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Background: The changes in the microenvironment of degenerative intervertebral discs cause oxidative stress injury and excessive apoptosis of intervertebral disc endogenous stem cells. The purpose of this study was to explore the possible mechanism of the protective effect of melatonin on oxidative stress injury in NPMSCs induced by H2O2. Methods: The Cell Counting Kit-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of melatonin. ROS content was detected by 2′7′-dichlorofluorescin diacetate (DCFH-DA). Mitochondrial membrane potential (MMP) was detected by the JC-1assay. Transferase mediated d-UTP Nick end labeling (TUNEL) and Annexin V/PI double staining were used to determine the apoptosis rate. Additionally, apoptosis-associated proteins and PI3K/Akt signaling pathway-related proteins were evaluated by immunofluorescence, immunoblotting and PCR. ECMs were evaluated by RT‒PCR and immunofluorescence. In vivo, X-ray, Magnetic resonance imaging (MRI) and Histological analyses were used to evaluate the protective effect of melatonin. Results: Melatonin had an obvious protective effect on NPMSCs treated with 0–10 μM melatonin for 24 h. In addition, melatonin also had obvious protective effects on mitochondrial dysfunction, decreased membrane potential and cell senescence induced by H2O2. More importantly, melatonin could significantly reduce the apoptosis of nucleus pulposus mesenchymal stem cells induced by H2O2 by regulating the expression of apoptosis-related proteins and decreasing the rate of apoptosis. After treatment with melatonin, the PI3K/Akt pathway was significantly activated in nucleus pulposus mesenchymal stem cells, while the protective effect was significantly weakened after PI3K-IN-1 treatment. In vivo, the results of X-ray, MRI and histological analyses showed that therapy with melatonin could partially reduce the degree of intervertebral disc degeneration. Conclusion: Our research demonstrated that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of nucleus pulposus mesenchymal stem cells induced by oxidative stress via the PI3K/Akt pathway, which provides a novel idea for the therapy of intervertebral disc degeneration. The translational potential of this article: This study indicates that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of NPMSCs through activating the PI3K/Akt pathway. Melatonin might serve as a promising candidate for the prevention and treatment of Intervertebral disc degeneration disease (IVDD) in the future.

Background Different treatment methods have been developed for acute Achilles tendon rupture (ATR), including conservative treatment, minimally invasive or transdermal surgery, and open surgery, and there is no consensus about which method is superior. It is important to clarify the presence of Achilles tendon (AT) degeneration, the rupture site, and the rupture shape before surgery to determine whether minimally invasive or open surgery should be selected, thereby reducing the re‐rupture rate following acute ATR. The aim of this study was to investigate the diagnostic value of MRI in identifying the presence of AT degeneration, the rupture site, and the rupture shape for acute closed ATR. Methods From January 2016 to December 2019, patients with acute closed ATR who had undergone repair surgery were retrospectively enrolled. All patients received MRI examination, and the distance between the insertion site and broken end and the rupture shape (types I, II, and III) were independently determined by two observers. Then, the stump of the AT was exposed during the operation. The rupture site and rupture shape were recorded and compared and analyzed with the MRI results. Consistency analyses (using Cohen's kappa coefficient or intraclass correlation coefficient‐ICC) and calculation of diagnostic performance indexes were, respectively, conducted to evaluate the diagnostic value of the MRI. Results This study included 47 consecutive patients with acute ATR, with an average age of 38.4 years. Among them, 40 were male, and seven were female. The intraoperative exploration demonstrated a total of 34 (72.3%), 10 (21.3%), and three (6.4%) patients with type I, II, and III ruptures, respectively. The average distance between the insertion site and the proximal broken end measured intraoperatively was 4.07 ± 1.57 cm. High or excellent consistencies were found for ATR classifications (kappa: 0.739–0.770, p

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.

Peritoneal metastasis is one of the most common forms of death for gastrointestinal cancers, however, its cell composition is incompletely understood. Here, the authors use single cell RNA-seq of peritoneal metastases from 35 patients and show diversity in immune cells, and plasticity in cancer cell phenotypes and autophagy related genes as biomarkers of prognosis.

Image inpainting is a technique that uses information from known areas of an image to repair missing or damaged areas of the image.Image editing software based on it has made it easy to edit and modify the content of digital images without any specialized foundation.When image inpainting techniques are used to maliciously remove the content of an image, it will cause confidence crisis on the real image.Current researches in image inpainting forensics can only effectively detect a certain type of image inpainting.To address this problem, a passive forensic method for image inpainting was proposed, which is based on a two-branch network.The high-pass filtered convolutional network in the dual branch first used a set of high-pass filters to attenuate the low-frequency components in the image.Then features were extracted using four residual blocks, and two transposed convolutions were performed with 4x up-sampling to zoom in on the feature map.And thereafter a 5×5 convolution was used to attenuate the tessellation artifacts from the transposed convolutions to generate a discriminative feature map on the high-frequency components of the image.The dual-attention feature fusion branch in the dual branch first added a local binary pattern feature map to the image using a preprocessing block.Then the dual-attention convolution block was used to adaptively integrate the image’s local features and global dependencies to capture the differences in content and texture between the inpainted and pristine regions of the image.Additionally, the features extracted from the dual-attention convolution block were fused, and the feature maps were up-sampled identically to generate the discriminative image content and texture on the feature maps.The extensive experimental results show the proposed method improved the F1 score by 2.05% and the Intersection over Union(IoU) by 3.53% for the exemplar-based method and by 1.06% and 1.22% for the deep-learning-based method in detecting the inpainted region of the removed object.Visualization of the results shows that the edges of the removed objects can be accurately located on the detected inpainted area.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35–0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08–1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725–0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03–1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09–1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Objective To reflect the potential epidemiological characteristics of Achilles tendon (AT) rupture in Shanghai, China, which has been rarely reported before. Methods This work is a descriptive epidemiology study. A total of 302 cases of AT rupture admitted to our department between 01/2013 and 02/2020 are analyzed according to telephone follow‐up and medical records. Male to female ratio is 10.3 and the average age is 37.5 years. The record of each case includes age, gender, Body mass index (BMI), quinolone use, corticoid exposure and related medical history/comorbidities. If the case is sports‐related (SR), details including kind of sports, intensity of exercise, exercise time before rupture, specific action that causes rupture and situation of warm‐up are collected. Two independent sample t‐tests and Pearson chi‐square tests are used for statistical analysis. Results A total of 252 ruptures are SR. Male to female ratio is 15.6 in SR cases. Most SR ruptures occur in patients aged 25–39 years. Ball games are major sports responsible for rupture: basketball in 95 (37.7%), badminton in 68 (27.0%) and soccer in 62 (24.6%). Acceleration and running start is the specific action that cause most (37.7%) ruptures. AT cases are observed in 91 patients with warm‐up and 161 without preparation before exercise. As a result, more ruptures happened within 10 min' sports in 161 unprepared (22.4%) than in 91 prepared (5.5%) cases. In SR cases, 107 and 145 cases are observed on weekends and weekdays. Of the 302 total cases, 64 are associated with Achilles tendinopathy. Frequently reported factors such as quinolone use and corticoid exposure are found only in two and 11 of all cases, respectively. Conclusion Middle‐aged males are common victims of AT rupture in Shanghai. Sports including basketball, badminton, soccer and actions involving in sudden and severe contraction of AT cause most ruptures. Warm‐up before exercise reduces rupture in short time. Factors such as quinolone, corticoid and Achilles tendonitis still need attention.

Abstract We propose three scenarios for compact hybrid stars composed of nuclear and dark matter. These hybrid stars could provide alternative interpretations to the LIGO/Virgo events GW170817 and GW190425. To demonstrate our proposal, we solve the Tolman–Oppenheimer–Volkoff configurations of hybrid stars by using the SLy4, APR4, and SKb equations of state (EoS) for nuclear matter, and an EoS for a bosonic self interacting dark matter (SIDM) proposed by Colpi et al. (Phys Rev Lett 57:2485, 1986). We then obtain their mass–radius and tidal Love number (TLN)-mass relations, and further examine the possible saddle instability of these compact objects by the generalized Bardeen–Thorne–Meltzer (BTM) criteria. Our results show that the hybrid star scenarios are able to explain GW170817 and GW190425. Some hybrid stars can have compact neutron or mixed cores around 10 km while possessing thick dark matter shells, thus they can be more massive than the maximum mass of the typical neutron stars but are electromagnetically detected with about the same size of neutron stars. Reversely, we also infer the dark matter model from the parameter estimation of GW190425. Our proposed hybrid stars can be further tested by the coming LIGO/Virgo O3 events.

Abstract Background This study was aimed to develop a novel dynamic measurement technique for testing the material properties and investigating the effect of continuous compression load on the structural and mechanical properties of human heel pad during actual gait. Methods The dual fluoroscopic imaging system (DFIS) and dynamic foot-ground contact pressure-test plate were used for measuring the material properties, including primary thickness, peak strain, peak stress, elastic modulus, viscous modulus and energy dissipation rate (EDR), both at time zero and following continuous loading. Ten healthy pilot subjects, aged from 23 to 72 (average: 46.5 ± 17.6), were enrolled. A “three-step gait cycle” is performed for all subjects, with the second step striking at a marked position on the force plate with the heel to maintain the location of the tested foot to be in the view of fluoroscopes. The subjects were measured at both relaxed (time-zero group) and fatigue (continuous-loading group) statuses, and the left and right heels were measured using the identical procedures. Results The peak strain, peak stress, elastic modulus, and EDR are similar before and after continuous load, while the viscous modulus was significantly decreased (median: 43.9 vs. 20.37 kPa•s; p

Abstract Background Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). Methods The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan–Meier curves. Results The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177–0.325, p

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p = 0.044) and heart (p = 0.001) components at theM1 and M5 regions (p = 0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p = 0.049) and myogenic (p = 0.032) components at the M1 region, as well as in the endothelial (p < 0.001) component at the M5 region and in the myogenic component at the dorsal foot (p = 0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at theM5 region (p = 0.050) and heel area (p = 0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p = 0.017) and heel area (p = 0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients. [ABSTRACT FROM AUTHOR]

BackgroundGlioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis.MethodsA necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features.ResultsThree necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis.ConclusionsOur necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.

ObjectiveThis study was aimed to compare the material properties of heel pad between diabetes patients and healthy adults, and investigate the impact of compressive loading history and length of diabetes course on the material properties of heel pad.MethodsThe dual fluoroscopic imaging system (DFIS) and dynamic foot-ground contact pressure-test plate were used for measuring the material properties, including primary thickness, peak strain, peak stress, stiffness, viscous modulus and energy dissipation ratio (EDR), both at time zero and following continuous loading. Material properties between healthy adults and DM patients were compared both at time zero and following continuous weight bearing. After then, comparison between time-zero material properties and properties following continuous loading was performed to identify the loading history-dependent biomechanical behaviour of heel pad. Subgroup-based sensitivity analysis was then conducted to investigate the diabetes course (

Background: For patients who treated with tacrolimus after kidney transplant, therapeutic drug monitoring is essential to improve their prognosis. However, previous detection methods have limitations, such as the overestimation and unacceptable bias in the immunoassays. Precision medicine has been challenged. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is recognized as the gold standard due to its accuracy and specificity, but lack of throughput and complex process limits its clinical application. Therefore, an accurate, simple and high throughput method for tacrolimus monitoring is needed for clinical practice. Methods: A modified LC-MS/MS method was introduced and validated. Whole blood samples were prepared by a one-step protein precipitation method. Chromatographic separation was achieved using a Phenomenex Kinetex 2.6 μm XB-C18 2.1 × 50 mm column with a total run time of 3.5 min to avoid matrix effect. An electrospray ionization source (ESI) was used in positive ion multiple reaction monitoring (MRM) mode for mass spectrometric detection. In order to protect the mass spectrometer, only part of the sample after LC separation was allowed to enter the mass spectrum, through a two HPLC systems coupled one mass spectrometry design. In this way, the instrument throughput is also improved and realizing the detection of 2 samples within 3.5 min and carried out a shorter analyzing time for each sample of 1.75 min. Additionally, we calculated tacrolimus-intrapatient variant (Tac-IPV) based on this modified method and assessed the prognostic value of Tac-IPV in Chinese kidney transplant patients. Results: The LC-MS/MS was modified by streamlining the procedure and increasing the throughput. The method proved to be accurate and reproducible with all performance parameters suitably meeting the clinical requirements over a calibration ranged from 0.37 to 42.90 ng/mL. Parameters such as linearity, limit of quantification (LoQ) and dilution integrity were validated with a clinical reportable range from 0.37 to 343.20 ng/mL, which was particularly useful for high drug concentrations patients (rare but very serious). Both cross-contamination and matrix effects were negligible. Clinical data of 83 patients showed that Tac-IPV was associated with poor kidney transplant outcome in Chinese (Hazard Ratio (HR) = 3.96, 4.75; 95% Cl: 1.10–14.21, 1.23–18.36; P < 0.05). Conclusions: This modified LC-MS/MS method possessed high throughput and simple sample preparation, allowing it to meet daily clinical needs. At the same time, Tac-IPV based on this modified LC-MS/MS had excellent prognostic value in kidney transplantation. These advantages have great significance for the individualized treatment of Chinese kidney transplant patients and broad application of Tac-IPV.

Gliomas are the most aggressive and common type of malignant brain tumor, with limited treatment options and a dismal prognosis. Angiogenesis, a hallmarks of cancer, is one of two critical events in the progression of gliomas. Accumulating evidence has demonstrated that in glioma dysregulated molecules like long noncoding RNAs (lncRNAs), are closely linked to tumorigenesis and prognosis. However, the effects of and mechanisms of action of lncRNAs during tumor angiogenesis are poorly understood. The effect of lncRNA RP11-732M18.3 on angiogenesis was elucidated through an intracranial orthotopic glioma model, immunohistochemistry, and an in vitro angiogenesis assay. Co-culture experiments and cell migration assays were performed to investigate the function of lncRNA RP11-732M18.3 in vitro. lncRNA RP11-732M18.3 increased CD31+ microvessel density, and overexpression of lncRNA RP11-732M18.3 resulted in poor mouse survival. lncRNA RP11-732M18.3 promoted endothelial cell migration and tube formation. Nomogram and Kaplan-Meier survival analyses indicated that higher VEGFA is correlated with a poor prognosis. Mechanistically, lncRNA RP11-732M18.3 promotes angiogenesis by increasing the nuclear level of EP300 and facilitating the transcription and secretion of VEGFA. Our study contributes to the latest understanding of glioma angiogenesis and prognosis. lncRNA RP11-732M18.3 may be a potential treatment target in glioma.

BackgroundWhether women have a higher risk of adverse events compared with men following coronary angiography (CAG) and percutaneous coronary intervention (PCI) remains controversial. We aimed to investigate the sex differences in characteristics, treatments and outcomes among patients undergoing CAG and PCI in a large Chinese cohort.MethodsWe analyzed patients undergoing CAG and/or PCI in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Clinical characteristics, treatment (discharge medication and PCI) and in-hospital outcomes (mortality and major bleeding) were compared between women and men.ResultsTotally 141,459 patients underwent CAG (44,362 [31.4%] women), of which 69,345 patients underwent PCI (15,376 [22.2%] women). Women were older (64.4 vs. 60.8 years), had more chronic comorbidities and lower PCI rate for stable coronary artery disease (CAD) than men (52.8 vs. 64.2%). Women received less CAG and PCI procedures. Among women undergoing PCI they received similar discharge medication treatment. In addition, women undergoing PCI had mildly lower rate of major bleeding (0.2 vs. 0.3%, P = 0.033) but higher in-hospital mortality (1.2 vs. 0.8%, P < 0.001). After adjustment, women had a higher risk in the major bleeding (adjusted odds ratio, 2.04 [95% CI: 1.07 to 3.62]), and the in-hospital mortality (adjusted odds ratio, 1.87 [95% CI: 1.36 to 2.56]).ConclusionAmong our Chinese cohort, women are older with more chronic comorbidities, receiving less PCI procedure and similar discharge medication treatment. Women have nearly 90% higher risk of in-hospital mortality and over 1-fold increased risk of major bleeding after PCI compared with men.

The gold standard for identifying pathogens causing osteomyelitis (OM) is intraoperative tissue sampling culture (TSC). However, its positive rate remains inadequate. Here, we evaluated the efficiency of a novel strategy, known as devitalized bone surface culture (BSC), for detecting OM-related microorganisms and compared it to TSC. Between December 2021 and July 2022, patients diagnosed with OM and received both methods for bacterial identification were screened for analysis. In total, 51 cases were finally recruited for analysis. The mean age was 43.6 years, with the tibia as the top infection site. The positive rate of BSC was relatively higher than that of TSC (74.5% vs. 58.8%, p = 0.093), though no statistical difference was achieved. Both BSC and TSC detected definite pathogens in 29 patients, and their results were in accordance with each other. The most frequent microorganism identified by the BSC method was Staphylococcus aureus. Moreover, BSC took a significantly shorter median culture time than TSC (1.0 days vs. 3.0 days, p < 0.001). In summary, BSC may be superior to TSC for identifying OM-associated pathogens, with a higher detectable rate and a shorter culture time.

Investigating Na‐ion battery (SIB) materials is complicated by the absence of a well‐performing (reference) electrode material since sodium metal cannot be considered as a quasi‐reference electrode. Taking advantage of the activity of both Ni and Mn, herein, the P2‐type and Mn‐rich Na0.6Ni0.22Al0.11Mn0.66O2 (NAM) material, known to be an excellent positive electrode, is investigated as a negative electrode. To prove NAM stability as both positive and negative electrode, symmetric cells have been assembled without pre‐sodiation, which showed a reversible capacity of 73 mA h g−1 and a remarkable capacity retention of 82.6 % after 500 cycles. The outstanding cycling performance is ascribed to the high stability of the active material at both the highest and lowest Na‐ion storage plateaus and the rather limited electrolyte decomposition and solid‐electrolyte‐interphase (SEI) formation occurring. The long‐term stability of NAM at both electrodes enables its use as a "reference" electrode for the investigation of other positive and negative electrode materials for SIBs, resembling the role played by lithium titanate (LTO) and lithium iron phosphate (LFP) in LIBs. [ABSTRACT FROM AUTHOR]

Meige syndrome is a rare neurological disease characterized by segmental dystonia, specifically blepharospasm and oromandibular dystonia. These symptoms are often accompanied by complex movements of the eyelids, lower facial muscles, mandible, and neck muscles. Bilateral blepharospasm is the most common feature of this disease. In this case report, we present the successful treatment of refractory blepharospasm in a 72-year-old woman with Meige syndrome via 2 incisions resulting from myectomy and in situ surgery. [ABSTRACT FROM AUTHOR]

A bilinear map whose domain and target sets are identical is called a self-bilinear map. Original self-bilinear maps are defined over cyclic groups. Since the map itself reveals information about the underlying cyclic group, the Decisional Diffie–Hellman Problem (DDH) and the computational Diffie–Hellman (CDH) problem may be solved easily in some specific groups. This brings a lot of limitations to constructing secure self-bilinear schemes. As a compromise, a self-bilinear map with auxiliary information was proposed in CRYPTO'2014. In this paper, we construct this weak variant of a self-bilinear map from generic sets and indistinguishable obfuscation. These sets should own several properties. A new notion, One Way Encoding System (OWES), is proposed to summarize these properties. The new Encoding Division Problem (EDP) is defined to complete the security proof. The OWES can be built by making use of one level of graded encoding systems (GES). To construct a concrete self-bilinear map scheme, Garg, Gentry, and Halvei(GGH13) GES is adopted in our work. Even though the security of GGH13 was recently broken by Hu et al., their algorithm does not threaten our applications. At the end of this paper, some further considerations for the EDP for concrete construction are given to improve the confidence that EDP is indeed hard. [ABSTRACT FROM AUTHOR]

Western dietary patterns (WDP) and typical food groups may play a major role in the risk of behavioral health disorders. Nevertheless, the relationships between WDP, common food categories, and mental health disorders lack consistency and remain incompletely understood in relation to potential mechanisms. Therefore, the objective of the present study was conducted to synthesize available evidence linking WDP and typical food groups to these outcomes. Web of Science, PubMed, EMBASE, and MEDLINE were searched up to August 2023. Random effect meta-analyses were performed to obtain pooled odds ratio and the relative risk for the prevalence of outcomes and the incidence of outcomes, respectively. A total of 54 articles were included. WDP was associated with increased risk of both depression (1.19; 95% CI: 1.06–1.32) and depressive symptoms (1.20; 95% CI: 1.08–1.34). Except for high-fat dairy products, food groups are associated with an increased risk of anxiety, depression, and depressive symptoms. This review presents evidence to further understand the relationship between WDP, typical food groups, and the incidence of behavioral health disorders, and more randomized controlled trials and cohort studies are urgently required to confirm these findings and elucidate potential mechanisms. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: Oral submucous fibrosis (OSF) is a common chronic condition with poor prognosis, and existing therapies for OSF are limited in effectiveness. This study was designed to explore the role of miR-497 in arecoline (AR)-induced OSF.Materials and Methods: After miR-497 was silenced or overexpressed in buccal mucosa fibroblasts (BMFs), different concentrations of AR (5-200 μg/ml) were applied to incubate BMFs, and 50 μg/ml of AR was chosen for subsequent experiments. Thereafter, collagen gel contraction assay was used to detect the contractile capacity of BMFs. Transwell assay and wound healing assay were applied to detect migration and invasiveness of the cells. In addition, immunofluorescence staining, qRT-PCR and western blot were conducted to measure the expression of miR-497, collagen I and α-SMA, as well as the phosphorylation of Smad2 and Smad3.Results: After successful inhibition or overexpression of miR-497 in AR-induced BMFs, the results showed that miR- 497 inhibition suppressed the contractility, migration and invasiveness of AR-induced BMFs, whereas overexpression of miR-497 produced the opposite. In addition, miR-497 inhibition down-regulated the expression level of collagen I and α-SMA in AR-exposed BMFs. Furthermore, TGF-β1 expression, Smad2 and Smad3 phosphorylation were also repressed in AR-induced BMFs after miR-497 inhibition. Correspondingly, overexpression of miR-497 reversed the expression of the aforementioned proteins.Conclusion: miR-497 inhibition may attenuate OSF by inhibiting myofibroblast transdifferentiation in BMFs via the TGF-β1/Smads signaling pathway, indicating that miR-497 might represent an underlying target for treating OSF. [ABSTRACT FROM AUTHOR]

The development of an exceptionally sensitive diagnostic technique for early identification of aquaculture diseases, specifically Aeromonas hydrophila, is essential for efficient management of disease outbreaks at aquaculture locations. In this research, a swift and sensitive diagnostic assay employing Loop-mediated isothermal amplification (LAMP) of Aeromonas hydrophila was devised and compared to the conventional qPCR method documented by Rong Wang. Validation of the diagnostic assay was carried out using actual samples obtained from aquaculture fish. The findings revealed that based on the rapid detection of crude bacterial genomic DNA, the fluorescent LAMP assay possessed a lower limit of detection (LOD) of 0.559 ng/μL (0.315–1.693, 95% CI), while the LOD for qPCR stood at 4.301 ng/μL (2.084–8.876, 95% CI). Both techniques demonstrated outstanding specificity, exhibiting no cross-reactivity with bacteria from the same or closely related genera. A total of 74 fish samples suspected to be infected with the fish disease were gathered, with 26 and 23 samples testing positive for Aeromonas hydrophila via LAMP and qPCR, respectively. The concordance analysis for LAMP and qPCR methods generated a Kappa value of 0.909 (0.778–1.000, 95% CI), signifying a high degree of diagnostic consensus. This study highlights that the LAMP assay eliminates the thermal cycle temperature change process of qPCR, uses lysate to crudely extract bacterial genomic DNA, and can complete the detection within 40 min, rendering it a practical and efficient alternative for monitoring disease outbreaks at aquaculture sites. [ABSTRACT FROM AUTHOR]

The industrial transfer of heavy industries such as non-metallic mineral manufacturing, metal smelting and manufacturing from the eastern coast of China to the central region is beneficial to the economic development of the central region on the one hand, but increases carbon emissions in the central region on the other hand. In February 2022, the National Development and Reform Commission approved the "14th Five-Year Plan for the Development of the Urban Agglomeration in the Middle Reaches of the Yangtze River". This indicates that the urban agglomeration of the middle reaches of the Yangtze River is an important region for implementing green development in the central area. The spatial and temporal evolution of carbon emissions and influencing factors in this region are the foundation for achieving carbon peaking and the carbon neutrality goal. This paper calculates the total carbon emissions of the cities in the urban agglomeration of the middle reaches of the Yangtze River and uses models such as spatial autocorrelation, geographically weighted regression, and Geodetector to explore the spatial–temporal pattern of carbon emissions. The results show the following: (1) The total carbon emissions of the middle reaches of the Yangtze River urban agglomeration showed fluctuations during 2010–2020, and the carbon emission reduction effect is unstable. Additionally, the carbon emissions of the middle reaches of the Yangtze River city cluster show obvious spatial variability, but the high carbon emission area is always concentrated in Wuhan, and this remains unchanged. (2) In 2010, 2014 and 2017, population size was the most important factor affecting carbon emission divergence, and in terms of interaction, the interaction between energy intensity and GDP and urbanization is the reason for the increasing carbon emissions. (3) The influence of population size on carbon emissions decreases from north to south, the influence of energy intensity on carbon emissions shows a spread from the most influential region in the northwest to the centre and then to the northeast, and the GDP per capita has little influence on the difference of carbon emissions spatial distribution. [ABSTRACT FROM AUTHOR]

Aquatic environments are important reservoirs for drug resistance. Aquatic foods may act as carriers to lead antibiotic-resistant commensal bacteria into the human gastrointestinal system, then contacting gut microbiota and spreading antibiotic resistance. Here, several shrimp farms were investigated to identify colistin resistance among commensal bacteria of aquaculture. A total of 884 (41.6%) colistin-resistant isolates were identified among 2126 strains. Electroporation demonstrated that colistin-resistant fragments were present in some commensal bacteria that could be transferred to other bacteria. Most of the resistant bacteria were Bacillus spp., with 69.3% of the Bacillus species exhibiting multiple drug resistance. Bacillus licheniformis was prevalent, with 58 strains identified that comprised six sequence types (ST) based on multilocus sequence typing. Whole-genome sequencing and comparisons with previous B. licheniformis genomes revealed a high degree of genomic similarity among isolates from different regions. Thus, this species is widely distributed, and this study provides new insights into global antibiotic-resistant characteristics of B. licheniformis. Sequence analyses further revealed some of these strains are even pathogenic and virulent, suggesting the antibiotic resistance and hazards of commensal bacteria in aquaculture should be considered. Considering the "One Health" perspective, improved monitoring of aquatic food is needed to prevent the spread of drug-resistant commensal bacteria from food-associated bacteria to humans. [ABSTRACT FROM AUTHOR]

In order to realize the high efficiency and precision clamping of large workpieces with several processes and multiple species processing, the distribution number and position of the zero point clamping unit in the flexible quick-change process system for big thin-walled cylindrical structural parts are presented. The error model of the flexible quick-change process system is established by the Monte Carlo method, which is used to optimize the system structure design. The error variation of the flexible quick-change process system under the action of transposition and extreme working conditions such as cutting force is revealed, and further analysis on the sensitivity of the workpiece's global displacement error and global attitude error to each error source is carried out. After the optimization, a high-quality, cost-effective, flexible quick-change clamping system is created. The three-coordinate measurement experiment is used to test the functionality and accuracy of the flexible quick-change process system. A significantly improved level of the system's repetitive positioning accuracy (less than 0.01 mm) is detected. Importantly, the flexible quick-change system obtained by the combinatorial optimal design method has been successfully applied to the production of aerospace components with improved quality and efficiency. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a malignant tumor with an extremely poor prognosis, especially in progressive patients. Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment option for OS. Due to tumor heterogeneity, only a minority of patients benefit from immunotherapy. Therefore, it is urgent to explore a model that can accurately assess the response of OS to immunotherapy. In this study, we obtained the single-cell RNA sequencing datasets of OS patients from public databases and defined 34 cell clusters by dimensional reduction and clustering analysis. PTPRC was applied to identify immune cell clusters and nonimmune cell clusters. Next, we performed clustering analysis on the immune cell clusters and obtained 25 immune cell subclusters. Immune cells were labeled with CD8A and CD8B to obtain CD8+ T cell clusters. Meanwhile, we extracted the differentially expressed genes (DEGs) of CD8+ T cell clusters and other immune cell clusters. Furthermore, we constructed a prognostic model (CD8-DEG model) based on the obtained DEGs of CD8+ T cells, and verified the excellent predictive ability of this model for the prognosis of OS. Moreover, we further investigated the value of the CD8-DEG model. The results indicated that the risk score of the CD8-DEG model was an independent risk factor for OS patients. Finally, we revealed that the risk score of the CD8-DEG model correlates with the immune profile of OS and can be used to evaluate the response of OS to immunotherapy. In conclusion, our study revealed the critical role of CD8 cells in OS. The risk score model based on CD8-DEGs can provide guidance for prognosis and immunotherapy of OS. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV‐producing cells has never been demonstrated. Here, as a proof‐of‐concept, we demonstrate that EV‐G12D‐mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL‐17A/FGF21 axis. Mechanistically, in contrast to cytosol derived G12D‐mutant KRAS complex from EVs‐producing cells, EV‐G12D‐mutant KRAS interacts with a group of extracellular vesicular factors via fibronectin‐1 (Fn1), which drives the activation of the IL‐17A/FGF21 inflammation pathway in EV recipient cells. We show that: (i), depletion of EV‐Fn1 leads to a reduction of a number of inflammatory cytokines including IL‐17A; (ii) induction of IL‐17A promotes lung inflammation, which in turn leads to IL‐17A mediated induction of FGF21 in the lung; and (iii) EV‐G12D‐mutant KRAS complex mediated lung inflammation is abrogated in IL‐17 receptor KO mice. These findings establish a new concept in EV function with potential implications for novel therapeutic interventions in EV‐mediated disease processes. [ABSTRACT FROM AUTHOR]