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Abstract The lip-splitting approach enables excellent access to all areas of the mouth and pharynx to remove tumors; however, traditional lower lip-splitting incisions produce an unsatisfactory scar. To achieve better functional and aesthetic results, we used a Z-shaped incision and compared the functional and aesthetic outcomes of the straight and Z-shaped incisions. Sixty patients who fulfilled the inclusion criteria were randomly divided into two groups and underwent lip-splitting between March 2021 and September 2023. Eventually, 77 patients were reviewed within 6 months and evaluated using the lip function assessment scale, patient and observer scar assessment scale, naïve observer scar assessment scale, and a clinical examination. The Z-shaped incision group performed better in terms of the lip pout movement at 3 months and in the subjective overall opinion, color, irregularity, and pigmentation at 6 months. The Z-shaped incision group had a lower incidence of notched vermilion. In conclusion, Z-shaped lower lip-splitting incisions have better functional and aesthetic outcomes than traditional straight incisions. Trial registration: Public title: Difference between the effect of Z-shaped and vertical incisions of labiobuccal flap on the recovery of lower lip scars. Registration date: 09/03/2021. Registration number: ChiCTR2100044084. Registry URL: http://www.chictr.org.cn .

Abstract Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P

Drunken horse grass (Achnatherum inebrians (Hance) Keng) is a toxic perennial bunchgrass native to Northwestern China. Epichloë endophytic fungi infection could enhance the stress tolerance of drunken horse grass. However, there is a scarcity of literature regarding the effects of intraspecific competition. As a result, we anticipated that the intraspecific competitive dynamics between endophyte-infected (EI) and endophyte-free (EF) plants would become more transparent for four years by planted as the proportions of 2:1, 1:1, and 1:2. The results showed the EI plants exhibited more biomass, seed yields, and survival rates than EF plants. Endophyte infection also facilitated a competitive advantage by enhancing photosynthesis and soil nutrition. Our findings constituted the inaugural investigation into the influence of the intraspecific competitive ability of grass infected with Epichloë endophyte fungi. EI plants caused them to become stronger and stronger, while EF became weaker and weaker by timing and planting proportion increasing, and EF drunken horse grass could be replaced by EI. These conclusions were instrumental in elucidating why the endophytic fungal infection rate of drunken horse grass is 100% observed in natural wilderness. Epichloë endophyte could reduce plant diversity and enhance the dominance of EI plants in intraspecific competition; drunken horse grass may be threatening the persistence of native plant species.

Abstract: Zero-valent iron (ZVI) contamination from steel works poses significant threats to soil quality and ecosystem health, particularly affecting soil microaggregates, which are fundamental to soil structure and function. In this study, we systematically investigated the impact of gradient ZVI pollution on the organic geochemical environment of soil microaggregates around steel works located in the core water source area of the Middle Route of the South-to-North Water Diversion Project in China. Advanced analytical techniques, including X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray fluorescence spectroscopy (XRF), inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), were employed to comprehensively characterize the geochemical processes, mineralogy, and organic matter environment of soil microaggregates. The findings revealed that soils near the steel works were acidified and strongly oxidized, with heavy metal contents, particularly Fe, significantly decreasing with increasing distance from the steel works (Fe content decreased from 27,516.2 mg/kg to 23,492.6 mg/kg). The pH of soils near the steel works was lower, while oxidation-reduction potential (ORP) and electrical conductivity were higher. XPS analysis indicated a higher content of reactive oxygen species (ROS) near the steel works and significantly lower soil organic matter content. The iron valence distribution showed spatial differences, with higher Fe2⁺ content on the surface of soil microaggregates near the steel works and Fe³⁺ dominating in areas farther away. These results suggest an evolutionary sequence of ZVI from Fe (0) oxidation to Fe(II) and then to Fe(III). The formation of dissipative structures in soil microaggregates due to ZVI contamination significantly affects soil physicochemical properties and the organic environment. This study provides valuable insights into the multifaceted impacts of industrial activities on soil ecosystems and offers a scientific basis for soil conservation and remediation strategies.

Summary: Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion “selectively” revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.

Abstract Background Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one’s lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus. Methods In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg’s FSN was calculated for both binary and continuous measures. Results We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression. Conclusions The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.

Abstract Background Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. Methods A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. Results Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. Conclusions LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression. Graphical Abstract The up-regulated lncRNA Anxa10-203 in the trigeminal ganglion of CCI-ION mice interacts with DHX30 to contribute to the excitability of TG neurons and orofacial pain by enhancing Mc1r mRNA stability.

To investigate the splitting tensile characteristics of a new building material, namely magnesium-based wood-like material (MWM), the cubic splitting tensile tests were carried out at a loading rate of 200 N/s. Full-field displacements and crack behaviors were measured using Digital Image Correlation, and the splitting tensile strength is 1.79 MPa. The elastic Young modulus, Poisson’s ratio, and axial compressive strength were measured as 2.21 GPa, 0.21, 8.76 MPa respectively. In the splitting tensile tests, primary cracks were observed to initiate from the geometric centre of the specimen and then extend to the loading ends where secondary cracks appeared. A new method for identifying cracking modes showed the secondary cracks were mainly caused by shear and tensile-shear failure, whereas the primary cracks were caused by tensile failure. An accurate method for estimating the elastic Young modulus, simultaneously with the determination of the splitting tensile strength of MWM cubes is proposed.

Infections caused by multidrug-resistant (MDR) bacteria have become a major challenge for global healthcare systems. The search for antibacterial compounds from plants has received increasing attention in the fight against MDR bacteria. As a medicinal and edible plant, Lophatherum gracile Brongn. (L. gracile) has favorable antibacterial effect. However, the main antibacterial active compound and its antimicrobial mechanism are not clear. Here, our study first identified the key active compound from L. gracile as luteolin. Meanwhile, the antibacterial effect of luteolin was detected by using the broth microdilution method and time-kill curve analysis. Luteolin can also cause morphological structure degeneration and content leakage, cell wall/membrane damage, ATP synthesis reduction, and downregulation of mRNA expression levels of sulfonamide and quinolones resistance genes in multidrug-resistant Escherichia coli (MDR E. coli). Furthermore, untargeted UPLC/Q-TOF-MS-based metabolomics analysis of the bacterial metabolites revealed that luteolin significantly changed riboflavin energy metabolism, bacterial chemotaxis cell process and glycerophospholipid metabolism of MDR E. coli. This study suggests that luteolin could be a potential new food additive or preservative for controlling MDR E. coli infection and spread.

Zinc-ion batteries (ZIBs) emerge as leading candidates for a flexible energy storage system, distinguished by high capacity, affordability, and inherent safety. The integration of hydrogel electrolytes, particularly those with saturated aqueous solvents, has significantly enhanced the electrochemical performance of ZIBs while preserving their essential flexibility. Nonetheless, challenges in electrochemical performance under specific conditions highlight the nascent stage of this technology, with numerous technical hurdles awaiting resolution. Addressing these challenges, recent investigations have leveraged the unique properties of cellulose hydrogel—namely, its exceptional toughness, tensile strength, extreme temperature resilience, stimulus responsiveness, and self-healing capabilities—to innovate multifunctional flexible zinc-based batteries. This paper conducts a comprehensive review of the physicochemical attributes of cellulose hydrogel electrolytes within ZIBs. We thoroughly analyze their performance under diverse environmental conditions, offering insights into the current landscape and their future potential. By examining these aspects, we aim to underscore the developmental prospects and the challenges that lie ahead for hydrogel electrolytes in ZIBs, paving the way for further advancement in this promising field.

Amaranthus retroflexus L. is a troublesome dicot weed in crop fields and has developed high resistance to nicosulfuron in China. The objective of this study was to determine the effects of specific resistance mutations (A205V, D376E, W574L, S653T, and S653N) of the acetohydroxy acid synthase enzyme (AHAS) on the resistance of A. retroflexus to nicosulfuron. The resistance mutations in A. retroflexus not only conferred 17.17- to 31.70-fold resistance to nicosulfuron but also greatly decreased AHAS sensitivity and increased AHAS binding affinity to substrate pyruvate, which mechanisms were primarily responsible for the observed A. retroflexus resistance. Molecular docking results indicated that these resistance mutations altered AHAS binding free energy with nicosulfuron. All the resistance mutations showed less sensitivity to feedback inhibition by branched-chain amino acids, but the mutations did not necessarily affect biosynthesis in A. retroflexus. This report to compares the various mutations of ArAHAS in vitro and contributes to understanding herbicide resistance in this field weed.

The Epichloë genus represents a significant group of above-ground endophytes extensively researched for their potential applications in agriculture and ecology. Additionally, Epichloë species synthesize bioactive alkaloids, which generally cause health problems in livestock and have detrimental effects on the performance of insect herbivores. Psathyrostachys lanuginosa serves as a valuable forage grass for livestock owing to its high nutritional value and resilience in adverse environmental conditions. Nevertheless, to date, no reports have documented Epichloë as endophytes of P. lanuginosa. In this study, four strains (PF5, PF9, QG2, and QG4) were isolated and identified through morphological, molecular, and phylogenetic analyses as endophytes of P. lanuginosa. Morphological analysis indicated colony characteristics and conidia features consistent with symbiotic Epichloë, with no significant differences observed in growth rates or conidia dimensions among the four strains. Phylogenetic analysis confirmed all strains as E. bromicola. Additionally, alkaloid biosynthetic genes were detected, revealing differences in the potential synthesis of peramine and indole diterpenoid alkaloids among strains from different geographic origins. However, all four E. bromicola strains exhibited similar potential for synthesizing ergot alkaloids, but not loline alkaloids. Overall, this study identified P. lanuginosa as a novel host for E. bromicola and provided insights into the alkaloid profiles of these strains, laying a solid foundation for the scientific and rational utilization of Epichloë resources.

Staphylococcus aureus strains cause the majority of pneumonia cases and are resistant to various antibiotics. Given this background, it is very important to discover novel host-targeted therapies. Licochalcone A (LAA), a natural plant product, has various biological activities, but its primary targets in S. aureus pneumonia remain unclear. Therefore, the purpose of this study was to identify its molecular target against S. aureus pneumonia. Network pharmacology analysis, histological assessment, enzyme-linked immunosorbent assays, and Western blotting were used to confirm the pharmacological effects. Network pharmacology revealed 33 potential targets of LAA and S. aureus pneumonia. Enrichment analysis revealed that these potential genes were enriched in the Toll-like receptor and NOD-like receptor signaling pathways. The results were further verified by experiments in which LAA alleviated histopathological changes, inflammatory infiltrating cells and inflammatory cytokines (TNF, IL-6, and IL-1β) in the serum and bronchoalveolar lavage fluid in vivo. Moreover, LAA treatment effectively reduced the expression levels of NF-κB, p-JNK, p-p38, NLRP3, ASC, caspase 1, IL-1β, and IL-18 in lung tissue. The in vitro experimental results were consistent with the in vivo results. Thus, our findings demonstrated that LAA exerts anti-infective effects on S. aureus-induced lung injury via suppression of the Toll-like receptor and NOD-like receptor signaling pathways, which provides a theoretical basis for understanding the function of LAA against S. aureus pneumonia and implies its potential clinical application.

ABSTRACTThe clavicipitaceous fungus Epichloë gansuensis forms symbiotic associations with drunken horse grass (Achnatherum inebrians), providing biotic and abiotic stress protection to its host. However, it is unclear how E. gansuensis affects the assembly of host plant-associated bacterial communities after ammonium nitrogen (NH4+-N) treatment. We examined the shoot- and root-associated bacterial microbiota and root metabolites of A. inebrians when infected (I) or uninfected (F) with E. gansuensis endophyte. The results showed more pronounced NH4+-N-induced microbial and metabolic changes in the endophyte-infected plants compared to the endophyte-free plants. E. gansuensis significantly altered bacterial community composition and β-diversity in shoots and roots and increased bacterial α-diversity under NH4+-N treatment. The relative abundance of 117 and 157 root metabolites significantly changed with E. gansuensis infection under water and NH4+-N treatment compared to endophyte-free plants. Root bacterial community composition was significantly related to the abundance of the top 30 metabolites [variable importance in the projection (VIP) > 2 and VIP > 3] contributing to differences between I and F plants, especially alkaloids. The correlation network between root microbiome and metabolites was complex. Microorganisms in the Proteobacteria and Firmicutes phyla were significantly associated with the R00693 metabolic reaction of cysteine and methionine metabolism. Co-metabolism network analysis revealed common metabolites between host plants and microorganisms.IMPORTANCEOur results suggest that the effect of endophyte infection is sensitive to nitrogen availability. Endophyte symbiosis altered the composition of shoot and root bacterial communities, increasing bacterial diversity. There was also a change in the class and relative abundance of metabolites. We found a complex co-occurrence network between root microorganisms and metabolites, with some metabolites shared between the host plant and its microbiome. The precise ecological function of the metabolites produced in response to endophyte infection remains unknown. However, some of these compounds may facilitate plant-microbe symbiosis by increasing the uptake of beneficial soil bacteria into plant tissues. Overall, these findings advance our understanding of the interactions between the microbiome, metabolome, and endophyte symbiosis in grasses. The results provide critical insight into the mechanisms by which the plant microbiome responds to nutrient stress in the presence of fungal endophytes.

Abstract Background The factors associated with postoperative hypokalemia in patients with oral cancer remain unclear. We determined the preoperative factors associated with postoperative hypokalemia in patients with oral cancer following en bloc cancer resection and established a nomogram for postoperative hypokalemia prediction. Methods Data from 381 patients with oral cancer who underwent en bloc cancer resection were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the risk factors for postoperative hypokalemia. We used receiver operating characteristic (ROC) curves to quantify the factors’ effectiveness. A nomogram was created to show each predictor’s relative weight and the likelihood of postoperative hypokalemia development. The multinomial regression model’s effectiveness was also evaluated. Results Preoperative factors, including sex, preoperative serum potassium level, and preoperative platelet-to-lymphocyte ratio (PLR), were significantly associated with postoperative hypokalemia. Based on the ROC curve, the preoperative serum potassium and PLR cut-off levels were 3.98 mmol/L and 117, respectively. Further multivariate analysis indicated that female sex, preoperative serum potassium level

Alternaria gansuensis, a seed-borne fungus of standing milkvetch (Astragalus adsurgens), is the most common pathogen of this plant species and causes yellow stunt and root rot. Although plant resistance to this disease has been identified, a better understanding of the nature of this resistance will help improve and optimize its implementation in standing milkvetch. The effects of A. gansuensis on the physiology of standing milkvetch were assessed in a 4-week study comparing a resistant plant variety, Shanxi, and a susceptible variety, Ningxia. In the first week, there was an obvious decrease in photosynthesis (P) in inoculated plants, especially in the susceptible variety, but there were no changes in stomatal conductance (Sc). From the second week on, P and Sc decreased progressively, and significant stem lesions were observed concomitantly. Water use efficiency (WUE) increased slightly in the second week but then decreased significantly from the third week. Physiological changes observed for the resistant variety of standing milkvetch were less dramatic than those of the susceptible variety. Hyphae were observed around inoculation lesions of the plants. Culture filtrate (CF) of A. gansuensis induced changes in extracellular pH and conductivity, especially in the susceptible variety samples. Tissue integrity changes in the plants correlated with the decrease in P. Secondary metabolite compounds were extracted from the plants and 21 types of compounds were identified. The composition and proportion of secondary metabolites were markedly altered by the pathogen, and these differences may indicate potential mechanisms of disease resistance to A. gansuensis in standing milkvetch.

Leymus chinensis is a high-quality forage with wide distribution. Disease is an important factor affecting the yield and quality of L. chinensis. To investigate the effect of grazing on the phyllosphere microbiome community and leaf spot disease in L. chinensis, high-throughput sequencing technology was used to study the differences in the composition and structure of the phyllosphere fungal and bacterial communities of healthy and diseased leaves under different grazing intensities. The results showed that grazing significantly reduced leaf spot disease incidence and severity. There were significant differences in the phyllosphere microbiome composition between healthy and diseased leaves, and interestingly, diseased leaves showed more complex microbial activity. Grazing altered the relative abundance of micro-organisms and affected microbial dispersal and colonization either directly through behavior or indirectly by altering plant community structure. In this study, we found that the phyllosphere microbiome responded strongly to pathogen infection, and that plants recruited beneficial microbes to protect themselves after disease development. Grazing could regulate microbial community composition and structure, either directly or indirectly, and plays a crucial role in maintaining the health of L. chinensis.

Epichloë fungal endophytes hold promise in sustainable agriculture by fortifying cool-season grasses such as Elymus spp. against various stresses. Elymus spp. are widely distributed in Northwest China with a high incidence of endophyte infections. In this study, we identified 20 Epichloë endophytic fungal strains carried by five Elymus spp. from five areas of Northwest China and systematically characterized their morphology, molecular phylogeny, mating type, and alkaloid diversity for the first time. The morphological characterization underscores strain diversity, with variable colony textures and growth rates. A phylogenetic analysis confirms all strains are E. bromicola, emphasizing their taxonomic status. Alkaloid-encoding gene profiling delineates distinct alkaloid synthesis capabilities among the strains, which are crucial for host adaptability and resistance. A mating-type analysis reveals uniformity (mtAC) across the Epichloë strains, simplifying breeding strategies. Notably, the Epichloë strains exhibit diverse alkaloid synthesis gene profiles, impacting host interactions. This research emphasizes the ecological significance of Epichloë endophytes in Elymus spp. ecosystems, offering insights into their genetic diversity and potential applications in sustainable agriculture.

Abstract Background To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive minimal benefit from further cardiac imaging testing (CIT) is important for patients with stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS). Although several diagnostic strategies have been recommended by the most recent guidelines, few randomized controlled trials (RCTs) have prospectively investigated the actual effect of applying these strategies in clinical practice. Methods OPERATE (OPtimal Evaluation of stable chest pain to Reduce unnecessAry utilization of cardiac imaging TEsting) trial is an investigator-initiated, multicenter, coronary computed tomography angiography (CCTA)-based, 2-arm parallel-group, double-blind, pragmatic and confirmative RCT planning to include 800 subjects with SCP suggestive of CCS. After enrollment, all subjects will be randomized to two arms (2016 U.K. National Institute of Health and Care Excellence guideline-determined and 2019 European Society of Cardiology guideline-determined diagnostic strategy) on a 1:1 basis. According to each strategy, CCTA should be referred and deferred for a subject in high and low risk group, respectively. The primary (effectiveness) endpoint is CCTA without obstructive coronary artery disease. Safety of each strategy will be mainly assessed by 1-year major adverse cardiovascular event rates. Discussion The OPERATE trial will provide comparative effectiveness and safety evidences for two different diagnostic strategies for patients with SCP suggestive of CCS, with the intension of improving the diagnostic yield of CCTA at no expense of safety. Clinical trial registration ClinicalTrial.org Identifier NCT05640752.

Background/purpose: Fibrosis is present in various physiologic and pathologic conditions of salivary glands (SGs). This study aimed to identify novel biomarkers of SG fibrosis by next-generation sequencing. Materials and methods: We established the SG fibrosis mouse model by excretory main duct ligation. Next-generation sequencing, differentially expressed gene (DEG) analysis, and gene set enrichment analysis was performed by comparing ligated and control SGs. We used algorithms of Cytohubba, molecular complex detection, Lasso logistic regression, and support vector machine to identify the key biomarkers. Selected key biomarkers were verified by the polymerase chain reaction and immunohistochemistry. We also retrieved and analyzed the key gene expression in the fibrosis of the heart, liver, lung, and kidney to ensure the generalization of key biomarkers in SG fibrosis. Results: Both interlobular and intralobular fibrosis was confirmed in the ligated SGs, with improved expressions of collagen I and transforming growth factor β. Next-generation sequencing identified 2666 upregulated DEGs and 336 downregulated DEGs, which were highly enriched in the extracellular matrix-related pathways. Multiple algorithms identified 15 key biomarkers in SG fibrosis, including Thrombospondin-1 (THBS1) and Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3). The mRNA and protein expression of THBS1 and P4HA3 was verified in mice. THBS1 was also highly expressed in lung and kidney fibrosis, whereas P4HA3 was upregulated in liver fibrosis. Conclusion: THBS1 and P4HA3 may be potential biomarkers for SG fibrosis. They may be also applicable in the diagnosis of multi-organ fibrosis.

Abstract Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.

Abstract Macrophage‐myofibroblast transition (MMT) is a newly discovered pathway for mass production of pro‐tumoral cancer‐associated fibroblasts (CAFs) in non‐small cell lung carcinoma (NSCLC) in a TGF‐β1/Smad3 dependent manner. Better understanding its regulatory signaling in tumor microenvironment (TME) may identify druggable target for the development of precision medicine. Here, by dissecting the transcriptome dynamics of tumor‐associated macrophage at single‐cell resolution, a crucial role of a hematopoietic transcription factor Runx1 in MMT formation is revealed. Surprisingly, integrative bioinformatic analysis uncovers Runx1 as a key regulator in the downstream of MMT‐specific TGF‐β1/Smad3 signaling. Stromal Runx1 level positively correlates with the MMT‐derived CAF abundance and mortality in NSCLC patients. Mechanistically, macrophage‐specific Runx1 promotes the transcription of genes related to CAF signatures in MMT cells at genomic level. Importantly, macrophage‐specific genetic deletion and systemic pharmacological inhibition of TGF‐β1/Smad3/Runx1 signaling effectively prevent MMT‐driven CAF and tumor formation in vitro and in vivo, representing a potential therapeutic target for clinical NSCLC.

ABSTRACTZika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.

Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized.

Background/purpose: Analysis of endoplasmic reticulum stress (ERS)-related long noncoding RNAs (LncRNAs) may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to comprehensively analyze the ERS-related LncRNAs signature and its effects on the prognosis, tumorigenesis, and tumor immune microenvironment in HNSCC. Materials and methods: The transcriptome data of HNSCC were obtained from TCGA. Least absolute shrinkage selection operator algorithm, and multivariate Cox regression were used to screen LncRNAs for the signature construction. Somatic mutation, gene enrichment, and immune infiltration analyses were further performed. Results: 458 ERS-related LncRNAs were identified and 55 of which were correlated with HNSCC prognosis. Ten ERS-related LncRNAs were selected to establish a risk prediction signature. When dividing patients into high-risk and low-risk groups by signature score, high-risk group correlated with worse survival rates (hazard ratio = 1.211; 95% confidence interval 1.123–1.306, P

Background/purpose: Chronic obstructive sialadenitis (COS) is a condition that severely reduced patients’ quality of life. This study aimed to analyze the effects of SIS3, a specific inhibitor of small mothers against decapentaplegic 3 (SMAD3), on the submandibular gland (SMG) dysfunction, fibrosis, and inflammation. Materials and methods: The dominant duct in the SMG was ligated in mice, followed by intraperitoneal injection of SIS3 (2 mg/kg/day) or Dimethyl sulfoxide (DMSO) saline for 7 days. In the sham group, this duct was surgically identified but not ligated. Saliva flow, histological structure, fibrosis, Transforming growth factor-β1 (TGF-β)/SMAD3 signaling, and inflammatory cytokines, were analyzed. Results: SIS3 rescued ligation-induced SMG dysfunction and improved the saliva flow rate compared to DMSO. SIS3 alleviated acinar atrophy and ductal dilation and maintained the morphology of the basal membrane. SIS3 reduces interlobular and intralobular fibrosis and collagen deposition. We observed reduced SMAD3 phosphorylation and TGF-β expression. The SIS3 group showed downregulation of np_5318 and miR-21 and upregulation of miR-29 b compared to the DMSO group. Moreover, SIS3 controlled the inflammatory cytokine release, including interleukin-6 and interleukin-1β. Conclusion: SIS3 protected duct-ligated SMGs against fibrosis and dysfunction by inhibiting the TGF-β/SMAD3 signaling and inflammatory cytokine expression. SIS3 may serve as a promising treatment for chronic obstructive sialadenitis.

OBJECTIVES/GOALS: There are gain-of-function genomic alterations in FGFR genes that guide personalized treatment in some patients with cholangiocarcinoma (10%) and bladder cancer (30%) who can benefit from targeted therapies. We sought to evaluate other genomic alterations in cancer involving FGFRs and assess whether they are gain-of-function. METHODS/STUDY POPULATION: We collaborated with Foundation Medicine Inc (FMI), for the assessment of 300,000 sequenced tumors and a retrospective analysis of recent publications, to identify novel candidate FGFR alterations. We propose to transiently transfect HEK293T cells with an empty vector (EV), FGFR1-4 wild-type (WT), and these variants and use a luminescent-proximity based high-throughput assay, AlphaLISA, and Western blot to assess FGFR and phosphorylated downstream signaling proteins, FRS2, AKT and ERK, and their sensitivity to FGFR inhibitors: pemigatinib, erdafitinib, futibatinib, RLY-4008, and TYRA-200. RESULTS/ANTICIPATED RESULTS: Through our collaboration we identified >100 novel candidate FGFR1-4 variants of unknown significance (VUS) including extracellular-in-frame deletions (EIDs), kinase domain duplications (KDDs), insertions/deletions (INDELs), short number variants (SNVs), and truncations. Immunoblot analysis confirmed the presence of desired EV, FGFR WT, and VUS’ in HEK293T cells. We anticipate the FGFR EIDs and KDDs to display an increased presence of in the respective pFGFR, pFRS2, pERK, and pAKT as compared to the EV and FGFR WT by both immunoblot and AlpahLISA analysis. Additionally, we anticipate the VUS’ to be sensitive to FGFR inhibitors: pemigatinib, erdafitinib, futibatinib, RLY-4008, and TYRA-200 using the AlphaLISA assay. DISCUSSION/SIGNIFICANCE: These findings suggest that the novel FGFR VUS’ are capable of constitutive activation of FGFR kinase activity, and they preliminary demonstrate that these newly identified FGFR alterations are therapeutically targetable. Thus, providing rationale for further clinical evaluation to identify new cohorts of FGFR inhibitor responders.

Knorringia sibirica is a typical species of Polygonaceae with high medicinal and ecological value. However, there are few available phylogenetic and genetic studies about the chloroplast genome of K. sibirica. In the current study, a comprehensive examination of the chloroplast genome of K. sibirica was performed. The K. sibirica chloroplast genome is 161,384 bp, circular with a typical quadripartite structure, and comprised of guanine + cytosine content of 37.63%. The genome consists of 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Seventy simple sequence repeats were identified in the genome. When compared with three closely related species, the result revealed that the chloroplast genome of K. sibirica was conserved in genome composition and structure. The specific sites in the genome suitable for DNA barcodes were identified by calculation of the nucleotide diversity. Finally, a phylogenetic tree of 49 species in Polygonaceae was constructed using the whole chloroplast genome. The phylogenetic analysis suggested that Knorringia is an independent genus in the Polygonea tribe. This research could provide support for the utilization of genetic sources and the evolutionary study of K. sibirica.

Abstract Background Triglyceride glucose (TyG) index is a new marker associated with atherosclerosis. This study aimed to assess the association between TyG index and the severity of coronary artery disease (CAD) in patients with coronary heart disease (CHD) and further explore the association between TyG index and CAD severity in different glucose metabolic states. Methods This multi-centre retrospective study included 731 patients with CHD between January 1, 2014 and September 30, 2020 in China. All patients were stratified into groups based on the tertiles of TyG index (T1: 5.48 ≤ TyG index ≤ 7.17; T2: 7.18 ≤ TyG index ≤ 7.76; T3: 7.77 ≤ TyG index ≤ 10.82). The number of diseased vessels [single-vessel and multi-vessel CAD (≥ 50% stenosis in ≥ 2 large vessels)] represented the severity of CAD, which was measured using coronary angiography (CAG). Glucose metabolic states were defined by the American Diabetes Association as normal glucose regulation (NGR), prediabetes mellitus (Pre-DM), and diabetes mellitus (DM). Results The baseline analysis results showed significant differences in the clinical and biological characteristics of CHD patients according to TyG index tertiles (P

Background There is commonly a discrepancy between conference abstracts and published article abstracts in prosthodontic randomized controlled trials (RCTs), which may mislead the scholars those attend conferences. Objective To identify the characteristics predicting inconsistency between conference abstracts and published article abstracts in prosthodontic RCTs. Methods The conference abstracts of prosthodontic RCTs presented at the IADR general sessions from 2002 to 2015 were searched. Electronic searches of MEDLINE, EMBASE, the Cochrane Library, and Google Scholar databases were conducted to match full-text publications for conference abstracts. Two investigators extracted basic characteristics and assessed the consistency and reporting quality independently and in duplicate. The linear regression model was used to analyze the predictors of inconsistency. Results A total of 147 conference abstracts were matched with published articles. Results for the secondary outcome measure, Statistical analysis, and precision measure were less than 50% consistent, and even nearly 5% of the studies had opposite conclusions. Multiple linear regression analysis showed that three factors were correlated with lower inconsistency, including continent of origin (p = 0.011), presentation type (p = 0.017), and difference in reporting quality (p = 0.013). Conclusion Conference attendees should cautiously treat the findings of the conference abstracts. Researchers should improve the precision of the information delivered at conferences. We recommend the authors of RCTs to explain the primary difference between conference abstracts and article abstracts.

BackgroundAmong patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients.MethodsBetween January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression.ResultsOverall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden >70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92–6.44], a low-density non-calcified plaque (LDNCP) volume >30 mm3 (HR: 3.40, 95% CI: 2.07–5.56), a minimal luminal area (MLA)

Purpose To quantitatively assess and compare the clinical outcomes, including survival rate, success rate, and peri-implant indices of titanium and zirconium implants in randomized controlled trials. Methods The electronic databases searched included the Cochrane Central Register of Controlled Trials (CENTRAL), Medline via Ovid, EMBASE, and Web of Science. Randomized controlled trials (RCTs) that reported the effects of zirconium implants on primary outcomes, such as survival rate, success rate, marginal bone loss (MBL), and probing pocket depth (PPD), compared to titanium implants were included in this review. Two reviewers independently screened and selected the records, assessed their quality, and extracted the data from the included studies. Results A total of four studies from six publications reviewed were included. Two of the comparative studies were assessed at minimal risk of bias. Zirconium implants may have a lower survival rate (risk ratio (RR) = 0.91, CI [0.82–1.02], P = 0.100, I2 = 0%) and a significantly lower success rate than titanium implants (RR = 0.87, CI [0.78–0.98], P = 0.030, I2 = 0%). In addition, there was no difference between the titanium and zirconium implants in terms of MBL, PPD, bleeding on probing (BOP), plaque index (PI), and pink esthetic score (PES) (for MBL, MD = 0.25, CI [0.02–0.49], P = 0.033, I2 = 0%; for PPD, MD = −0.07, CI [−0.19–0.05], P = 0.250, I2 = 31%). Conclusion Zirconium implants may have higher failure rates due to their mechanical weakness. Zirconium implants should be strictly assessed before they enter the market. Further studies are required to confirm these findings.

Soil biogeochemical processes have the potential to impact water quality in source areas of water diversion projects. This study aimed to explore the differences in biochemical processes and mechanisms at the microaggregate scale for different land use types in the water source area of China's Middle Route of the South-to-North Water Diversion Project. The study compared four typical land use types—forests, shrublands, terraces, and cultivated land—by characterizing the microaggregates using various analytical techniques, including scanning electron microscopy (SEM), SEM-EDS plane scan analysis, X-ray diffraction (XRD), X-ray fluorescence (XRF) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. Microaggregates from forests and shrublands had a flocculent spatial structure, while those from terraces had a nondirectional plate-like spatial structure, and those from cultivated land had a laminar spatial structure. Additionally, elements such as Mg, Al, and Fe were enriched in clay particles when combined with microaggregates. The mineral composition of clay varied significantly between different land use practices, with illite, chlorite, anorthite, albite, and quartz present in higher proportions in terraces and cultivated land than in forests and shrublands. Moreover, the contents of transitional elements such as Ti, Fe, Zn, Y, and Zr increased with each successive land use practice. Soil organic matter (SOM) was observed to decline in the order of forest > shrubland > terraces > cultivated land. Over-tillage appeared to be the primary mechanism of organic matter loss due to long-term tillage. The results of this study provide valuable insights into soil erosion and chemical transport dynamics. The mineral composition and spatial structure of microaggregates are important determinants of soil biochemical processes and mechanisms, which can influence water quality. The findings suggest that forest and shrubland management practices may be more conducive to maintaining soil health and water quality in source areas of water diversion projects.

Ruan Hua Tang (RHT) and Ruan Hua Fang (RHF) are two Chinese herbal mixtures that have been used in clinical cancer treatment for decades. This study validated our hypothesis that RHT and RHF can inhibit lung tumor development in the mouse model of Benzo(a)pyrene-induced lung tumorigenesis. An RHT oral solution was diluted to 9% and 18% in water. RHF was mixed into the diet at 15% and 30% of total food in the final doses. Two weeks after injecting BP into mice, we administered RHT and RHF for eighteen weeks. We found that 9% and 18% RHT reduced tumor multiplicity by 36.05% and 38.81% (both p < 0.05) and the tumor load by 27.13% and 55.94% (p < 0.05); 15% and 30% RHF inhibited tumor multiplicity by 12.75% and 39.84% (p < 0.01) and the tumor load by 18.38% and 61.68% (p < 0.05). Ki67 expressions in the 9% and 18% RHT groups were 19.55% and 11.51%, significantly lower than in the control (33.64%). The Ki67 levels in the 15% and 30% RHF groups were 15.56% and 14.04%, significantly lower than in the control (27.86%). Caspase 3 expressions in the 9% and 18% RHT groups were 5.24% and 7.32%, significantly higher than in the control (2.39%). Caspase 3 levels in the 15% and 30% RHF groups were 6.53% and 4.74%, significantly higher than in the control (2.07%). The bio-absorption was confirmed via a pharmacokinetic test. This study showed that RHT and RHF are safe and can inhibit lung tumor development, with anti-proliferative and pro-apoptotic effects.

Accurate estimation of the road adhesion coefficient can help drivers and vehicles perceive changes in road state effectively, reducing the occurrence of traffic crashes accordingly. Therefore, this paper proposes a road adhesion coefficient estimation method based on vehicle-road coordination and deep learning. Firstly, a vehicle-based data feedback system combined with a vehicle-road network cloud is introduced, and CarSim simulation is used to expand the data set and train the model effectively. Then, the dynamic analysis of the whole vehicle is carried out, and the vehicle operation data related to the adhesion coefficient are obtained as the input of the estimation model. Then a combined model of road adhesion coefficient estimation based on self-attention (SA), convolutional neural network (CNN), and long short-term memory (LSTM) is established, to reduce the instability of the prediction, Q-learning is used to optimize the weight of the model. Finally, the model is verified by the simulation data and the actual vehicle-based data. The results show that the vehicle-based data feedback system combined with the vehicle-road network Ccloud is effective, and compared with other commonly used model, the estimation model proposed in this paper can effectively predict the road adhesion coefficient.

Mincle is essential for tumor-associated macrophage (TAM)-driven cancer progression and represents a potential immunotherapeutic target for cancer. Nevertheless, the lack of a specific inhibitor has largely limited its clinical translation. Here, we successfully developed a gene therapeutic strategy for silencing Mincle in a virus-free and tumor-specific manner by combining RNA interference technology with an ultrasound-microbubble-mediated gene transfer system (USMB). We identified a small hairpin RNA (shRNA) sequence shMincle that can silence not only Mincle expression but also the protumoral effector production in mouse bone marrow- and human THP-1-derived macrophages in the cancer setting in vitro. By using our well-established USMB system (USMB-shMincle), the shMincle-expressing plasmids were delivered in a tissue-specific manner into xenografts of human lung carcinoma A549 and melanoma A375 in vivo. Encouragingly, we found that USMB-shMincle effectively inhibited the protumoral phenotypes of TAMs as well as the progression of both A549 and A375 xenografts in a dose-dependent manner in mice without significant side effects. Mechanistically, we identified that USMB-shMincle markedly enhanced the anticancer M1 phenotype of TAMs in the A549 and A375 xenografts by blocking the protumoral Mincle/Syk/nuclear factor κB (NF-κB) signaling axis. Thus, USMB-shMincle may represent a clinically translatable novel and safe gene therapeutic approach for cancer treatment.

Aquaponics is considered a new industrialized food production approach to meet the increasing needs of expanding urbanization. In this system, nutrient recovery from aquaculture sludge can achieve zero solid waste discharge and supplement nutrients to hydroponics system, which yield environmental and economic benefits. Anaerobic and aerobic mineralization are common approaches for the nutrient conversion of aquaculture sludge, but they are challenged by low-value products, nutrient loss, and large amounts of biomass by-products produced during the process. In this review paper, phototrophic bioconversion of aquaculture sludge by anoxygenic phototrophic bacteria (APB) is proposed to minimize carbon and nutrient dissipation, through which the resulting mineral nutrients can be taken up by plants and the assimilated protein-rich biomass can be utilized by aquaculture animals as food. Pre-treatment to solubilize aquaculture sludge is essential to obtain bioavailable substrates, because aquaculture sludge cannot be utilized by APB in the organic solid form. The characteristics of anaerobic and aerobic solubilization processes are discussed, and the performance of phototrophic bioconversion by APB under anaerobic and aerobic conditions is compared. A multi-loop aquaponic system with four ecological coupling models was developed for the recovery of APB-based nutrients. The symbiotic mechanism between the solubilization and phototrophic bioconversion process should be focused in the future.

Background: Botulinum toxin type A injection, a noninvasive alternative method for treating masseteric hypertrophy, is inadequate for treating patients with a round lower face. This study aimed to investigate the operative technique and clinical results of liposuction followed by botulinum toxin type A injections in patients with masseteric hypertrophy and excessive subcutaneous fat. Methods: Sixty-five patients (50 women and 15 men) were treated using this technique between May 2014 and January 2019. Their mean age was 26.3 years (range, 18–35 years) and the mean follow-up period was 13 months (range, 8–18 months). Results: All patients achieved slimmer lower cheeks with improved jaw definitions after the procedure. Among the 65 patients, 61 (94%) expressed satisfaction with the results and believed that the procedure produced their desired face shape. No major complications were observed. The effect of this combination treatment remained stable for 12 months after the procedure. Conclusion: The authors believe that liposuction followed by botulinum toxin type A injections is an effective technique for the treatment of masseteric hypertrophy and excessive subcutaneous fat. It is also a relatively simple and safe treatment approach.

Abstract Fluorescent labeling and dynamic tracking is a powerful tool for exploring virus infection mechanisms. However, for small-sized viruses, virus tracking studies are usually hindered by a lack of appropriate labeling methods that do not dampen virus yield or infectivity. Here, we report a universal strategy for labeling viruses with chemical dyes and Quantum dots (QDs). Enterovirus 71 (EV71) was produced in a cell line that stably expresses a mutant methionyl-tRNA synthetase (MetRS), which can charge azidonorleucine (ANL) to the methionine sites of viral proteins during translation. Then, the ANL-containing virus was easily labeled with DBCO-AF647 and DBCO-QDs. The labeled virus shows sufficient yield and no obvious decrease in infectivity and can be used for imaging the virus entry process. Using the labeled EV71, different functions of scavenger receptor class B, member 2 (SCARB2), and heparan sulfate (HS) in EV71 infection were comparatively studied. The cell entry process of a strong HS-binding EV71 strain was investigated by real-time dynamic visualization of EV71-QDs in living cells. Taken together, our study described a universal biocompatible virus labeling method, visualized the dynamic viral entry process, and reported details of the receptor usage of EV71. Graphic Abstract

BackgroundAcute coronary syndrome (ACS) is the most time-sensitive acute cardiac event that requires rapid dispatching and response. The medical priority dispatch system (MPDS), one of the most extensively used types of emergency dispatch systems, is hypothesized to provide better-quality prehospital emergency treatment. However, few studies have revealed the impact of MPDS use on the process of ACS care. ObjectiveThis study aimed to investigate whether the use of MPDS was associated with higher prehospital diagnosis accuracy and shorter prehospital delay for patients with ACS transferred by an emergency medical service (EMS), using a national database in China. MethodsThis retrospective analysis was based on an integrated database of China’s MPDS and hospital registry. From January 1, 2016, to December 31, 2020, EMS-treated ACS cases were divided into before MPDS and after MPDS groups in accordance with the MPDS launch time at each EMS center. The primary outcomes included diagnosis consistency between hospital admission and discharge, and prehospital delay. Multivariable logistic regression and propensity score–matching analysis were performed to compare outcomes between the 2 groups for total ACS and subtypes. ResultsA total of 9806 ACS cases (3561 before MPDS and 6245 after MPDS) treated by 43 EMS centers were included. The overall diagnosis consistency of the after MPDS group (Cohen κ=0.918, P

IntroductionEpichloë bromicola is a cultivable fungal endophyte that lives in symbiosis with wild barley (Hordeum brevisubulatum) to which it confers salt tolerance. This study tested the hypothesis that E. bromicola derived from wild barley has the potential to increase salt tolerance in cultivated barley under salt stress.MethodsTo test this hypothesis, the growth response, physiological parameters, and metabolic profiles of barley plants inoculated with E. bromicola (E+) and those not inoculated with E. bromicola (E–) were compared under salt stress.ResultsCompared with E– barley plants, E+ barley plants had significantly increased plant height, shoot biomass, total biomass, chlorophyll content, osmotic synthesis, and accumulation of stress adaptation metabolites. E. bromicola increased the salt stress tolerance of cultivated barley, and the positive effects correlated with different salt stress conditions.DiscussionThese results suggest that E. bromicola has promising potential for enhancing the salt tolerance of barley. New insights into the mechanisms underlying this barley–fungal endophyte association are provided, and interesting questions regarding the role of E. bromicola in fungus-enhanced tolerance to salt stress in this symbiosis are raised.

Summary: Background: Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency with high mortality, so identifying modifiable risk factors of AAD is of great public health significance. The associations of non-optimal temperature and temperature variability with AAD onset and the disease burden have not been fully understood. Methods: We conducted a time-stratified case-crossover study using a nationwide registry dataset from 1,868 hospitals in 313 Chinese cities. Conditional logistic regression and distributed lag models were used to investigate associations of temperature and temperature changes between neighboring days (TCN) with the hourly AAD onset and calculate the attributable fractions. We also evaluated the heterogeneity of the associations. Findings: A total of 40,270 eligible AAD cases were included. The exposure-response curves for temperature and TCN with AAD onset risk were both inverse and approximately linear. The risks were present on the concurrent hour (for temperature) or day (for TCN) and lasted for almost 1 day. The cumulative relative risks of AAD were 1.027 and 1.026 per 1°C lower temperature and temperature decline between neighboring days, respectively. The associations were significant during the non-heating period, but were not present during the heating period in cities with central heating. 23.13% of AAD cases nationwide were attributable to low temperature and 1.58% were attributable to temperature decline from the previous day. Interpretation: This is the largest nationwide study demonstrating robust associations of low temperature and temperature decline with AAD onset. We, for the first time, calculated the corresponding disease burden and further showed that central heating may be a modifier for temperature-related AAD risk and burden. Funding: This work was supported by the National Natural Science Foundation of China (92043301 and 92143301), Shanghai International Science and Technology Partnership Project (No. 21230780200), the Medical Research Council-UK (MR/R013349/1), and the Natural Environment Research Council UK (NE/R009384/1).

ContextPrevious studies on the association between thyroid function and carotid plaque have shown contradictory results, which may be attributable to the sensitivity to thyroid hormone indices. This study aimed to analyze the association between thyroid hormone sensitivity and risk of carotid plaque in patients with coronary heart disease (CHD) and further explore this association according to sex, age, smoking, and drinking status.MethodsThis large-scale, multi-center, retrospective, cross-sectional study included 6679 patients with CHD (age 35–75). Central sensitivity to thyroid hormone was evaluated by the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), and thyrotroph thyroxine resistance index (TT4RI). Peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Taking no carotid plaque as a reference, this study used logistic regression to analyze the association between central and peripheral thyroid hormone sensitivity and carotid plaque in patients with CHD.ResultsOf the 6679 patients with CHD, 4843 (72.50%) had carotid plaque. In the multi-adjusted models, the TFQI (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.26–1.78; P < 0.001), PTFQI (OR: 1.76; 95% CI: 1.46–2.12; P < 0.001), TSHI (OR: 1.21; 95% CI: 1.10–1.33; P < 0.001), and TT4RI (OR: 1.00; 95% CI: 1.00–1.01; P = 0.003) were positively associated with the risk of carotid plaque. Compared with that in females and people > 60 years, the OR value for carotid plaque was higher in males and people ≤ 60 years. Similarly, smokers and drinkers had higher OR values for carotid plaque than non-smokers and non-drinkers. Conversely, FT3/FT4 ratio (OR: 0.75; 95% CI: 0.70–0.81; P < 0.001) was negatively associated with carotid plaque, and the OR value for carotid plaque was lower in males, patients ≤ 60 years, smokers, and drinkers.ConclusionThis study showed that thyroid hormone sensitivity is significantly associated with carotid plaque in patients with CHD. This association is more significant in males, patients ≤ 60 years, smokers, and drinkers.

This article reports the complete chloroplast genome of Achnatherum inebrians, a poisonous herb that is widely distributed in the rangelands of Northern China. The genome is 137 714 bp in total and consists of a large single‐copy (81 758 bp) region and small single‐copy (12 682 bp) region separated by a pair of inverted repeats (21 637 bp). The genome contains 130 genes, including 84 protein‐coding genes, 38 tRNA genes and 8 ribosomal RNA genes, and the guanine + cytosine content is 36.17%. We subsequently performed comparative analysis of complete genomes from A. inebrians and other Poaceae‐related species from GenBank. Thirty‐eight simple sequence repeats were identified, further demonstrating rapid evolution in Poaceae. Finally, the phylogenetic trees of 37 species of Poaceae and 2 species of Amaranthaceae were constructed by using maximum likelihood and Bayesian inference methods, based on the genes of the complete chloroplast genome. We identified hotspots that can be used as molecular markers and barcodes for phylogenetic analysis, as well as for species identification. Phylogenetic analysis indicated that A. inebrians is a member of the genus Stipa rather than Achnatherum.

Summary: Background: The associations of ambient temperature with acute myocardial infarction (AMI) have seldom been examined based on the time of symptom onset. Methods: We conducted a time-stratified case-crossover study among 1,046,773 eligible AMI patients from 2,093 hospitals in 324 Chinese cities from January 1, 2015 to June 30, 2021, after excluding those transferred from other hospitals or having not reported the time of symptom onset. Hourly exposure to ambient temperature was calculated as multiple moving 24-h averages (days) before hourly onset of AMI symptoms. Conditional logistic regression and distributed lag non-linear models with a duration of 0–21 days were used to estimate the cumulative associations of non-optimum temperature with AMI onset and the corresponding disease burden nationally. Subgroup analyses by region and period were conducted. Specifically, cities with and without centralized heating system were classified into heating and non-heating regions, respectively. The whole year in heating region was divided into heating and non-heating periods based on the duration of centralized heating in each city. Findings: Almost monotonically increasing risks were observed for both overall AMI and its two subtypes when ambient temperature declined. The effects of extremely low temperature occurred immediately on the concurrent day, and lasted up to almost 3 weeks. The excess risks of AMI onset associated with non-optimum ambient temperatures were observed during the whole year in the non-heating region and non-heating period in the heating region, but not during heating period. Specifically, odds ratios of AMI onset associated with extremely low temperature cumulated over 0–21 days were 1.24 (95% CI: 1.13–1.37), 1.46 (95% CI: 1.20–1.76), and 1.62 (95% CI: 1.46–1.81) in the heating region during non-heating period, in the non-heating region during winter and non-winter period, respectively. The heat effects on AMI onset were very modest and transient. Totally, 13.26% of AMI cases could be attributable to non-optimum temperatures nationally. The burden of AMI attributable to non-optimum temperature was much smaller in heating region than in non-heating region. Somewhat stronger effects were observed in females and patients aged older than 65. Interpretation: This nationwide study provided robust evidence that non-optimum ambient temperature may significantly trigger AMI onset, and for the first time estimated the disease burden after accounting for spatial and seasonal heterogeneity. Centralized heating might substantially mitigate AMI burden due to non-optimum temperature. Funding: Shanghai International Science and Technology Partnership Project, National Natural Science Foundation of China, Talent Training Program of Zhongshan Hospital, Fudan University.

Background: Sodium glucose cotransporter 2 inhibitors (SGLT-2i) are oral hypoglycemic drugs that can reduce the risk of deteriorating heart failure (HF) or cardiovascular death in patients with HF. Although some animal models have shown that SGLT-2i can effectively inhibit reperfusion injury after acute myocardial infarction (AMI), there is no clinical evidence to prove that SGLT-2i can also play a significant role in improving reperfusion injury in patients with AMI. Therefore, PREDOMINACE study enrolled patients with acute anterior large ST-segment elevation myocardial infarction, who are at high risk of developing HF in the future. The aim of this trial is to study the prevention effects of dapagliflozin on early ventricular dysfunction and remodeling in patients with acute anterior ST-segment elevation myocardial infarction (STEMI), and to explore the efficacy and safety of dapagliflozin in the treatment of patients with diabetes and without diabetes after acute anterior STEMI. Methods: Within a multi-center, randomized, single-blind, controlled trial we will recruit patients with acute anterior STEMI from the Second Hospital of Tianjin Medical University and Tianjin Chest Hospital, who are randomly divided into intervention group or control group in a 1:1 ratio. The intervention group was given dapagliflozin (10 mg once daily) before primary percutaneous coronary intervention (PPCI) and 30 days after PPCI, while the control group is not given SGLT-2i. The primary endpoint is the impact of dapagliflozin on changes of NT-proBNP levels in 30 days of acute anterior STEMI. Secondary endpoints include changes in echocardiographic left ventricular remodeling parameters (LVESV, LVEDV, EF), and the changes of ECG (Q wave leads 30 days after PPCI/ST-segment elevation leads at baseline,ST-segment decline degree 24 h and 7 days after PPCI). Hospitalization rate due to HF or other causes, incidence of malignant arrhythmias, and all-cause mortality will be assessed as exploratory secondary endpoints. Discussion: The PREDOMINACE trial will test dapagliflozin in patients with acute anterior STEMI, regardless of the presence or absence of diabetes. Therefore, the PREDOMINACE trial may support that the effects of SGLT-2i on improving cardiac remodeling, reducing cardiac pre and after load and improving cardiac metabolism are independent of its antidiabetic effects. Results will provide the clinical rationale for SGLT-2i to improve prognosis in patients with AMI.Trial registration: Chinese Clinical Trial Registry. Identifier: ChiCTR2100048157. Registered 23 September 2021.

Juglone has been extensively reported as a natural antitumor pigment. However, it is easy to be oxidized due to active hydroxy in the quinone. Here, we designed some new juglone derivatives, as the hydroxy was replaced by methyl (D1), allyl (D2), butyl (D3), and benzyl (D4) groups. Nuclear magnetic resonance spectra and mass spectrometry were applied to confirm the derivatives and oxidative products of juglone. U87 and U251 cell lines were used for tests in vitro, and primary human glioblastoma cells were applied for in vivo experiments. The CCK8 and EdU assay demonstrated the anti-tumor effect of the four derivatives, and IC50 for U87 was 3.99, 3.28, 7.60, and 11.84 μM, respectively. In U251, IC50 was 7.00, 5.43, 8.64, and 18.05 μM, respectively. D2 and D3 were further selected, and flow cytometry showed that apoptosis rates were increased after D2 or D3 treatment via ROS generation. Potential targets were predicted by network pharmacology analysis, most of which were associated with apoptosis, cell cycle, and metabolism pathway. CDC25B and DUSP1 were two of the most likely candidates for targets. The orthotopic glioblastoma model was established to evaluate the anti-glioma effect and side-effect of juglone derivatives, and the in vivo experiments confirmed the anti-glioma effects of juglone derivatives. In conclusion, new derivatives of juglone were created via chemical group substitution and could inhibit glioma cell viability and proliferation and induce apoptosis rate via ROS generation.

Abstract Background Further understanding of the distribution and changing characteristics of dental diseases is of great significance for all dental emergency centers for strengthening the medical staff’s treatment knowledge abilities and effective use of emergency resources in the face of public health emergencies involving highly infectious respiratory diseases. Methods The medical records of 4158 dental emergency patients in 2019 and 2020 were retrospectively analyzed and divided into pre-SARS-COV-2 group and SARS-COV-2 group according to time. The demographic data, date and time, diagnosis, and treatment methods of the two groups were statistically described, and the chi-squared test was used to analyze the differences. The medical records of 4158 dental emergency patients during the same period of two years in 2019 and 2020 were retrospectively analyzed and divided into SARS-COV-2 pre-group and SARS-COV-2 group according to time. The demographic data, date and time, diagnosis and treatment methods of the two groups were statistically described, and the chi-square test was used to determine the differences. Results During the SARS-COV-2 pandemic, the number of dental emergency visits increased by 29.7%. During the pandemic, males (n = 286, 58.1%) were more likely to visit dental emergency centers for trauma than females (n = 206, 41.9%) (P

Aiming at the delay caused by the phase-locked loop (PLL) and harmonic detection in the traditional control of a series active power filter (SAPF), a deadbeat direct control (DBDC)-based finite control set model predictive control (FCS-MPC) strategy for the SAPF is proposed in this work. Firstly, a reference voltage generation mechanism based on direct control is established, which avoids the delay in harmonic detection, thus improving the dynamic response performance of the system. Secondly, the reference current generation mechanism suitable for the SAPF is derived and established using the deadbeat control (DBC) in the αβ coordinate system, based on which the FCS-MPC system is constructed. It eliminates the complex coordinate transformation and PLL and effectively compensates for the full-frequency harmonic voltage. Finally, the proposed control strategy is verified by a simulation and an experiment. The results suggest that the proposed control strategy can effectively compensate for the load voltage and suppress harmonic distortion for the temporary swell and sag of the grid voltage, sudden load changes, and harmonic distortion conditions.