Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 00:00-00, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.

BACKGROUND: Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. METHODS: Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. RESULTS: In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001). CONCLUSIONS: Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.

Insights into drought stress response mechanism of tobacco during seed germination by integrated analysis of transcriptome and metabolome.

Drought stress inhibits seed germination, plant growth and development of tobacco, and seriously affects the yield and quality of tobacco leaves. However, the molecular mechanism underlying tobacco drought stress response remains largely unknown. In this study, integrated analysis of transcriptome and metabolome was performed on the germinated seeds of a cultivated variety K326 and its EMS mutagenic mutant M28 with great drought tolerance. The result showed that drought stress inhibited seed germination of the both varieties, while the germination rate of M28 was faster than that of K326 under drought stress. Besides, the levels of phytohormone ABA, GA19, and zeatin were increased by drought stress in M28. Five vital pathways were identified through integrated transcriptomic and metabolomic analysis, including zeatin biosynthesis, aspartate and glutamate synthesis, phenylamine metabolism, glutathione metabolism, and phenylpropanoid synthesis. Furthermore, 20 key metabolites in the above pathways were selected for further analysis of gene modular-trait relationship, and then four highly correlated modules were found. Then analysis of gene expression network was carried out of Top30 hub gene of these four modules, and 9 key candidate genes were identified, including HSP70s, XTH16s, APX, PHI-1, 14-3-3, SCP, PPO. In conclusion, our study uncovered some key drought-responsive pathways and genes of tobacco during seeds germination, providing new insights into the regulatory mechanisms of tobacco drought stress response.

Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

Mechanisms underlying LncRNA SNHG1 regulation of Alzheimer's disease involve DNA methylation.

Alzheimer's disease (AD) is a neurodegenerative disease associated with long non-coding RNAs and DNA methylation; however, the mechanisms underlying the role of lncRNA small nucleolar RNA host gene 1 (lncRNA SNHG1) and subsequent involvement of DNA methylation in AD development are not known. The aim of this study was to examine the regulatory mechanisms attributed to lncRNA SNHG1 gene utilizing 2 strains of senescence-accelerated mouse prone 8 (SAMP8) model of AD and compared to senescence-accelerated mouse resistant (SAMR) considered a control. Both strains of the mouse were transfected with either blank virus, psLenti-U6-SNHG1(low gene expression) virus, and psLenti-pA-SNHG1(gene overexpression) virus via a single injection into the brains for 2 weeks. At 2 weeks mice were subjected to a Morris water maze to determine any behavioral effects followed by sacrifice to extract hippocampal tissue for Western blotting to measure protein expression of p-tau, DNMT1, DNMT3A, DNMT3B, TET1, and p-Akt. No marked alterations were noted in any parameters following blank virus transfection. In SAMP8 mice, a significant decrease was noted in protein expression of DNMT1, DNMT3A, DNMT3B, and p-Akt associated with rise in p-tau and TET1. Transfection with ps-Lenti-U6-SNHG1 alone in SAMR1 mice resulted in a significant rise in DNMTs and p-Akt and a fall in p-tau and TET1. Transfection of SAMP8 with ps-Lenti-U6-SNHG1 blocked effects on overexpression noted in this mouse strain. However, knockdown of lncRNA SNHG1 yielded the opposite results as found in SAMR1 mice. In conclusion, the knockdown of lncRNA SNHG1 enhanced DNA methylation through the PI3K/Akt signaling pathway, thereby reducing the phosphorylation levels of tau in SAMP8 AD model mice with ameliorating brain damage attributed to p-tau accumulation with consequent neuroprotection.

Closed-Loop Polymer-to-Polymer Upcycling of Waste Poly (Ethylene Terephthalate) into Biodegradable and Programmable Materials.

Poly(ethylene terephthalate) (PET), extensively employed in bottles, film, and fiber manufacture, has generated persistent environmental contamination due to its non-degradable nature. The resolution of this issue requires the conversion of waste PET into valuable products, often achieved through depolymerization into monomers. However, the laborious purification procedures involved in the extraction of monomers pose challenges and constraints on the complete utilization of PET. Herein, a strategy is demonstrated for the polymer-to-polymer upcycling of waste PET into high-value biodegradable and programmable materials named PEXT. This process involves reversible transesterifications dependent on ester bonds, wherein commercially available X-monomers from aliphatic diacids and diols are introduced, utilizing existing industrial equipment for complete PET utilization. PEXT features a programmable molecular structure, delivering tailored mechanical, thermal, and biodegradation performance. Notably, PEXT exhibits superior mechanical performance, with a maximal elongation at break of 3419.2 % and a toughness of 270.79 MJ m-3 . These characteristics make PEXT suitable for numerous applications, including shape-memory materials, transparent films, and fracture-resistant stretchable components. Significantly, PEXT allows closed-loop recycling within specific biodegradable analogs by reprograming PET or X-monomers. This strategy not only offers cost-effective advantages in large-scale upcycling of waste PET into advanced materials but also demonstrates its enormous prospect in environmental conservation.

Thiopseudomonas acetoxidans sp. nov., an aerobic acetic and butyric acids oxidizer isolated from anaerobic fermentation liquid of food waste.

A Gram-stain-negative, oxidase-negative, rod-shaped, motile, facultatively anaerobic bacterial strain, designated as CY1220T, was isolated from an anaerobic fermentation liquid of food waste treatment plant. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain CY1220T belongs to the genus Thiopseudomonas, with the highest sequence similarity to Thiopseudomonas alkaliphila B4199T (95.91%), followed by Thiopseudomonas denitrificans X2T (95.56%). The genomic DNA G + C content of strain CY1220T was 48.6 mol%. The average nucleotide identity values and digital DNA-DNA hybridization values between strain CY1220T and the type species of T. alkaliphila and T. denitrificans were in the range of 70.8-71.6% and 19.2-20.0%, respectively, below the thresholds for species delineation. The strain was able to grow utilizing acetic acid and butyric acid (AABA) as the sole carbon source in aerobic conditions. Genomic analysis predicted that the strain could synthesize vitamin B12 and ectoine. The predominant cellular fatty acids were C18:1 ω7c and/or C18:1 ω6c, C16:0, C16:1 ω7c and/or C16:1 ω6c and C12:0. The polar lipids comprised diphosphatidylglycerol, unknown polar lipid, phosphatidylethanolamine, phosphatidylglycerol, and phospholipid. Q-8 (2.1%) and Q-9 (97.9%) were detected as the respiratory quinones. Based on its phenotypic, genotypic and genomic characteristics, strain CY1220T represents a novel species in the genus Thiopseudomonas, for which the name Thiopseudomonas acetoxidans sp. nov. is proposed. The type strain is CY1220T (= GDMCC 1.3503 T = JCM 35747 T).

LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and frequent cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) play regulatory roles and serve as biomarkers of multiple cancers, including ESCC. Our previous studies have confirmed that lncRNA Kinectin 1 antisense RNA 1 (KTN1-AS1) is highly expressed in ESCC and exerts oncogene function through RBBP4/HDAC1 complex. OBJECTIVE: Our present study focused on exploring a novel molecular mechanism of KTN1-AS1 in ESCC. METHODS: In this study, qRT-PCR assay, Western blot assay, Luciferase reporter assay, and RNA immunoprecipitation assay were conducted. RESULTS: We found that KTN1-AS1 could bind to miR-885-5p in ESCC cells, and miR-885-5p was low expressed in ESCC. Overexpression of miR-885-5p inhibited esophageal cancer cells proliferation and invasion in vitro. Mechanistic analysis demonstrated that miR-885-5p specifically targeted striatin 3 (STRN3), and KTN1-AS1/miR-885-5p promoted the EMT process by Hippo pathway in STRN3/YAP1 dependent manner. CONCLUSION: To sum up, KTN1-AS1 facilitates ESCC progression by acting as a ceRNA for miR-885-5p to regulate STRN3 expression and the Hippo pathway, and KTN1-AS1 maybe used as a promising therapeutic target for ESCC.

An ancient cis-element targeted by Ralstonia solanacearum TALE-like effectors facilitates the development of a promoter trap that could confer broad-spectrum wilt resistance.

Ralstonia solanacearum, a species complex of bacterial plant pathogens that causes bacterial wilt, comprises four phylotypes that evolved when a founder population was split during the continental drift ~180 million years ago. Each phylotype contains strains with RipTAL proteins structurally related to transcription activator-like (TAL) effectors from the bacterial pathogen Xanthomonas. RipTALs have evolved in geographically separated phylotypes and therefore differ in sequence and potentially functionality. Earlier work has shown that phylotype I RipTAL Brg11 targets a 17-nucleotide effector binding element (EBE) and transcriptionally activates the downstream arginine decarboxylase (ADC) gene. The predicted DNA binding preferences of Brg11 and RipTALs from other phylotypes are similar, suggesting that most, if not all, RipTALs target the Brg11-EBE motif and activate downstream ADC genes. Here we show that not only phylotype I RipTAL Brg11 but also RipTALs from other phylotypes activate host genes when preceded by the Brg11-EBE motif. Furthermore, we show that Brg11 and RipTALs from other phylotypes induce the same quantitative changes of ADC-dependent plant metabolites, suggesting that most, if not all, RipTALs induce functionally equivalent changes in host cells. Finally, we report transgenic tobacco lines in which the RipTAL-binding motif Brg11-EBE mediates RipTAL-dependent transcription of the executor-type resistance (R) gene Bs4C from pepper, thereby conferring resistance to RipTAL-delivering R. solanacearum strains. Our results suggest that cell death-inducing executor-type R genes, preceded by the RipTAL-binding motif Brg11-EBE, could be used to genetically engineer broad-spectrum bacterial wilt resistance in crop plants without any apparent fitness penalty.

The positive impact of the NtTAS14-like1 gene on osmotic stress response in Nicotiana tabacum.

KEY MESSAGE: NtTAS14-like1 enhances osmotic tolerance through coordinately activating the expression of osmotic- and ABA-related genes. Osmotic stress is one of the most important limiting factors for tobacco (Nicotiana tabacum) growth and development. Dehydrin proteins are widely involved in plant adaptation to osmotic stress, but few of these proteins have been functionally characterized in tobacco. Here, to identify genes required for osmotic stress response in tobacco, an encoding dehydrin protein gene NtTAS14-like1 was isolated based on RNA sequence data. The expression of NtTAS14-like1 was obviously induced by mannitol and abscisic acid (ABA) treatments. Knock down of NtTAS14-like1 expression reduced osmotic tolerance, while overexpression of NtTAS14-like1 conferred tolerance to osmotic stress in transgenic tobacco plants, as determined by physiological analysis of the relative electrolyte leakage and malonaldehyde accumulation. Further expression analysis by quantitative real-time PCR indicated that NtTAS14-like1 participates in osmotic stress response possibly through coordinately activating osmotic- and ABA-related genes expression, such as late embryogenesis abundant (NtLEA5), early responsive to dehydration 10C (NtERD10C), calcium-dependent protein kinase 2 (NtCDPK2), ABA-responsive element-binding protein (NtAREB), ABA-responsive element-binding factor 1 (NtABF1), dehydration-responsive element-binding genes (NtDREB2A), xanthoxin dehydrogenase/reductase (NtABA2), ABA-aldehyde oxidase 3 (NtAAO3), 9-cis-epoxycarotenoid dioxygenase (NtNCED3). Together, this study will facilitate to improve our understandings of molecular and functional properties of plant TAS14 proteins and to improve genetic evidence on the involvement of the NtTAS14-like1 in osmotic stress response of tobacco.

Pediatric pituitary neuroendocrine tumors-a 13-year experience in a tertiary center.

Introduction: Pediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified. Methods: We conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor. Results: 232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery. Conclusion: Pediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.

Effects of family-centered positive psychological intervention on psychological health and quality of life in patients with breast cancer and their caregivers.

PURPOSE: Positive psychological intervention could improve individual's psychological health and quality of life. This study aimed to examine the effectiveness of family-centered positive psychological intervention on resilience, hope, perceived benefits, and quality of life in breast cancer patients and their caregivers. METHODS: A two-group, randomized controlled study, including 98 dyads of breast cancer patients and caregivers, was conducted. Dyads were randomly assigned to intervention (n = 49) and control (n = 49) groups. Both the control and intervention groups received 4 weeks of health education, while the intervention group additionally received a 4-week family-centered positive psychological intervention. Outcome measures compared at baseline (T1), immediately after the intervention (T2), and at 1-month follow-up (T3), included validated measures of resilience (Connor-Davidson Resilience Scale), hope (Herth Hope Index), perceived benefits (Perceived Benefits of Diagnosis and Treatment of Breast Cancer, Positive Aspects of Caregiving), and quality of life (Functional Assessment of Cancer Therapy-Breast, Caregiver Quality of Life Scale). RESULTS: Resilience, hope, perceived benefits, and quality of life of dyads were significantly higher in the intervention group than those in the control group at T2 and T3 (all p < 0.05). Linear mixed model analysis demonstrated a significant interaction effect of group × time × role (p = 0.007) on hope and a significant difference in the improvement of hope (p < 0.05) between patients and their caregivers. CONCLUSIONS: Our family-centered positive psychological intervention was effective in improving psychological health and quality of life for breast cancer patients and caregivers. This study provides evidence for the effectiveness of positive clinical psychological interventions. TRIAL REGISTRATION: ChiCTR2300072809.

A dual-targeting peptide for glioblastoma screened by phage display peptide library biopanning combined with affinity-adaptability analysis.

The obstruction of blood-brain barrier (BBB) and the poor specific targeting are still the major obstacles and challenges of targeted nano-pharmaceutical therapy for glioblastoma (GBM) up to now. It is critical to find appropriate targeting ligands that can effectively mediate the nano-pharmaceuticals to penetrate brain capillary endothelial cells (BCECs) and then specifically bind to glioblastoma cells (GCs). Herein, a dual-targeting ligand for GBM was screened by the combination of phage display peptide library biopanning and affinity-adaptability analysis. Based on the acquisition of sub-library of peptide which exhibited the specific affinity to both BCECs and GCs, a comparison parameter of relative affinity was deliberately introduced to evaluate the relative affinity of candidate peptides to U251-MG cells and bEnd.3 cells. The optimized WTW peptide (sequenced as WTWEYTK) was provided with a high relative affinity (RU/B = 2.44), implying that its high affinity to U251-MG cells and moderate affinity to bEnd.3 cells might synergistically promote its receptor-mediated internalization and transport, the dissociation from bEnd.3, and the binding to U251-MG. The results of BBB model trials in vitro showed that the BBB penetration efficiency and GBM accumulation of WTW peptide were significantly higher than those of WSL peptide, GNH peptide, and REF peptide. Results of orthotopic GBM xenograft model assays in vivo also indicated that WTW peptide had successfully penetrated the BBB and improved accumulation in GBM. The screened WTW peptide might be the potential dual-targeting ligand to motivate the advancement of GBM targeted therapy.

Laser operation at 1.2†µm in Ho3+-doped ZBYA glass fibers.

Powerful 1.2-µm laser operation was produced in Ho3+-doped single-cladding, in-house fabricated ZrF4-BaF2-YF3-AlF3 (ZBYA) glass fibers. The fibers were fabricated based on ZBYA glass with a composition of ZrF4-BaF2-YF3-AlF3. Pumped by an 1150-nm Raman fiber laser, the maximum combined laser output power emitted from both sides of a 0.5-mol% Ho3+-doped ZBYA fiber was 6.7 W, with a slope efficiency of 40.5%. We also observed lasing at 2.9 µm with an output power of 350 mW, which was ascribed to the transition of Ho3+:5I6 → 5I7. The effect of rare earth (RE) doping concentration and the length of the gain fiber were also investigated to determine their effect on laser performance at 1.2 µm and 2.9 µm.

The immune escape mechanism of nasopharyngeal carcinoma.

Tumor cells are known for being able to evade immune system surveillance, a hallmark of malignancy. Complicated immune escape mechanisms in the tumor microenvironment (TME) provide favorable conditions for tumor invasion, metastasis, treatment resistance, and recurrence. Epstein-Barr virus (EBV) infection is closely related to the pathogenesis of nasopharyngeal carcinoma (NPC), and the co-existence of EBV-infected NPC cells and tumor-infiltrating lymphocytes represents a distinctive, highly heterogeneous, and suppressive TME that supports immune escape and promotes tumorigenesis. Understanding the complex interaction between EBV and NPC host cells and focusing on the immune escape mechanism of TME may help to identify specific immunotherapy targets and to develop effective immunotherapy drugs.

Metabolic engineering of a 1,8-cineole synthase enhances aphid repellence and increases trichome density in transgenic tobacco (Nicotiana tabacum L.).

BACKGROUND: The green peach aphid (Myzus persicae Sulzer) is a harmful agricultural pest that causes severe crop damage by directly feeding or indirectly vectoring viruses. 1,8-cineole synthase (CINS) is a multiproduct enzyme that synthesizes monoterpenes, with 1,8-cineole dominating the volatile organic compound profile. However, the relationship between aphid preference and CINS remains elusive. RESULTS: Here, we present evidence that SoCINS, a protein from garden sage (Salvia officinalis), enhanced aphid repellence and increased trichome density in transgenic tobacco. Our results demonstrated that overexpression of SoCINS (SoCINS-OE) led to the emission of 1,8-cineole at a level of up to 181.5 ng per g fresh leaf. Subcellular localization assay showed that SoCINS localized to chloroplasts. A Y-tube olfactometer assay and free-choice assays revealed that SoCINS-OE plants had a repellent effect on aphids, without incurring developmental or fecundity-related penalties. Intriguingly, the SoCINS-OE plants displayed an altered trichome morphology, showing increases in trichome density and in the relative proportion of glandular trichomes, as well as enlarged glandular cells. We also found that SoCINS-OE plants had significantly higher jasmonic acid (JA) levels than wild-type plants. Furthermore, application of 1,8-cineole elicited increased JA content and trichome density. CONCLUSION: Our results demonstrate that SoCINS-OE plants have a repellent effect on aphids, and suggest an apparent link between 1,8-cineole, JA and trichome density. This study presents a viable and sustainable approach for aphid management by engineering the expression of 1,8-cineole synthase gene in plants, and underscores the potential usefulness of monoterpene synthase for pest control. © 2023 Society of Chemical Industry.

FOXK1 regulates malignant progression and radiosensitivity through direct transcriptional activation of CDC25A and CDK4 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with poor prognosis, necessitating identification of oncogenic mechanisms for novel therapeutic strategies. Recent studies have highlighted the significance of the transcription factor forkhead box K1 (FOXK1) in diverse biological processes and carcinogenesis of multiple malignancies, including ESCC. However, the molecular pathways underlying FOXK1's role in ESCC progression are not fully understood, and its potential role in radiosensitivity remains unclear. Here, we aimed to elucidate the function of FOXK1 in ESCC and explore the underlying mechanisms. Elevated FOXK1 expression levels were found in ESCC cells and tissues, positively correlated with TNM stage, invasion depth, and lymph node metastasis. FOXK1 markedly enhanced the proliferative, migratory and invasive capacities of ESCC cells. Furthermore, silencing FOXK1 resulted in heightened radiosensitivity by impeding DNA damage repair, inducing G1 arrest, and promoting apoptosis. Subsequent studies demonstrated that FOXK1 directly bound to the promoter regions of CDC25A and CDK4, thereby activating their transcription in ESCC cells. Moreover, the biological effects mediated by FOXK1 overexpression could be reversed by knockdown of either CDC25A or CDK4. Collectively, FOXK1, along with its downstream target genes CDC25A and CDK4, may serve as a promising set of therapeutic and radiosensitizing targets for ESCC.

Effects of neoadjuvant chemotherapy combined with breast-conserving surgery on the breast cancer condition and immune and inflammatory indexes of patients with breast cancer.

OBJECTIVE: To determine the effects of neoadjuvant chemotherapy combined with breast-conserving surgery (BCS) on the breast cancer (BC) condition and immune and inflammatory indexes of patients with BC. METHODS: A total of 114 patients with BC admitted to the First People's Hospital of Shangqiu from March 2018 to March 2020 were retrospectively enrolled in this study. Fifty-four patients who underwent radical mastectomy alone were enrolled into the control group (Con group), and the other 60 patients who received neoadjuvant chemotherapy combined with BCS were assigned to the observation group (Obs group). The two groups were compared in terms of surgical indexes, therapeutic effects, immune indexes including immunoglobulin IgG, IgA, IgM, and inflammatory indexes. Cox regression analysis was conducted to analyze the independent prognostic factors of overall survival (OS) and disease-free survival (DFS). RESULTS: After therapy, the Obs group yielded a significantly higher effective therapy rate than the Con group and experienced notably shorter hospital stay and operation time than the Con group. In addition, the Obs group showed significantly higher levels of IgG, IgA and IgM and significantly lower levels of TNF-α and IL-6 than the Con group after therapy. According to Cox regression analysis, clinical stage and HER2 were independent prognostic factors impacting patients' OS and DFS. CONCLUSION: Neoadjuvant chemotherapy combined with BCS can substantially alleviate the disease condition, effectively improve the immune ability, and lower the inflammation level of BC patients, without impacting their 2-year OS and DFS.

Construction of a cutoff and fusion model of breast cancer patients in family: a grounded theory study.

PURPOSE: To construct a coping model for interactions between breast cancer patients and their families across the disease trajectory using the patients' voice, and to establish a mechanism for restoring family balance when faced with stresses related to breast cancer. METHODS: This study employed a longitudinal qualitative study design using constructivist grounded theory. We divided breast cancer trajectory into four periods: suspicion, diagnosis, treatment, and rehabilitation. We then interviewed patients during each of these periods. RESULTS: Twenty patients with breast cancer were interviewed. A cutoff and fusion model of the breast cancer patient's interactions with her family contained three coping themes: independence, coexistence, and interconversion. The coping trajectory of breast cancer patients in their families has specific themes in each period, such as anxiety, information, emotion, and experience. CONCLUSION: We constructed a cutoff and fusion model of breast cancer patients' coping trajectory in their families. This model not only explains the opposite, coexistent, and interconvertible relationship between cutoff and fusion but also the specific challenges requiring cutoff and fusion during the four periods. Our findings highlight the dynamic balance of cutoff and fusion for patients' coping in their families. IMPLICATIONS FOR PRACTICE: This model helps clinical staff understand the coping of breast cancer patients in their families. When providing family education, clinical staff should suggest that they not only provide support to the patient but give each other space as well.

Identification of a Specific Phage as Growth Factor Alternative Promoting the Recruitment and Differentiation of MSCs in Bone Tissue Regeneration.

Inefficient use and loss of exogenously implanted mesenchymal stem cells (MSCs) are major concerns in MSCs-based bone tissue engineering. It is a promising approach to overcome the above issues by recruiting and regulation of endogenous MSCs. However, there are few substances that can recruit MSCs effectively and specifically to the site of bone injury. In this study, we identified a phage clone (termed P11) with specific affinity for MSCs through phage display biopanning, and further investigated the effects of P11 on the cytological behavior of MSCs and macrophages. The results showed that P11 could bind MSCs specifically and promote the proliferation and migration of MSCs. Meanwhile, P11 could polarize macrophages to the M1 phenotype and significantly changed their morphology, which further enhanced the chemotaxis of MSCs. Additionally, RNA-seq results revealed that P11 could promote the secretion of osteogenesis-related markers in MSCs through the TPL2-MEK-ERK signaling pathway. Altogether, P11 has great potential to be used as growth factor alternatives in bone tissue engineering, with the advantages of cheaper and stable activity. Our study also advances the understanding of the effects of phages on macrophages and MSCs, and provides a new idea for the development in the field of phage-based tissue engineering.