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Abstract Background Unfavorable temperatures significantly constrain the quality formation of Dendrobium officinale, severely limiting its food demand. Salicylic acid (SA) enhances the resistance of D. officinale to stress and possesses various analogs. The impact and mechanism of the SA family on improving the quality of D. officinale under adverse temperature conditions remains unclear. Results Combined with molecular docking analysis, chlorophyll fluorescence and metabolic analysis after treatments with SA analogues or extreme temperatures are performed in this study. The results demonstrate that both heat and cold treatments impede several main parameters of chlorophyll fluorescence of D. officinale, including the ΦPSII parameter, a sensitive growth indicator. However, this inhibition is mitigated by SA or its chemically similar compounds. Comprehensive branch imaging of ΦPSII values revealed position-dependent improvement of tolerance. Molecular docking analysis using a crystal structure model of NPR4 protein reveals that the therapeutic effects of SA analogs are determined by their binding energy and the contact of certain residues. Metabolome analysis identifies 17 compounds are considered participating in the temperature-related SA signaling pathway. Moreover, several natural SA analogs such as 2-hydroxycinnamic acid, benzamide, 2-(formylamino) benzoic acid and 3-o-methylgallic acid, are further found to have high binding ability to NPR4 protein and probably enhance the tolerance of D. officinale against unfavorable temperatures through flavone and guanosine monophosphate degradation pathways. Conclusions These results reveal that the SA family with a high binding capability of NPR4 could improve the tolerance of D. officinale upon extreme temperature challenges. This study also highlights the collaborative role of SA-related natural compounds present in D. officinale in the mechanism of temperature resistance and offers a potential way to develop protective agents for the cultivation of D. officinale.

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P

Abstract Background The study aimed to evaluate the diagnostic efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) parameters in distinguishing sinonasal lymphoma from sinonasal carcinoma. Methods Forty-two participants with histologically confirmed sinonasal lymphomas and fifty-two cases of sinonasal carcinoma underwent imaging with a 3.0T MRI scanner. DCE-MRI and DWI were conducted, and various parameters including type of time-intensity curve(TIC), time to peak, peak enhancement, peak contrast enhancement, washout rate, apparent diffusion coefficient (ADC), and relative ADC were measured. Binary logistic regression and receiver operating characteristic (ROC) curve analysis were employed to assess the diagnostic capability of individual and combined indices for differentiating nasal sinus lymphoma from nasal sinus carcinoma. Results Sinonasal lymphoma predominantly exhibited type II TIC(n = 20), whereas sinonasal carcinoma predominantly exhibited type III TIC(n = 23). Significant differences were observed in all parameters except washout ratio (p

Abstract Background Bow Hunter’s syndrome (BHS), also known as rotational vertebral artery occlusion (RVAO), is a rare condition characterized by dynamic vertebrobasilar insufficiency due to position-dependent occlusion of the vertebral artery (VA). In the existing literature, most cases of BHS are attributed to osteophytic compression originating from the occipital condyle or within the transverse foramen, often accompanied by anatomical abnormalities of the VA. However, cases presenting solely with VA anomalies in the absence of any cervical vertebral structural abnormality are rare. This case report presents a unique instance of BHS in a 56-year-old male, attributed to the anomalous origin of the right VA and the absence of the left VA, without cervical structural abnormalities. Case presentation The patient exhibited symptoms like episodic dizziness and vertigo, which were exacerbated by rightward head rotation and alleviated upon returning to a neutral position. Diagnostic evaluation, including digital subtraction angiography, revealed that the right VA originated from the right common carotid artery and compression-induced stenosis of the right VA during head rotation. Conservative management, including avoidance of certain head movements and anti-arteriosclerosis medication, led to symptom resolution over a two-year follow-up period. Conclusions This report contributes to the understanding of BHS by highlighting a rare vascular anomaly presentation and incorporates a review of 14 similar case reports in the literature describing that an anatomical abnormality of the VA is mainly responsible for the pathology of BHS in the absence of cervical vertebral anomalies, thus emphasizing the need for careful diagnostic and management strategies.

Purpose: This study aimed to identify the altered pathways and genes associated with freezing damage in human sperm during cryopreservation by multiomics analysis. Materials and Methods: Fifteen fresh human semen samples were collected for transcriptomic analysis, and another 5 fresh human semen samples were obtained for metabolomic analysis. For each semen sample, 1 mL was cryopreserved, and another 1 mL was left untreated for paired design. The results were then combined with previously published proteomic results to identify key genes/pathways. Results: Cryopreservation significantly reduced sperm motility and mitochondrial structure. Transcriptomic analysis revealed altered mitochondrial function, including changes in tRNA-methyltransferase activity and adenosine tri-phosphate/adenosine di-phosphate transmembrane transporter activity. Metabolomic analysis showed that the citrate cycle in mitochondria was significantly altered. Combining transcriptomic, proteomic, and metabolomic analyses revealed 346 genes that were altered in at least two omics analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that metabolic pathways were significantly altered and strongly associated with mitochondria. Five genes were altered in all three omics analyses: COL11A1, COL18A1, LPCAT3, NME1, and NNT. Conclusions: Five genes were identified by multiomics analysis in human cryopreserved sperm. These genes might have specific functions in cryopreservation. Explorations of the functions of these genes will be helpful for sperm cryopreservation and sperm motility improvement or even for reproduction in the future.

Abstract Fly ash derived from municipal solid waste incinerators (MSWIs) harbors significant quantities of heavy metals with high leaching toxicity, resulting in detrimental environmental effects. Pb2+ in fly ash is the ion most likely to exceed permissible levels. However, chemical stabilization methods demonstrate poor efficacy in stabilizing Pb2+ under acidic conditions. Herein, we have developed a robust acid-resistant chelating polymer (25DTF) for enhanced stabilization of Pb2+ in fly ash. 25DTF was synthesized through the reaction of formaldehyde with 2,5-dithiourea. 25DTF exhibited remarkable chelation efficiency, nearing 100%, for Pb2+ in fly ash. 25DTF demonstrated exceptional chelation efficiency, surpassing 99.9%, when interacting with Pb2+ in fly ash at pH ≤ 7. Even under acidic conditions, 25DTF effectively prevented the secondary dissolution of Pb2+. Additionally, it indicated outstanding Pb2+ chelation efficiency across diverse regions of China. The 25DTF chelating agent shows considerable potential in alleviating metal ion contamination in soil, wastewater, and urban environmental management, thereby fostering advancements in environmental stewardship.

Impatiens beipanjiangensis Jian Xu & H. F. Hu (Balsaminaceae), a new species of Impatiens subg. Clavicarpa discovered in Guizhou, China, is described and illustrated in this study along with its molecular phylogenetic analysis. I. beipanjiangensis is similar to I. liboensis, I. chishuiensis and I. clavigera in morphology, but I. tubulosa has the closest relationship to it. However, there are various ways in which the new species can be easily distinguished from these four species: Inferior nodes swollen rhizoid, pale green and with hooked outer sepals, longer lateral united petals, subovate auricle, deeper lower sepal and shorter spur that is reflexed towards the lower sepal. Furthermore, I. beipanjiangensis is distinguished from other Impatiens species, based on morphological, micromorphological and palynological evidence and molecular data (PP 0.967).

Abstract Rammed earth is a kind of cleaning material, widely used in all kinds of buildings in the world. The Great Wall of ancient China is a typical world cultural site built from rammed earth. The rammed earth Great Wall of Shanhaiguan is close to Bohai Bay, which has suffered from long-term erosion by rain, causing a series of problems such as soil loss, collapse and gully flushing. The protection materials of the rammed earth site have always puzzled scholars. However, during the rainy season, it was found that some of the walls at Xiaowan Gouge and Nantuzhuang Gouge in the Shanhaiguan Great Wall had unwashed traces, the soil surface of the walls was intact, and the anti-erosion ability of the walls was significantly higher than that of other places. In order to explore the reasons for its strong anti-erosion ability in the natural state of rammed earth wall, guide the protection of rammed earth Great Wall, and carry out different experimental tests to explore its anti-erosion reasons and internal mechanisms. Firstly, the characteristics of rammed soil were understood through the composition test of rammed soil, and the indoor and outdoor erosion test was carried out to determine that the anti-erosion reason was the protection of gray-green soil crust. The property and composition of soil crust were determined through the immersion test and genome sequencing. Finally, the protection mechanism of soil crust was analyzed by scanning electron microscopy.

Purpose: The coexistence of growth hormone-secreting pituitary adenoma (GHPA) and Graves' disease (GD) is rare. This study aimed to investigate the relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) levels and thyroid function in patients with GHPA combined with GD and to explore the underlying mechanisms. Methods: Eleven patients with GHPA combined with GD during 2015-2022 were collected by searching the medical record system of Beijing Tiantan Hospital, Capital Medical University. Changes in GH/IGF-1 levels and thyroid function were compared before and after the application of antithyroid drugs (ATD) and before and after transsphenoidal surgery (TSS) or somatostatin analog (SSA) treatment, respectively. Results: After the application of ATD, with the decrease of thyroid hormone levels, GH/IGF-1 levels also decreased gradually. In patients without ATD application, after surgery or SSA treatment, thyroid hormone levels decreased as GH/IGF-1 decreased. Conclusion: Hyperthyroidism due to GD promotes the secretion of GH/IGF-1, and when thyroid hormone levels were decreased by the use of ATD, GH and IGF-1 levels were also decreased, suggesting that thyroid hormones may influence the synthesis and secretion of GH/IGF-1. The use of ATD to control thyrotoxicosis before TSS is not only beneficial in reducing the risk of anesthesia but may help to promote biochemical control of GHPA. On the other hand, high levels of GH/IGF-1 in patients with GHPA also exacerbate GD hyperthyroidism, which is ameliorated by a decrease in GH/IGF-1 levels by TSS or SSA treatment, suggesting that the GH–IGF-1 axis promotes growth, thyroid function, and thyroid hormone metabolism.

Abstract Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

ObjectiveTo determine the relationship between school bullying victimization and social mindfulness and its mechanism in light of the interdependence and schema theories.MethodThe Chinese version of the Delaware Bullying Victimization Scale-student, Emotion Regulation Questionnaire, Self-Concept Clarity Scale and The Social Mindfulness Self-report Scale (SMSRS) were distributed to 553 middle school students.Results(1) The correlations of school bullying victimization with social mindfulness, self-concept clarity, and cognition reappraisal were statistically significant. (2) School bullying victimization had a significant effect on social mindfulness. (3) The simple mediating role of self-concept clarity and cognition reappraisal between school bullying victimization and social mindfulness were significant. (4) Self-concept clarity and cognition reappraisal played a chain mediating role between school bullying victimization and social mindfulness.

Summary: Background: Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings: No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation: hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

Abstract Diamond possesses excellent thermal conductivity and tunable bandgap. Currently, the high‐pressure, high‐temperature, and chemical vapor deposition methods are the most promising strategies for the commercial‐scale production of synthetic diamond. Although diamond has been extensively employed in jewelry and cutting/grinding tasks, the realization of its high‐end applications through microstructure engineering has long been sought. Herein, we discuss the microstructures encountered in diamond and further concentrate on cutting‐edge investigations utilizing electron microscopy techniques to illuminate the transition mechanism between graphite and diamond during the synthesis and device constructions. The impacts of distinct microstructures on the electrical applications of diamond, especially the photoelectrical, electrical, and thermal properties, are elaborated. The recently reported elastic and plastic deformations revealed through in situ microscopy techniques are also summarized. Finally, the limitations, perspectives, and corresponding solutions are proposed.

BackgroundThe newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients.MethodsLiterature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software.ResultsFive studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p

Summary: Background: The combined vincristine, pegylated liposomal doxorubicin (PLD), and cyclophosphamide (VPC) regimen has never been studied in pediatric patients. Methods: This open-label, single-center, single-arm phase I study utilizing a “3 + 3” design enrolled children with relapsed/refractory (R/R) solid tumors. Three dose levels of PLD (Duomeisu®) were studied (30, 40, or 50 mg/m2) in combination with cyclophosphamide (1500 mg/m2), mesna (1500 mg/m2), and vincristine (1.5 mg/m2, maximum 2 mg) once every 3 weeks. The primary endpoints included safety, the maximum tolerated dose (MTD) of PLD (Duomeisu®), and the recommended phase 2 dose (RP2D) of PLD (Duomeisu®) for further phase 2 investigation. The secondary endpoints were objective response rate (ORR) and disease control rate (DCR). This study is registered with ClinicalTrials.gov, NCT04213612. Findings: Between January 7, 2020, and November 18, 2021, 34 patients were eligible and evaluable for toxicity, while 26 patients were evaluable for response. The MTD of PLD (Duomeisu®) was 30 mg/m2. The most common adverse event (AE) was grade 3 or 4 neutropenia (61.8%). The most common grade 1 or 2 non-hematologic AE and cardiotoxicity effects were vomiting (35.3%) and abnormal electrocardiogram T waves (20.6%), respectively. ORR and DCR to VPC regimen after two cycles were 50.0% and 92.3%, respectively. Targeted gene panel sequencing revealed the activation of TP53 mutation may be an adverse prognostic factor. Interpretation: The VPC regimen showed a promising safety profile and had preliminary efficacy in children with R/R solid tumors. The RP2D for PLD (Duomeisu®) combined with cyclophosphamide and vincristine is 30 mg/m2 once every 3 weeks. Funding: CSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang, the National Key Research and Development Program of China [No. 2022YFC2705005], the National Natural Science Foundation of China [No. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].

Ammonia (NH3) is an ideal green fuel with high energy density and plays an indispensable role in fertilizer production. Electrochemical reduction of nitrate (NO3–), a toxic pollutant in groundwater, has shown promising as a viable approach to converting waste into valuable NH3 under ambient conditions, offering an alternative to the energy-intensive Haber-Bosch process. Due to their high efficiency, copper (Cu)-based materials have shown great potential as electrocatalysts for the NO3– reduction reaction (NO3–RR) to NH3. In this review, we provide a comprehensive summary of the fundamental principles underlying nitrate reduction over Cu-based electrocatalysts and discuss various strategies to enhance the performance of NO3– reduction, including facets, morphologies, size, surface functionalization, compositional engineering, and defect engineering. We also delve into the relationship between the electrocatalytic performance and structure characteristics of electrocatalysts and thoroughly examine the reaction mechanism involved in NO3–RR. Furthermore, we highlight the existing challenges and prospective paths forward in this area of study. This review offers valuable insights and guidance for the strategic design and optimization of Cu-based electrocatalysts for NO3–RR applications.

Background: Adverse childhood experiences (ACE) encompass traumatic events occurring before age 18, with lasting impacts on health. While ACE disclosure is important for understanding these effects, some individuals decline to respond to ACE-related survey items due to sensitivity, privacy concerns, or psychological distress. This study explores the relationship between non-response to ACE items and health outcomes, shedding light on the implications for those who choose not to disclose. Methods: We performed a secondary analysis of the 2021 Behavioral Risk Factor Surveillance System (BRFSS)—a national telephone survey querying health behaviors and conditions. Sociodemographic factors, ACE exposure, and non-response to ACE items were analyzed. Results: Individuals who decline to respond to ACE items exhibit similar patterns of health behaviors and conditions as those reporting ACE exposure. Non-response is linked to both healthier behaviors (lifetime HIV testing) and riskier behaviors (higher odds of smoking and e-cigarette use). Moreover, non-responders have higher odds of being underweight or obese, experiencing concentration difficulties, reporting poor self-rated health, and reporting multiple health diagnoses including depression, diabetes, high blood pressure, heart attack, and stroke. Conclusions: The study underscores the need to address health disparities associated with ACE, regardless of disclosure status. Healthcare interventions should target respondents and non-respondents of ACE screeners, tailoring strategies to promote healthier coping mechanisms and mitigate maladaptive behaviors. These results emphasize the importance of trauma-informed care, early intervention, and targeted public health initiatives for individuals affected by ACE, irrespective of their disclosure choices.

Abstract Background Neural stem cells (NSCs), especially human NSCs, undergo cellular senescence characterized by an irreversible proliferation arrest and loss of stemness after prolonged culture. While compelling correlative data have been generated to support the oxidative stress theory as one of the primary determinants of cellular senescence of NSCs, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and cellular senescence of NSCs has yet to be firmly established. Human SOD1 (hSOD1) is susceptible to oxidation. Once oxidized, it undergoes aberrant misfolding and gains toxic properties associated with age-related neurodegenerative disorders. The present study aims to examine the role of oxidized hSOD1 in the senescence of NSCs. Methods NSCs prepared from transgenic mice expressing the wild-type hSOD1 gene were maintained in culture through repeated passages. Extracellular vesicles (EVs) were isolated from culture media at each passage. To selectively knock down oxidized SOD1 in NSCs and EVs, we used a peptide-directed chaperone-mediated protein degradation system named CT4 that we developed recently. Results In NSCs expressing the hSOD1 from passage 5, we detected a significant increase of oxidized hSOD1 and an increased expression of biomarkers of cellular senescence, including upregulation of P53 and SA-β-Gal and cytoplasmic translocation of HMGB1. The removal of oxidized SOD1 remarkably increased the proliferation and stemness of the NSCs. Meanwhile, EVs derived from senescent NSCs carrying the wild-type hSOD1 contained high levels of oxidized hSOD1, which could accelerate the senescence of young NSCs and induce the death of cultured neurons. The removal of oxidized hSOD1 from the EVs abolished their senescence-inducing activity. Blocking oxidized SOD1 on EVs with the SOD1 binding domain of the CT4 peptide mitigated its toxicity to neurons. Conclusion Oxidized hSOD1 is a causal factor in the cellular senescence of NSCs. The removal of oxidized hSOD1 is a strategy to rejuvenate NSCs and to improve the quality of EVs derived from senescent cells.

Abstract Allergic rhinitis (AR) remains a major health problem worldwide. Compared with traditional oral drugs, nasal administration avoids first-pass metabolism and achieve faster and more effective efficacy. In this study, we used the ion crosslinking method to prepare quercetin–chitosan nasal adaptive nanomedicine (QCS) delivery system and evaluated in the treatment of allergic rhinitis mice models. The obtained positively charged nanoparticles with a particle size of 229.2 ± 0.2 nm have excellent characteristics in encapsulation efficiency (79.604%), drug loading rate (14.068%), drug release (673.068 μg) and stability(> 7 days). Excitingly, QCS treatment significantly reduced the number of sneezing and nasal rubbing events in AR mice, while reducing the levels of inflammatory factors such as immunoglobulin E (IgE), interleukin (IL)-17, tumor necrosis factor (TNF)-α, and (IL)-6 to alleviate AR symptoms. Hematoxylin–eosin (HE) staining also showed the damaged nasal mucosa was improved. These experimental results suggest that QCS can effectively suppress allergic inflammation in a mouse model and hold promise as a therapeutic option for allergic rhinitis.

Abstract To explore the clinical effect of standing bed combined with early anti-gravity running table training in the healing and functional recovery of anterior rotation external rotation ankle fractures. Fifty-two patients with ankle fractures of degree III or degree IV of PER admitted to Pingle Orthopaedic and Traumatology Hospital of Shenzhen City between September 2021 and January 2023 were selected for observation, and they were divided into 26 cases in each group according to the method of randomised numerical table into the control group and the observation group. The patients in the control group started the routine rehabilitation treatment on the 1st day after operation, and in the 0–2 weeks after operation, the affected limb was elevated and ankle pump training was carried out; in the 3–6 weeks after operation, joint mobility training, strength training and soft tissue release were carried out; and in the 6–8 weeks after operation, weight-bearing training was increased. The observation group added standing bed training on the 7th postoperative day and anti-gravity running table training on the 28th postoperative day on the basis of the treatment protocol of the control group. Bone density, ankle mobility and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores, pain, ankle mobility and swelling evaluations were compared between the 2 groups before and after 8 weeks of treatment, and the quality scores of bone scabs were compared between the 2 groups after 4 weeks of treatment. There was no statistical significance in the comparison of the items between the two groups before treatment (all P > 0.05), and the difference in the bone scab quality score was not statistically significant after 4 weeks of treatment (P > 0.05), and after 8 weeks of treatment, the bone scab quality score, bone mineral density and AOFAS scores, pain, ankle mobility, and evaluations were higher than those of the control group (all P 0.05). Standing bed combined with early anti-gravity running table training applied to postoperative patients with PER III or IV degree ankle fracture can reduce the degree of pain and improve the ankle joint function.

Abstract Endocrine receptors play an essential role in tumor metabolic reprogramming and represent a promising therapeutic avenue in pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by a nutrient-deprived microenvironment. To meet their ascendant energy demands, cancer cells can internalize extracellular proteins via macropinocytosis. However, the roles of endocrine receptors in macropinocytosis are not clear. In this study, we found that progesterone receptor (PGR), a steroid-responsive nuclear receptor, is highly expressed in PDAC tissues obtained from both patients and transgenic LSL-Kras G12D/+ ; LSL-Trp53 R172H/+ ; PDX1-cre (KPC) mice. Moreover, PGR knockdown restrained PDAC cell survival and tumor growth both in vitro and in vivo. Genetic and pharmacological PGR inhibition resulted in a marked attenuation of macropinocytosis in PDAC cells and subcutaneous tumor models, indicating the involvement of this receptor in macropinocytosis regulation. Mechanistically, PGR upregulated CDC42, a critical regulator in macropinocytosis, through PGR-mediated transcriptional activation. These data deepen the understanding of how the endocrine system influences tumor progression via a non-classical pathway and provide a novel therapeutic option for patients with PDAC.

Abstract Background The mechanisms and risk factors underlying ovarian cancer (OC) remain under investigation, making the identification of new prognostic biomarkers and improved predictive factors critically important. Recently, circulating metabolites have shown potential in predicting survival outcomes and may be associated with the pathogenesis of OC. However, research into their genetic determinants is limited, and there are some inadequacies in understanding the distinct subtypes of OC. In this context, we conducted a Mendelian randomization study aiming to provide evidence for the relationship between genetically determined metabolites (GDMs) and the risk of OC and its subtypes. Methods In this study, we consolidated genetic statistical data of GDMs with OC and its subtypes through a genome-wide association study (GWAS) and conducted a two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method served as the primary approach, with MR-Egger and weighted median methods employed for cross-validation to determine whether a causal relationship exists between the metabolites and OC risk. Moreover, a range of sensitivity analyses were conducted to validate the robustness of the results. MR-Egger intercept, and Cochran’s Q statistical analysis were used to evaluate possible heterogeneity and pleiotropy. False discovery rate (FDR) correction was applied to validate the findings. We also conducted a reverse MR analysis to validate whether the observed blood metabolite levels were influenced by OC risk. Additionally, metabolic pathway analysis was carried out using the MetaboAnalyst 5.0 software. Results In MR analysis, we discovered 18 suggestive causal associations involving 14 known metabolites, 8 metabolites as potential risk factors, and 6 as potential cancer risk reducers. In addition, three significant pathways, "caffeine metabolism," "arginine biosynthesis," and "citrate cycle (TCA cycle)" were associated with the development of mucinous ovarian cancer (MOC). The pathways "caffeine metabolism" and "alpha-linolenic acid metabolism" were associated with the onset of endometrioid ovarian cancer (OCED). Conclusions Our MR analysis revealed both protective and risk-associated metabolites, providing insights into the potential causal relationships between GDMs and the metabolic pathways related to OC and its subtypes. The metabolites that drive OC could be potential candidates for biomarkers.

Abstract The non-classical anodic H2 production from 5-hydroxymethylfurfural (HMF) is very appealing for energy-saving H2 production with value-added chemical conversion due to the low working potential (~0.1 V vs RHE). However, the reaction mechanism is still not clear due to the lack of direct evidence for the critical intermediates. Herein, the detailed mechanisms are explored in-depth using in situ Raman and Infrared spectroscopy, isotope tracking, and density functional theory calculations. The HMF is observed to form two unique inter-convertible gem-diol intermediates in an alkaline medium: 5-(Dihydroxymethyl)furan-2-methanol anion (DHMFM−) and dianion (DHMFM2−). The DHMFM2− is easily oxidized to produce H2 via H− transfer, whereas the DHMFM− is readily oxidized to produce H2O via H+ transfer. The increases in potential considerably facilitate the DHMFM− oxidation rate, shifting the DHMFM− ↔ DHMFM2− equilibrium towards DHMFM− and therefore diminishing anodic H2 production until it terminates. This work captures the critical intermediate DHMFM2− leading to hydrogen production from aldehyde, unraveling a key point for designing higher performing systems.

Abstract Most current research is devoted to electrochemical nitrate reduction reaction for ammonia synthesis under alkaline/neutral media while the investigation of nitrate reduction under acidic conditions is rarely reported. In this work, we demonstrate the potential of TiO2 nanosheet with intrinsically poor hydrogen-evolution activity for selective and rapid nitrate reduction to ammonia under acidic conditions. Hybridized with iron phthalocyanine, the resulting catalyst displays remarkably improved efficiency toward ammonia formation owing to the enhanced nitrate adsorption, suppressed hydrogen evolution and lowered energy barrier for the rate-determining step. Then, an alkaline-acid hybrid Zn-nitrate battery was developed with high open-circuit voltage of 1.99 V and power density of 91.4 mW cm–2. Further, the environmental sulfur recovery can be powered by above hybrid battery and the hydrazine-nitrate fuel cell can be developed for simultaneously hydrazine/nitrate conversion and electricity generation. This work demonstrates the attractive potential of acidic nitrate reduction for ammonia electrosynthesis and broadens the field of energy conversion.

Reducing plant height (PH) is one of the core contents of the “Green Revolution”, which began in the 1960s in wheat. A number of 27 reduced-height (Rht) genes have been identified and a great number of quantitative trait loci (QTLs) for PH have been mapped on all 21 chromosomes. Nonetheless, only several genes regulated PH have been cloned. In this study, we found the interval of QTL QPh-1B included an EST-SSR marker swes1079. According to the sequence of swes1079, we cloned the TaOSCA1.4 gene. We developed a CAPS marker to analyze the variation across a natural population. The result showed that the PH was significantly different between the two haplotypes of TaOSCA1.4–1B under most of the 12 environments and the average values of irrigation and rainfed conditions. This result further demonstrated that TaOSCA1.4 was associated with PH. Then, we validated the TaOSCA1.4 via RNAi technology. The average PHs of the wild-type (WT), RNAi lines 1 (Ri-1) and 2 (Ri-2) were 94.6, 83.6 and 79.2 cm, respectively, with significant differences between the WT and Ri-1 and Ri-2. This result indicated that the TaOSCA1.4 gene controls PH. TaOSCA1.4 is a constitutively expressed gene and its protein localizes to the cell membrane. TaOSCA1.4 gene is a member of the OSCA gene family, which regulates intracellular Ca2+ concentration. We hypothesized that knock down mutants of TaOSCA1.4 gene reduced regulatory ability of Ca2+, thus reducing the PH. Furthermore, the cell lengths of the knock down mutants are not significantly different than that of WT. We speculate that TaOSCA1.4 gene is not directly associated with gibberellin (GA), which should be a novel mechanism for a wheat Rht gene.

Paclitaxel (trade name Taxol) is a rare diterpenoid with anticancer activity isolated from Taxus. At present, paclitaxel is mainly produced by the semi-synthetic method using extract of Taxus tissues as raw materials. The studies of regulatory mechanisms in paclitaxel biosynthesis would promote the production of paclitaxel through tissue/cell culture approaches. Here, we systematically identified 990 transcription factors (TFs), 460 microRNAs (miRNAs), and 160 phased small interfering RNAs (phasiRNAs) in Taxus chinensis to explore their interactions and potential roles in regulation of paclitaxel synthesis. The expression levels of enzyme genes in cone and root were higher than those in leaf and bark. Nearly all enzyme genes in the paclitaxel synthesis pathway were significantly up-regulated after jasmonate treatment, except for GGPPS and CoA Ligase. The expression level of enzyme genes located in the latter steps of the synthesis pathway was significantly higher in female barks than in male. Regulatory TFs were inferred through co-expression network analysis, resulting in the identification of TFs from diverse families including MYB and AP2. Genes with ADP binding and copper ion binding functions were overrepresented in targets of miRNA genes. The miRNA targets were mainly enriched with genes in plant hormone signal transduction, mRNA surveillance pathway, cell cycle and DNA replication. Genes in oxidoreductase activity, protein-disulfide reductase activity were enriched in targets of phasiRNAs. Regulatory networks were further constructed including components of enzyme genes, TFs, miRNAs, and phasiRNAs. The hierarchical regulation of paclitaxel production by miRNAs and phasiRNAs indicates a robust regulation at post-transcriptional level. Our study on transcriptional and posttranscriptional regulation of paclitaxel synthesis provides clues for enhancing paclitaxel production using synthetic biology technology.

BackgroundEngaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual’s positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect.MethodsBased on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200–499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM.ResultsThe core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts.ConclusionAs HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

BackgroundThe association between air pollution, lung function, gastroesophageal reflux disease, and Non-alcoholic fatty liver disease (NAFLD) remains inconclusive. Previous studies were not convincing due to confounding factors and reverse causality. We aim to investigate the causal relationship between air pollution, lung function, gastroesophageal reflux disease, and NAFLD using Mendelian randomization analysis.MethodsIn this study, univariate Mendelian randomization analysis was conducted first. Subsequently, Steiger testing was performed to exclude the possibility of reverse association. Finally, significant risk factors identified from the univariate Mendelian analysis, as well as important factors affecting NAFLD from previous observational studies (type 2 diabetes and body mass index), were included in the multivariable Mendelian randomization analysis.ResultsThe results of the univariable Mendelian randomization analysis showed a positive correlation between particulate matter 2.5, gastroesophageal reflux disease, and NAFLD. There was a negative correlation between forced expiratory volume in 1 s, forced vital capacity, and NAFLD. The multivariable Mendelian randomization analysis indicated a direct causal relationship between gastroesophageal reflux disease (OR = 1.537, p = 0.011), type 2 diabetes (OR = 1.261, p

BackgroundThe marine pearl culture industry is a key industry in the Beibu Gulf of China that achieves large-scale pearl production by artificial nucleus insertion in pearls. High-quality pearls can produced by xenotransplantation, but allotransplantation or xenotransplantation can lead to various immune responses, resulting in nucleus rejection or even the recipient shell death and thereby causing significant losses in pearl production.MethodsFew studies have investigated the immune defenses of oysters related to allografts and xenografts. In this study, transcriptomic comparisons of allograft and xenograft Pinctada fucata haemocytes were conducted to identify genes associated with immune responses.ResultsA total of 33.11 Gbp of clean reads were generated from five P. fucata haemocytes. De-novo assembly of quality-filtered reads generated a total of 26,526 unigenes, with 22,002 known genes and 4,524 predicted novel genes. In addition, 34,904 novel transcripts were detected, with 15,620 novel alternative splicing isoforms of known protein coding genes and 4,605 belonging to novel protein coding genes, with the remaining 14,679 comprising long non-coding RNA transcripts. Functional enrichment analysis of immune-related differentially expressed genes (DEGs) using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases revealed 36–44 significantly enriched GO terms and 34 significantly enriched KEGG pathways. Ten DEGs were subjected to validation of expression levels using RT-q PCR analysis, revealing generally consistent values as the high-throughput sequencing data.ConclusionOyster haemocytes were comprehensively evaluated in this study using transcriptomic comparisons and with a focus on immune-related functional genes and pathways. The results revealed numerous DEGs related to immune function that can serve as the basis for subsequent immune response analysis of allotransplantation and xenotransplantation.

The bonding performance between new and old concrete affects the reliability and service life of the repair structure. However, the bonding interface is complex and has many influencing factors, so selecting appropriate repair materials and evaluation methods for repair structures under different service environments is important. This paper presents a comprehensive overview of the factors that influence bonding properties. These include the choice of repair materials, the condition of the existing concrete, the type of interfacial agents used, the service environment, and the testing methods employed. The paper concludes by examining the challenges and opportunities in developing interface bonding properties to provide insights and research directions for future theoretical analysis and experimental research.

An eleven-wavelength-switchable thulium-doped fiber laser was proposed and demonstrated, incorporating an improved geta-shaped cavity providing bidirectional amplification, and a sandwich four-mode fiber Mach–Zehnder interferometer filter with curvature sensitivity. The filter was fabricated by splicing a segment of four-mode fiber (FMF) between two segments of a no-core fiber (NCF), with two segments of a single mode fiber (SMF) fused outside the two NCFs, and the structural order was SMF-NCF-FMF-NCF-SMF (SNFNS). The mode interference of the SNFNS filter was investigated theoretically in detail. The curvature characteristic was measured experimentally, and the maximum curvature sensitivity of the filter was 5.83 dB/m−1 in the ranges of 1.51 ∼ 2.26 m−1. By adjusting the curvature of the filter and polarization controllers, switchable eleven single-wavelength output can be obtained. The stability of the single-wavelength output was monitored with the fluctuations of the center wavelength and output power being less than 0.05 nm and 0.90 dB, respectively. Additionally, a slope efficiency of 9.797 % was achieved using a bidirectional amplifier configuration. The proposed laser may be suitable for mode-division multiplexing systems and optical sensor applications.

Abstract To study the effect of using Nordic hamstring exercise method on muscle strength and knee joint stability of patients after ACL reconstruction. 60 patients admitted to our hospital for ACL reconstruction were randomly divided into a test group (n = 30, applying Nordic hamstring exercise) and a control group (n = 30, applying conventional rehabilitation training methods), and the difference in the circumference of the thighs of the patients in the two groups was analysed after training, and the peak torque (PT), total torque (PT), and flexion and extension strength were measured by using the Biodex system3 Multi-joint Isokinetic Testing System at knee joints with an angular velocity of 60°/s and 120°/s. The peak torque (PT), total work (TW), and average peak torque (AVG PT) were measured by extension and flexion strength at angular velocity, and the Lysholm Knee Score was used to assess the knee function of 60 patients. There was no difference in the difference in thigh circumference between the two groups before surgery (P > 0.05); the difference in thigh circumference between the patients in the test group at 12 and 24 weeks after surgery was (− 0.35 ± 0.22) cm and (0.12 ± 0.03) cm, respectively, which were higher than those in the control group, (− 0.51 ± 0.15) cm and (− 0.41 ± 0.34) cm (P

The COVID-19 pandemic has presented substantial challenges to higher education, leading to economic loss and disruptions in STEM courses. This study addresses these issues through the successful implementation of a problem-based learning research project within the Instrumental Chemistry course at Georgia Gwinnett College (GGC). Focused on instrumental chemistry, the project spans various categories, requiring students to propose solutions to real-case scenarios using specific analytical instruments. Despite the shift to a hybrid teaching modality, students exhibited commendable preparation and investigation skills, as demonstrated by their projects. Assessment data, including a student survey and written report evaluations, underscore significant skill improvements in literature survey, instrument selection, experimental design, and data analysis. This problem-based learning approach not only mitigated the disruptions caused by the pandemic but also fostered enhanced capabilities and motivation among students. The study’s findings contribute insights into the adaptability and effectiveness of problem-based learning in analytical chemistry education within a hybrid teaching framework, offering valuable considerations for future educational strategies in STEM disciplines and beyond.

Abstract Aggressiveness and drug resistance are major challenges in the clinical treatment of glioblastoma (GBM). Our previously research reported a novel candidate oncogene ribosomal protein L22 like 1 (RPL22L1). The aim of this study was to elucidate the potential role and mechanism of RPL22L1 in progression and temozolomide (TMZ) resistance of GBM. Online database, tissue microarrays and clinical tissue specimens were used to evaluate the expression and clinical implication of RPL22L1 in GBM. We performed cell function assays, orthotopic and subcutaneous xenograft tumor models to evaluate the effects and molecular mechanisms of RPL22L1 on GBM. RPL22L1 expression was significantly upregulated in GBM and associated with poorer prognosis. RPL22L1 overexpression enhanced GBM cell proliferation, migration, invasion, TMZ resistance and tumorigenicity, which could be reduced by RPL22L1 knockdown. Further, we found RPL22L1 promoted mesenchymal phenotype of GBM and the impact of these effects was closely related to EGFR/STAT3 pathway. Importantly, we observed that STAT3 specific inhibitor (Stattic) significantly inhibited the malignant functions of RPL22L1, especially on TMZ resistance. RPL22L1 overexpressed increased combination drug sensitive of Stattic and TMZ both in vitro and in vivo. Moreover, Stattic effectively restored the sensitive of RPL22L1 induced TMZ resistance in vitro and in vivo. Our study identified a novel candidate oncogene RPL22L1 which promoted the GBM malignancy through STAT3 pathway. And we highlighted that Stattic combined with TMZ therapy might be an effective treatment strategy in RPL22L1 high-expressed GBM patients.

Fe–TiB2 composite shows great potential in lightweight materials for automotive parts due to its lightweight, high strength and high specific modulus etc. However, challenges remain with regard to establishing a fine hot working process of Fe–TiB2 composites. Here, a series of isothermal hot compression tests was conducted to systematically investigate the microstructure evolution and the dynamic recrystallization (DRX) mechanisms of as-cast Fe–TiB2 composites at different sets of hot deformation parameters. The results indicate the true stress drops more significantly after reaching its peak at low temperatures compared to high temperatures, since low temperatures favors the DRX through particle stimulated nucleation (PSN) in Fe–TiB2 composites, as featured by layers of DRXed grains surrounding TiB2 particles. Continuous dynamic recrystallization (CDRX) process gradually dominates as strain rate increase from 0.01 s−1 to 1 s−1 in Fe–TiB2 composites hot compressed to the true strain of 0.69 at 900 °C, as evidenced by the presence of DRXed grains with larger size and uniform distribution in matrix. DRX through PSN is the primary DRX mechanism at low temperature and low strain rate, while CDRX dominates the DRX mechanism at high temperature and high strain rate. Both DRX behaviors deepen with the increase of the strain. Different hot deformation parameters favor different DRX mechanisms. The increase in temperature and strain rate leads to a transition of the dominant recrystallization mechanism from the DRX through PSN to CDRX which is attributed to the competition for stored energy between the DRX through PSN and CDRX process.

Abstract Owing to the complexity and variability of global climate, the study of extreme events to ensure food security is particularly critical. The standardized precipitation requirement index (SPRI) and chilling injury index (ICi) were introduced using data from agrometeorological stations on the Songliao Plain between 1981 and 2020 to identify the spatial and temporal variability of drought, waterlogging, and low-temperature cold damage during various maize growth periods. Compound drought and low-temperature cold damage events (CDLEs) and compound waterlogging and low-temperature cold damage events (CWLEs) were then identified. To measure the intensity of compound events, the compound drought and low-temperature cold damage magnitude index (CDLMI), and compound waterlogging and low-temperature cold damage magnitude index (CWLMI) were constructed by fitting marginal distributions. Finally, the effects of extreme events of various intensities on maize output were examined. The findings demonstrate that: (1) There were significant differences in the temporal trends of the SPRI and ICi during different maize growth periods. Drought predominated in the middle growth period (MP), waterlogging predominated in the early growth period (EP) and late growth period (LP), and both drought and waterlogging tended to increase in intensity and frequency. The frequency of low-temperature cold damage showed a decreasing trend in all periods. (2) The CDLMI and CWLMI can effectively determine the intensity of CDLEs and CWLEs in the study area; these CDLEs and CWLEs had higher intensity and frequency in the late growth period. (3) Compared to single events, maize relative meteorological yield had a more significant negative correlation with the CDLMI and CWLMI.

Abstract Background Oral health and frailty are significantly related and should be well examined, especially in late life. Few studies have explored the relationship of oral health knowledge, attitudes, and practices with frailty and examined sociodemographic variations in this association. This study aimed to examine the association between oral health knowledge, attitudes, practices and frailty, with a special focus on comparing differences in their association among the Chinese community-dwelling older population. Methods This study included 4218 community-dwelling older adults (aged ≥ 60 years) who participated in a cross-sectional survey. Sociodemographic characteristics, oral health knowledge, attitudes, practices, and frail status (non-frailty, pre-frailty, and frailty) were collected with a face-to-face questionnaire-based interview. Multivariate logistic regression models were used to evaluate the association of oral health knowledge, attitudes, and practices with frailty. Results Of the 4218 participants, 36.2% (n = 1527) and 18.8% (n = 792) were classified as pre-frailty and frailty. Age, gender and educational attainments differences existed in the association of oral health knowledge with frailty. Urban-rural differences in the association of oral health knowledge and practices with frailty were also found. Specifically, oral health knowledge was significantly related to frailty only among participants aged 70–79 years (adjusted odds ratio [95% confidence interval]) (1.08 [1.02–1.15]), females (1.05 [1.00–1.10]), rural residents (1.06 [1.01–1.12]), and those who were primary school and lower education (1.06 [1.01–1.11]), whereas oral health practices were related to frailty only among urban participants (0.96 [0.92–1.00]). Conclusion This study confirmed the different associations of oral health knowledge and practices with frailty among community-dwelling older people in China. Further research is needed to better understand the abovementioned differences and public health strategies are required to improve oral health literacy and thereby contain the development of frailty in later life.

Abstract Background Serum exosomes play important roles in intercellular communication and are promising biomarkers of several autoimmune diseases. However, the biological functions and potential clinical importance of long non-coding RNAs (lncRNAs) and mRNAs from serum exosomes in rheumatoid arthritis (RA) have not yet been studied. Methods Serum exosomal lncRNAs and mRNAs were isolated from patients with RA and osteoarthritis (OA) and healthy controls. The differentially expressed lncRNAs (DE-lncRNAs) and mRNA profiles in the serum exosomes of patients with RA were analysed using high-throughput sequencing, and their functions were predicted using Gene Ontologyenrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analysis. We constructed a DE-lncRNA-mRNA network and a protein–protein interaction network of differentially expressed mRNAs (DE-mRNAs) in RA using the Cytoscape software. The expression of several candidate a DE-lncRNAs and DE-mRNAs in the serum of patients with RA, patients with OA, and healthy controls was confirmed by qRT-PCR. We assessed the diagnostic ability of DE-lncRNAs and DE-mRNAs in patients with RA using receiver operating characteristic analysis. Furthermore, we analysed the characteristics of immune cell infiltration in RA by digital cytometry using the CIBERSORT algorithm and determined the correlation between immune cells and several DE-lncRNAs or DE-mRNAs in RA. Results The profiles of serum exosomal lncRNAs and mRNAs in patients with RA were different from those in healthy controls and patients with OA. The functions of both DE-lncRNAs and DE-mRNAs in RA are associated with the immune response and cellular metabolic processes. The RT-PCR results show that NONHSAT193357.1, CCL5, and MPIG6B were downregulated in patients with RA. The combination of three DE-mRNAs, CCL5, MPIG6B, and PFKP, had an area under the curve of 0.845 for differentiating RA from OA. Digital cytometry using the CIBERSORT algorithm showed that the neutrophil counts were higher in patients with RA than those in healthy controls and patients with OA. Conclusions These findings help to elucidate the role of serum exosomal lncRNAs and mRNAs in the specific mechanisms underlying RA.

Abstract Herbicide residuals have posed severe threat to food safety and public health; thus, the development of smart, portable, efficient, and accurate on‐site detection system is in urgent demand. Here, a multi‐emitting fluorescent system‐assisted lab‐in‐a‐syringe (LIS) device was developed for the on‐site and background‐free determination of 2,4‐dichlorophenoxyacetic acid (2,4‐D). 2,4‐D‐responsive cascade reactions were constructed: 2,4‐D could specifically suppress alkaline phosphatase (ALP) activity and restrain the generation of ascorbic acid (AA), MnO2 nanosheets would oxidize AA into dehydroascorbic acid that subsequently reacts with o‐phenylenediamine (OPD) to generate blue‐emission product (λem, 435 nm), whereas remained MnO2 nanosheets and OPD further produced yellow‐emission product (λem, 570 nm). Red‐emission carbon dots (RCDs, λem, 680 nm), synthesized via the solvothermal treatment of cilantro, were introduced to construct a multi‐emitting fluorescent system. Then, four paper pads, respectively, dropped with ALP, sodium l‐ascorbyl‐2‐phosphate, MnO2 nanosheets + RCDs, and OPD were held into reusable plastic filters and assembled paper‐based LIS device to trigger cascade reactions (total analysis time, 65 min) and eliminate background interference. As a result, with the support of color recognizer application in smartphone, fluorescent color on detection pads from blue–purple to red to yellow was achieved for the sensitive and visual detection of 2,4‐D with LOD of 5.0 μg L−1, recoveries of 94.6%–106.8%, and relative standard deviations of 2.3%–6.8%. Obviously, this strategy provides a robust, visual, and background‐free platform for 2,4‐D detection, which expands application prospects in the field of herbicide analysis.

Abstract The strength of evidence regarding long-term changes to fitness resulting from the coronavirus disease 2019 (COVID-19) lockdowns is deficient. This two-site retrospective study aimed to investigate the long-term changes in physical fitness among young adults a year after the onset of the pandemic using a robust historical control. University freshmen who underwent physical fitness tests in 2019 and completed a follow-up in 2020 (study group) were included. The primary focus was to compare the current cohort with a historical control group who completed the same tests a year prior (2018). A total of 5376 individuals were recruited, of which 2239 were in the study group. Compared with the control, the study group exhibited a decrease in anaerobic fitness, with an overall difference of −0.84 (95% confidence interval [CI], [−1.33 to −0.36]); declines in aerobic fitness, with a difference of −2.25 [−3.92 to −0.57] for males and −4.28 [−4.97 to −3.59] for females; a reduced explosive fitness (−2.68 [−3.24 to −2.12]); and a decreased upper-body strength in females (−1.52 [−2.16 to −0.87]). The fitness of young adults has been considerably compromised by COVID-19 lockdowns, highlighting the importance of promoting physical activity to prevent long-term health implications.

Due to their excellent properties, antimicrobial fiber membranes are widely applied in bioprotective materials. This work addresses the preparation of thermoplastic polyurethane (TPU)-based fiber membranes with active antimicrobial properties. 2-hydroxypropyl trimethyl ammonium chloride-terminated hyperbranched polymer (HBP-HTC) was synthesized and used as an antimicrobial agent. The fiber membranes were obtained by electrospinning a mixed solution of HBP-HTC and TPU. Different electrospinning conditions were investigated, such as the spinning voltage and drum rotation speed. The fiber membrane prepared under a 22 kV anode voltage and 100 rpm rotation speed had an average fiber diameter of 1.66 μm with a concentrated diameter distribution. Antibacterial tests showed that when the fiber membrane was loaded with 1500 mg/kg of HBP-HTC, the antibacterial rates of E. coli as well as S. aureus both reached 99.99%, exhibiting excellent proactive antimicrobial performance. Moreover, the protective performance of the fiber membrane was outstanding, with a filtration efficiency of 99.9%, a hydrostatic pressure resistance greater than 16,758 Pa, and a moisture permeability of 2711.0 g⋅(m2⋅d)−1.

The current thermal balance of permafrost in northeastern China has been upset by human engineering construction disturbances and global warming. This has resulted in a rise in ground temperature and a fall in the permafrost table, which has a major impact on the stability, longevity, and operational safety of highway subgrades. To solve the issues above, the ground temperature monitoring data at K60+230 of the Shiwei–Labudalin highway were analyzed, and the numerical simulation of the temperature field change over 15 years was carried out for the ordinary subgrade as well as for sections of block-stone material subgrade with 1 m of straight-filled and different thicknesses of replacement fill (1 m, 2 m, 3 m, 4 m) by applying Comsol Multiphysis software. The results show that the temperature field of the subgrade exhibits significant asymmetry. There are variations in the rate of decline at different sites during the course of the 15 years when compared to where the permafrost table was located at the start of the study. Still, the rate of decline of the permafrost table is decreasing yearly. The straight-filled 1 m block-stone subgrade has a permafrost table 0.77 m higher in the bottom portion of its top surface than the ordinary subgrade. The replacement 1 m, 2 m, 3 m, and 4 m block-stone subgrade has a permafrost table in the lower portion of the top surface that is 1.05 m, 2.12 m, 3.32 m, and 4.75 m higher than the ordinary subgrade. The replacement block-stone subgrades, as opposed to ordinary subgrades, can strengthen the foundation, raise the permafrost table, and effectively reduce the impact of the upper boundary temperature on the lower permafrost. They can also increase the stability of permafrost subgrades. Of them, the block-stone filling with a thickness of 4 m and a particle size of 6–8 cm had the best impact.

The flying foxes optimization (FFO) algorithm stimulated by the strategy used by flying foxes for subsistence in heat wave environments has shown good performance in the single-objective domain. Aiming to explore the effectiveness and benefits of the subsistence strategy used by flying foxes in solving optimization challenges involving multiple objectives, this research proposes a decomposition-based multi-objective flying foxes optimization algorithm (MOEA/D-FFO). It exhibits a great population management strategy, which mainly includes the following features. (1) In order to improve the exploration effectiveness of the flying fox population, a new offspring generation mechanism is introduced to improve the efficiency of exploration of peripheral space by flying fox populations. (2) A new population updating approach is proposed to adjust the neighbor matrices to the corresponding flying fox individuals using the new offspring, with the aim of enhancing the rate of convergence in the population. Through comparison experiments with classical algorithms (MOEA/D, NSGA-II, IBEA) and cutting-edge algorithms (MOEA/D-DYTS, MOEA/D-UR), MOEA/D-FFO achieves more than 11 best results. In addition, the experimental results under different population sizes show that the proposed algorithm is highly adaptable and has good application prospects in optimization problems for engineering applications.

Icing in cut slopes is a serious risk to transportation safety in cold regions. Research on the occurrence process and mechanism of icing is a prerequisite for proposing effective management measures. We took the cut slopes of the K162 section of the Beihei Highway as the research object. We used a combination of field investigation, geological exploration, monitoring, and simulation to study and analyze the power source, occurrence process, and triggering mechanism of icing in cut slopes. The results show that the geologic type of this cut slope is a mudstone–sandstone interaction stratum. Abundant shallow groundwater is the source of water for icing. The excavation of cut slopes extends the effect of negative temperatures on groundwater flow during the winter period. The process of ice formation in cut slopes can be described as follows: As the environmental temperature drops, the surface soil begins to freeze, resulting in a gradual narrowing of the water channel; then, the groundwater flow is blocked, so that the internal pressure begins to rise. When the internal pressure of the pressurized groundwater exceeds the strength of the frozen soil, groundwater overflows from the sandstone layer to the surface, forming icing. The high pore water pressure inside the cut slope is the precursor for the occurrence of icing. The dynamic pressure of the pore water pressure is the main driving force for the formation of icing in cut slopes. The obstruction of the water channel due to ground freezing is the triggering condition for ice formation in cut slopes.

The wavelength attack utilizes the dependence of beam splitters (BSs) on wavelength to cause legitimate users Alice and Bob to underestimate their excess noise so that Eve can steal more secret keys without being detected. Recently, the wavelength attack on Gaussian-modulated continuous-variable quantum key distribution (CV-QKD) has been researched in both fiber and atmospheric channels. However, the wavelength attack may also pose a threat to the case of ocean turbulent channels, which are vital for the secure communication of both ocean sensor networks and submarines. In this work, we propose two wavelength attack schemes on underwater discrete modulated (DM) CV-QKD protocol, which is effective for the case with and without local oscillator (LO) intensity monitor, respectively. In terms of the transmittance properties of the fused biconical taper (FBT) BS, two sets of wavelengths are determined for Eve’s pulse manipulation, which are all located in the so-called blue–green band. The derived successful criterion shows that both attack schemes can control the estimated excess noise of Alice and Bob close to zero by selecting the corresponding condition parameters based on channel transmittance. Additionally, our numerical analysis shows that Eve can steal more bits when the wavelength attack controls the value of the estimated excess noise closer to zero.

IntroductionRemorins (REMs) are plant-specific membrane-associated proteins that play important roles in plant–pathogen interactions and environmental adaptations. Group I REMs are extensively involved in virus infection. However, little is known about the REM gene family in sugarcane (Saccharum spp. hyrid), the most important sugar and energy crop around world.MethodsComparative genomics were employed to analyze the REM gene family in Saccharum spontaneum. Transcriptomics or RT-qPCR were used to analyze their expression files in different development stages or tissues under different treatments. Yeast two hybrid, bimolecular fluorescence complementation and co-immunoprecipitation assays were applied to investigate the protein interaction.ResultsIn this study, 65 REMs were identified from Saccharum spontaneum genome and classified into six groups based on phylogenetic tree analysis. These REMs contain multiple cis-elements associated with growth, development, hormone and stress response. Expression profiling revealed that among different SsREMs with variable expression levels in different developmental stages or different tissues. A pair of alleles, ScREM1.5e-1/-2, were isolated from the sugarcane cultivar ROC22. ScREM1.5e-1/-2 were highly expressed in leaves, with the former expressed at significantly higher levels than the latter. Their expression was induced by treatment with H2O2, ABA, ethylene, brassinosteroid, SA or MeJA, and varied upon Sugarcane mosaic virus (SCMV) infection. ScREM1.5e-1 was localized to the plasma membrane (PM), while ScREM1.5e-2 was localized to the cytoplasm or nucleus. ScREM1.5e-1/-2 can self-interact and interact with each other, and interact with VPgs from SCMV, Sorghum mosaic virus, or Sugarcane streak mosaic virus. The interactions with VPgs relocated ScREM1.5e-1 from the PM to the cytoplasm.DiscussionThese results reveal the origin, distribution and evolution of the REM gene family in sugarcane and may shed light on engineering sugarcane resistance against sugarcane mosaic pathogens.

Oxidative stress (OS) is regarded as the dominant theory for aging. While compelling correlative data have been generated to support the OS theory, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and aging has not been firmly established. Superoxide dismutase 1 (SOD1) is a primary antioxidant in all cells. It is, however, susceptible to oxidation due to OS and gains toxic properties to cells. This study investigates the role of oxidized SOD1 derived from amyotrophic lateral sclerosis (ALS) linked SOD1 mutations in cell senescence and aging. Herein, we have shown that the cell line NSC34 expressing the G93A mutation of human SOD1 (hSOD1G93A) entered premature senescence as evidenced by a decreased number of the 5-ethynyl-2′-deoxyuridine (EdU)-positive cells. There was an upregulation of cellular senescence markers compared to cells expressing the wild-type human SOD1 (hSOD1WT). Transgenic mice carrying the hSOD1G93A gene showed aging phenotypes at an early age (135 days) with high levels of P53 and P16 but low levels of SIRT1 and SIRT6 compared with age-matched hSOD1WT transgenic mice. Notably, the levels of oxidized SOD1 were significantly elevated in both the senescent NSC34 cells and 135-day hSOD1G93A mice. Selective removal of oxidized SOD1 by our CT4-directed autophagy significantly decelerated aging, indicating that oxidized SOD1 is a causal factor of aging. Intriguingly, mitochondria malfunctioned in both senescent NSC34 cells and middle-aged hSODG93A transgenic mice. They exhibited increased production of mitochondrial-derived vesicles (MDVs) in response to mild OS in mutant human SOD1 (hSOD1) transgenic mice at a younger age; however, the mitochondrial response gradually declined with aging. In conclusion, our data show that oxidized SOD1 derived from ALS-linked SOD1 mutants is a causal factor for cellular senescence and aging. Compromised mitochondrial responsiveness to OS may serve as an indicator of premature aging.