Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.

Copper is an essential trace element for the human body, and its requirement for optimistic immune functions has been recognized for decades. How copper is involved in the innate immune pathway, however, remains to be clarified. Here, we report that copper serves as a signal molecule to regulate the kinase activity of alpha-kinase 1 (ALPK1), a cytosolic pattern-recognition receptor (PRR), and therefore promotes host cell defense against bacterial infection. We show that in response to infection, host cells actively accumulate copper in the cytosol, and the accumulated cytosolic copper enhances host cell defense against evading pathogens, including intracellular and, unexpectedly, extracellular bacteria. Subsequently, we demonstrate that copper activates the innate immune pathway of host cells in an ALPK1-dependent manner. Further mechanistic studies reveal that copper binds to ALPK1 directly and is essential for the kinase activity of this cytosolic PRR. Moreover, the binding of copper to ALPK1 enhances the sensitivity of ALPK1 to the bacterial metabolite ADP-heptose and eventually prompts host cells to elicit an enhanced immune response during bacterial infection. Finally, using a zebrafish in vivo model, we show that a copper-treated host shows an increased production of proinflammatory cytokines, enhanced recruitment of phagosome cells, and promoted bacterial clearance. Our findings uncover a previously unrecognized role of copper in the modulation of host innate immune response against bacterial pathogens and advance our knowledge on the cross talk between cytosolic copper homeostasis and immune system.

Proteomics Profiling Reveals the Molecular Signatures and Potential Therapeutic Targets of Human Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC), a malignant tumor distinctly characterized by ethnic and geographic distribution, is highly prevalent in Southern China and Southeast Asia. However, the molecular mechanisms of NPC have not been fully revealed at the proteomic level. In this study, 30 primary NPC samples and 22 normal nasopharyngeal epithelial tissues were collected for proteomics analysis, and a relatively complete proteomics landscape of NPC was depicted for the first time. By combining differential expression analysis, differential co-expression analysis, and network analysis, potential biomarkers and therapeutic targets were identified. Some identified targets were verified by biological experiments. We found that 17-AAG, a specific inhibitor of the identified target heat shock protein 90 (HSP90), could be a potential therapeutic drug for NPC. Finally, consensus clustering identified two NPC subtypes with specific molecular features. The subtypes and the related molecules were verified by an independent data set and may have different progression-free survival. The results of this study provide a comprehensive understanding of the proteomics molecular signatures of NPC and provide new perspectives and inspiration for prognostic determination and treatment of NPC.

Sesamin inhibits RANKL-induced osteoclastogenesis and attenuates LPS-induced osteolysis via suppression of ERK and NF-κB signalling pathways.

Infection by bacterial products in the implant and endotoxin introduced by wear particles activate immune cells, enhance pro-inflammatory cytokines production, and ultimately promote osteoclast recruitment and activity. These factors are known to play an important role in osteolysis as well as potential targets for the treatment of osteolysis. Sesamin has been shown to have a variety of biological functions, such as inhibiting inflammation, anti-tumour and involvement in the regulation of fatty acid and cholesterol metabolism. However, the therapeutic effect of sesamin on osteolysis and its mechanism remain unclear. Present studies shown that in the condition of in vitro, sesamin could inhibit osteoclastogenesis and bone resorption, as well as suppressing the expression of osteoclast-specific genes. Further studies on the mechanism suggest that the effect of sesamin on human osteoclasts was mediated by blocking the ERK and NF-κB signalling pathways. Besides, sesamin was found to be effective in treating LPS-induced osteolysis by decreasing the production of pro-inflammatory cytokines and inhibiting osteoclastogenesis in vivo. Sesamin was non-toxic to heart, liver, kidney, lung and spleen. Therefore, sesamin is a promising phytochemical agent for the therapy of osteolysis-related diseases caused by inflammation and excessive osteoclast activation.

Introgression of chromosome 5P from Agropyron cristatum enhances grain weight in a wheat background.

KEY MESSAGE: A grain weight locus from Agropyron cristatum chromosome 5P increases grain weight in different wheat backgrounds and is localized to 5PL (bin 7-12). Thousand-grain weight is an important trait in wheat breeding, with a narrow genetic basis being the main factor limiting improvement. Agropyron cristatum, a wild relative of wheat, harbors many desirable genes for wheat improvement. Here, we found that the introduction of the 5P chromosome from A. cristatum into wheat significantly increased the thousand-grain weight by 2.55-7.10 g, and grain length was the main contributor to grain weight. An increase in grain weight was demonstrated in two commercial wheat varieties, indicating that the grain weight locus was not affected by the wheat background. To identify the chromosome segment harboring the grain weight locus, three A. cristatum 5P deletion lines, two wheat-A. cristatum 5P translocation lines and genetic populations of these lines were used to evaluate agronomic traits. We found that the translocation lines harboring the long arm of A. cristatum chromosome 5P (5PL) exhibited high grain weight and grain length, and the genetic locus associated with increased grain weight was mapped to 5PL (bin 7-12). An increase in grain weight did not adversely affect other agronomic traits in translocation line 5PT2, which is a valuable germplasm resource. Overall, we identified a grain weight locus from chromosome 5PL and provided valuable germplasm for improving wheat grain weight.

Chromosomal mapping of a major genetic locus from Agropyron cristatum chromosome 6P that influences grain number and spikelet number in wheat.

KEY MESSAGE: A novel locus on Agropyron cristatum chromosome 6P that increases grain number and spikelet number was identified in wheat-A. cristatum derivatives and across 3 years. Agropyron cristatum (2n = 4x = 28, PPPP), which has the characteristics of high yield with multiple flowers and spikelets, is a promising gene donor for wheat high-yield improvement. Identifying the genetic loci and genes that regulate yield could elucidate the genetic variations in yield-related traits and provide novel gene sources and insights for high-yield wheat breeding. In this study, cytological analysis and molecular marker analysis revealed that del10a and del31a were wheat-A. cristatum chromosome 6P deletion lines. Notably, del10a carried a segment of the full 6PS and 6PL bin (1-13), while del31a carried a segment of the full 6PS and 6PL bin (1-8). The agronomic characterization and genetic population analysis confirmed that the 6PL bin (9-13) brought about an increase in grain number per spike (average increase of 10.43 grains) and spikelet number per spike (average increase of 3.67) over the three growing seasons. Furthermore, through resequencing, a multiple grain number locus was mapped to the physical interval of 593.03-713.89 Mb on chromosome 6P of A. cristatum Z559. The RNA-seq analysis revealed the expression of 537 genes in the del10a young spike tissue, with the annotation indicating that 16 of these genes were associated with grain number and spikelet number. Finally, a total of ten A. cristatum-specific molecular markers were developed for this interval. In summary, this study presents novel genetic material that is useful for high-yield wheat breeding initiatives to meet the challenge of global food security through enhanced agricultural production.

Pre-breeding of spontaneous Robertsonian translocations for density planting architecture by transferring Agropyron cristatum chromosome 1P into wheat.

KEY MESSAGE: We developed T1AL·1PS and T1AS·1PL Robertsonian translocations by breakage-fusion mechanism based on wheat-A. cristatum 1P(1A) substitution line with smaller leaf area, shorter plant height, and other excellent agronomic traits Agropyron cristatum, a wild relative of wheat, is a valuable germplasm resource for improving wheat genetic diversity and yield. Our previous study confirmed that the A. cristatum chromosome 1P carries alien genes that reduce plant height and leaf size in wheat. Here, we developed T1AL·1PS and T1AS·1PL Robertsonian translocations (RobTs) by breakage-fusion mechanism based on wheat-A. cristatum 1P (1A) substitution line II-3-1c. Combining molecular markers and cytological analysis, we identified 16 spontaneous RobTs from 911 F2 individuals derived from the cross of Jimai22 and II-3-1c. Fluorescence in situ hybridization (FISH) was applied to detect the fusion structures of the centromeres in wheat and A. cristatum chromosomes. Resequencing results indicated that the chromosomal junction point was located at the physical position of Triticum aestivum chromosome 1A (212.5 Mb) and A. cristatum chromosome 1P (230 Mb). Genomic in situ hybridization (GISH) in pollen mother cells showed that the produced translocation lines could form stable ring bivalent. Introducing chromosome 1PS translocation fragment into wheat significantly increased the number of fertile tillers, grain number per spike, and grain weight and reduced the flag leaf area. However, introducing chromosome 1PL translocation fragment into wheat significantly reduced flag leaf area and plant height with a negative effect on yield components. The pre-breeding of two spontaneous RobTs T1AL·1PS and T1AS·1PL was important for wheat architecture improvement.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide and has a poor prognosis. Autophagy regulation has been proposed as a possible treatment option for HNSCC. Schisandrin B (Sch B) exerts anticancer effects by regulating apoptosis and autophagy, but the anticancer effect of Sch B in HNSCC remains unclear. This study aimed to investigate the effects of Sch B on human Cal27 HNSCC cells and to further reveal its potential regulatory mechanisms. The anticancer effect of Sch B was evaluated in vitro by flow cytometry, clonogenic assays, and Western blot analysis. The regulatory mechanism of Sch B-induced apoptosis and autophagy was further explored by polymerase chain reaction, luciferase assay, and reactive oxygen species (ROS) detection. The results showed that Sch B significantly induced apoptosis and autophagy in Cal27 cells and that inhibition of autophagy enhanced the apoptotic effect of Sch B on Cal27 cells. Additionally, Sch B-activated autophagy in Cal27 cells was dependent on the nuclear factor-kappa B (NF-κB) pathway, and ROS acted as a regulator of the NF-B pathway. N-acetylcysteine, a scavenger of ROS, inhibited Sch B-dependent autophagy via the NF-κB pathway. Based on the results, Sch B is a potential therapeutic agent for HNSCC and activates the NF-κB pathway by increasing ROS production, which subsequently promotes autophagy in HNSCC cells. Therefore, the strategy of enhancing the anticancer effect of Sch B by inhibiting autophagy deserves further attention.

Application of modified spiral tracheoplasty in thyroid carcinoma with trachea invasion: a retrospective analysis of 15 cases.

BACKGROUND: To describe the indications, techniques and preliminary experience of modified spiral tracheoplasty in the reconstruction of large tracheal defect after thyroidectomy. METHODS: The medical records of patients who underwent tracheal torsion to repair large tracheal defects after thyroid carcinoma surgery from January 2019 to January 2022 were retrospectively reviewed. The extent of tracheal defect, duration of tracheal reconstruction, postoperative complications and surgery results were analyzed. RESULTS: The duration of tracheal reconstruction was 30-60 min. No postoperative bleeding, incision infection, tracheostomy stenosis occurred. Recurrent laryngeal nerve palsy occurred in 5 patients. All patients were followed up for 24 to 60 months. The 2-year overall survival rate was 100%, the 2-year local control rate of trachea was 100%, and the 2-year tumor-free survival rate was 81.8%. CONCLUSION: The modified spiral tracheoplasty is a safe and effective method to repair the large defect of trachea after thyroid carcinoma invading the trachea.

Identification of HTRA1, DPT and MXRA5 as potential biomarkers associated with osteoarthritis progression and immune infiltration.

BACKGROUND: Our study aimed to identify potential specific biomarkers for osteoarthritis (OA) and assess their relationship with immune infiltration. METHODS: We utilized data from GSE117999, GSE51588, and GSE57218 as training sets, while GSE114007 served as a validation set, all obtained from the GEO database. First, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were performed to identify hub modules and potential functions of genes. We subsequently screened for potential OA biomarkers within the differentially expressed genes (DEGs) of the hub module using machine learning methods. The diagnostic accuracy of the candidate genes was validated. Additionally, single gene analysis and ssGSEA was performed. Then, we explored the relationship between biomarkers and immune cells. Lastly, we employed RT-PCR to validate our results. RESULTS: WGCNA results suggested that the blue module was the most associated with OA and was functionally associated with extracellular matrix (ECM)-related terms. Our analysis identified ALB, HTRA1, DPT, MXRA5, CILP, MPO, and PLAT as potential biomarkers. Notably, HTRA1, DPT, and MXRA5 consistently exhibited increased expression in OA across both training and validation cohorts, demonstrating robust diagnostic potential. The ssGSEA results revealed that abnormal infiltration of DCs, NK cells, Tfh, Th2, and Treg cells might contribute to OA progression. HTRA1, DPT, and MXRA5 showed significant correlation with immune cell infiltration. The RT-PCR results also confirmed these findings. CONCLUSIONS: HTRA1, DPT, and MXRA5 are promising biomarkers for OA. Their overexpression strongly correlates with OA progression and immune cell infiltration.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Effect of Emergency Plan and First Aid Procedure on Injury Control and Precise Treatment of Patients with Acute Traumatic Cervical Spinal Cord Injury.

Objective: To investigate the effect of emergency plans and first aid procedures on injury control and precise treatment in patients with acute traumatic cervical spinal cord injury. Given the challenges in managing acute traumatic cervical spinal cord injuries and the need for efficient emergency plans and first aid procedures, the importance of this study is self-evident. Methods: A total of 103 patients with acute traumatic cervical spinal cord injury were enrolled in our study from January 2017 to December 2022, and these patients were divided into two groups according to the time of admission: 51 cases from January 2017 to December 2019 were in the control group, and 52 cases from January 2020 to December 2022 were in the study group. The control group was given routine emergency care. The study group received emergency plans and first aid procedures that included rapid assessment, optimized patient handling and transport, and immediate medical intervention. We compared the International Classification of Functioning, Disability and Health (ICF) scores, the Short Form Health Survey (SF-36) scores, the Activities of Daily Living (ADL) scores, and the occurrence of adverse events 3 months after rescue between the two groups. Results: The study group demonstrated significantly shorter times for prehospital emergency rescue, waiting time upon admission, time from admission to treatment, mechanical ventilation duration, and ICU stay when compared to the control group (P < .05). The intubation rate and mortality rate in the research group were 28.85% and 11.54%, respectively, compared to 31.37% and 13.73% in the control group, with no statistically significant differences (P > .05). Three months after the rescue, the study group showed significantly lower scores in environmental factors, activities and participation, body structure, and body function compared to the control group (P < .05). Three months after the rescue, the research group had significantly higher SF-36 scores (P < .05), and their ADL scores were significantly lower than those of the control group (P < .05). The research group had an adverse event rate of 3.85%, significantly lower than the control group's rate of 19.61% (P < .05). The study group experienced improvements in emergency response and hospital procedure times, higher SF-36 and ADL scores, and lower rates of adverse events, suggesting significant potential for improving patient outcomes in cases of acute traumatic cervical spinal cord injury. This demonstrates the effectiveness of the emergency plans that have been implemented and may influence the approach to emergency medical care in similar situations in the future. Conclusions: Emergency plans and first aid procedures can effectively shorten the first aid time, promote rehabilitation, reduce adverse events, and improve the quality of daily life in patients with acute traumatic cervical spinal cord injury. Based on these findings, future practice or policy may need to be adjusted to further enhance patient care quality.

Analysis of the Effect of Rapid Rehabilitation Nursing in the Perioperative Period of Brucellar Spondylitis.

Objective: To explore the effect of rapid rehabilitation nursing in patients with brucellar spondylitis during the perioperative period. Methods: A total of 68 patients with brucellar spondylitis who underwent surgical treatment in our hospital from August 2019 to May 2022 and met the inclusion criteria were enrolled as study subjects. The patients were divided into a conventional group and a rehabilitation group with 34 cases each according to different nursing methods. The conventional group received routine nursing intervention and the rehabilitation group received perioperative rapid rehabilitation nursing intervention. The clinical data of patients were recorded, and the length of hospital stay, nursing intervention effect, pain perception, kyphotic Cobb angle changes, perioperative complications, and the satisfaction scores of patients were compared between the two groups. Results: The hospitalization time of patients in the rehabilitation group was significantly shorter and the clinical effective rate was significantly higher in the rehabilitation group than that of the conventional group, P < .05. The VAS scores of the rehabilitation group were significantly lower than the conventional group at each time point, P < .05. The total incidence of complications and the kyphotic Cobb angle at 3 days and 2 weeks post-operation of the rehabilitation group was significantly lower than the conventional group, P < .05; while the patient satisfaction was significantly higher in the rehabilitation group, P < .05. Conclusion: Rapid recovery nursing intervention for patients with brucellar spondylitis has a definite effect in the perioperative period, which can effectively reduce the pain experience of patients, improve the treatment effect, shorten the hospitalization time of patients, reduce the occurrence of perioperative complications, improve patient satisfaction, and promote the functional recovery of patients. The findings are significant and warrant the clinical promotion and application of fast recovery nursing intervention in the perioperative period of brucellar spondylitis.

Effects of oropharyngeal exercises on CPAP compliance: A prospective intervention study.

PURPOSE: To investigate the effects of oropharyngeal exercise on continuous positive airway pressure (CPAP) compliance in patients with moderate to severe obstructive sleep apnea over a period of 6 months. MATERIALS AND METHODS: This study was conducted as a prospective, observational, and interventional investigation. A total of 70 patients with moderate to severe obstructive sleep apnea were randomly assigned to either the oropharyngeal exercise group (n = 44) or the sham-therapy group (n = 26). The compliance of the enrolled patients with CPAP therapy was assessed at baseline, 3-month follow-up and 6-month follow-up. Objective sleep data, questionnaire and CPAP use time were collected over a half-year period (i.e., baseline, 6 months, and 12 months). RESULTS: The study found that the average use time of CPAP within one month was significantly longer in the oropharyngeal exercises group compared to the sham-therapy group at the 3-month assessment (5.5 ± 1.2 vs 4.8 ± 1.3 h per night; p=0.030), and much significantly longer at 6-months assessment (6.0 ± 1.4 vs 4.9 ± 1.3 h per night; p=0.001). Furthermore, the average use time of CPAP increased over time, with the oropharyngeal exercises group exhibiting a more pronounced growth from baseline to the six-month follow-up (4.8 ± 1.0 h per night to 6.0 ± 1.3 h per night, p < 0.001) compared to the sham-therapy group (4.8 ± 1.3 h per night to 4.9 ± 1.3 h per night, p=0.952). Additionally, the oropharyngeal exercise group demonstrated an improvement in the Epworth sleepiness scale compared to the sham-therapy group at the 3-month follow-up (6.0 ± 2.0 vs 8.8 ± 3.2; p < 0.001), as well as decreased significantly at 6-month follow-up (p = 0.032). CONCLUSIONS: CPAP adherence can be improved with oropharyngeal exercises therapy among moderate to severe OSA patients. Notably, the average duration of CPAP usage and reduction in daytime sleepiness were maintained even after six months of oropharyngeal exercise therapy.

Influential factors of the prognosis of patients with winter sports-induced traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema after emergency surgical treatment.

Objective: To explore relevant influencing factors of the prognosis of patients with winter sports-induced traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema after emergency surgical treatment. Methods: A retrospective analysis was performed on 73 cases of traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema in The First Hospital Affiliated to Hebei North University from January 2020 to October 2022. The enrolled patients were divided into the good prognosis (n=17) group and poor prognosis (n=56) group according to the recovery of neurological function after six months of follow-up. The risk factors affecting the prognosis of patients with traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema after emergency surgery were analyzed by binary Logistic regression. Results: Among the enrolled 73 patients with traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema, 56 cases showed significant improvement in ASIA Grade-6 months after operation, with an improvement rate of 76.71%. Further Logistic regression analysis revealed that concomitant diabetes, preoperative MSCC>40.83% and recovery rate of AMS <40.13% 3d after operation were independent risk factors affecting the poor prognosis of patients with traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema. Conclusions: Emergency surgery can improve the neurological function of patients with cervical spinal cord injury complicated with intramedullary hemorrhage and edema caused by winter sports. Concomitant diabetes, preoperative MSCC and recovery rate of AMS 3d after operation are the main factors affecting the prognosis of patients with emergency surgery.

How about the RCTs' quality of acupuncture treatment for female urinary incontinence in recent 20 years? A report quality assessment.

PURPOSE: To evaluate the quality of randomized controlled trials (RCTs) of acupuncture on female urinary incontinence (UI). METHODS: We searched for related RCTs of acupuncture on female UI from seven databases (PubMed, Embase, Cochrane library, Web of Science, Medline, ClinicalKey, and Clinical trials). We applied CONSORT (2010 year) and STRICTA criteria to evaluate the relevant factors of included RCTs. Two trained researchers scored independently, and concordance was assessed by Cohen's к-statistic. The median and interquartile range summarized the CONSORT and STRICTA scores of the included studies. In addition, two independent sample t tests were used to assess the differences in the study quality between the 2000-2010 and the 2011-2022 years. RESULTS: A total of 25 RCTs were finally included, and the scores were consistent between different assessors. The average CONSORT score was 10.50 (IQR 9.0-15.0) (total score was 25.0). Overall, the studies generally included scientific background (24/25, 96%), inclusion and exclusion criteria (24/25, 96%), outcome indicators (24/25, 96%), randomization methods (21/25, 84%), generalizability (19/25, 76%), and financial support (15/25, 60%). Most lacked sample size calculation (5/25, 20%), type of randomization (5/25, 20%), blinding (6/25, 24%), case screening period and follow-up (4/25, 16%), and study registration (6/25, 24%), etc. The average STRICTA score was 3.380 (IQR 3.02-3.95) (total score was 6.0). There had a lack of education on treatment methods for patients (3/25, 12%) and the qualification of acupuncturists (6/25, 24%). CONCLUSION: The overall quality of RCTs on acupuncture treatment of female UI was suboptimal. It is still necessary to improve the research methods, especially the application of random methods, blinding, the interpretation of treatment, and the identification qualification of acupuncturists.

The Genomic Variation and Differentially Expressed Genes on the 6P Chromosomes in Wheat-Agropyron cristatum Addition Lines 5113 and II-30-5 Confer Different Desirable Traits.

Wild relatives of wheat are essential gene pools for broadening the genetic basis of wheat. Chromosome rearrangements and genomic variation in alien chromosomes are widespread. Knowledge of the genetic variation between alien homologous chromosomes is valuable for discovering and utilizing alien genes. In this study, we found that 5113 and II-30-5, two wheat-A. cristatum 6P addition lines, exhibited considerable differences in heading date, grain number per spike, and grain weight. Genome resequencing and transcriptome analysis revealed significant differences in the 6P chromosomes of the two addition lines, including 143,511 single-nucleotide polymorphisms, 62,103 insertion/deletion polymorphisms, and 757 differentially expressed genes. Intriguingly, genomic variations were mainly distributed in the middle of the chromosome arms and the proximal centromere region. GO and KEGG analyses of the variant genes and differentially expressed genes showed the enrichment of genes involved in the circadian rhythm, carbon metabolism, carbon fixation, and lipid metabolism, suggesting that the differential genes on the 6P chromosome are closely related to the phenotypic differences. For example, the photosynthesis-related genes PsbA, PsbT, and YCF48 were upregulated in II-30-5 compared with 5113. ACS and FabG are related to carbon fixation and fatty acid biosynthesis, respectively, and both carried modification variations and were upregulated in 5113 relative to II-30-5. Therefore, this study provides important guidance for cloning desirable genes from alien homologous chromosomes and for their effective utilization in wheat improvement.

Anti-polycystic ovary syndrome effect of electroacupuncture: IMD inhibits ER stress-mediated apoptosis and autophagy in granulosa cells.

Polycystic ovary syndrome (PCOS) is a complicated endocrinopathy affecting women at reproductive age. Increasing evidence has shown the anti-PCOS effect of electroacupuncture (EA), a modified approach of traditional Chinese medical therapy "acupuncture". However, the underlying mechanism of EA-alleviated PCOS waits further explored. In this study, experimental PCOS were induced in rats by dehydroepiandrosterone (DHEA) injection. Testosterone (T)-induced human ovarian granulosa cell (GC) line KGN was used to mimic PCOS in vitro. EA significantly alleviated histological changes and hormone disruption in PCOS rats. Besides, EA inhibited cell apoptosis, autophagy and the activation of endoplasmic reticulum (ER) stress-related PERK/eIF2α/ATF4/CHOP signaling in ovaries of PCOS rats. More interestingly, intermedin (IMD), a member of calcitonin gene-related peptide (CGRP), was evidently up-regulated in ovarian GCs after EA treatment, and its main bioactive form IMD1-53 suppressed cell apoptosis, autophagy and PERK/eIF2α/ATF4/CHOP signaling in T-induced KGN cells. Consistent with IMD1-53, ER stress inhibitor 4-PBA exerted an inhibitory effect on T-induced cell apoptosis and autophagy in KGN cells. Collectively, this study validates the protective effect of EA on DHEA-induced PCOS, and proposes that IMD relieved apoptosis and autophagy in T-induced granulosa cells via inhibiting ER stress.

Chromosomal mapping of a locus associated with adult-stage resistance to powdery mildew from Agropyron cristatum chromosome 6PL in wheat.

KEY MESSAGE: The powdery mildew resistance locus was mapped to A. cristatum chromosome 6PL bin (0.27-0.51) and agronomic traits evaluation indicated that this locus has potential breeding application value. Agropyron cristatum (2n = 4x = 28, PPPP) is a wild relative of wheat with an abundance of biotic and abiotic stress resistance genes and is considered one of the best exogenous donor relatives for wheat breeding. A number of wheat-A. cristatum derived lines have been generated, including addition lines, translocation lines and deletion lines. In this study, the 6P disomic addition line 4844-12 (2n = 2x = 44) was confirmed to have genetic effects on powdery mildew resistance. Four 6P deletion lines (del16a, del19b, del21 and del27) and two translocation lines (WAT638a and WAT638b), derived from radiation treatment of 4844-12, were used to further assess the 6P powdery mildew resistance locus by powdery mildew resistance assessment, genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH) and 6P specific sequence-tagged-site (STS) markers. Collectively, the locus harboring the powdery mildew resistance gene was genetically mapped to a 6PL bin (0.27-0.51). The genetic effects of this chromosome segment on resistance to powdery mildew were further confirmed by del16a and del27 BC3F2 lines. Comprehensive evaluation of agronomic traits revealed that the powdery mildew resistance locus of 6PL (0.27-0.51) has potential application value in wheat breeding. A total of 22 resistant genes were annotated and 3 specific gene markers were developed for detecting chromatin of the resistant region based on genome re-sequencing. In summary, this study could broaden the powdery mildew resistance gene pool for wheat genetic improvements.

Introgression of chromosome 1P from Agropyron cristatum reduces leaf size and plant height to improve the plant architecture of common wheat.

KEY MESSAGE: Introducing Agropyron cristatum chromosome 1P into common wheat can significantly reduce the plant height and leaf size, which can improve the plant architecture of common wheat. A new direction in crop breeding is the improvement of plant architecture for dense plantings to obtain higher yields. Wild relatives carry an abundant genetic variation that can increase the diversity of genes for crop genetic improvement. In this study, the A. cristatum 1P addition line, 1PS and 1PL telosomic addition lines were obtained by backcrossing the addition/substitution line II-3-1 (2n = 20'' W + 1P" + 2P") with the commercial recurrent parent cv. Jimai 22. Four continuous years of agronomic trait investigation in the genetic populations suggested that the introduction of A. cristatum chromosome 1P into wheat can significantly improve wheat plant architecture by reducing the plant height, leaf length and leaf width. A. cristatum chromosome arm 1PS reduced the plant height and leaf length of wheat, whereas introducing A. cristatum chromosome arm 1PL reduced the plant height, leaf length and leaf width. Altogether, our results demonstrated that A. cristatum chromosome 1P carries the dominant genes for small leaves and a dwarf habit for the enhancement of plant architecture in wheat. This study highlights wild relative donors as new gene resources for improving wheat plant architecture for dense planting.

Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli.

Despite the broad-spectrum antimicrobial activities of silver, its internal usage is restricted, owing to the toxicity. Strategies to enhance its efficacy are highly desirable but rely heavily on the understanding of its molecular mechanism of action. However, up to now, no direct silver-targeting proteins have been mined at a proteome-wide scale, which hinders systemic studies on the biological pathways interrupted by silver. Herein, we build up a unique system, namely liquid chromatography gel electrophoresis inductively coupled plasma mass spectrometry (LC-GE-ICP-MS), allowing 34 proteins directly bound by silver ions to be identified in Escherichia coli. By using integrated omic approaches, including metalloproteomics, metabolomics, bioinformatics, and systemic biology, we delineated the first dynamic antimicrobial actions of silver (Ag+) in E. coli, i.e., it primarily damages multiple enzymes in glycolysis and tricarboxylic acid (TCA) cycle, leading to the stalling of the oxidative branch of the TCA cycle and an adaptive metabolic divergence to the reductive glyoxylate pathway. It then further damages the adaptive glyoxylate pathway and suppresses the cellular oxidative stress responses, causing systemic damages and death of the bacterium. To harness these novel findings, we coadministrated metabolites involved in the Krebs cycles with Ag+ and found that they can significantly potentiate the efficacy of silver both in vitro and in an animal model. Our study reveals the comprehensive and dynamic mechanisms of Ag+ toxicity in E. coli cells and offers a novel and general approach for deciphering molecular mechanisms of metallodrugs in various pathogens and cells to facilitate the development of new therapeutics.