Search

Abstract Introduction Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). Methods Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. Results Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99–1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97–1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95–1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91–1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. Conclusions This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

Abstract Objectives To validate the correlation between histopathological findings and quantitative magnetic resonance imaging (qMRI) fat fraction (FF) and water T2 mapping in patients with idiopathic inflammatory myopathy (IIM). Methods The study included 13 patients with histopathologically confirmed IIM who underwent dedicated thigh qMRI scanning within 1 month before open muscle biopsy. For the biopsied muscles, FF derived from the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) and T2 time from T2 mapping with chemical shift selective fat saturation were measured using a machine learning software. Individual histochemical and immunohistochemical slides were evaluated using a 5-point Likert score. Inter-reader agreement and the correlation between qMRI markers and histopathological scores were analyzed. Results Readers showed good to perfect agreement in qMRI measurements and most histopathological scores. FF of the biopsied muscles was positively correlated with the amount of fat in histopathological slides (p = 0.031). Prolonged T2 time was associated with the degree of variation in myofiber size, inflammatory cell infiltration, and amount of connective tissues (p ≤ 0.008 for all). Conclusions Using the machine learning-based muscle segmentation method, a positive correlation was confirmed between qMRI biomarkers and histopathological findings of patients with IIM. This finding provides a basis for using qMRI as a non-invasive tool in the diagnostic workflow of IIM. Relevance statement By using ML-based muscle segmentation, a correlation between qMRI biomarkers and histopathology was found in patients with IIM: qMRI is a potential non-invasive tool in this clinical setting. Key points • Quantitative magnetic resonance imaging measurements using machine learning-based muscle segmentation have good consistency and reproductivity. • Fat fraction of idiopathic inflammatory myopathy (IIM) correlated with the amount of fat at histopathology. • Prolonged T2 time was associated with muscle inflammation in IIM. Graphical Abstract

Abstract The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

BackgroundPost-catheter removal sepsis (PCRS) is a notable complication of indwelling central venous catheters (CVCs) in neonates, which is postulated to be secondary to the disruption of biofilms formed along catheter tips up on CVCs removal. It remains controversial whether this could be prevented by antibiotic use upon CVCs removal. We aimed to evaluate the protective effect of antibiotic administration at the time of CVCs removal.MethodsWe searched through PubMed, EMBASE, Cochrane databases and reference lists of review articles for studies comparing the use of antibiotics versus no use within 12 h of CVCs removal. Risk of bias was assessed using the modified Newcastle-Ottawa Scale and Cochrane risk-of-bias tool accordingly. Results of quantitative analyses were presented as mean differences (MD) or odds ratio (OR). Subgroup and univariate meta-regression analyses were performed to identify heterogeneity.ResultsThe review included 470 CVCs in the antibiotic group and 658 in the control group. Antibiotic use within 12 h of CVCs removal did not significantly reduce the incidence of PCRS (OR = 0.35, 95% CI: 0.08–1.53), but was associated with a lower incidence of post-catheter removal blood stream infection (OR = 0.31, 95% CI: 0.11–0.86). Dosage of vancomycin and world region were major sources of heterogeneity.ConclusionAntibiotic administration upon CVCs removal does not significantly reduce the incidence of PCRS but offers less post-catheter removal blood stream infection. Whether this will be converted to better clinical outcomes lacks evidential support. Further randomized controlled studies with longer follow-up are needed.SummaryResults of our meta-analysis suggest that antibiotic use at planned central line removal removal does not significantly reduce the incidence of PCRS but offers less blood stream infection, which might contribute to future management of central lines in neonates. Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42022359677).

Abstract Background Little is known about the rate of real-world inpatient rehabilitation therapy (IRT) after stroke. We aimed to determine the rate of inpatient rehabilitation therapy and its associated factors in patients who undergo reperfusion therapy in China. Methods This national prospective registry study included hospitalized ischemic stroke patients aged 14–99 years with reperfusion therapy between January 1, 2019, and June 30, 2020, collecting hospital-level and patient-level demographic and clinical data. IRT included acupuncture or massage, physical therapy, occupational therapy, speech therapy, and others. The primary outcome was the rate of patients receiving IRT. Results We included 209,189 eligible patients from 2191 hospitals. The median age was 66 years, and 64.2% were men. Four in five patients received only thrombolysis, and the rest 19.2% underwent endovascular therapy. The overall rate of IRT was 58.2% (95% CI, 58.0–58.5%). Differences in demographic and clinical variables existed between patients with and without IRT. The rates of acupuncture or massage, physical therapy, occupational therapy, speech therapy, and other rehabilitation interventions were 38.0%, 28.8%, 11.8%, 14.4%, and 22.9%, respectively. The rates of single and multimodal interventions were 28.3% and 30.0%, respectively. A lower likelihood of receiving IRT was associated with being 14–50 or 76–99 years old, female, from Northeast China, from Class-C hospitals, receiving only thrombolysis, having severe stroke or severe deterioration, a short length of stay, Covid-19 pandemic and having intracranial or gastrointestinal hemorrhage. Conclusion Among our patient population, the IRT rate was low with limited use of physical therapy, multimodal interventions, and rehabilitation centers and varied by demographic and clinical features. The implementation of IRT remains a challenge for stroke care, warranting urgent and effective national programs to enhance post-stroke rehabilitation and the adherence to guidelines.

Grafting, one of the artificial propagation methods used in plants, is now widely used in flower breeding, vegetable cultivation and stress response research. In order to discover the reason for success of heterograft and information exchange mechanisms, we used Artemisia annua (Aa) as scion and Nicotiana benthamiana (Nb) as rootstock to build a grafting model. After grafting 30 days co-growth, 7,794 DEGs (different expression genes) and 8,214 DEGs were identified in Aa scion and Nb rootstock, respectively. Most of the DEGs belong to defense response and signal transduction in scion and substance metabolism in rootstock, which indicate that the diverging response mechansim of grafted parts. Fifty Nb genes and 20 Aa genes were detected in Aa scion and Nb rootstock, which were regarded as potentially active genes during the grafting process. The most abundant miRNAs are miR159 and miR166, which may be closely related to their conservation and physiological functions. Besides, miR159 and miR166 could quickly respond to internal change, therefore the two miRNAs should be considered as biomarkers of successful grafting models. And then, as simultaneously screened miRNAs, miR396 and miR6149 could be potential biomarker in Aa and Nb, respectively. Through the analysis of the miRNA-target gene network in differentially expressed miRNAs, transcription factor R2R3-MYB, bHLH, GRAS, GAMYB, SBP-box, MADS-box, IIS in scion and NF-Y in rootstock were regarded as key genes involved in growth and development of grafted plants. The content of ABA, JA, CK was calculated in grafted plants and showed its respective functions.

Abstract Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post‐traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual‐homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate‐hyaluronic acid‐based hydrogel spray device encapsulating a curcumin‐loaded zeolitic imidazolate framework‐8@ceric oxide (ZIF‐8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo‐crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA‐seq results demonstrated that CZCH achieved dual‐homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations.

The patella's inferior pole transmits force generated by contraction of the quadriceps muscle to the tibial tuberosity through the attached patellar ligament, thus completing knee extension. Therefore, fractures of the patella's inferior pole disrupt the coherence of mechanical transmission in the lower extremities. There appears to be no consensus among trauma centers regarding the treatment of infrapatellar pole fractures, primarily because there is no consistent design or application of internal fixation for this type of fracture. We designed a new internal implant similar to the smile necklace based on our previous study. This smile‐necklace plate (SNP) has the advantage of both plate fixation and tension‐band wiring fixation, permitting early rehabilitation, especially in osteoporotic comminuted infrapatellar pole fractures. Finite element analysis helped verify the biomechanical advantages of the SNP in comparison with existing studies. Hence, this novel implant is a promising treatment option for inferior pole patellar fractures.

IntroductionScutellaria baicalensis Georgi is a traditional Chinese medicinal plant with broad pharmacological activities whose main active ingredient is the flavonoid baicalin. Given its medicinal value and increasing market demand, it is essential to improve the plant’s baicalin content. Flavonoid biosynthesis is regulated by several phytohormones, primarily jasmonic acid (JA).MethodsIn this study, we conducted transcriptome deep sequencing analysis of S. baicalensis roots treated with methyl jasmonate for different durations (1, 3, or 7 hours). Leveraging weighted gene co-expression network analysis and transcriptome data, we identified candidate transcription factor genes involved in the regulation of baicalin biosynthesis. To validate the regulatory interactions, we performed functional assays such as yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays.ResultsOur findings demonstrated that SbWRKY75 directly regulates the expression of the flavonoid biosynthetic gene SbCLL-7, whereas SbWRKY41 directly regulates the expression of two other flavonoid biosynthetic genes, SbF6H and SbUGT, thus regulating baicalin biosynthesis. We also obtained transgenic S.baicalensis plants by somatic embryo induction and determined that overexpressing SbWRKY75 increased baicalin content by 14%, while RNAi reduced it by 22%. Notably, SbWRKY41 indirectly regulated baicalin biosynthesis by modulating the expression of SbMYC2.1, SbJAZ3 and SbWRKY75.DiscussionThis study provides valuable insights into the molecular mechanisms underlying JA-mediated baicalin biosynthesis in S. baicalensis. Our results highlight the specific roles of transcription factors, namely SbWRKY75 and SbWRKY41, in the regulation of key biosynthetic genes. Understanding these regulatory mechanisms holds significant potential for developing targeted strategies to enhance baicalin content in S. baicalensis through genetic interventions.

Abstract Heterotopic ossification (HO) is the abnormal formation of bone in extraskeletal sites. However, the mechanisms linking HO pathogenesis with bone mass dysfunction remain unclear. Here, we showed that mice harboring injury-induced and BMP4-dependent HO exhibit bone mass loss similar to that presented by patients with HO. Moreover, we found that injury-induced hyperinflammatory responses at the injury site triggered HO initiation but did not result in bone mass loss at 1 day post-injury (dpi). In contrast, a suppressive immune response promoted HO propagation and bone mass loss by 7 dpi. Correcting immune dysregulation by PD1/PDL1 blockade dramatically alleviated HO propagation and bone mass loss. We further demonstrated that fetuin-A (FetA), which has been frequently detected in HO lesions but rarely observed in HO-adjacent normal bone, acts as an immunomodulator to promote PD1 expression and M2 macrophage polarization, leading to immunosuppression. Intervention with recombinant FetA inhibited hyperinflammation and prevented HO and associated bone mass loss. Collectively, our findings provide new insights into the osteoimmunological interactions that occur during HO formation and suggest that FetA is an immunosuppressor and a potential therapeutic option for the treatment of HO.

Osteoarthritis (OA) is a chronic arthritic disease characterized by cartilage degradation, synovial inflammation, and subchondral bone lesions. The studies on the pathogenesis of OA are complex and diverse. The roles of receptors signaling in chondrocyte anabolism, inflammatory factors expression of synovial fibroblast, and angiogenesis in subchondral bone are particularly important for exploring the pathological mechanism of OA and clinical diagnosis and treatment. By reviewing the relevant literature, this article elaborates on the abnormal expression of receptors and the signaling transduction pathways from different pathological changes of OA anatomical components, aiming to provide new research ideas and clinical therapeutic value for OA pathogenesis.

Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements.

Abstract Background Current findings on the impact of weather conditions on osteoarthritis (OA) and rheumatoid arthritis (RA) are sparse and not conclusive. This study aimed to investigate the relationship between temperature change and OA/RA admission. Methods Daily OA/RA admission, meteorological data and pollutants from 1 January 2014 to 31 December 2017 in Hefei, China, were collected. We quantified the relationship between ambient temperature and OA/RA admission using a distributed lag nonlinear model (DLNM). Stratified analyses by gender and age were also examined. Results Temperature decrease was significantly associated with RA admission (25th percentile of temperature versus 50th percentile of temperature), with the acute and largest effect at current days lag (RR: 1.057, 95%CI: 1.005–1.111). However, no significant association between temperature and OA admission was observed. When conducting subgroup analyses by individual characteristics, we found that females and patients aged 41–65 years were more vulnerable to temperature decrease than males, patients aged 0–40 and ≧66 years, respectively. Conclusions This study suggested that temperature decrease was a risk factor for increases in RA admission. Females and patients aged 41–65 years were particularly vulnerable to the effect of temperature decrease.

BackgroundThere is no effective regimen to reduce the mortality of patients treated with intravenous thrombolysis or endovascular therapy (EVT). Therefore, we aimed to examine whether sequential therapy by rehabilitation could effectively reduce the in-hospital mortality of patients treated with reperfusion therapy.MethodsThis prospective registry study included patients with ischemic stroke who were treated by intravenous thrombolysis or endovascular therapy at Stroke Center Work Plan in China between 1 October 2018 and 31 July 2020. The patients were divided into 2 groups: those with (IRT+) or without (IRT–) inpatient rehabilitation therapy (IRT). The primary outcome was all-cause in-hospital mortality. We used Cox proportional hazards models and conducted a propensity score matching analysis to calculate hazard ratios (HRs) for mortality in the thrombolysis-only and EVT groups.ResultsOf the 189,519 patients in the thrombolysis-only group, 35.7% were women, and the median (interquartile range, IQR) age, onset-to-needle time, and follow-up time were 66 (57–74) years, 165 (119–220) min, and 9 (5–12) days, respectively. Among the 45,211 patients in the EVT group, 35.9% were women, and the median (interquartile range, IQR) age, onset-to-puncture time, and follow-up time were 66 (56–74) years, 297 (205–420) min, and 11 (6–16) days, respectively. In the thrombolysis-only group with a median (IQR) initial National Institutes of Health Stroke Scale (NIHSS) score of 6 (3–11), 105,244 patients (55.5%) treated with IRT had significantly lower all-cause in-hospital mortality [0.6 vs. 2.3%; adjusted HR 0.18 (95% confidence interval (CI) 0.16–0.2)] than those without IRT. In the EVT group with a median (IQR) initial NIHSS score of 15 (10–20), 31,098 patients (68.8%) treated with IRT also had significantly lower all-cause in-hospital mortality [2 vs. 12.1%; adjusted HR, 0.13 (95% CI 0.12–0.15)]. IRT remained significantly associated with reduced in-hospital mortality in sensitivity, subgroup, and propensity score matching analyses among both the thrombolysis-only and EVT groups.ConclusionAmong the patients with ischemic stroke treated with intravenous thrombolysis or endovascular therapy, sequential therapy by rehabilitation was associated with lower all-cause in-hospital mortality. These findings suggest the necessity of promoting inpatient rehabilitation therapy after reperfusion in patients with ischemic stroke.

BackgroundRobot-assisted nephroureterectomy (RANU) and laparoscopic nephroureterectomy (LNU) are two minimally invasive surgical management for upper urinary tract urothelial carcinomas (UTUC). Though more high-tech, it remains largely unclear whether RANU provides additional benefits over LNU. We aimed to quantitatively compare the perioperative and oncologic outcomes between RANU and LNU.MethodsThe systematic review was performed based on a registered protocol (registration number CRD42022319086). We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2022) for comparative studies reporting perioperative and oncologic outcomes independently in RANU and LNU groups. Selection of studies and data extraction were performed independently by two researchers. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD) or Odds ratio (OR), as appropriate. Subgroup and univariate meta-regression analyses were performed to identify interstudy heterogeneities.ResultsThe review included 8470 patients undergoing RANU and 19872 patients undergoing LNU from 12 comparative original studies. RANU was associated with fewer overall complications (OR=0.71, 95%CI: 0.62 to 0.81), longer operative time (MD=27.70, 95%CI: 0.83 to 54.60) and shorter length of stay (MD=-0.53, 95%CI: -0.98 to -0.07) compared to LNU. In addition, patients receiving RANU were more likely to have lymph node dissected (OR=2.61, 95%CI: 1.86 to 3.65). Recurrence and survival outcomes did not differ between two surgical procedures. Sample size, types of LNU and world region were major sources of heterogeneity.ConclusionFor UTUC patients, RANU offers fewer complications and shorter hospitalization. However, RANU requires longer operative time and shares similar oncologic outcomes compared to LNU. Further randomized designed studies are warranted.Systematic Review Registrationwww.crd.york.ac.uk/prospero/, identifier CRD42022319086.

Prostate cystadenoma is a rare benign prostatic neoplasm, which grows outside prostate and locates midline between the urinary bladder and rectum. It usually presents as multilocular cysts, thus, named giant multilocular prostate cystadenoma. The definite diagnosis is difficult to be made before surgery, and it depends on histopathology. Here, we report a rarer condition of prostate cystadenoma, which manifests as a giant unilocular cyst with a solid nodule inside. The 55-year-old Chinese male patient presented with dysuria and constipation. MRI revealed a 10.5 × 8.2 cm mono-cystic lesion displacing the rectum to the posterior, prostate, and bladder to the anterior, with a 2.8 × 2.1 cm solid nodule at the anterior wall. 18F-FDG PET/CT demonstrated an elevated SUVmax (3.5) of the solid nodule. Laparoscopic pelvic mass resection was performed and prostate cystadenoma was diagnosed. In conclusion, when a mass of single locular cyst sits in the male pelvis, the diagnosis of prostate cystadenoma could not be excluded.

Artemisinin is an important drug for resistance against malaria. Artemisinin is derived from the glandular trichome of leaves, stems, or buds of the Chinese traditional herb Artemisia annua. Increasing the trichome density may enhance the artemisinin content of A. annua. It has been proven that cyclins are involved in the development of trichomes in tomato, Arabidopsis, and tobacco, but it is unclear whether the cyclins in A. annua influence trichome development. In this study, we showed that AaCycTL may regulate trichome development and affect the content of artemisinin. We cloned AaCycTL and found that it has the same expression files as the artemisinin biosynthesis pathway gene. We overexpressed AaCycTL in Arabidopsis, and the results indicated that AaCycTL changed the wax coverage on the surface of Arabidopsis leaves. The trichome density decreased as well. Using yeast two-hybrid and BiFC assays, we show that AaCycTL can interact with AaTAR1. Moreover, we overexpressed AaCycTL in A. annua and found that the expression of AaCycTL was increased to 82–195%. Changes in wax coverage on the surface of transgenic A. annua leaves or stems were found as well. We identified the expression of the artemisinin biosynthesis pathway genes ADS, CYP71AV1, and ALDH1 has decreased to 88–98%, 76–97%, and 82–97% in the AaCycTL-overexpressing A. annua lines, respectively. Furthermore, we found reduced the content of artemisinin. In agreement, overexpression of AaCycTL in A. annua or Arabidopsis may alter waxy loading, change the initiation of trichomes and downregulate trichome density. Altogether, AaCycTL mediates trichome development in A. annua and thus may serve to regulate trichome density and be used for artemisinin biosynthesis.

Objective: The objective of our study was to introduce community quarantine strategy against coronavirus disease 2019 (COVID-19) in Anhui and evaluate the effectiveness of community quarantine based on trauma center (TC) patients. Method: The structure of community quarantine strategy was illustrated. Distribution of injuries among patients in two TCs between January 24, 2020 and February 24, 2020 was described. Multiple linear regression was used to analyze the correlation between the distribution of Injuries in TCs and the number of COVID-19-associated cases. Results: A total of 757 TC patients in the two hospitals were enrolled. The number of traffic injuries and outdoor injuries showed a significant decrease in the early stage and began to increase on February 17. The number of indoor injuries neither decreased nor increased. Multiple linear regression analysis revealed a significant correlation between COVID-19-associated cases and traffic and outdoor injuries. Conclusion: From the perspective of the injuries in TCs, community quarantine strategy was effectively implemented and significantly slowed the outbreak of COVID-19 in Anhui. However, the implementation and maintenance of the strategy is costly and requires the participation of the entire population.

Objective(s): Previous study has indicated that triiodothyronine (T3) facilitated cartilage degeneration in osteoarthritis (OA). This study aimed to investigate the effects of T3 on angiogenesis-related factor expression in human osteoblasts of OA subchondral bone.Materials and Methods: The subchondral bone specimens were obtained from OA patients and healthy participants. The expressions of VEGF, HIF-1α, AKT, and phosphorylated AKT was detected by immunohistochemistry, Western blotting, and RT-qPCR in OA. Angiogenesis-related factor expression in OA osteoblasts was measured by treating different concentrations of T3. The hypoxia model and PX-478 (HIF-1α inhibitor) were employed to confirm the regulative role of HIF-1α for VEGF expression. The level of VEGF secretion was examined in osteoblasts supernatant using ELISA. Results: Immunohistochemistry showed strong staining of VEGF and HIF-1α in OA subchondral bone. The expression of VEGF, HIF-1α, and p-AKT in OA osteoblasts was higher than that of normal osteoblasts at protein and mRNA levels. The physiological concentration of T3 (10-7 M) in OA osteoblasts up-regulated the expression of VEGF, HIF-1α, and p-AKT after 24 hr and 48 hr culture, while a higher dose of T3 displayed the adverse effects. Additionally, VEGF and p-AKT expression was down-regulated when PX-478 inhibited HIF-1α protein. Conclusion: Our results suggested that local T3 could effectively increase angiogenesis-related factor expression by PI3K/AKT signaling pathway, and HIF-1α regulated the VEGF expression in OA osteoblasts.

The effect of modified atmosphere packaging (MAP) in combination with cold storage on physicochemical and microbiological changes of farmed pufferfish was studied during 14 days of storage. Results showed that samples with MAP3 (gas composition of 60% CO2, 5% O2, 35% N2) treatment had the significantly lower total volatile basic nitrogen, K value, and total viable counts. The water holding capacity, low field NMR analysis and MRI indicated that MAP3 was more effective in maintaining the water content and water migration. Analyses of free amino acids (FAAs) also indicated that MAP3 treatment had a positive effect on preventing the degradation of proteins and retained better flavour quality.

Abstract Background Klippel-Trenaunay syndrome (KTS) is a rare complex vessel malformation syndrome characterized by venous varicosities, capillary malformations, and limb hypertrophy. However, extensive heterotopic ossification (HO) secondary to this syndrome is extremely rare. Case presentation We report the case of a patient with previously undiagnosed KTS and extensive HO who presented with a femoral fracture secondary to a motor vehicle accident. Extensive ossification, which leads to compulsive contracture deformity and dysfunction of the leg, was distributed on the flexor muscle side, as revealed by the radiograph. The diagnosis was finally established by combining imaging and histological analysis with classical clinical symptoms. Amputation was performed at the fracture site proximal to the infected necrotic foci. Open management of the fracture was challenging owning to the pervasive ossification and tendency for excessive bleeding. Gene sequencing analysis showed homozygous mutation of FoxO1 gene. Conclusions Definitive diagnosis of a combination of KTS and extensive HO requires detailed imaging analysis and pathologic evidence. Mutation of the FoxO1 gene, which regulates bone formation by resistance to oxidative stress in osteoblasts, is a potential factor in the microenvironment of malformed vessels caused by KTS.

Abstract Background Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. Results In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. Conclusion These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1–STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.

Phytohormones affect plant growth and development. Many phytohormones are involved in the initiation of trichome development, which can help prevent damage from UV radiation and insect bites and produce fragrance, flavors, and compounds used as pharmaceuticals. Phytohormones promote the participation of transcription factors in the initiation of trichome development; for example, the transcription factors HDZIP, bHLH and MYB interact and form transcriptional complexes to regulate trichome development. Jasmonic acid (JA) mediates the progression of the endoreduplication cycle to increase the number of multicellular trichomes or trichome size. Moreover, there is crosstalk between phytohormones, and some phytohormones interact with each other to affect trichome development. Several new techniques, such as the CRISPR-Cas9 system and single-cell transcriptomics, are available for investigating gene function, determining the trajectory of individual trichome cells and elucidating the regulatory network underlying trichome cell lineages. This review discusses recent advances in the modulation of trichome development by phytohormones, emphasizes the differences and similarities between phytohormones initially present in trichomes and provides suggestions for future research.

Glioblastoma is the most common and aggressive malignancy in the adult central nervous system. Cytomegalovirus (CMV) plays a crucial role in the pathogenesis and treatment of glioblastoma. We reviewed the epidemiology of CMV in gliomas, the mechanism of CMV-related carcinogenesis, and its therapeutic strategies, offering further clinical practice insights. To date, the CMV infection rate in glioblastoma is controversial, while mounting studies have suggested a high infection rate. The carcinogenesis mechanism of CMV has been investigated in relation to various aspects, including oncomodulation, oncogenic features, tumor microenvironment regulation, epithelial–mesenchymal transition, and overall immune system regulation. In clinical practice, the incidence of CMV-associated encephalopathy is high, and CMV-targeting treatment bears both anti-CMV and anti-tumor effects. As the major anti-CMV treatment, valganciclovir has demonstrated a promising survival benefit in both newly diagnosed and recurrent glioblastoma as an adjuvant therapy, regardless of surgery and the MGMT promoter methylation state. Immunotherapy, including DC vaccines and adoptive CMV-specific T cells, is also under investigation, and preliminary results have been promising. There are still questions regarding the significance of CMV infection and the carcinogenic mechanism of CMV. Meanwhile, studies have demonstrated the clinical benefits of anti-CMV therapy in glioblastoma. Therefore, anti-CMV therapies are worthy of further recognition and investigation.

As an eco-friendly and efficient adsorbent for removal of potential toxic metals from aqueous solution, biochar has received widespread attention. In the present study, wheat straw biochar (BC) and corresponding modified biochar (HNC) were used to remove Cu2+, Cd2+ and Pb2+ from an aqueous solution. The influence of the environment factors on metals adsorption and adsorption mechanism were discussed in detail. The results showed that the HNC had porous structures and owned ample functional groups (−OH, −COOH and C−N groups) compared with the BC. In the single system, the adsorption capacities of HNC for Cu2+, Cd2+ and Pb2+ at a pH of 5.5 were 18.36, 22.83 and 49.38 mg/g, which were 76.89%, 164.36% and 22.75% higher than that of the BC, respectively. In addition, the adsorption process of Cu2+ and Cd2+ on BC and HNC fitted to the Langmuir isotherm model and pseudo-second-order kinetics, but the adsorption of Pb2+ on BC and HNC fitted to the Langmuir isotherm model and pseudo-first-order kinetics. Adsorption isotherms indicated that the adsorption of Cu2+, Cd2+ and Pb2+ by BC and HNC was a spontaneous endothermic process. The competitive adsorption of mixed metal ions (Cu2+, Cd2+ and Pb2+) revealed that HNC was more preferential to adsorb Cu2+ compared with Cd2+ and Pb2+. Furthermore, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses revealed that the main adsorption mechanisms were surface complexation and precipitation, and the adsorbed Cu2+, Cd2+ and Pb2+ on HNC mainly exist as CuO, Cd(OH)2, Pb3O4 and Pb(OH)2.

Femoral neck fractures (FNFs) are a great public health problem that leads to a high incidence of death and dysfunction. Osteonecrosis of the femoral head (ONFH) after internal fixation of FNF is a frequently reported complication and a major cause for reoperation. Early intervention can prevent osteonecrosis aggravation at the preliminary stage. However, at present, failure to diagnose asymptomatic ONFH after FNF fixation hinders effective intervention at early stages. The primary objective of this study was to develop a predictive model for postoperative ONFH using deep learning (DL) methods developed using plain X-ray radiographs and hybrid patient variables. A two-center retrospective study of patients who underwent closed reduction and cannulated screw fixation was performed. We trained a convolutional neural network (CNN) model using postoperative pelvic radiographs and the output regressive radiograph variables. A less experienced orthopedic doctor, and an experienced orthopedic doctor also evaluated and diagnosed the patients using postoperative pelvic radiographs. Hybrid nomograms were developed based on patient and radiograph variables to determine predictive performance. A total of 238 patients, including 95 ONFH patients and 143 non-ONFH patients, were included. A CNN model was trained using postoperative radiographs and output radiograph variables. The accuracy of the validation set was 0.873 for the CNN model, and the algorithm achieved an area under the curve (AUC) value of 0.912 for the prediction. The diagnostic and predictive ability of the algorithm was superior to that of the two doctors, based on the postoperative X-rays. The addition of DL-based radiograph variables to the clinical nomogram improved predictive performance, resulting in an AUC of 0.948 (95% CI, 0.920–0.976) and better calibration. The decision curve analysis showed that adding the DL increased the clinical usefulness of the nomogram compared with a clinical approach alone. In conclusion, we constructed a DL facilitated nomogram that incorporated a hybrid of radiograph and patient variables, which can be used to improve the prediction of preoperative osteonecrosis of the femoral head after internal fixation.

Osteoporosis (OP) is one of the common bone metabolic diseases that endangers postmenopausal women and the elders. Both excessive bone resorption caused by osteoclast over-activation and increased oxidative stress are associated with osteoporosis. Cinnamtannin B-1 (CB-1) is considered as a high-valued plant extract monomer due to its antioxidant properties. However, the mechanism of CB-1 impacts on reducing oxidative stress, inhibiting the production of reactive oxygen species (ROS) and osteoclast differentiation and preventing ovariectomy-induced osteoporosis are still unclear. In this study, the effects of CB-1 on nuclear factor κB (RANKL)-induced osteoclasts formation and differentiation in vitro and the potential therapeutic effect on ovariectomy (OVX)-induced osteoporosis in vivo are investigated. CB-1 was found to inhibit osteoclast formation and bone resorption function in a dose-dependent manner, and it inhibited specific genes related to osteoclast as well. Micro-CT and histopathological staining showed that CB-1 can effectively prevent OVX-induced osteoporosis. In addition, CB-1 treatment can effectively inhibit the production of reactive oxygen species (ROS) in vivo and in vitro. Mechanistically, CB-1 inhibits the activation of osteoclasts by inhibiting the activation of the NF-κB signaling pathway. In conclusion, CB-1 would be able to be used as a promising new drug strategy to inhibit RANKL-induced osteoclastogenesis and prevent ovariectomy-induced osteoporosis.

The effects of modified atmosphere packaging (MAP) in combination with superchilling (−1.3 °C) on the physicochemical properties, flavor retention, and organoleptic evaluation of turbot samples were investigated during 27 days storage. Results showed that high-CO2 packaging (70% or 60% CO2) combined with superchilling could reduce the productions of off-flavor compounds, including total volatile basic nitrogen (TVB-N) and ATP-related compounds. Twenty-four volatile organic compounds were determined by gas chromatography–mass spectrometry (GC/MS) during storage, including eight alcohols, 11 aldehydes, and five ketones. The relative content of off-odor volatiles, such as 1-octen-3-ol, 1-penten-3-ol, (E)-2-octenal, octanal, and 2,3-octanedione, was also reduced by high-CO2 packaging during superchilling storage. Further, 60% CO2/10% O2/30% N2 with superchilling (−1.3 °C) could retard the water migration on the basis of the water holding capacity, low field NMR, and MRI results, and maintain the quality of turbot according to organoleptic evaluation results during storage

The purpose of this research was to explore the fresh keeping effect of modified atmosphere packaging (MAP) with different gas ratios combined with gelatin active coatings containing eugenol on Chinese sea bass stored at −0.9 °C for 36 days. The results showed that MAP3 (60% CO2/10% O2/30% N2), together with gelatin active coatings containing eugenol, could prevent water loss, which maintained high field NMR, MRI, and organoleptic evaluation results. This hurdle technology could also effectively delay the bacterial reproduction, protein degradation, and alkaline accumulation, so it showed the lowest K value, total volatile basic nitrogen, free amino acids, total viable count, Pseudomonas spp., and H2S-producing bacteria, which better maintain the quality of sea bass.

Carvacrol is a natural compound known to be a highly effective antibacterial; however, it is a hydrophobic molecule, which is a limitation to its use within food packaging. Flaxseed gum (FG) films containing different contents of carvacrol (C) were produced by a film-casting method with sonication. The effects of sonication power and time on the properties of the FG-C films were investigated by measuring the film thickness, mechanical properties, contact angle, opacity, water vapor permeability (WVP), water sorption isotherm, Fourier transform infrared spectroscopy(FTIR), differential scanning calorimetry (DSC), antibacterial and antioxidant activities, and microstructure. The results showed that sonication power and time had significant effects on mechanical and barrier properties, film opacity, and degradability (p < 0.05). The tensile strength (TS) and elongation at break (EB) values exhibited an obvious improvement after sonication, and FG-0.5C-6030 had the lowest TS (33.40 MPa) and EB (4.46%) values. FG-C films formed a denser structure and the contact angle was improved as a result of sonication, which improved the integration of carvacrol into the FG matrix. In terms of microstructure, sonication resulted in a homogeneous and continuous crosssection of FG-C films, and regular surface and cross-sectional images were obtained through the highest acoustic intensity and longest time treatment. The FG films incorporated with carvacrol displayed antibacterial properties against Staphylococcus aureus, Vibrio parahaemolyticus, Shewanella putrefaciens, and Pseudomonas fluorescens, as well as increased antioxidant properties, and sonication was proven to enhance both of them.

The objective of this research was to explore the antimicrobial activity and mechanism of carvacrol against Vibrio Parahemolyticus, Shewanella putrefaciens, Staphylococcus aureus and Pseudomonas fluorescens and evaluate the effect of the addition of carvacrol/β-cyclodextrin emulsions to flaxseed gum (FSG)-sodium alginate (SA) edible films on the preservation of Chinese sea bass (Lateolabrax maculatus) fillets during refrigerated storage. The minimum inhibitory concentration (MIC) of carvacrol against V. parahemolyticus, S. putrefaciens, S. aureus and P. fluorescens were 0.5, 0.5, 0.125, and 0.5 mg/mL, respectively. Alkaline phosphatase activity assay, nucleotide and protein leakage, and scanning electron microscope demonstrated that carvacrol damaged the external structure of the tested bacterial cells causing leakage of cytoplasmic components. At the same time, when FSG-SA films containing carvacrol used as coating agents for Chinese sea bass fillets cold storage, FSG-SA films containing 1.0 or 2.0 mg/mL carvacrol could significantly reduce TVB-N content, K-value, the degree of microbial deterioration and maintain quality of sea bass fillets according to organoleptic evaluation results.

Objective To propose a nomogram for individual risk assessment of in-stent restenosis (ISR) after vertebral artery origin stenosis (VAOS) stenting. Methods We included 793 patients with VAOS treated with stenting from October 2006 to May 2013, with a median follow-up of 27.8 months. Cox regression and the least absolute shrinkage and selection operator (LASSO) regression were adopted for variable selection. The nomogram was formulated and validated by concordance indexes (C-indexes) and calibration curves. An in-stent restenosis risk table (ISR-RT) was subsequently generated for risk stratification. Differences between low-, intermediate-, and high-risk levels were shown by Kaplan-Meier curves and compared by log-rank test. Results The training and validation set included 594 and 199 patients, with a mean ISR rate of 37.2% and 35.2%, respectively. Stent type (HR=1.64, 95% CI 1.26 to 2.14), stent diameter (HR=2.48, 95% CI 1.77 to 3.48), history of peripheral vascular disease (HR=2.17, 95% CI 1.17 to 4.00), history of transit ischemic attack (HR=1.45, 95% CI 1.05 to 2.14), and left-side involvement (HR=1.33, 95% CI 1.04 to 1.69) were included in the nomogram. The C-indexes at 6 and 12 months were 0.650 and 0.611 in the training set, and 0.713 and 0.603 in the validation set, respectively. Compared with low-risk patients, the intermediateand high-level group had 1.46 (95% CI 1.05 to 2.04; p=0.0235) and 2.28 (95% CI 1.64 to 3.17; p<0.0001) higher chances of developing ISR in 2 years, respectively. Conclusions A nomogram and a risk evaluation table were developed with good predictive ability for in-stent restenosis among patients with VAOS, which could serve as a practical approach for individualized risk evaluation. [ABSTRACT FROM AUTHOR]