanding of RBPs in the mammalian testis, which harbors one of the most complex tissue transcriptomes. We adapted RNA interactome capture to mouse male germ cells, building an RBP atlas characterized by multiple layers of dynamics along spermatogenesis. Trapping of RNA-cross-linked peptides showed that the glutamic acid-arginine (ER) patch, a residue-coevolved polyampholytic element present in coiled coils, enhances RNA binding of its host RBPs. Deletion of this element in NONO (non-POU domain-containing octamer-binding protein) led to a defective mitosis-to-meiosis transition due to compromised NONO-RNA interactions. Whole-exome sequencing of over 1000 infertile men revealed a prominent role of RBPs in the human genetic architecture of male infertility and identified risk ER patch variants.

The hypothalamic supramammillary nucleus (SuM) projects heavily to the hippocampus to regulate hippocampal activity and plasticity. Although the projections from the SuM to the dentate gyrus (DG) and CA2 have been extensively studied, whether the SuM projects to CA1, the main hippocampal output region, is unclear. Here, we report a glutamatergic pathway from the SuM that selectively excites CA1 interneurons in the border between the stratum radiatum (SR) and the stratum lacunosum-moleculare (SLM). We find that the SuM projects selectively to a narrow band in the CA1 SR/SLM and monosynaptically excites SR/SLM interneurons, including vasoactive intestinal peptide-expressing (VIP + ) and neuron-derived neurotrophic factor-expressing (NDNF + ) cells, but completely avoids making monosynaptic contacts with CA1 pyramidal neurons (PNs) or parvalbumin-expressing (PV + ) or somatostatin-expressing (SOM + ) cells. Moreover, SuM activation drives spikes in most SR/SLM interneurons to suppress CA1 PN excitability. Taken together, our findings reveal that the SuM can directly regulate hippocampal output region CA1, bypassing CA2, CA3, and the DG., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Four newly identified benzophenone analogs [nigrophenone A-D (1-4)] and a pyrrolidinone analog [nigropyrrolidinone (5)], alongside thirteen known congeners (6-18), were isolated from Nigrospora sphaerica. Transcriptome analysis revealed that 6 might have the potential to modulate T-cell immunity. Quantitative measurements of the binding affinities between eighteen natural molecules and the immunological checkpoint receptors PD-1 and PD-L1 were performed using Surface Plasmon Resonance (SPR). The results of SPR analysis showed that 1-18 have K D values ranging from 1.8 to 99.5 μM for PD-1 and from 10.6 to 99.5 μM for PD-L1. Competitive inhibition studies, employing SPR and ELISA assays, have indicated that compounds 6, 10, 15, and 18 are capable of inhibiting the PD-1/PD-L1 interaction. Additionally, compound 6 exhibited notable in vitro anticancer potency through the augmentation of activating signals and the upregulation of PD-1 expression on CD8 + T cells, concurrently elevating the secretion of IFN-γ and IL-2, thereby inhibiting the proliferation of LLC and MC38 cells and promoting MC38 apoptosis. Moreover, compound 6 modulates the PI3K/Akt pathway, which is a key downstream effector of the PD-1/PD-L1 axis. These compounds are considered promising candidates for more in-depth exploration because they could significantly inhibit PD-1/PD-L1 interactions in tumor immunotherapy., 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 Inc. All rights reserved.)

Background: Osteoporosis (OP) has garnered significant attention due to its substantial morbidity and mortality rates, imposing considerable health burdens on societies worldwide. However, the molecular mechanisms underlying osteoporosis pathogenesis remain largely elusive, and the available therapeutic interventions are limited. Therefore, there is an urgent need for innovative strategies in the treatment of osteoporosis., Purpose: The primary objective of this study was to elucidate the molecular mechanisms underlying osteoporosis pathogenesis using single-cell RNA sequencing (scRNA-seq), thereby proposing novel therapeutic agents., Methods: The mice osteoporosis model was established through bilateral ovariectomy. Micro-computed tomography (μCT) and hematoxylin and eosin (H&E) staining were employed to assess the pathogenesis of osteoporosis. scRNA-seq was utilized to identify and analyze distinct molecular mechanisms and sub-clusters. Gradient dilution analysis was used to obtain specific sub-clusters, which were further validated by immunofluorescence staining and flow cytometry analysis. Molecular docking and cellular thermal shift assay (CETSA) were applied for screening potential agents in the TCMSPs database. Alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Osteogenic organoids analysis was employed to assess the proliferation and sphere-forming ability of BMSCs. Quantitative real-time PCR (qRT-PCR) and western blot analysis were conducted to investigate signaling pathways. Wound healing assay and tube formation analysis were employed to evaluate the angiogenesis of endothelial cells., Results: The scRNA-seq analysis revealed the crucial role of LEPR + BMSCs in the pathogenesis of osteoporosis, which was confirmed by immunofluorescence staining of the epiphysis. Subsequently, the LEPR + BMSCs were obtained by gradient dilution analysis and identified by immunofluorescence staining and flow cytometry. Accordingly, specnuezhenide (Spe) was screened and identified as a potential compound targeting METTL3 from the TCMSPs database. Spe promoted bone formation as evidenced by μ-CT, and H&E analysis. Additionally, Spe enhanced the osteogenic capacity of LEPR + BMSCs through ALP and ARS assay. Notably, METTL3 pharmacological inhibitors S-Adenosylhomocysteine (SAH) attenuated the aforementioned osteo-protective effects of Spe. Particularly, Spe enhanced the LEPR + BMSCs-dependent angiogenesis through the secretion of SLIT3, which was abolished by SAH in LEPR + BMSCs., Conclusion: Collectively, these findings suggest that Spe could enhance the osteogenic potential of LEPR + BMSCs and promote LEPR + BMSCs-dependent angiogenesis by activating METTL3 in LEPR + BMSCs, indicating its potential as an ideal therapeutic agent for clinical treatment of osteoporosis., 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.)

Phloem fiber is a key component of phloem tissue and is involved in supporting its structural integrity. NAC domain transcription factors are master switches that regulate secondary cell wall (SCW) biosynthesis in xylem fibers, but the mechanism by which NACs regulate phloem fiber development remains unexplored. Here, a NAC2-like gene in poplar, PagNAC2a, was shown to be involved in phloem fiber differentiation. qRT-PCR and GUS staining revealed that PagNAC2a was specifically expressed in the phloem zone of poplar stems. The overexpression of PagNAC2a in poplar increased plant biomass by increasing plant height, stem diameter, and leaf area. Stem anatomy analysis revealed that overexpression of PagNAC2a resulted in enhanced phloem fiber differentiation and cell wall deposition. In addition, PagNAC2a directly upregulated the expression of PagATL2, a gene involved in phloem development, as revealed by yeast one hybrid (Y1H) and electrophoretic mobility shift assay (EMSA) assays. Overall, we proposed that the PagNAC2a was a positive regulator of phloem fiber development in poplar, and these results provided insights into the molecular mechanisms involved in the differentiation of phloem fibers., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The impact of internet usage on mortality is not widely known. This study intended to investigate the associations between regular internet usage and the risks of all-cause and cause-specific mortality, while also ascertaining potential factors that may modify these correlations., Design: A community-based prospective cohort study., Setting and Participants: The study included 21,481 individuals [mean (SD) age, 64.1 (11.0) years] from the Health and Retirement Study, with data collected between 2006 and 2020., Methods: The Cox proportional hazards regression model was used to evaluate the associations between regular internet usage and the risks of all-cause and cause-specific mortality, adjusting for demographic factors, lifestyle behaviors, and other potential confounding factors. Moreover, we explored the association between daily hours of internet usage and the risk of outcomes., Results: Regular internet usage was significantly associated with a lower risk of all-cause mortality (hazard ratio, 0.78; 95% CI, 0.74-0.83) and cardiovascular mortality (hazard ratio, 0.72; 95% CI, 0.64-0.82). No significant interaction effects were observed for age, sex, regular exercise, or current alcohol consumption (all P interactions > .05). Additionally, estimations for daily hours of usage indicated a U-shaped relationship with all-cause mortality. Adults who used 2.1 to 4 hours per day had the lowest risk; however, not all estimations showed their significance on account of the limited sample size., Conclusions and Implications: Regular internet usage was associated with a lower risk of all-cause and cardiovascular mortality, which may prompt consideration of the beneficial impact of internet usage on lifespan., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the early predictive value of halving time (HT) of BCR-ABL IS for deep molecular response (DMR) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI)., Methods: The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed. Combined with the clinical characteristics of the patients and the efficacy analysis at each time point, a logistic regression model was used to explore the independent influencing factors of DMR, and combined HT of BCR-ABL IS with BCR-ABL IS level at 3 months to predict DMR of the patients., Results: Univariate and multivariate analyses showed that HT and 3-month BCR-ABL IS levels were independent influencing factors for MR4, MR4.5, and stable MR4.5 ( P < 0.05). ROC curve analysis determined that the best cut-off value of HT was 28 days. Compared with patients with HT>28 d, patients with HT≤28 d were more likely to obtain DMR at 2, 3, and 5 years, respectively (74.2% vs 27.3%, 71.2% vs 22.7%, and 63.6% vs 25.0%, all P < 0.001). The patients were divided into 4 groups according to BCR-ABL IS levels at 3 months and HT. Kaplan-Meier analysis showed that the patients in the BCR-ABL IS ≤10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABL IS ≤10% and HT>28 d group ( P < ＜0.05); Patients in the BCR-ABL IS >10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABL IS ＞10% and HT>28 d group ( P < 0.05)., Conclusion: In addition to BCR-ABL IS level, HT of BCR-ABL IS can be used as another important predictor of treatment efficacy in CML patients. The combination of BCR-ABL IS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.

Background: We aimed to verify the effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery by meta-analysis and trial sequential analysis (TSA)., Methods: From inception to May 14, 2024, PubMed, the Cochrane Library, Web of Science, and Embase databases were searched. TSA was used to determine an optimal sample size and control false-positive findings. The primary outcome was the time to first defecation (hours)., Results: Fourteen studies were included, with 1105 participants. Meta-analysis and TSA revealed firm evidence for benefits that electroacupuncture shorted the time to first defecation (mean difference [MD] -12.73 h, I 2  = 22%, P < 0.01), the time to first flatus (MD -7.03 h, I 2  = 25%, P < 0.01), the time to start of sips of water (MD -12.02 h, I 2  = 0%, P < 0.01), and the time to start of liquid diet (MD -12.97 h, I 2  = 0%, P < 0.01) compared with usual care. While compared with sham electroacupuncture, meta-analysis and TSA also confirmed that electroacupuncture shortened the time to first defecation (MD -10.81 h, I 2  = 31%, P = 0.02) and the time to first flatus (MD -10.81 h, I 2  = 0%, P < 0.01). However, TSA revealed that firm evidence for benefit or futility was not reached for the length of hospital stay and the rates of postoperative prolonged ileus., Conclusions: Electroacupuncture shortened the duration of postoperative ileus in patients undergoing abdominal surgery, and the adverse events related to electroacupuncture were minor. Further investigation of the effect of electroacupuncture on the risk of prolonged postoperative ileus is warranted in the future., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Contralateral cervical seventh (cC7) nerve to C7 transfer has been proven effective for treating spastic upper limb. However, for those whose major impairment is not in the C7 area, cC7 nerve transfer to other nerves may achieve a better outcome. The aim of this study was to explore the optimal surgical approach for transferring cC7 to 1 or 2 nerves in a cadaveric study, and to evaluate possible applications for patients with hemiplegia., Methods: Modified cC7 transfer to 1 (5 procedures) or 2 nonadjacent (3 procedures) nerve roots was proposed, and success rates of direct coaptation through 2 surgical approaches-the superficial surface of longus colli (sLC) and the deep surface of longus colli (dLC) approach-were compared. The length, diameter, and distance of relevant nerves were also measured in 25 cadavers., Results: Compared with the sLC approach, the distance of the dLC approach was 1.1 ± 0.3 cm shorter. The success rates for the sLC and dLC approaches were as follows: cC7 to C5 surgery, 94%, and reached 98%; cC7 to C6 surgery, 54% and 96%; cC7 to C7 surgery, 42% and 94%; cC7 to C8 surgery, 34% and 94%; cC7 to T1 surgery, 24% and 62%; cC7 to C5C7 surgery, 74% and 98%; cC7 to C6C8 surgery, 54% and 98%; and cC7 to C7T1 surgery, 42% and 88%., Conclusions: The dLC approach greatly improved the direct coaptation rate for cC7 nerve transfer. The modified cC7 nerve transfer procedures are technically feasible for further application in clinic., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types., (© 2024 John Wiley & Sons Ltd.)

Ferroelastic materials with high phase transition temperature have broad application prospects in information conversion and storage, shape memory, energy conversion, hyperelasticity, etc. However, most of the current reports focus on inorganic ferroelastic materials. Inorganic ferroelastic materials have the disadvantages of high energy consumption and harmful metals, which limit their application in practical work. In contrast, organic ferroelastic materials have the advantages of structural adjustability, environmental protection, easy processing, low cost, mechanical flexibility, and so on, which have great development potential in new ferroelastic materials. Here, we have successfully designed and synthesized a pair of homochiral enantiomers [(R/S)-4-fluorobenzoic acid-2-amino-2-phenylethanol] (R- and S-F) using the chemical design strategy of H/F substitution. Compared with the non-F substitution [(R/S)-benzoic acid-2-amino-2-phenylethanol] (R- and S-H), they undergo 2F1-type ferroelastic phase transitions at 370 K. Notably, the ferroelastic domains of R/S-F can be controlled through two physical channels that are temperature and stress, showing great potential in dual-channel switches., (© 2024 Wiley-VCH GmbH.)

Objective: Arthrodesis, usage of metallic implants for internal fixation, is commonly employed as the primary treatment modality for Müller-Weiss disease (MWD). Nevertheless, the efficacy of the current methods of fixation leaves room for improvement. Inadequate fixation strength and the risk of fixation failure are both critical concerns requiring attention. This study explored the clinical effects of implementing a modified fixation technique in talonavicular arthrodesis for the treatment of MWD., Methods: A total of 14 cases diagnosed with MWD undergoing talonavicular (TN) arthrodesis from January 2021 toMarch 2023 were included in the retrospective study. The fixation method for fusion involved the use of screws, with additional support from the shape-memory alloy (SMA) staple. Relevant clinical outcomes and complications were evaluated preoperatively and postoperatively. Paired-samples t-test was used for all data comparisons., Results: Radiographic evidence confirmed solid fusion, and follow-up evaluations showed satisfactory results in all cases. The American Orthopedic Foot and Ankle Society (AOFAS) scores were elevated from 32.21 ± 4.0 (range: 22-38) preoperatively to 86.5 ± 2.7 (range: 81-90) postoperatively (p < 0.001). The visual analog scale (VAS) scores declined from 7.40 ± 0.8 (range: 6-8.5) preoperatively to 1.21 ± 1.1 (range: 0-3) postoperatively (p < 0.001). The lateral Meary's angle changed from 13.50 ± 5.2 (range: 8-24) preoperatively to 4.14 ± 2.9 (range: 1-11) degrees postoperatively (p < 0.001). The calcaneal pitch angle increased from 10.07 ± 4.0 (range: 5-19) preoperatively to 14.35 ± 4.0 (range: 8-21) degrees postoperatively (p < 0.001). The talar-first metatarsal angle decreased from 11.71 ± 3.8 (range: 8-18) preoperatively to 4.28 ± 3.1 (range: 0-9) degrees postoperatively (p < 0.001). One patient was observed to experience delayed wound healing and wound infection. No nerve damage, malunion, pseudoarthrosis, or fixation failure were observed., Conclusion: The results indicated that the fusion of the TN joint using a combination of screws and shape memory alloy staples, could lead to favorable clinical outcomes and significantly enhance the quality of life for patients with MWD. This technique is not only safe and effective but also straightforward to perform., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Exploring and accurately detecting new adulteration markers in sesame oil is an important measure for sesame oil adulteration monitoring. In this study, two endogenous flavors sulfurol and γ-nonalactone which can be used as potential adulteration markers were first discovered in sesame oil and accurately quantified. First, the two endogenous flavors were discovered using gas chromatography-mass spectrometry (GC-MS), and their structures were confirmed by comparing the mass spectrograms with the NIST spectral library. Then the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using direct methanol extraction pretreatment and vanillin-D3 as an internal standard was developed for rapid quantitation and application. The method was successfully validated with recoveries ranging from 88.5% to 102.2% and relative standard deviations between 2.6% and 10.5% ( n = 6). The combined method of GC-MS and LC-MS/MS was indicated to be efficient and highly sensitive for detection of sulfurol and γ-nonalactone in edible oil. Subsequently, 31 sesame oils from the market were detected, revealing that 31 samples contained the identified flavors within a relatively consistent range. However, the concentration of these flavor substances in one sample was abnormally high, indicating that there was a potential risk of adulteration. Therefore, the developed method shows good potential for quality evaluation and adulteration screening of sesame oil.

Northeast China is an important ecological barrier in China, and an in-depth understanding of the spatial distribution in ecosystem services （ESs）, and the driving factors is crucial for realizing the subsequent management and protection of ESs. In the study, we quantitatively assessed the characteristics of spatial distribution in ESs in Northeastern China using the InVEST, RWEQ, and RUSLE models and identified the driving factors of ESs spatial distribution in conjunction with the geodetector based on meteorological data, remote sensing data, and socio-economic data. The results showed that the spatial distribution of ESs in Northeast China had obvious spatial heterogeneity. The high values of habitat quality （HQ）, carbon sequestration （CS） services, and soil conservation （SC） services were mainly distributed in the northern part of the four eastern leagues of the Inner Mongolia Autonomous Region, the northern part of Heilongjiang Province, and the eastern part of Northeast China, which were high in fraction vegetation cover, and low values were mainly found in southwestern and eastern Heilongjiang Province, western Jilin Province, and western Liaoning Province. The high values of the water yield （WY） service and wind prevention and sand fixation （WPSF） service were distributed in the east of the Inner Mongolia Autonomous Region and the east of Liaoning Province. The high values of WY services and WPSF services were distributed in the eastern part of Northeast China and the four eastern provinces of the Inner Mongolia Autonomous Region. According to the geodetector results, slope had the strongest explanatory power for the spatial distribution of SC services with a q -value of 0.31, land use/cover change had the strongest explanatory power for the spatial distribution of HQ and CS services with q -values of 0.64 and 0.52, respectively, and fraction vegetation coverage and annual precipitation had the strongest explanatory power for the spatial distribution of WPSF and WY services with q -values of 0.24 and 0.64, respectively, and there were interactions among all the driving factors. The spatial distribution of ESs in Northeast China was mainly influenced by natural factors. The results will provide a scientific basis for subsequent management and enhancement of ESs in Northeast China.

Soil heavy metals in karst areas have obvious high background value characteristics. Conducting county-level soil heavy metal ecological risk assessment and identifying heavy metal sources in karst areas are of great significance for soil pollution control and land resource management. Taking Pingguo City, a typical karst county in Guangxi Province, as the study object, 3 151 surface and deep soil samples were collected using the grid method and combined to form 785 analytical samples. The contents of eight heavy metal elements, including As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, were determined. The content characteristics and sources of heavy metals were analyzed using statistical analysis, interpolation analysis, factor analysis, and the absolute principal component-multiple linear regression model （APCS-MLR）. Using the content of heavy metal elements in deep soil （150-200 cm） as background values, the ecological risk assessment of heavy metals in surface soil （0-20 cm） in the study area was conducted using the geo-accumulation index （ I geo ） and potential ecological risk index （RI） methods. The results showed that the average content of heavy metal elements in the deep soil of the study area was significantly higher than the background value of the C layer soil in Guangxi Province, and the average content of heavy metal elements in the surface soil was significantly higher than the background value of the A layer soil in Guangxi Province. The spatial distribution of soil heavy metal element content generally showed the characteristics of high in karst areas and low in non-karst areas. The main sources of As, Cr, Ni, Pb, and Zn were soil parent materials, with contribution rates of 74.36%, 84.59%, 93.69%, 79.67%, and 78.17%, respectively. The main sources of Cd were soil parent material sources and unknown sources, with contribution rates of 37.33% and 31.05%, respectively. The main sources of Cu were soil parent materials and unknown sources, with contribution rates of 59.07% and 40.23%, respectively. The main sources of Hg were tectonic activity and mineralization, as well as unknown sources, with contribution rates of 52.49% and 30.65%, respectively. The geo-accumulation index （ I geo ） showed that the surface soil was mainly polluted by Cd, with mild or above pollution accounting for 47.78%. The potential ecological risk index （RI） showed that the proportion of surface soil heavy metal comprehensive potential ecological hazards with mild, moderate, strong, and very strong levels was 80.78%, 14.97%, 2.51%, and 1.64%, respectively.

Background: The present study investigated the structure, functional and physicochemical properties of lotus seed protein (LSP) under different pH environments. The structures of LSP were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy (FTIR), zeta potential, particle size distributions, free sulfhydryl and rheological properties. The functional and physicochemical properties of LSP were characterized by color, foaming property, emulsification property, solubility, oil holding capacity, water holding capacity, differential scanning calorimetry analysis and surface hydrophobicity., Results: LSP was mainly composed of eight subunits (18, 25, 31, 47, 51, 56, 65 and 151 kDa), in which the richest band was 25 kDa. FTIR results showed that LSP had high total contents of α-helix and β-sheet (44.81-46.85%) in acidic environments. Meanwhile, there was more β-structure and random structure in neutral and alkaline environments (pH 7.0 and 9.0). At pH 5.0, LSP had large particle size (1576.98 nm), high emulsion stability index (91.43 min), foaming stability (75.69%) and water holding capacity (2.21 g g -1 ), but low solubility (35.98%), free sulfhydryl content (1.95 μmol g -1 ) and surface hydrophobicity (780). DSC analysis showed the denaturation temperatures (82.23 °C) of LSP at pH 5.0 was higher than those (80.10, 80.52 and 71.82 °C) at pH 3.0, 7.0 and 9.0. The analysis of rheological properties showed that LSP gel had high stability and great strength in an alkaline environment., Conclusion: The findings of the present study are anticipated to serve as a valuable reference for the implementation of LSP in the food industry. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This study investigated the potential role and underlying mechanisms of oleanolic acid (OA), a pentacyclic triterpene with antioxidant and anti-inflammatory properties, in porcine oocytes during in vitro maturation (IVM). The results showed that supplementation with 5 μM OA during IVM resulted in a greater percentage of mature oocytes, parthenogenetically activated embryos and somatic cell nuclear-transferred embryos. This was evidenced by significant increases in the rate of first polar body expulsion, the expansion of cumulus granulosa cells and the total cell number in blastocysts. Further analysis revealed that OA promoted fatty acid accumulation and upregulated the mRNA expression of genes involved in fatty acid β-oxidation. OA significantly increased the intracellular mitochondrial membrane potential and ATP levels and effectively inhibited BAX/BCL2 and Cleaved Caspase3 protein expression. Notably, OA increased the protein levels of intracellular Nrf2 and HO-1, and the GSH levels and the activities of the antioxidant enzymes SOD and catalase (CAT), while reducing ROS levels. Mechanistically, OA activated the Nrf2/HO-1 signalling pathway, which is crucial for regulating the expression of antioxidant-related targets in IVM porcine oocytes. Our findings indicated that OA improved antioxidant capacity by activating the Nrf2/HO-1 signalling pathway, thereby promoting porcine oocyte maturation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio Hep/Port , Ratio Peri/Hep , and Ratio Port/Peri ) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio Peri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio Port/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Background: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones., Results: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways., Conclusion: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background : Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. Methods : We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. Results : 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. Conclusion : We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Oleanolic acid (OA) is a pentacyclic triterpenoid with antioxidant activity that can be an effective scavenger of free radicals in cells. This study was designed to investigate the effects of OA on porcine early embryo developmental competence in vitro and its possible mechanisms of action., Methods: In the present study, parthenogenetically activated porcine embryos were used as models to assess the effect of OA on the in vitro developmental capacity of early porcine embryos in vitro. Zygotic genome activation, mitochondrial function, oxidative stress, cell proliferation and apoptosis in early porcine embryos were examined after supplementing the culture medium with 5 μM OA., Results: The results showed that 5 μM OA supplementation not only significantly increased the blastocyst diameter in early porcine embryos on day 6 but also increased the total number of blastocysts. Furthermore, OA supplementation increased the blastocyst proliferation rate and decreased blastocyst apoptosis. Moreover, OA supplementation significantly increased the proportion of embryos that developed to the 4-cell stage after 48 h of in vitro culture and upregulated the expression of genes associated with zygotic genome activation (DPPA2 and ZSCAN4). Notably, OA alleviated oxidative stress by reducing the intracellular levels of reactive oxygen species and increasing the intracellular levels of reduced glutathione at the 4-cell stage and increased the activities of superoxide dismutase and catalase. Concurrently, OA significantly increased the mitochondrial membrane potential and intracellular ATP content., Conclusion: These results suggest that OA promotes the in vitro developmental competence of parthenogenetically activated porcine embryos by reducing oxidative stress and improving mitochondrial function during in vitro culture and that OA may contribute to the efficiency of in vitro embryo production.

Sclerotinia sclerotiorum (Lib.) de Bary is the causative agent of stem white mold disease which severely reduces major crop productivity including soybean and rapeseed worldwide. The current study aimed to explore plant growth-promoting traits and biocontrol of new isolated Bacillus subtilis BS-2301 to suppress S. sclerotiorum through various mechanisms. The results indicated that the BS-2301 exhibited strong biocontrol potential against S. sclerotiorum up to 74% both in dual culture and partition plate experiments. The BS-2301 and its crude extract significantly suppressed S. sclerotiorum growth involving excessive reactive oxygen species (ROS) production in mycelia for rapid death. Furthermore, the treated hyphae produced low oxalic acid (OA), a crucial pathogenicity factor of S. sclerotiorum . The SEM and TEM microscopy of S. sclerotiorum showed severe damage in terms of cell wall, cell membrane breakage, cytoplasm displacement, and organelles disintegration compared to control. The pathogenicity of S. sclerotiorum exposed to BS-2301 had less disease progression potential on soybean leaves in the detached leaf assay experiment. Remarkably, the strain also demonstrated broad-range antagonistic activity with 70%, and 68% inhibition rates against Phytophthora sojae and Fusarium oxysporum , respectively. Furthermore, the strain exhibits multiple plant growth-promoting and disease-prevention traits, including the production of indole-3-acetic acid (IAA), siderophores, amylases, cellulases and proteases as well as harboring calcium phosphate decomposition activity. In comparison to the control, the BS-2301 also showed great potential for enhancing soybean seedlings growth for different parameters, including shoot length 31.23%, root length 29.87%, total fresh weight 33.45%, and total dry weight 27.56%. The antioxidant enzymes like CAT, POD, SOD and APX under BS-2301 treatment were up-regulated in S. sclerotiorum infected plants along with the positive regulation of defense-related genes ( PR1-2 , PR10, PAL1 , AOS , CHS , and PDF1.2) . These findings demonstrate that the BS-2301 strain possesses a notable broad-spectrum biocontrol potential against different phytopathogens and provides new insight in suppressing S. sclerotiorum through various mechanisms. Therefore, BS-2301 will be helpful in the development of biofertilizers for sustainable agricultural practices., 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 Ayaz, Ali, Zhao, Chi, Ali, Rashid, Cao, He, Bukero, Huang and Qi.)

The hippocampal CA3 region plays an important role in learning and memory. CA3 pyramidal neurons (PNs) receive two prominent excitatory inputs-mossy fibers (MFs) from dentate gyrus (DG) and recurrent collaterals (RCs) from CA3 PNs-that play opposing roles in pattern separation and pattern completion, respectively. Although the dorsoventral heterogeneity of the hippocampal anatomy, physiology, and behavior has been well established, nothing is known about the dorsoventral heterogeneity of synaptic connectivity in CA3 PNs. In this study, we performed Timm's sulfide silver staining, dendritic and spine morphological analyses, and ex vivo electrophysiology in mice of both sexes to investigate the heterogeneity of MF and RC pathways along the CA3 dorsoventral axis. Our morphological analyses demonstrate that ventral CA3 (vCA3) PNs possess greater dendritic lengths and more complex dendritic arborization, compared with dorsal CA3 (dCA3) PNs. Moreover, using ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording, we found that the ratio of the RC-to-MF excitatory drive onto CA3 PNs increases substantially from dCA3 to vCA3, with vCA3 PNs receiving significantly weaker MFs, but stronger RCs, excitation than dCA3 PNs. Given the distinct roles of MF versus RC inputs in pattern separation versus completion, our findings of the significant dorsoventral variations of MF and RC excitation in CA3 PNs may have important functional implications for the contribution of CA3 circuit to the dorsoventral difference in hippocampal function., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore ER homeostasis under ER stress. However, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis Golgi anti-apoptotic proteins (GAAPs) are involved in resisting ER stress. To elucidate the function of GAAPs, PASTICCINO2 (PAS2), involved in very long-chain fatty acid (VLCFA) synthesis, was found to interact with GAAPs and IRE1. Single pas2 and gaap1/gaap2pas2 double mutants exhibited increased seedling damage and impaired UPR response under chronic ER stress. Site mutation combined with genetic analysis revealed that the role of PAS2 in resisting ER stress depended on its VLCFA synthesis domain. VLCFA contents were upregulated under ER stress, which required GAAPs. Exogenous VLCFAs partially restored the defect in UPR upregulation caused by PAS2 or GAAP mutations under chronic ER stress. These findings demonstrate that the association of PAS2 with GAAPs confers plant resistance to ER stress by regulating VLCFA synthesis and the UPR. This provides a basis for further studies on the connection between lipids and cell fate decisions under stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. 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.)

Background: Osteoporotic vertebral compression fracture (OVCF) is a common consequence of osteoporosis and can significantly impact the quality of life for affected individuals. Despite treatment options such as vertebroplasty and kyphoplasty, many patients continue to experience residual back pain (RBP) even after the fracture has healed. The incidence of RBP after OVCF treatment varies among studies, and there is a need for further research to understand the risk factors associated with RBP., Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines. Electronic databases were searched, and relevant studies were selected based on inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two authors. Statistical analysis included single-proportion meta-analyses and pooling of odds ratios (OR) using the inverse-variance method, to calculate the overall incidences of RBP and cement leakage and identify risk factors associated with RBP., Results: A total of 19 studies were included in the analysis. The overall incidences of RBP and cement leakage were found to be 16% and 18%, respectively. Several risk factors were identified, including gender, bone mineral density, depression, baseline visual analog scale (VAS) score, intravertebral vacuum cleft, number of fractured segments, cement distribution, history of vertebral fracture, thoracolumbar fascial injury, and fracture non-union., Conclusions: This study provides potential value within the scope of the incidence and risk factors of RBP following treatment of OVCFs. The identified risk factors can help clinicians identify high-risk patients and tailor appropriate interventions. Future research should focus on standardizing the definition of RBP and patient selection criteria to improve the accuracy of estimates and facilitate better management strategies for OVCF patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Traditional Chinese medicine(TCM) contains many high-value active ingredients, such as artemisinin, paclitaxel, vinblastine, and vincristine. However, these ingredients are present in low concentrations in the original plants, and their complex structures make extraction and separation challenging. To protect the limited resources of TCM, researchers have employed total chemical synthesis strategies to prepare structurally complex high-value active ingredients in TCM. However, harsh reaction conditions, lengthy routes, and low yields pose challenges to total chemical synthesis. With the development of synthetic biology, many high-value active ingredients can now be prepared through bio-cell engineering, complementing total chemical synthesis and offering new strategies for the preparation of high-value active ingredients in TCM. This article briefly reviewed the research progress in the biological and chemical synthesis of representative high-value active ingredients in TCM, including β-elemene, artemisinin, tanshinone, vincristine, and homoharringtonine. This article proposed a research paradigm that combined biological and chemical synthesis, including chemical enzyme-mediated structural modification of high-value active ingredients in TCM, semi-synthetic production of high-value active ingredients in TCM using biological synthesis, and biomimetic synthesis to facilitate the biological synthesis pathway of high-value active ingredients in TCM. It provided an important reference for the synthesis of high-value active ingredients in TCM.

Objective: To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma (DLBCL) in the rituximab era., Methods: The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab, cyclophosphamide, epirubicin, vincristine, prednisone (R-CHOP) or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed. The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed, Logistics regression model was used to analyzed the influencing factors of patients prognosis., Results: A total of 237 patients were enrolled, of which 54.4% (129 cases) were primary extranodal sources of DLBCL, and the most common extranodal sites were as follows: stomach (19.4%), colon (14.7%), tonsils (12.4%), skin/muscle (9.3%), central (7.7%), nasal/nasopharynx (6.2%), bone marrow (5.4%), testes (4.7%). The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow, central, liver, gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin, and the difference was statistically significant (PFS: 65.2% vs 76.7%, P =0.008; OS: 82.6% vs 88.3%, P =0.04). Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score >3 ( OR : 0.142, 95% CI : 0.041-0.495, P =0.002), non-germinal center source ( OR : 2.675，95% CI :1.069-6.694， P =0.036), and DEL patients ( OR : 0.327, 95% CI : 0.129-0.830, P =0.019). An NCCN-IPI score >3 was the only independent adverse prognostic factor for PFS ( OR : 0.235, 95% CI : 0.116-0.474, P < 0.001)., Conclusion: Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement, and the overall prognosis is worse than that of patients with lymph node origin. NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.

Marital concerns can trigger emotional stress, especially among long-term hospitalised individuals diagnosed with schizophrenia, significantly affecting their treatment and recovery. Unfortunately, rehabilitation programs tend to overlook the marital needs of individuals with diagnosed schizophrenia. This research aimed to investigate the content related to marital concerns of Chinese individuals diagnosed with schizophrenia who were undergoing extended hospitalisation. Fifteen participants diagnosed with schizophrenia were recruited through purposive sampling for face-to-face semi-structured interviews. The gathered data were analysed using Colaizzi's method, revealing three themes: (1) manifestations of marriage-related concerns, (2) effects of marriage on disease progression, and (3) the need for support from family and the hospital. This study offers new insights into marital concerns among long-term schizophrenia inpatients and underscores the significance of screening and intervention for such concerns. Healthcare professionals and family members should extend support to patients to foster confidence within their marital relationships., (© 2024 John Wiley & Sons Australia, Ltd.)

This paper discusses the problem of disease prevalence in clinical studies, focusing on multiple comparisons based on stratified partially validated series in the presence of a gold standard. Five test statistics, including two Wald-type test statistics, the inverse hyperbolic tangent transformation test statistic, likelihood ratio test statistic, and score test statistic, are proposed to conduct multiple comparisons. To control the overall type I error rate, several adjustment procedures are developed, namely the Bonferroni, Single-step adjusted MaxT, Single-step adjusted MinP, Holm's Step-down, and Hochberg's step-up procedures, based on these test statistics. The performance of the proposed methods is evaluated through simulation studies in terms of the empirical type I error rate and empirical power. Simulation results show that the Single-step adjusted MaxT procedure and Single-step adjusted MinP procedure generally outperform the other three procedures, and these two test procedures based on all test statistics have satisfactory performance. Notably, the Single-step adjusted MinP procedure tends to exhibit higher empirical power than the Single-step adjusted MaxT procedure. Furthermore, the Step-down and Step-up procedures show greater power compared to the Bonferroni method. The study also observes that as the validated ratio increases, the empirical type I errors of all test procedures approach the nominal level while maintaining higher power. Two real examples are presented to illustrate the proposed methods.

In recent years, studies have focused on the combined ecological risks posed by microplastics and other organic pollutants. Although both microplastics and progestin residues are frequently detected in the aquatic environments, their ecological implications remain unknown. Adult zebrafish were exposed to polystyrene microplastics (PS, 200 nm, 200 μg/L), norethindrone (NET, 69.6 ng/L), and their mixture (200 μg/L PS + 63.1 ng/L NET) for 30 days. The results demonstrated that exposure to PS and NET resulted in gill damage. Notably, the PS and PS+NET exhibited a significant decrease in glutathione (GSH) and oxidized glutathione (GSSG) content, as well as reduced antioxidase activity in the gills. The oxidative stress in PS+NET primarily originated from PS. The PS, NET, or their mixture resulted in a decrease in testosterone (T) and estradiol (E2) levels in female. Furthermore, compared to NET, the PS+NET showed a significant reduction in E2 levels, thereby augmenting the inhibitory effect on reproductive ability mediated by NET. However, males showed an increase in 11-ketodihydrotestosterone (11-KT) content, accompanied by a significant decrease in spermatogonia (Sg) and increase in spermatocytes (Sc). Consequently, it can be inferred that PS enhances the androgenic effect of NET. In female fish brain, NET alone resulted in transcriptional down-regulation of partial hormone receptors; however, co-administration of PS effectively mitigated the interference effects. Furthermore, transcriptional downregulation of 17-alpha-hydroxylase (cyp17), hydroxysteroid 3-beta dehydrogenase (hsd3b), estrogen receptor 1 (esr1), and estrogen receptor 2a (esr2b) genes in the ovary was found to be associated with the androgenic activity induced by NET. Moreover, in comparison to PS or NET alone, PS+NET resulted in a notable decrease in Cetobacterium abundance and an increase in Aeromonas population, suggesting that the co-exposure of PS+NET may exacerbate intestinal burden. The findings highlight the importance of studying the combined toxicity of PS and NET., 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.)

Asthma is a common chronic inflammatory disease of the lungs and airway, yet its inflammatory subtypes and potential pathogenesis have not been completely elucidated and require further study. With advances in epigenetic development, methylation has emerged as a new direction for identifying and decoding the occurrence and subtype manifestations of asthma. N 6 -methyladenosine (m 6 A), an RNA methylation modification occurring in the N 6 -position of adenosine, is a prevalent epigenetic modification observed in eukaryotes. It exerts significant control over mRNA metabolism by regulating alternative splicing, stability, export, and translation. The dynamic process of m 6 A methylation plays a crucial role in the pathogenesis of asthma and is tightly regulated by three types of regulators: writers, readers, and erasers. This article provides a comprehensive review of the association between m 6 A regulators and the pathogenesis of inflammatory subtypes of asthma, such as involvement of inflammatory cells and related inflammatory response. Furthermore, the findings presented herein provide new insights and a solid foundation for further research on m 6 A mRNA methylation as biomarkers for the diagnosis and development of personalized treatment for different subtypes of asthma, particularly neutrophilic asthma and eosinophilic asthma., 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 Gao, Hao, Wang and Gao.)

N -Alkoxyphthalimides, one kind of phthalimide derivative, have great importance in synthesis, mainly used as free radical precursors. While the phthalimide unit, for a long time, was treated as part of the waste stream. Construction of C-N bonds has always been a hot spot, especially in reductive cross-coupling. Herein, a nickel-catalyzed reductive cross-coupling reaction of N -methoxyphthalimides with alkyl halides is described, where N -methoxyphthalimides serve as nitrogen electrophiles. This tactic provides a new approach to construct C-N bonds under mild neutral conditions. Alkyl chlorides, bromides, iodides, and sulfonates are all fit to this transformation. Moreover, the reaction could tolerate a broad substrate scope, especially base-sensitive functional groups (boron or silicon groups), as well as competitive nucleophilic groups (phenols and amides), which are incompatible with traditional Gabriel synthesis under basic conditions, demonstrating a complementary role of this work to Gabriel synthesis.

The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn 2+ -doped ferroelectric organic-inorganic hybrid perovskite [(CH 3 ) 3 NCH 2 Cl]CdCl 3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.

Chromosomal sub-microscopic imbalances, such as microdeletions and microduplications, are associated with multiple genetic disorders. Here, we illustrate microdeletion 3q13.33q21.2 might be responsible for neurodevelopmental disorder in two patients. There are two patients with neurodevelopmental disorder in a family of seven. We used chromosomal microarray analysis to identify the microdeletion 3q13.33q21.2. Next-generation sequencing was utilized to exclude the presence of allelic mutations within the microdeletion region 3q13.33q21.2, which may have a potential role in the development of disease in patients affected with secondary genetic alterations. Patient 4 was diagnosed with dilated left third ventricle, neurodevelopmental disorder, and mild abnormalities in electroencephalogram through a series of clinical examinations. Patient 6 was diagnosed with attention deficit hyperactivity disorder, short stature, intellectual disability, and concurrent epilepsy. By investigating the 3q13.33q21.2 band of the University of California, Santa Cruz database, we screened out the genes related to developmental delay and intellectual disability, including ADCY5 SEMA5B andKPNA1, which were highly suspected to be related to intelligence. This region also involves CASR, a gene that has been reported to be associated with epilepsy. The ADCY5 and SEMA5B genes may be key genes to cause neurodevelopmental disorder. Abnormal expression of the CASR gene may lead to the occurrence of epilepsy., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)