Certain studies have reported various insulin resistance responses to ambient heavy metal pollution, but few have reported such responses to occupational heavy metal pollution. Even fewer have demonstrated a relationship between mixture effects of heavy metals and insulin resistance in welding workers. Overall, we recruited 53 welders and 48 administrative staff from a shipyard located in northern Taiwan. Personal exposure to heavy metals was monitored for PM2.5 and urine. Blood samples from each participant were collected from the antecubital vein after fasting. Urine samples from each participant were collected in the same period as blood samples. The geometric mean levels for chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), and cadmium (Cd) in the PM2.5 of the personal breathing zone and urinary Mn of welders were significantly higher than those in administrative staffs. Ambient Cr, Co, Ni, and Cu levels in the PM2.5 and urinary Cd were positively related to HOMA2-IR after adjusting for personal covariates (PM2.5-Cr: β=0.036, 95%C.I.: 0.002 to 0.070; PM2.5-Co: β=0.040, 95%C.I.: 0.002 to 0.077; PM2.5-Ni: β=0.054, 95%C.I.: 0.013 to 0.094; PM2.5-Cu: β=0.049, 95%C.I.: 0.010 to 0.088; U-Cd: β=0.209, 95%C.I.: 0.052 to 0.366, respectively). Our findings indicated the PM2.5 metal components and urinary metals were associated with increased insulin resistance in shipyard welders.

With the unceasing advancement in wide-bandgap (WBG) semiconductor technology, the minimal reverse-recovery charge Qrr and other more powerful natures of WBG transistors enable totem-pole bridgeless PFC to become a dominant solution for energy storage systems (ESS). This paper focuses on design and implementation of a control structure for a totem-pole boost PFC with newfangled enhancement-mode Gallium Nitride (eGaN) FETs, not only to simplify the control implementation, but also to achieve high power quality and efficiency. The converter is designed to convert a 90-264-VAC input to a 385-VDC output for a 2.6-kW output power. Lastly, to validate the methodology, an experimental prototype is characterized and fabricated. The uttermost efficiency at 230 VAC attains 99.14%. The lowest total harmonic distortion in the current (ITHD) at high line condition (230 V) reaches 1.52% while the power factor gains 0.9985.

Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn prevent lifestyle diseases such as obesity. Epidemiological evidences suggest that an overdose of artificial sweeteners could result to adverse effects after consumption. Thus, our study aims to systematically explore the potential adverse effects of eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharin and sucralose on cardiac performances of zebrafish (Danio rerio) and Daphnia as model animals. Embryonic zebrafish and Daphnia were exposed to eight artificial sweeteners at 100 ppb concentrations and their cardiac performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output and heartbeat regularity) were measured and compared. Saccharin significantly increased the heart rate of zebrafish larvae while a significant decrease was observed in Daphnia. Significant increase was also noted in zebrafish heart rate variability after incubation in acesulfame K, dulcin, sodium cyclamate, and sucralose. However, a significant increase in Daphnia was only observed after incubation in dulcin. Based on Principal Component Analysis (PCA) and hierarchical clustering results, several artificial sweetener samples were species-specific to zebrafish and Daphnia. Our study demonstrates the potential adverse physiological effects of artificial sweeteners in cardiovascular systems of zebrafish larvae and Daphnia.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

We assessed the growth performance, physiological traits, and gene expressions in steers fed with dietary rumen-protected L-tryptophan (RPT) under cold environment. Eight Korean native steers were assigned to two dietary groups, no RPT (Control) and RPT (0.1% RPT supplementation on a dry matter basis), 6 wks. Maximum and minimum temperatures throughout the experiment were 6.7°C and -7.0°C, respectively. Supplementation of 0.1% RPT to a total mixed ration did not increase body weight but had positive effects of elevating average daily gain (ADG) and reducing the feed conversion ratio (FCR) at day 27 and 48. Metabolic parameter showed higher glucose level (at day 27) in the 0.1% RPT group compared to the control group. Real-time PCR analysis showed no significant differences in the expression of muscle (MYF6, MyoD, and Desmin) metabolism genes between the two groups, whereas the expression of fat (PPARγ, C/EBPα, and FABP4) metabolism genes was lower in the 0.1% RPT group than in the control group. Thus, we demonstrate that long-term (6 wks) dietary supplementation of 0.1% RPT was beneficial owing to enhanced growth performance by increasing ADG and glucose level, decreasing FCR, and maintaining homeostasis in immune responses in beef steers during cold environment.

Potassium inwardly-rectifying channel, subfamily J, member 12 (KCNJ12) gene is one promising candidate for economic traits because of its crucial roles in myoblast development. Here, a missense mutation (Cys>Arg), was firstly detected to locate in exon 3 of KCNJ12 from three Chinese cattle breeds by DNA-pool sequencing. Then, we performed the association analysis of this SNP with stature in three Chinese cattle populations (n = 820). Significantly positive correlation was revealed by reduced animal general linear model and the genotype of CC is the most excellent genotype in three breeds. Further, we measured the expression profiling of the KCNJ12 gene in various cattle tissues and primary bovine skeletal muscle cells. Ubiquitous expression with high abundance in muscle was observed. Further, in primary bovine skeletal muscle cells, the KCNJ12 mRNA expression was gradually up-regulated in differentiation medium (DM) compared with that in growth medium (GM), suggesting that KCNJ12 gene is involved in bovine myocyte differentiation. Conclusively, KCNJ12 gene is a functional candidate gene which can be used as molecular marker for beef cattle breeding.

Japanese encephalitis is a zoonotic disease caused by Japanese encephalitis virus (JEV). It is mainly epidemic in Asia with an estimated 69,000 cases occurring per year. However, no approved agents are available for the treatment of JEV infection, and existing vaccines cannot resist various types of JEV strains. Drug repurposing is a new concept for finding new indication of existing drugs, and recently, it has been used to discover new antiviral agents. Identifying host proteins involved in the progress of JEV infection and using these proteins as targets are the center of drug repurposing for JEV infection. In this study, based on the gene expression data of JEV infection and the phenome-wide association study (PheWAS) data, we identified 286 genes participating in the progress of JEV infection using the systems biology methods. The enrichment analysis of these genes suggested that the genes identified by our methods were predominantly related to viral infection pathways and immune response-related pathways. We found that bortezomib which can target these genes may have potential effect on the treatment of JEV infection. Subsequently, we evaluated the antiviral activity of bortezomib using the JEV-infected mice model. The results showed that bortezomib can lower JEV-induced lethality in mice, alleviate suffering in JEV-infected mice and reduce the damage in brains caused by JEV infection. This work provides a new method for the development of antiviral agents.

There is a lack of data comparing sugammadex with anticholinesterase for the quality of anaesthesia recovery, especially following a single bolus dose of rocuronium. Thus, we evaluated the influence of reversal with sugammadex or neostigmine on post-operative quality of recovery by using the Post-operative Quality Recovery Scale (PQRS). A total of 86 patients undergoing trans-pars plana vitrectomy (TPPV) under general anaesthesia were intubated following a single bolus dose of rocuronium (0.6 mg/kg). At the end of surgery, patients were received either neostigmine or sugammadex. The quality of recovery was assessed using the PQRS at 15 minutes and 40 minutes after surgery, and on post-operative day 1. The recovery rate in the physiological domain was higher in the sugammadex group at 15 minutes after surgery (P = 0.02). Though there were no significant differences in the overall cognitive recovery domain, patients in the sugammadex group could recall more numbers in reverse order. However, there were no significant differences between the groups in the other domains of the PQRS. The use of sugammadex may increase the quality of the post-operative physiological recovery at early post-operative periods compared with neostigmine use following a single bolus dose of rocuronium in patients undergoing TPPV with general anaesthesia.

Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify novel therapeutic agents. A rat IgAN model was established by administration of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, which simultaneously established blood stasis and a heat syndrome model. The animals were sacrificed to detect changes in protein levels in urine and blood. Immunofluorescence was performed to assess IgA deposition in the glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematology and eosin, periodic acid-Schiff, TUNEL, and immunohistochemical staining were performed to evaluate histopathological changes in kidney tissues. Additionally, target-related proteins were measured by western blotting. Periostracum cicadae resulted in a reduction in blood and urine protein levels. Serum TNF-α, IL-1β, and IL-6 levels significantly decreased in the periostracum cicadae-treated groups compared to the IgAN group. Furthermore, a reduction in MCP-1, TLR4, and IgA expression levels and a dose- dependent increase in caspace-3 expression were observed in response to periostracum cicadae treatment. TGF-β1 levels decreased, whereas that of Fas increased in the kidney tissues of the periostracum cicadae-treated groups. The findings of the present study indicate that periostracum cicadae induces apoptosis and improves kidney inflammation and fibrosis in IgA nephropathy rat models.

The knowledge of protein function is essential for the study of biological processes, the understanding of disease mechanism and the exploration of novel therapeutic target. Apart from experimental methods, a number of in-silico approaches have been developed and extensively used for protein function prediction. Among these approaches, BLAST predicts functions based on protein sequence similarity, and machine learning predicts functional families from protein sequences irrespective of their similarity, which complements BLAST and other methods in predicting diverse classes of proteins including distantly related proteins and homologous proteins of different functions. However, their identification accuracies and the false discovery rate have not yet been assessed so far, which greatly limits the usage of these prediction algorithms. Herein, a comprehensive comparison of the performances among four popular functional prediction algorithms (BLAST, SVM, PNN and KNN) was conducted. In particular, the performance of these algorithms were systematically assessed by four metrics (sensitivity, specificity, accuracy and Matthews correlation coefficient) based on the independent test datasets generated from 93 protein families defined by UniProtKB Keywords. Moreover, the false discovery rates of these algorithms were evaluated by scanning the genomes of four representative model species (homo sapiens, arabidopsis thaliana, saccharomyces cerevisiae and mycobacterium tuberculosis). As a result, the substantially higher sensitivity and stability of BLAST and SVM were observed compared with that of PNN and KNN. But the machine learning algorithms (PNN, KNN and SVM) were found capable of significantly reducing the false discovery rate (SVM < PNN ≈ KNN). In summary, this study comprehensively assessed the performance of four popular algorithms applied to protein function prediction, which could facilitate the selection of the most appropriate method in the related biomedical research.

The effect of low cycle fatigue (LCF) pre-damage on the subsequent very high cycle fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF pre-damage is applied under 1.8% strain amplitude up to various fractions of the expected life and subsequent VHCF properties are determined using ultrasonic fatigue tests. Results show that 5% of LCF pre-damage insignificantly affects the VHCF limit due to the absent of pre-crack, but decreases the subsequent fatigue crack initiation life estimated by Pairs’ law. Pre-cracks introduced by 10% and 20% of LCF pre-damage significantly reduce the subsequent VHCF limits. The crack initiation site shifts from subsurface-induced fracture for undamaged and 5% of LCF pre-damage specimens to surface pre-crack for 10% and 20% of LCF pre-damage specimens in very high cycle region. The fracture mechanism analysis indicate that LCF pre-crack will re-start to propagate under subsequently low stress amplitude when stress intensity factor of pre-crack is larger than its threshold. Furthermore, the predicted fatigue limits based on EI Haddad model for the LCF pre-damage specimens well agree with the experimental results.

A marine fibrinolytic compound FGFC1 enhancing fibrinolysis was obtained involving in enzymatic kinetic parameters of reciprocal activation system with single chain urokinase type plasminogen activator and plasminogen. FGFC1, a kind of bisindole alkaloid from a metabolite of rare marine fungi Starchbotrys longispora FG216, modulated enzymatic kinetic parameters including fibrinolytic reaction rate and fibrin degradation characteristics. The enzymatic kinetics of fibrinolysis was described based on enzymatic reaction of chromogenic-substrate associated with p-nitroaniline (p-NA). While single chain urokinase-type plasminogen activator (pro-uPA) actived plasminogen, K_cat and k_cat/k_m increased significantly with increase of FGFC1 concentration. Moreover, K_cat and k_cat/k_m exhibited 26.5-fold and 22.8-fold enhanced activity at the concentration of 40 μg•mL⁻¹ of FGFC1, respectively. The results suggested that FGFC1 improved significantly the maximum catalytic efficiency and the total catalytic activity of fibrinolysis base on the reciprocal activation of pro-uPA and plasminogen. K_m increased with increasing FGFC1 concentration, which indicated that FGFC1 decreased slightly the affinity activity of pro-uPA and plasminogen versus enzyme substrate. The marine bisindole alkaloid FGFC1 enhanced fibrinolysis which was taken on enzymatic kinetic characteristics.

Three dimension (3D) Multi-input-multi-output (MIMO) scheme, which exploits another dimension of the spatial resource, is one of the enabling technologies for the next generation mobile communication. As the elevation angle in 3D-MIMO channel model might varies against the height of the base station transmit antenna, it has to be taken into account carefully. In this paper, the impact of antenna height on the channel characteristics of 3D MIMO channel is investigated by using the intelligent ray launching algorithm (IRLA). Three typical street scenarios, i.e., the straight street, the fork road and the cross road, are selected as benchmarks. On the basis of simulations, joint and marginal probability density functions (PDFs) of both the elevation angle of departure (EAoD) and the elevation angle of arrival (EAoA) are obtained. The elevation angle spread (AS) and the delay spread (DS) under various antenna heights are also discussed. Simulation results indicate that the PDFs of EAoD and EAoA vary characteristics under different street scenarios. Moreover, the minimum value of the DS can be achieved when the antenna height is half of the building height.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

This study investigated the impact of chitosan (CH, 1%) and aloe vera gel (AL, 30%) edible coatings on the preservation of blue honeysuckle quality during a 28-day storage at -1°C. Coating with CH, AL, and CH+AL led to notable enhancements in several key attributes. These included increased firmness, total soluble solids, acidity, pH, and antioxidant capacity (measured through DPPH, ABTS, and FRAP assays), as well as the preservation of primary (ascorbic acid) and secondary metabolites (TPC, TAC, and TFC). These coatings also resulted in reduced weight loss, respiration rate, color, abscisic acid, ethylene production, and malondialdehyde content. Notably, the CH+AL treatment excelled in preserving secondary metabolites and elevating FRAP-reducing power, demonstrating a remarkable 1.43-fold increase compared to the control after 28 days. Overall, CH+AL exhibited superior effects compared to CH or AL treatment alone, offering a promising strategy for extending shelf life and preserving quality of blue honeysuckle during storage.

Purpose: To explore parents’ perceptions of the educational intervention programme regarding their children’s postoperative pain management. Design and Methods: A qualitative descriptive study was conducted. Thirty-two parents whose children underwent inpatient elective surgery were recruited from the two intervention groups (received an educational booklet and a video, with or without an hour of face-to-face teaching session) for this qualitative evaluation of the intervention. Participants were asked to comment on the content and delivery methods of the intervention via individual face-to-face semi-structured interviews. Thematic analysis was used to identify themes from the data. Results: Three themes were generated from 32 participants’ interview data: current pain management practices, experiences and benefits of the educational intervention, and suggestions to improve pain management. Conclusions: Our findings suggested that the educational intervention in children’s postoperative pain management was helpful for parents and their children. However, it is necessary to improve educational materials and equip healthcare professionals with non-pharmacological pain relief methods. Practice Implications: Our findings reveal the current challenges in extensively adopting non-pharmacological pain relief methods. Healthcare professionals can do more to routinely integrate pharmacological and non-pharmacological pain management strategies in relieving pain effectively. Future research could develop technology-based programmes to increase ease of access. Trial Registration Number: ISRCTN24910957.

Aim: To improve risk stratification in early-stage endometrial cancer (EC), we performed mo-lecular classification, and L1CAM immunohistochemistry (IHC) for additional risk assessment. Method: We analyzed archival tumor tissue from 247 early-stage EC patients. POLE mutations were detected using a Droplet digital polymerase chain reaction assay and Sanger sequencing, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI test. Additionally, we conducted IHC of p53 and L1CAM. Results: The 247 ECs were categorized into four subgroups: POLE-mutated (13.0%), MMR-deficient (27.9%), p53-abnormal (8.5%), and non-specific molecular profile (NSMP, 50.6%). We further subcategorized NSMP subgroup into NSMP-L1CAMneg (44.9%) and NSMP-L1CAMpos (5.7%), which we refer to as the molecu-lar-L1CAM classification. The molecular-L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p <0.001, each). Similarly, the simplified L1CAM-p53 categorization, for practical use, remained an independent prognostic factor for RFS and OS (p <0.001, p =0.003, respectively). Conclusion: Integrating the molecu-lar-L1CAM classification or the simplified L1CAM/p53 categorization can enhance risk stratifi-cation in early-stage EC, providing valuable prognostic information to guide treatment deci-sions and improve patient outcomes.

The papaya mealybug Paracoccus marginatus is an invasive, polyphagous pest and poses a quarantine threat to tropical and subtropical countries. Infested commodity internationally should be undergoing phytosanitary treatment, while irradiation is recommended to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-d-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy, respectively. Radiotolerance was compared using fiducial overlapping and lethal dose ratio (LDR) test, resulting in insignificant difference except for LDR test at LD90 (leading 90% mortality at 95% confidence level (CL)); the estimated dose for 99.9968% mortality at 95% CL was 176.5–185.2 Gy, which was validated in the confirmatory tests using gamma irradiation because gammy and X-rays have equal biological effect on pests. Therefore, a total of estimating 60,386 gravid females of papaya mealybug irradiated with 146.8–185.0 Gy resulted in no F1 nymphs developing. Eggs can therefore be used as an alternative to gravid females for dose-response tests; the recommended minimum dose for phytosanitary treatment of P. marginatus on infested commodity is 185 Gy, with treatment efficacy ≥ 99.9950% at 95% CL.

Natural image matting is an essential technique for image processing that enables various applications, such as image synthesis, video editing, and target tracking. However, the existing image matting methods may fail to produce satisfactory results when computing resources are limited. Sampling-based methods can reduce the dimensionality of the decision space and therefore reduce computational resources by employing different sampling strategies. While these approaches reduce computational consumption, they may miss an optimal pixel pair when the number of available high-quality pixel pairs is limited. To address this shortcoming, we propose a novel multi-criterion sampling strategy that avoids missing high-quality pixel pairs by incorporating multi-range pixel pair sampling and high-quality samples selection method. This strategy is employed to develop a multi-criterion matting algorithm via Gaussian process, which searches for the optimal pixel pair by using the Gaussian process fitting model instead of solving the original pixel pair objective function. Experimental results demonstrate that our proposed algorithm outperforms other methods even with 1% computing resources, and achieves alpha matte results comparable to those yielded by the state-of-the-art optimization algorithms.

Core-shell particles are heterogenous micro- or nanoparticles with solid, liquid or gas core encapsulated by a protective solid shell. The unique composition of core and shell materials imparts smart properties to the particles. Core-shell particles are gaining increasing attention as tuneable and versatile carriers for pharmaceutical and biomedical applications including targeted drug delivery, controlled drug release, and biosensing. This review first provides an overview of fabrication methods for core-shell particles, followed by a brief discussion on their application and a detailed analysis on manipulation including assembly, sorting, and triggered release. We compile current methodologies employed for manipulation of core-shell particles and demonstrate how existing methods of assembly and sorting micro/nanospheres can be adopted or modified for core-shell particles. Various triggered release approaches for diagnostics and drug delivery are also discussed in detail.

Deep convolutional neural networks (CNNs) have been widely used in various medical imaging tasks. However, due to the intrinsic locality of convolution operation, CNNs generally cannot model long-range dependencies well, which are important for accurately identifying breast cancer from unregistered multi-view mammograms. This motivates us to leverage the architecture of Vision Transformers to capture long-range relationships of multiple mammograms from the same patient. For this purpose, we employ local Transformer blocks to separately learn patch relationships within a specific view (CC/MLO) of one side (right/left) of mammogram. The outputs from different views and sides are concatenated and fed into global Transformer blocks, to jointly learn patch relationships between two different views of the left and right breasts. To evaluate the proposed model, we retrospectively assembled a dataset involving 949 sets of CC and MLO view mammograms, which include 470 malignant cases and 479 normal or benign cases. We trained and evaluated the model using a five-fold cross-validation method. Without any arduous preprocessing steps (e.g., optimal window cropping, chest wall or pectoral muscle removal, two-view image registration, etc.), our two-view Transformer-based model achieves lesion classification accuracy of 77.0% and area under ROC curve (AUC = 0.814), outperforming state-of-the-art multi-view CNNs by 3.1% and 3%, respectively. Meanwhile, the new two-view model improves mammographic case classification accuracies of two single-view models by 7.4% (CC) and 4.5% (MLO), respectively. The promising results unveil the great potential of using Transformers to develop high-performing computer-aided diagnosis (CADx) schemes of mammography.

This paper realizes early bearing fault warning through bearing fault time series prediction, and proposes a bearing fault time series prediction model based on optimized maximum correlation kurtosis deconvolution (MCKD) and long short-term memory (LSTM) recurrent neural network to ensure bearings operation reliability. The model is based on lifecycle vibration signal of the bearing, to begin, the cuckoo search (CS) is utilized to optimize the parameter filter length L and deconvolution period T of MCKD, taking into account the influence and periodicity of the bearing time series, the fault impact component of the optimized MCKD deconvolution time series is improved. Then select the LSTM learning rate α depending on deconvolution time series. Finally, the dataset obtained through various preprocessing approaches are used to train and predict the LSTM model. The average prediction accuracy of the optimized MCKD-LSTM model is 26 percent higher than that of the original time series, proving the efficiency of this method, and the prediction results track the real fault data well, according to the XI'AN JIAOTONG University XJTU-SY bearing dataset.

Microbubbles and nanobubbles can be prepared using various shells, such as phospholipids, polymers, proteins, and surfactants. They are echogenic and can be used as contrast agents for ultrasonic and photoacoustic imaging. These bubbles can be engineered in various sizes as vehicles for gas and drug delivery applications with novel properties and flexible structures. Hypoxic areas in tumors develop owing to an imbalance of oxygen supply and demand. In tumors, hypoxic regions have shown more resistance to chemotherapy, radiotherapy, and photodynamic therapies. The efficacy of photodynamic therapy depends on the availability of oxygen in the tumor to generate reactive oxygen species. Micro/nanobubbles have been shown to reverse hypoxic conditions and increase tissue oxygen levels. This review summarizes the synthesis methods and shell compositions of micro/nanobubbles and methods deployed for oxygen delivery. In addition, the shortcomings and prospects of engineering micro/nanobubbles are discussed for their potential use in photodynamic therapy.

Purpose: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods: In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µL/min and 10 µL/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. Results: At 5 µL/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µL/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µL/min (first ablation: 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation: 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two medical conditions, and the effect modification by sex and neuropsychiatric comorbidities in a nationwide population. To compare the risk of precocious puberty between ASD and non-ASD cases, we conducted Cox regression analysis, using ASD as exposure and time-to-precocious puberty as outcome. We adjusted for sex, attention-deficit/hyperactivity disorder (ADHD), tics disorder, obsessive–compulsive disorder (OCD), anxiety disorder, intellectual disability, and epilepsy. We performed a moderation analysis to examine the potential moderating effects by sex or comorbidities. Patients with ASD were prone to have precocious puberty, with an adjusted hazard ratio (aHR) of 1.80 (95% CI: 1.61-2.01). For the effect modification, sex, specifically females, moderated the association between ASD and precocious puberty, with relative excess risk due to interaction (RERI) 7.35 (95% CI 4.90-9.80). No significant effect modification was found for any of the comorbidities within the scope of additive effect modification. We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders. Girls with ASD are at particularly higher risk to develop precocious puberty.

Refractive index measurements have been an important task for a long time because that index plays an essential role in describing the optical properties of a material. Many methods have been developed to perform that task. Some of them use interferometry to achieve high precision, however these configurations are complicated. Some measure the critical angle using simple structures, but the accuracy is not satisfactory because it is difficult to judge the exact critical angle with intensity variations. Here we propose several new schemes based on measuring the polarization change in the total internal reflection. The proposed method has the merits of simple structure and easy incident angle determination that gives the maximum phase change. Additionally, it is possible to find the material dispersion by measuring the wavelength dependence of the polarization ellipticity. Some useful formulas relating the refractive index with the maximum phase change are obtained. This work can provide valuable alternatives for index measurement.

One of the most crucial elements in deeply understanding humans on a psychological level is manifested through facial expressions. The analysis of a human behavior can be informed by their facial expressions, making it essential to employ indicators such as expression (Expr), valence-arousal (VA), and action units (AU). In this paper, we introduce the method proposed in the Challenge of the 6th Workshop and Competition on Affective Behavior Analysis in-the-wild (ABAW) at CVPR 2024. Our proposed method utilizes the multi-modal Aff-wild2 dataset, which is splitted into spatial and audio modalities. For the spatial data, we extract features using a SimMiM model that was pre-trained on a diverse set of facial expression data. For the audio data, we extract features using a WAV2VEC model. To fusion the extracted spatial and audio features, we employed the cascaded cross-attention mechanism of a transformer.

Introduction: This study aims to elucidate the clinical diagnostic value of S100 Calcium Binding Protein beta (S100B) in epilepsy, a topic of ongoing debate among European and Asian epilepsy research centres.Methods and analysis: A structured long-term research plan was developed, comprising three phases. Phase one involves observational studies investigating the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. Phase two integrates observational and randomised controlled data to establish baseline S100B levels across diverse epilepsy demographics, underpinning the predictive value of S100B for epilepsy. Phase three focuses on randomised controlled trials to evaluate the diagnostic accuracy of S100B as an epilepsy biomarker.Ethics and dissemination: All enrolled patients will provide written consent. The ethics committee of the Second People’s Hospital of Gansu Province, Affiliated Hospital of Northwest Minzu University, China, approved the study (GSSEY2022-KY009-01).Registration: The study is registered with PROSPERO (CRD42023425431).

Five new cembrane-type diterpenes, lobocalines A–E (1–5), and four new steroids, lobocalines F–I (9–12), along with six known related compounds (6–8 and 13–15) were isolated from the Yalong Bay soft coral Lobophytum catalai. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ analysis, time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations, X-ray diffraction analyses, and the comparison with the reported spectroscopic data of known compounds. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol B (15) was firmly revised as 15a. In in vitro bioassays, compound 2 showed moderate antibacterial activities against fish pathogenic bacteria Streptococcus parauberis KSP28 and Phoyobacterium damselae FP2244 with minimum inhibitory concentration (MIC) values of 8.7 and 17.3 µg/mL, respectively. All the steroids exhibited antibacterial activities against the S. parauberis KSP28 with MIC values ranging from 12.3 to 53.6 µg/mL. Compounds 2, 7 and 14 have remarkable inhibitory effects on the hemolysin production of Staphylococcus aureus, while compounds 8–12 have medium inhibitory effects on the pyocyanin production in Pseudomonas aeruginosa.

The cooking method is extremely important for the production of low-salt, wet-marinated, fermented golden pomfret because it strongly influences its flavor components and organoleptic quality. There are also significant differences in flavor preferences in different populations. The present study analyzed differences in the aroma characteristics of wet-marinated fermented golden pomfret after boiling, steaming, microwaving, air frying and baking using a combination of an electronic nose, GC-IMS and SPME-GC-MS. Electronic nose PCA showed that the flavors of the boiled (A), steam (B) and microwave (C) treatment groups were similar, and the flavors of baking (D) and air frying (E) were similar. A total of 72 flavor compounds were detected in the GC-IMS analysis, and comparative analysis of the cooked wet-marinated and fermented golden pomfret yielded a greater abundance of flavor compounds. SPME-GC-MS analysis detected 108 flavor compounds, and the results were similar to the baking and air frying. Twelve key flavor substances, including hexanal, isovaleraldehyde, and (E)-2-dodecenal, were identified by orthogonal partial least squares discriminant analysis (OPLS-DA) and VIP analysis. These results show that cooking method is a key factor in the flavor distribution of wet-marinated fermented golden pomfret, and consumers can choose the appropriate cooking method accordingly.

In tire tread applications, achieving enhanced abrasion resistance, wet grip, and rolling resistance is crucial for optimizing overall performance. To realize improvements in these attributes for silica-filled tire tread compound, it becomes imperative to improve dispersity of silica filler with investigating the effect of each component in tire tread compound. In this work, we study the effect of styrene content within solution styrene butadiene rubber (SSBR) on the properties of tire tread compounds. A higher styrene segment within SSBR contributes to increased silica dispersion and crosslink density. Thus, tire tread compounds featuring SSBR with increased styrene content not only improve physical and mechanical properties but also enhance major characteristics tailored for tire tread applications. These findings provide valuable insights into advancing the reinforced performance of tire tread compounds through the strategic utilization of SSBR enriched in styrene content.

Existing research concerning the effects of the sitting birth position during the second stage of labour on maternal and neonatal outcomes remains controversial, and there is a lack of studies to explore its effect on the childbirth experience. The objective of this study is to explore whether the sitting birth position would influence maternal and neonatal outcomes, as well as the childbirth experience reported by Chinese women using the Childbirth Experience Questionnaire (CEQ). A total of 296 women (including primiparous women and multiparous women) were enrolled in our study, and they were divided into the sitting position cohort (n=106) or the lithotomy position cohort(n=116). The study found that primiparous women in the sitting position cohort had a shorter duration of the second stage of labour, higher spontaneous vaginal birth rates, lower episiotomy rates and better childbirth experience (p<0.01). There was no significant difference for perineal lacerations, 2h-postpartum haemorrhage (P>0.05) between the two cohorts of primiparous women. After adjusting for confounding factors through multiple linear and logistic regression analyses, the results remained consistent with those reported above. No neonate in each cohort had Apgar scores at 1min and 5 min postpartum less than 7 or the Cord artery pH less than 7.00, regardless of parity. In addition, among multiparous women, there was no significant difference in any maternal and neonatal outcomes and women’s CEQ scores (p>0.05) between two cohorts. Based on the findings, we recommend that women could take the sitting birth position into account when giving birth for a positive childbirth experience, especially for primiparous women. The study could also serve as a reference for healthcare providers in the management of childbirth positions and the development of high-quality maternal care.

Ageing may be characterized by progressive loss of cognitive function as well as decrease in physical activities, in addition to change in appearance. Previously, we reported that intracerebroventricular transplantation of a human neural stem cell (NSC) line (F3) over-expressing choline acetyltransferase (F3.ChAT) gene, an enzyme responsible for acetylcholine synthesis, markedly improved cognitive function and physical activity of aged animals by enhancing acetylcholine and growth factors (GFs) and neurotrophic factors (NFs). In the present study, 10-month-old F344 rats were intravenously transplanted with F3 or F3.ChAT NSCs (1 x 106 cells) once a month to 21st month of age when the cumulative mortality reached 20%, and physical activity and learning/memory function were investigated, in addition to the analyses of brain acetylcholine concentration, and cholinergic and dopaminergic system restoration. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both the cognitive (passive avoidance and water-maze performances) and physical (locomotor and rota-rod activities) functions, in parallel with the elevation of acetylcholine levels in cerebrospinal fluid and in muscles, in which F3.ChAT cells were superior to F3 parental cells. Stem cell transplantation down-regulated CCL11, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, and preserved brain and muscular capillaries, recovering muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage of multiple organs including muscles and the brain. The results indicate that NSCs over-expressing ChAT gene improve cognitive function and physical activity of ageing animals by protecting and recovering functions of multiple organs including cholinergic and dopaminergic systems as well as muscles from oxidative injuries through secretion of acetylcholine and GFs/NFs, increased antioxidant elements, and enhanced blood flow.

Laminitis is considered as an important underlying cause of lameness diseases, yet its specific pathogenesis remains unclear. Autophagy is an intracellular degradation mechanism that controls recycling of membrane-associated integrin and may aid in the progression of metabolic diseases. But the significance of autophagy for initiation and development of laminitis is unknown. The present study aimed to explore autophagy activity in the laminar tissue of dairy cows with oligofructose-induced laminitis. Twelve healthy non-pregnant Holstein cows were randomly divided to 2 groups of 6 cows each, entitled the control group and the oligofructose overload group (OF group), respectively. At 0 h, cows in OF group were gavaged with oligofructose (17 g/kg BW) dissolved in warm deionized water (20 mL/kg BW) through oral rumen tube, and dairy cows in control group were gavaged with the same volume of deionized water by the same method. At -72 h before perfusion as well as 0 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, and 72 h after perfusion, clinical evaluations in both groups were monitored. After 72 h, laminar tissues of dairy cows in both groups were collected to examine genes and proteins. We found the significantly higher (P<0.05) levels of mRNA ATG5, ATG12, and Becilin1, but P62 and mTOR were extensively lower (P<0.01) in the laminar tissue of the OF group than the control group. Protein expression level of Becilin-1 was higher significantly (P<0.05), and the protein expression level of LC3II was lower significantly (P<0.05) in OF group than control group. However, the expression of P62 reduced (P>0.05) non-significantly in OF group than control group. The distribution of Beclin1 protein in laminar tissue increased (P<0.01) significantly, and distribution of P62 protein decreased (P<0.05) significantly in OF group than control group. In conclusion, laminar tissue damage occurred during the onset of laminitis, which promoted the occurrence of autophagy, and confirmed that autophagy was involved in the regulation and pathogenesis of laminitis in dairy cows.

The level of technological development of any civilization can be gaged in large part by the amount of energy they produce for their use, but also encompasses that civilization’s stewardship of their home world. Following the Kardashev definition, a Type I civilization is able to store and use all the energy available on its planet. In this study, we develop a model based on Carl Sagan’s K formula and use this model to analyze the consumption and energy supply of the three most important energy sources: fossil fuels (e.g., coal, oil, natural gas, crude, NGL and feedstocks), nuclear energy and renewable energy. We also consider environmental limitations suggested by United Nations Framework Convention on Climate Change, the International Energy Agency, and those specific to our calculations to predict when humanity will reach the level of a Kardashev scale Type I civilization.

Ho Chi Minh City (HCMC), the most crowded city and economic hub of Viet Nam, has been experiencing land subsidence over the past decades. This effort aims to contribute the spatial distribution of subsidence in HCMC in its horizontal and vertical components using synthetic aperture radar interferometry (InSAR) time series. To this purpose, an advanced Persistent Scatterers and Distributed Scatterers (PSDS) InSAR technique was applied to two European Space Agency (ESA) Sentinel-1 datasets consisting of 96 ascending and 202 descending images, acquired from 2014 to 2020 over the HCMC area. A time series of 33 COSMO-SkyMed ascending images was also used for comparison. The combination of ascending and descending satellite passes is used to decompose the light of sight velocities into horizontal east-west and vertical components. Taking into account the presence of east-west horizontal motion, our findings indicate that the accuracy of the decomposed vertical velocity can be improved by up to 3 mm/year for Sentinel-1 data. The obtained results revealed that subsidence is most pronounced in the areas along the Sai Gon River, in the northwest-southeast axis, and in the southwest of the city, with a maximum value of 80 mm/yr, which is in accordance with the findings of the literature. The amplitude of east-west horizontal velocities is relatively small and large-scale eastward movement can be observed in the west of the city at a rate of 3-5 mm/yr. This confirmed that the displacement in Ho Chi Minh City area is mainly vertical downward. Together, these results reinforced the remarkable suitability of ESA's SAR Sentinel-1 for subsidence applications, even for non-European countries such as Vietnam and Southeast Asia.

The upregulated expression of thyrosine kinase AXL has been reported in several hematologic and solid human tumors including gastric, breast, colorectal, prostate, and ovarian cancers. Thus, AXL can potentially serve as a diagnostic and prognostic biomarker for various cancers. This paper reports the first-ever use of loop-mediated isothermal amplification (LAMP) of the AXL gene as a diagnostic method for ovarian cancer. We demonstrated simple instrumentation toward a point-of-care device to perform LAMP. This paper also reports the first-ever use of core-shell beads as a microreactor to perform LAMP as an attempt to promote environmentally friendly laboratory practices.

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

We show the enhancement in the intensity and emission rate of perovskite cesium lead bromide (CsPbBr3) and formamidinium lead bromide (FAPbBr3) nanocrystals in the presence of single and double gold layer cavities, which we refer to as Metal-Emitter (ME) and Metal-Emitter-Metal (MEM) nanostructures. Up to 1.9-fold photoluminescence intensity and up to 5.4-fold emission rate enhancements were obtained for FAPbBr3 nanocrystals confined by double gold layers, which are attributed to plasmonic confinement from the gold layers. The experimentally obtained values are validated by analytical calculations and electromagnetic simulations. Such an effective method of manipulation of the spontaneous emission rate by simple plasmonic nanostructures can be utilized in sensing and detection applications.

Thymic stromal lymphopoietin (TSLP) is a cytokine and is closely related to Interleukin (IL) - 7, and hTSLP can activation through the human thymus dendritic cell in thymic to indirectly promote the differentiation of natural Regulatory T cells (Tregs) of the thymus. In this study, we focused on recombinant TSLP to determine its effects on the differentiation of CD4+CD25-T cells separated from the thymus of myasthenia gravis (MG) patients. Our results demonstrated that exogenous TSLP could increase CD4+CD25+T/CD4+T cells ratio, up-regulate the expression of Foxp3 mRNA and protein expression in CD4+CD25+Treg cells. Furthermore, we found that CD4+CD25+ Treg cells induced by exogenous TSLP could secrete IL - 10, Transforming growth factor (TGF) - β and the ability to inhibit CD4+T cell proliferation improved. These results indicate that TSLP may promote the differentiation of thymic CD4+CD25-T cells of MG patient to CD4+CD25+Foxp3+ regulatory T cells and enhance the function of immune suppression.

Integrating optical coherence tomography (OCT) into the pre-surgical stage of cataract management holds significant clinical and economic potential, particularly in low-to-middle-income countries like Kazakhstan. This study aimed to evaluate these impacts by prospectively recruiting 124 patients, aged 70±8 years, from two ophthalmology surgical centers in Almaty, Kazakhstan. Patients undergoing phacoemulsification of cataracts with monofocal intraocular lens (IOL) implantation between January and December 2022 were divided into two groups: the OCT group (n=75) received pre-operative OCT, while the Control group (n=49) did not. Visual acuity (VA) was measured pre- and post-surgery, and the cost-effectiveness of the surgical strategies was analyzed. The OCT group experienced a significantly greater improvement in VA (-0.647±0.232 logMAR) compared to the Control group (-0.543±0.244 logMAR), with a notable interaction between time and group (F(df) = 217.2, p &lt; 0.001). Additionally, pre-existing concomitant diseases were diagnosed in 25.3% of cases in the OCT group and 28.6% in the Control group. The economic analysis revealed that the integration of OCT facilitated multiple surgeries in one appointment, thereby reducing overall costs. These findings suggest that implementing OCT in the pre-surgical stage of cataract management can significantly enhance visual outcomes and decrease the cost of ophthalmology services in Kazakhstan.

Silicon carbide particle-reinforced aluminum matrix (SiCp/Al) composites are significant lightweight metal matrix composites extensively utilized in precision instruments and aerospace sectors. Nevertheless, the inclusion of rigid SiC particles exacerbates tool wear in mechanical machining, resulting in a decline in the quality of surface finish. This work undertakes a comprehensive investigation into the problem of tool wear in SiCp/Al composite materials throughout the machining process. Initially, a comprehensive investigation was conducted to analyze the effects of cutting velocity vc, feed per tooth fz, milling depth ap, and milling width ae on tool wear during high-speed milling under SCCO2-MQL (Supercritical Carbon Dioxide Minimum Quantity Lubrication) ultrasonic vibration conditions. Furthermore, a prediction model for tool wear was developed by employing the orthogonal test method and multiple linear regression. The model's relevance and accuracy were confirmed using F-tests and t-tests. Ultimately, through the utilization of a genetic algorithm, the milling parameters were optimized, resulting in the identification of the most optimal combination of parameters. Empirical findings suggest that the careful selection of milling parameters can significantly mitigate tool wear, extend the lifespan of the tool, and enhance the quality of the surface. This work serves as a significant point of reference for the processing of SiCp/Al composite materials.

Construction using earth materials demonstrates ecological sustainability using locally sourced natural materials and environmentally friendly demolition methods. In this study, the environmental impact of adding cement to soil materials for rammed-earth farmhouse construction in rural China was investigated and comparatively simulated using the One Click LCA database, focusing on the conflict between sustainability objectives and the practical aspects of cement addition. By analyzing how the addition of cement aligns with local construction practices and by addressing the debate surrounding the inclusion of cement in rammed earth construction, our objective is to provide insights into achieving a balance between the environmental impact and the pragmatic considerations of using cement in earthen building practices. Three local structure scenarios are evaluated via simulations: a cement-stabilized rammed earth wall, a fired brick wall, and a localized reinforced concrete frame structure. The quantitative environmental impacts are assessed, and the qualitative differences in adaptation, economic sustainability, and other factors are examined in the context of present-day development in rural China. The results show that the use of cement-stabilized rammed earth wall-supported structures is associated with higher embodied carbon emissions compared to structures supported by reinforced concrete frames and enclosed by brick walls; however, these emissions are lower than those for brick wall-supported structures, while effectively meeting the structural requirements. In addition, the use of cement-stabilized earth for perimeter walls simplifies material management and disposal throughout the building's life cycle, and the cost-effectiveness of cement has been found to be substantially greater than that of reinforced concrete frames and brick structures, improving economic viability and social acceptability, especially among low-income communities in rural areas.

Effects of pulsed electromagnetic fields (PEMF) on immunological factors in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) model were investigated. Hairless mice were randomly assigned to control, acetone and olive oil solution-treated (AOO), PEMF 15 Hz, PEMF 75 Hz, and sham groups (n=5 each). AOO solution was used to dissolve DNCB. Both PEMF and sham groups were exposed to similar DNCB doses, causing similar AD symptoms. After AD induction for five weeks, only the PEMF group was exposed to PEMF stimulations (15 Hz, 75 Hz, and 15 mT) for two weeks inside the solenoid coil. In both groups, splenomegaly was observed, as AD was induced by hyperimmune reactions caused by DNCB sensitization. However, splenomegaly did not occur in the PEMF-exposed groups, and spleen weight decreased similarly to that of the control. Hence, the total splenocytes in the PEMF group were similar to those in the control group, whereas the sham group showed thrice the number of splenocytes compared to the PEMF group. The serum immunoglobulin E levels did not significantly change in the PEMF group; however, they increased more than fourfold in the sham group. These results demonstrate that PEMF stimulation ameliorates the abnormal symptoms caused by hyperimmune reactions.

Objective: The long-term care insurance (LTCI) system was introduced in 2000 to provide financial support for long-term care services to older adults. What is known on this topic report focuses on a comparative analysis of how the LTCI system has affected older people in Japan. Methods: We obtained data from the literature about the LTCI system, compared and analysed the collected articles, and concluded. Results: The LTCI system has improved access to long-term care services, with more older adults receiving care than before the system’s implementation. This service has improved the quality of life for many elderly individuals who require assistance with daily activities. Furthermore, the LTCI system has alleviated the financial burden of long-term care services since the insurance covers a large portion of the costs. It has made older adults maintain their independence and dignity, as they can afford the necessary care without relying solely on their savings or burdening their families. Conclusions: Japan’s LTCI system has positively impacted older adults by improving access to long-term care services and alleviating financial burdens. However, challenges such as increasing demand and variations in service quality need to be addressed to ensure the system effectively supports older people in Japan.

Therapeutic hypothermia (TH) has emerged as a promising approach with neuroprotective effects that can mitigate secondary brain damage and intracranial pressure in the acute phase after successful mechanical thrombectomy. However, the effect of TH on cognitive impairment has yet fully elucidated. In the present study, we demonstrated whether TH can improve cognitive impairment in a transient middle cerebral artery occlusion (tMCAO) mouse model Nine-week-old C57BL/6N mice (male) were randomized to three groups: sham, tMCAO, and tMCAO with TH. One month after model induction, cognitive function test and regional cerebral glucose metabolism were evaluated using the Y-maze test and positron emission tomography with fluorine-18 fluorodeoxyglucose, respectively. tMCAO led to cognitive impairment, which was improved by TH. The cerebral glucose metabolism of the thalamus was significantly recovered in the TH group compared to that in the tMCAO group. These results suggest that TH might have potential as a therapeutic strategy for improving the ischemia/reperfusion-induced cognitive impairment.

Food-grinding occurs in rodents and is influenced by multiple-factors. However, the factors affecting this behavior remain unclear. In this study, we aimed to investigate the effect of food restriction on food grinding by Brandt’s voles (Lasiopodomys brandtii), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of Staphylococcus, Aerococcus, Jeotgalicoccus, and Un--s-Clostridiaceae bacterium GM1. Strong correlations between the ground-to-consumed food ratio and the abundance of fecal microbiota were found for Un--s-Clostridiaceae bacterium GM1 and Aerococcus. The content of fecal acetate and propionate for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Further, the relative amount of ground food and ground-to-consumed food ratio were both positively correlated with the acetate content. Our study indicated that food restriction can effectively inhibit food grinding. Further, Un--s-Clostridiaceae bacterium GM1 abundance, Aerococcus abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and metabolite short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance.

This paper reports aligned activities to promote energy and resource-efficient construction practice in Vietnam. First, the governance framework is introduced, including government decrees and technical standards. Then, a laboratory with building physics measurement technology is designed and partly set up at the local partner Vietnam Institute for Building Materials (VIBM), which can be used to determine the essential characteristic values required for the implementation of energy standards. The basis for the prioritization of the characteristic values are the requirements of the National technical regulation on energy efficient buildings of Vietnam – QCVN09:2017/BXD. Furthermore, basic characteristic values from international standards are described, which can also be used for calculations to optimize the energy consumption of buildings. In order to be able to carry out transient hygrothermal computer simulations, special characteristic values were also included. These are particularly useful for the research and development of new building materials and the evaluation of entire buildings in terms of thermal and moisture protection In order to communicate the material properties to the market and enable informed decision making by the stakeholders, a labeling system has been developed. Thereby, the practical means for implementing governance instruments are provided, and the related technical applications are supported.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (20052018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio [HR], 1.121; 95% confidence interval [CI], 0.9501.323; p = 0.1755). The highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.9501.323, p = 0.0497). Medium (1.229, 1.0081.499, p = 0.0410) and high daily doses of ICS (1.637, 1.2412.160, p = 0.0005) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may not increase the risk of developing NTM disease in patients with COPD. However, physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

The interfacial mechanics and electrical properties of the SiC reinforced copper matrix composites were studied via the first principles method. The work of adhesion (Wad) and the interfacial energies were calculated to evaluate the stabilities of the SiC/Cu interfacial models. The carbon terminated (CT)-SiC/Cu interfaces were predicted more stable than those of the silicon terminated (ST)-SiC/Cu from the results of the Wad and interfacial energies. The interfacial electron properties of SiC/Cu were studied via the charge density distribution, charge density difference, electron localized functions and partial density of the state. The covalent C-Cu bonds were formed based on the results of the electron properties, which further explained the fact that the interfaces of the CT-SiC/Cu are stable than those of the ST-SiC/Cu. The interfacial mechanics of the SiC/Cu were investigated via the interfacial fracture toughness and ultimate tensile stress, and the results indicate that both CT- and ST-SiC/Cu interfaces are hard to fracture. The ultimate tensile stress of the CT-SiC/Cu is nearly 23GPa, which is smaller than those of the ST-SiC/Cu of 25 GPa. The strains corresponding to their ultimate tensile stresses of the CT- and ST-SiC/Cu are about 0.28 and 0.26, respectively. The higher strains of CT-SiC/Cu indicate their stronger plastic properties on the interfaces of the composites.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Most studies on the association of in utero exposure to cigarette smoking and childhood overweight or obesity (OWO) were based on maternal self-reported smoking data and few were based on objective biomarkers. In this study, we evaluated the associations between self-reported and biomarkers of in utero exposure to cigarette smoking with risk of childhood OWO. We analyzed data from 2351 mother-child pairs in the Boston Birth Cohort, a US low-income minority cohort that enrolled children at birth and followed prospectively up to age 18 years. In utero smoking exposure was measured by maternal self-report and by maternal and cord plasma cotinine and hydroxycotinine metabolites. We assessed the individual and joint associations of each smoking exposure measure and maternal OWO with childhood OWO using multinomial logistic regressions. We used nested logistic regressions to investigate the childhood OWO prediction performance when adding maternal and cord plasma biomarkers as input covariates on top of self-reported data. Our results demonstrated that in utero cigarette smoking exposure defined by self-report and by maternal or cord metabolites were consistently associated with increased risk of long-term child OWO. Adding maternal and cord plasma biomarker information to self-reported data improved the prediction accuracy of long-term child OWO risk.

The accurate assessment and monitoring of soil erosion is of great significance for guiding food production and ensuring ecological security, and it is a current research hotspot. In this paper, remote sensing and geographic information systems (GISs) are combined with the Revised Universal Soil Loss Equation (RUSLE model) to carry out research on soil erosion monitoring and make a quantitative evaluation. According to five factors, including rainfall erosivity, soil erodibility, topography, vegetation cover, crop management and water and soil conservation measures, the distribution of the soil erosion rate in Jilin Province in 2019 was mapped, and the soil erosion rate was divided into 5 levels according to the degree of erosion, including very slight, slight, moderate, severe and extremely severe erosion. Based on the segmented S-slope factor model and the unique topographical features of the study area, the relationships among the soil erosion rate, erosion risk level, erosion area, erosion amount and slope angle (θ) were systematically analysed, and a slope angle of 15° was identified as the threshold for soil erosion on sloped farmland in Jilin Province. The total soil erosion in Jilin Province was 402.14×106 t in 2019, the average soil erosion rate was 21.6 t·ha-1·a-1, and the average soil loss thickness was 1.6 mm·a-1; these values were far greater than the soil erosion rate risk threshold of 10 t ·Ha-1·a-1. Thus, the province has a strong level of soil erosion. We conclude that soil degradation is accelerating, and food production and the ecological environment will face severe challenges. It is suggested that soil erosion control should be carried out according to different types and slopes of land, with an emphasis on the management of forestland and farmland because forestland and farmland are currently the first types of land to be managed in Jilin Province. This paper aims to explore a timely, fast, efficient and convenient soil erosion monitoring and evaluation method and provide effective monitoring tools for agricultural water and soil conservation, ecological safety management and stable food production in Jilin Province and similar black soil areas.

Background: Accurate prediction of patients’ response to therapy is clinically indispensable, howbeit challenging. With increased understanding of the human genome and malignancies, there is the renaissance of in silico pharmacogenomics with renewed interest in drug response predictability based on gene-drug interaction. Objective: Evidence-based transcript-proteome profiling is essential for synthesizing clinically applicable algorithms for predicting response to anticancer therapy, including immune checkpoint blockade (ICBT); thus, saving physicians’ time, reducing polypharmacy, and curtailing unnecessary treatment expense. In this study, we tested and validated the hypothesis that a selected proteomic signature in ICBT-naïve patients is sufficient for the prediction of response to ICBT. Methods: Using a multimodal approach consisting of computational pharmacogenomics, transcript-proteome analytics, mathematical modeling, and machine learning systems; we delineated therapy-sensitivity and stratified patients into graduated response groups based on their proteomic profile. Protein expression levels in our cohort tissue specimens were evaluated based on T cell- and non-T cell- inflamed phenotypes by immunohistochemistry. Results: We established β-catenin, PDL1, CD3 and CD8 expression-based ICBT response model. Statistical regression models validated the predictive association between our predefined algorithms and therapeutic outcome. Interestingly, our 4-gene prediction classifier was constitutively independent of tumor tissue origin, correctly stratified patients into high-, low-, and non- responders pre-treatment, with high prediction accuracy, and exhibited good association with patients’ performance status and prognosis (p < 0.01). Conclusion: Our findings demonstrate the possibility of accurate proteomics based ICBT response prediction and provide a putative basis for drug response prediction based on selective proteome profile in untreated cancer patients.

Electrically conductive polymer composites are in high demand for modern technologies, however, the intrinsic brittleness of conducting conjugated polymers and the moderate electrical conductivity of engineering polymer/carbon composites have highly constrained their applications. In this work, super high electrical conductive polymer composites were produced by a novel hot embossing design. The polydimethylsiloxane (PDMS) composites containing short carbon fiber (SCF) exhibited an electrical percolation threshold at 0.45 wt%, and reached a saturated electrical conductivity of 49 S/m at 8 wt% of SCF. When reduced the sample thickness from 1.0 mm to 0.1 mm by the hot embossing process, a compression-induced percolation threshold occurred at 0.3 wt%, while the electrical conductivity was further enhanced to 378 S/m at 8 wt% SCF. Furthermore, the additional of a second nanofiller of 1 wt%, such as carbon nanotube or conducting carbon black further increased the electrical conductivity of the PDMS/SCF (8 wt%) composites to 909 S/m and 657 S/m, respectively. The synergy of the densified conducting filler network by the mechanical compression and the hierarchical micro-/nanoscale filler approach has realize super high electrical conductive yet mechanical flexible polymer composites for modern flexible electronics applications.

Pancreatic ductal adenocarcinoma (PDA) remains the most lethal malignancy due to lack of an effective treatment. P21-activated kinases (PAKs) play key roles in PDA growth, and the PAK inhibitor PF-3758309 synergistically reduced PDA growth with gemcitabine. The aim of this study was to determine the effect of PF-3758309 with multiple chemotherapeutic reagents on a panel of patient-derived PDA cell lines. Cells were treated with PF-3758309 plus or minus gemcitabine, 5-fluorouracil (5-FU) or abraxane, and cell proliferation was determined. Protein expression profiles were measured by Western blot. PDA cells were subcutaneously injected into the flanks of SCID mice which were then treated with PF-3758309, gemcitabine, PF-3758309 plus gemcitabine, or gemcitabine plus abraxane. Tumour growth was measured by volume and weight. PF-3758309 enhanced the inhibitory effects of 5-FU, gemcitabine and abraxane on a panel of patient-derived PDA cells, inhibited HIF-1 protein expression and reduced the protein levels of palladin and -SMA in these cells. The combination of PF-3758309 with gemcitabine maximally inhibited PDA growth in vivo, which was comparable to the combination of gemcitabine with abraxane. PF-3758309 enhanced the suppressive effects of multiple chemotherapeutic reagents on the growth of a panel of patient-derived PDA cell lines. The combination of PF-3758309 with gemcitabine provides a potential treatment option with less toxicity than gemcitabine plus abraxane.

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

Water pollution associated with flooding is one of the major problems in cities in the global South. However, studies of water quality dynamics during flood events are not often reported in literature, probably due to difficult conditions for sampling during flood events. Water quality parameters in open water (canals, rivers, and lakes), floodwater on roads and water in sewers have been monitored during the extreme fluvial flood event on 7 October 2013 in Can Tho city, Vietnam. This is the pioneering study of urban flood water pollution in real time in Vietnam. The results showed that water quality is very dynamic during flooding, especially at the beginning of the event. In addition, it was observed that the pathogen and contaminant levels in the floodwater are almost as high as in sewers. The findings show that population exposed to flood water runs a health risk that is nearly equal to that of being in contact with sewer water. Therefore the people of Can Tho not only face physical risk due to flooding, but also exposed to health risk.

The healthcare system is crucial to the development, standard of living, and sustainability of any country. Amid the pandemic, most developed countries are experiencing varying levels of difficulty managing their healthcare systems. Overloading of healthcare services is common, leading to prolonged waiting times for medical services; thus, the wastage of hospital resources must be addressed seriously. In this paper, we examine the problem of no-shows in outpatient clinics. Through a review of the literature and practical industrial experience, we identify the processes of these clinics. We then propose a robust optimisation approach for overbooking using a traditional overbooking model and a robust system. This model aims to mitigate the significant parameter uncertainties encountered during the pandemic. Considering risk aversion, the optimal policy for overbooking can be established while accounting for the costs associated with overbooking. The main contribution of this paper is the introduction of an alternative method to address the uncertainty of no-shows using an overbooking technique.

Background: Capmatinib and savolitinib, selective MET inhibitors, are widely used to treat various MET-positive cancers. In this study, we aimed to determine the effects of these inhibitors on MET-amplified gastric cancer (GC) cells. Methods: After screening 37 GC cell lines, the following cell lines were found to be MET-positive with copy number variation &gt; 10: SNU-620, ESO51, MKN-45, SNU-5, and OE33 cell lines. Nest, we assessed the cytotoxic response of these cell lines to capmatinib or savolitinib alone using cell counting kit-8 and clonogenic cell survival assays. Western blotting was performed to assess the effects of capmatinib and savolitinib on the MET signaling pathway. Xenograft studies were performed to evaluate the in vivo therapeutic efficacy of savolitinib in MKN-45 cells. Results: Savolitinib and capmatinib exerted anti-proliferative effects on MET-amplified GC cell lines in a dose-dependent manner. Savolitinib inhibited the phosphorylation of MET and downstream signaling pathways, such as the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways, in MET-amplified GC cells. Additionally, savolitinib significantly decreased the number of colonies formed on the soft agar and exerted dose-dependent anti-tumor effects in a MKN-45 GC cell xenograft model. Furthermore, combination of trastuzumab and capmatinib exhibited enhanced inhibition of AKT and ERK activation in human epidermal growth factor receptor-2 (HER2)- and MET-positive OE-33 cells. Conclusions: Therefore, targeting MET with savolitinib and capmatinib efficiently suppressed the growth of MET-amplified GC cells. Moreover, these MET inhibitors exerted synergistic effects with trastuzumab on HER2- and MET-amplified GC cells.

Recently, methods to detect DoS and spoofing attacks that occur on in-vehicle networks using CAN Protocol are being studied through deep learning models such as CNN, RNN, and LSTM. These studies have produced significant results in the field of In-Vehicle Network attack detection using deep learning models. In addition, significant results are being achieved through research on applying time series-based deep learning models such as LSTM to detect DoS attacks and replay attacks occurring in in-drone networks by expanding them to drones using the UAVCAN protocol. In this paper, we conducted an experiment to detect in-drone network attacks through non-time series analysis using machine learning models and deep learning models, and through appropriate learning for each attack type, it can also be analyzed through non-time series analysis. The results showed that it was possible to detect attacks.

This research introduces a pioneering solution to the challenges posed by gastrointestinal tract (GI) cancer in radiation therapy, focusing on the imperative task of precise organ segmentation for minimizing radiation-induced damage. GI imaging has historically used manual demarcation, which is laborious and uncomfortable for patients. We address this by introducing the ResECA-U-Net deep learning model, a novel combination of the UNet and ResNet34 architectures. Furthermore, we further augment its functionality by incorporating the Efficient Channel Attention (ECA-Net) methodology. By utilizing data from the UW-Madison Carbone Cancer Centre, we carefully investigate several image processing techniques designed to capture critical local characteristics. With its foundation in computer vision concepts, the ResECA-U-Net model is excellent at extracting fine details from GI images. Sophisticated metrics such as intersection over union (IoU) and the dice coefficient are used to evaluate performance. Our study's outcomes demonstrate the effectiveness of the suggested method, yielding an impressive 96.27% Dice coefficient and 91.48% IoU. These results highlight the significant contribution that our strategy has made to the advancement of cancer therapy. Beyond its scientific merits, this work has the potential to significantly enhance cancer patients' quality of life and provide better long-term outcomes. Our work is a significant step towards automating and optimizing the segmentation process, which can potentially change how GI cancer is treated completely.

Sleep fragmentation (SF) can increase inflammation and production of reactive oxygen species (ROS), leading to metabolic dysfunction. SF is associated with inflammation of adipose tissue and insulin resistance. Several studies suggested that melatonin may have beneficial metabolic effects by activating AMP-activated protein kinase (AMPK). However, it is unclear whether melatonin affects the AMPK signaling pathway in SF-induced metabolic dysfunction. Therefore, we hypothesize that SF induces metabolic impairment and inflammation in white adipose tissue (WAT), as well as altered intracellular homeostasis. We further hypothesize that these conditions could be improved by melatonin treatment. We conducted an experiment using adult male C57BL/6 mice, which were divided into three groups: control, SF, and SF with melatonin treatment (SF+Mel). The SF mice were housed in SF chambers, while the SF+Mel mice received daily oral melatonin. After 12 weeks, glucose tolerance test, insulin tolerance test, adipose tissue inflammation, and AMPK assessments were performed. The SF mice showed increased weight gain, impaired glucose regulation, inflammation, and decreased AMPK in WAT compared to the controls. Melatonin significantly improved these outcomes by mitigating SF-induced metabolic dysfunction, inflammation, and AMPK downregulation in adipose tissue. The therapeutic efficacy of melatonin against cardiometabolic impairments in SF may be due to its ability to restore adipose tissue homeostatic pathways.

: The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM from lung adenocarcinoma at our institute for 5 years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

Staphylococcus aureus(S. aureus) is associated with mastitis in dairy cows, this study investigates the therapeutic effect of maggot antimicrobial peptides on S. aureus induced mastitis in mice. The maggot AMP was isolated and purified, tested for antimicrobial activity, and used to treat a pathological model of rat mastitis. The concentration of 1.5mg/（Kg. BW）AMP was selected as intramammary treatment in S. aureus-induced mastitis in mice. The mice were divided into four groups of 30 mice each: group I (healthy control), group II (disease control), group III (AMP), and group IV (ciprofloxacin). To evaluate the therapeutic efficacy of maggot AMP in mastitis induced by S. aureus based on clinical presentation, mammary gland structure, bacterial load, histopathology, and cure. During the 7-day treatment period, all the mice in Group II died in the afternoon of the fifth day, and the clinical signs of the mice in Group III began to improve on the third day, as evidenced by the gradual recovery of the mice's mental status, dietary intake, and water intake. During the treatment period, the bacterial load count of Group III was significantly lower than that of Group II but higher than that of Group IV, while the bacterial load count of Group III gradually decreased and approached that of Group IV from the fifth to the seventh day. The levels of TNF-α in groups III and IV were significantly lower than those in group II, suggesting that maggot AMP has a certain inhibitory effect on TNF-α. Treatment with AMP@ 1.5 mg/(Kg. BW) showed restoration of clinical signs, reduced bacterial load, and lower TNF-α levels in mice, leading to significant improvement in histopathological changes as compared to disease controls. The final cure rate was 40% for mice in Group III compared to 70% for mice in Group IV, compared to all mice in Group II that died. From this study, it can be concluded that maggot AMP can be used as a potential alternative treatment option to antibiotics for the treatment of bovine mastitis.

Precipitates are the primary source of strength for the Al-Mg-Si alloy. Aluminum alloy in the peak-aged state mainly contain β'' and β' precipitates. In the past, most of the literature only considered the strengthening effect of β''. Here we develop a single crystal intensity model including both precipitate enhancement effects for the first time. This model was subsequently implemented into a crystal plastic finite element method to model the uniaxial tensile process of a polycrystalline aggregate model of Al-Mg-Si alloy. The simulation results for uniaxial stretching are in good agreement with the experimental results, confirming that the constitutive parameters used for the single crystal strength model with two precipitates are based on realistic physical implications. Furthermore, by comparing the uniaxial tensile simulation results of a peak-aged alloy considering the actual precipitated phase composition of the alloy with those assuming that the precipitated phase is only the β'' phase, the predicted tensile strength of the former is around 5.65% lower than that of the latter, suggesting that the two kinds of precipitation should be considered separately when simulating the mechanical response of Al-Mg-Si alloy. It is highly expected that the present simulation strategy is not limited to the Al-Mg-Si alloys, and it can be equally applied to the other age-enhanced alloys.

Purpose: Therapeutic targeting of RAF1 is promising, but it requires further investigation for the relation between clinical features and RAF1 aberrations regarding the MAPK signaling pathway in various solid tumors to realize the precision medicine. Methods: Between October 2019 and June 2023, Samsung Medical Center, 3,895 patients with metastatic cancer patients received a next-generation sequencing (NGS) using TruSight Oncology 500 (TSO500) assay as a routine clinical practice. We surveyed the incidence of RAF1 aberration including mutation (single-nucleotide variant [SNV]), amplification (copy-number variation), and fusion. Results: In 3,895 metastatic cancer patients, 77 (2.0%) had RAF1 aberrations in their tumor specimen. Of 77 patients, 44 (1.1%) had RAF1 mutations (SNV), 25 (0.6%) had RAF1 amplification and 10 (0.3%) had RAF1 fusions. Among 10 patients with RAF1 fusion, concurrent RAF1 amplification and RAF1 mutation were detected in one patient each. The most common tumor types were bladder cancer (11.5%), followed by ampulla of Vater (AoV) cancer (5.3%), melanoma (3.0%), gallbladder (GB) cancer (2.6%), and gastric cancer (2.3%). Microsatellite instability high (MSI-H) tumors were found in 5 out of 76 patients (6.6%) with RAF1 aberration, while MSI-H tumors were found only in 2.1% of patients with wild-type RAF1 cancer (p < 0.0001). Conclusion: We showed that when patients with metastatic solid cancer receive NGS test, approximately 2.0% have RAF1 aberrations in their tumor specimen.

Leber’s hereditary optic neuropathy (LHON) is a common mitochondrial genetic disease, causing irreversible blindness in young individuals. Current treatments are inadequate, and there is no definitive cure. This study evaluates the effectiveness of delivering wildtype human NADH ubiquinone oxidoreductase subunit 4 (hND4) gene using mito-targeted AAV(MTSAAV) to rescue LHOH mice. We observed declining pattern electroretinograms amplitudes as mice aged across all groups (P&lt; 0.001), with significant differences among groups (P = 0.023, Control vs. LHON, P = 0.008; Control vs. Rescue, P = 0.228). Inner retinal thickness and intraocular pressure do not change significantly with age or groups. Compared to LHON mice, those rescued with wildtype hND4 exhibit improved retinal visual acuity (0.29± 0.1 cy/deg vs.0.15 ± 0.1 cy/deg) and increased functional hyperemia response (effect of flicker, P&lt;0.001, effect of Group, P=0.004; Interaction Flicker x Group, P&lt;0.001). Postmortem analysis shows a marked reduction in retinal ganglion cell density in the LHON group compared to the other groups (Effect of Group, P&lt;0.001, Control vs. LHON, P&lt;0.001, Control vs. Rescue, P=0.106). These results suggest that MTSAAV-delivered wildtype hND4 gene rescues, at least in part, visual impairment in an LHON mouse model and has the therapeutic potential to treat this disease.

Abstract: This study observes the characteristics and influencing factors of carbon fluxes of the Momoge salt marsh ecosystem over four years, which behaves as a CO2 sink. The daily, seasonal, and interannual variations of CO2 fluxes in the Momoge salt marshes were observed using the eddy covariance method and compared with various environmental factors. An overall daily “U” shaped distribution was observed, with uptake during the day (negative values) and release at night (positive values). Annually, the carbon fluxes in the study area roughly exhibit a “V” shape. Carbon fluxes during the non-growing season predominantly showed positive values, indicating the release of CO2 into the atmosphere. Photosynthetically active radiation was the primary influencing factor affecting hourly and daytime variations in net ecosystem exchange (NEE) during the growing season, while temperature was the main factor influencing nighttime NEE dynamics. Air temperature, soil temperature, photosynthetically active radiation, precipitation, and water level all had significant impacts on daily net CO2 exchange. At the monthly scale, larger values of soil temperature, air temperature, photosynthetically active radiation, and aboveground biomass correspond to a stronger carbon absorption capacity of the ecosystem. Overall, temperature remains the primary factor for carbon fluxes in the Momoge wetlands.

Kiwifruits are often exposed to various temperature fluctuation (TF) during postharvest storage. To evaluate the effect of TF on the qualities of kiwifruits, fruits were stored at 2 ºC, 2 ºC or 5 ºC (TF2ºC-5ºC), 2 ºC or 7 ºC (TF2ºC-7ºC), alternating every 12 h. Observations revealed that kiwifruits stored at constant 2 °C showed the lowest loss of weight and vitamin C due to the minimum ethylene production and respiratory rate compared to that of TF2ºC-5ºC and TF2ºC-7ºC. Moreover, the results of RT-qPCR verifed that the expression of genes encoding polygalacturonase, β-galacturonidase, and pectin methyl esterase was significantly increased by the treatment of TF. Hence, TF accelerated the degradation of the cell walls, softening, translucency and relative conductivity of the flesh of kiwifruits. Besides, the impact of TF2ºC-7ºC on kiwifruits was more significant relative to TF2ºC-5ºC. The present study provides a theoretical basis for kiwifruit during cold storage.

Chemical investigation of the Chinese soft coral Lobophytum sp. has resulted in the isolation of six new compounds, namely lobosteroids A–F (1–6), along with four known compounds. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis. These steroids characterized by either the presence of an α,β-αꞌ,βꞌ-unsaturated carbonyl or an α,β-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation sites of side chains. The prelimi-nary antibacterial bioassay showed all compounds exhibited significant antibacterial activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28 and Phoyobacterium damselae FP2244 with all inhibition rates more than 90% at the concentration of 150 µM. And at the same concentration, compounds 2, 6–10 also displayed potent inhibitory effects against vancomy-cin-resistant Enterococcus faecium bacteria G7 with all inhibition rates more than 90%.

In the present study, a nanostructured FeAl coating was prepared by cold spraying of ball milled powder. Annealing treatment was applied to the coating to investigate its effect on the microstructure, phase structure and microhardness of the cold-sprayed nanostructured FeAl coating. The results showed that the FeAl phase was kept unchangeable when the coating annealed at the temperature above 500oC. Annealing temperature significantly influenced the microstructure and microhardness of cold-sprayed FeAl coating. With raising annealing temperature, the lamellar structure in the as-sprayed coating disappeared and a dense coating microstructure with fully bonding of deposited particles at their interfaces was achieved after annealing at 950oC. Nanograin growth of the FeAl phase occurred at an annealing temperature higher than 800oC. The microhardness of cold-sprayed FeAl coating remained about 400 Hv0.1 at the annealing temperature below 800oC and decreased to 300 Hv0.1 at 1100oC.

The TGACG motif-binding factor1 (TGA1) transcription factor, a significant protein in the bZIP transcription factor family, exhibits a myriad of functions, contributes to numerous biological events, and holds substantial application potential. In this study, our analysis revealed a diverse range of photoregulatory and hormone regulatory elements within the MtTGA1 promoter region. The expression profile of MtTGA1 indicated its highest expression in the root, with its regulation influenced by SA, ABA, BR, and GA. Under salt stress conditions, transgenic plants demonstrated significantly longer root lengths and heightened activities of antioxidant enzymes such as ascorbic acid catalase (APX), peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) in their roots and leaves compared to control plants. Simultaneously, the levels of endogenous hormones ABA and BR escalated in transgenic plants, with a marked change in the morphology of their leaf cells. Transcriptome analysis identified a total of 193 differentially expressed genes, implicating a wide array of biological processes. Furthermore, we found that MtTGA1 is able to interact with Medicago truncatula SPX domain containing protein 1 (SPX1). In conclusion, the MtTGA1 transcription factor plays a crucial role in enhancing salt tolerance, which provides new insights for improving plant survival under salt stress conditions.

Diethyldithiocarbamate (DDTC) has been employed in the sulfide ore flotation process, due to its excellent collection performance. Herein, we investigated the interfacial adsorption behavior of DDTC on four mineral phases of high-sulfur residue — sulfur, pyrite, sphalerite and lead sulfate. The adsorption behavior — adsorption structure and energy and electron localization function cross section — of DDTC and H2O were explored using density function theory calculation. The result was helpful to construct a co-adsorption model of DDTC and H2O, which was validated by the pure minerals flotation operation and the characterization of fourier transform infrared spectra. The co-adsorption model indicated that the DDTC adsorption on the sulfur, sphalerite and lead sulfate was weak with physical bonding, while its adsorption on the pyrite was strong with chemical bonding. Practical bench-scale operation of high-sulfur residue flotation was performed, whose result was different from that obtained from the pure mineral flotation. To explain the difference, our developed model predictions and the mineral fugacity pattern analysis on the high-sulfur residue flotation were synergistically used. Overall, this work first proposed the co-adsorption model of DDTC and H2O and provided important insights into the interfacial adsorption in the high-sulfur residue flotation.

Surface-enhanced Raman spectroscopy (SERS) is commonly used for super-selective analysis through nanostructured silver layers in the environment, food quality, biomedicine, and materials science. To fabricate a high-sensitivity but more accessible device of SERS, dc magnetron sputtering technology was used to realize high sensitivity, low cost, stable deposition rate, and rapid mass production. This study investigated various thicknesses of a silver film ranging from 3.0 to 12.1 nm by field-emission-scanning-electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy. In the rhodamine 6G (R6G) testing irradiated by a He-Ne laser beam, the analytical enhancement factor (AEF) of 9.35x108, the limit of detection (LOD) of 10-8 M, and the relative standard deviation (RSD) of 1.61% were better than other SERS substrates fabricated by the same dc sputtering process because the results show that the 6 nm thickness silver layer has the highest sensitivity, stability, and lifetime. The paraquat and acetylcholine analytes were further investigated and high sensitivity was also achievable. The proposed SERS samples were evaluated and stored in a low humidity environment for up to forty weeks, and no spectrum attenuation could be detected. Soon, the proposed technology to fabricate high sensitivity, repeatability, and robust SERS substrate will be an optimized process technology in multiple applications.

Levels of synthetic musk fragrances (SMFs) and various personal care products (PCPs) were measured in the Han River and its tributaries in Seoul, Korea. The most abundant SMF in all river and PCP samples was 4,6,6,7,8,8-hexamethyl-1,3,4,7-tetrahydrocyclopenta[g]isochromene (HHCB), followed by 1-(3,5,5,6,8,8-hexamethyl-6,7-dihydronaphthalen-2-yl)ethanone (AHTN), musk ketone (MK), and 1,1,2,3,3-pentamethyl-2,5,6,7-tetrahydroinden-4-one (DPMI). There was a significant correlation between the SMF concentration in the PCPs and the Han River samples. Moving from upstream to downstream in the Han River, the median SMF concentration was 6.756, 2.945, 0.304, and 0.141 μg/L in the sewage treatment plant (STP) influent, effluent, tributaries, and mainstream, respectively, implying that effective SMF removal was achieved during the sewage treatment process, followed by dilution in the receiving water. Four STPs using advanced biological treatment processes had removal efficiencies of 55.8%, 50.6%, 43.3% for HHCB, AHTN, and MK, respectively. The highest SMF concentrations in the tributaries were observed at locations close to the STPs. Our study confirmed that the main source of SMFs in the receiving water were sewage effluent containing untreated SMFs, which are largely originated from household PCPs, especially hair care products (e.g., shampoo) and perfumes.

Cardiovascular disease (CVD) is the number one cause of death worldwide. This condition resulted in huge research on CVD increasing the need for animal models suitable for the in vivo research. Daphnia and Zebrafish are good animal models for cardiovascular research due to their relative body transparency and easy culture property. Several methods have been developed to conduct cardiac performance measurement in Daphnia and Zebrafish. However, most of the methods only able to obtain heartbeat rate. The other important cardiac endpoints like stroke volume, ejection fraction, fraction shortening, cardiac output and heartbeat regularity must use other programs for measurement. To overcome this limitation, in this study, we successfully developed a one-stop ImageJ-based method using kymograph macros language that able to obtain multiple cardiac performance endpoints simultaneously for the first time. To validate its utility, we incubate Daphnia magna at different ambient temperatures and exposed zebrafish with astemizole to detect the corresponding cardiac performance alterations. In summary, the kymograph method reported in this study provides a new, easy to use, and inexpensive one-stop method on obtaining multiple cardiac performance endpoints with high accuracy and convenience.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

Innovations and improvements in hydraulic fracturing and horizontal well technologies have contributed to the success of the shale gas industry; however, the industry is also challenged by freshwater use and environmental health issues. Increasing water impact makes precise quantification of water consumption important. The objective in this study was to better understand water sustainability and availability of the projected shale gas from 2018 to 2030 in the Weiyuan play, China. The water footprint framework was used to quantify the potential water use and environmental impacts on different time scales. The results showed that the water use per well ranged from 11351.3 to 60664.73 m3, with a median of 36013.94 m3, totaling ~3.44 Mm3 for 97 wells. Yearly evaluation results showed that the gray water footprint was the main contributor and accounted for 83.82% to 96.76%, which was dependent on different scenarios of treatment percentages. The monthly environmental impact results indicated that the annual streamflow statistics were more likely to prevent water withdrawal. Water quality issues may be alleviated through recycling and retreatment measures that improve current waste water management strategies. Resource regulators should manage their water resources by matching water demand to water availability or replenishment.

Purpose: To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO). Methods: In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 µM DETA-NO) on outflow facility were compared to controls (n=8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 µM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macro script and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results: The facility increased after DETA-NO (0.189±0.081 μL/min·mmHg, p=0.034) and AIT (0.251±0.094 μL/min·mmHg, p=0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (0.190±0.074 μL/min·mmHg, p=0.023) and CSA by 13.9% (p<0.001). L-NAME + ET-1 decreased CSA by -8.6% (p<0.001). NO increased the diameter of focal constrictions 5.0±3.8 fold. Conclusions: NO can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.

Digital twin technology is revolutionizing traditional manufacturing paradigms. In modern manufacturing systems, digital twin technology is fraught with challenges due to the scarcity of labeled data. Specifically, existing supervised machine learning algorithms, with their reliance on voluminous training data, find their applicability constrained in real-world production settings. This paper introduces an unsupervised 3D reconstruction approach tailored for industrial applications, aimed at bridging the data void in creating digital twin models. Our proposed model, by ingesting high-resolution 2D images, autonomously reconstructs precise 3D digital twin models without the need for manual annotations or prior knowledge. Through comparisons with multiple baseline models, we demonstrate the superiority of our method in terms of accuracy, speed, and generalization capabilities. This research not only offers an efficient approach to industrial 3D reconstruction but also paves the way for the widespread adoption of digital twin technology in manufacturing.

Lodging poses a significant challenge to rice yield, prompting the need to identify elite alleles for lodging resistance traits to improve cultivated rice varieties. In this study, a natural population of 518 rice accessions was examined to identify elite alleles associated with plant height (PH), stem diameter (SD), stem anti-thrust (AT/S), and various internode lengths: (first (FirINL), second (SecINL), third (ThirINL), fourth (ForINL), and fifth (FifINL) internode lengths). 262 SSR markers linked to these traits were uncovered through association mapping in two environmental conditions. Phenotypic evaluations revealed striking differences among cultivars, and genetic diversity assessments showed polymorphisms across the accessions. Favorable alleles were identified for PH, SD, AT/S, and 1 to 5 internode lengths, with specific alleles displaying considerable effects. Noteworthy alleles include RM6811-160 bp on chromosome 6 (which reduces PH) and RM161-145 bp on chromosome 5 (which increases SD). The study identified a total of 42 novel QTLs. Specifically, seven QTLs were identified for PH, four for SD, five for AT/S, five for FirINL, six for SecINL, five for ThirINL, six for ForINL, and four for FifINL. QTLs qAT/S-2, qPH2.1, qForINL2.1, and qFifINL exhibited the most significant phenotypic variance (PVE) of 3.99% for the stem lodging trait. AT/S, PH, ForINL and FifINL had additive effects of 5.31 kPa, 5.42 cm, 4.27cm and 4.27cm, respectively, offering insights into eight distinct cross-combinations for enhancing each trait. This research suggests the potential for cross-breeding superior parents based on stacked alleles, promising improved rice cultivars with enhanced lodging resistance to meet market demands.

Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autolo-gous cell lines. Being among the most commonly used large domesticated hoofed animals and serving as a vital source of food and bioreactors, cattle are among the many species in which PSCs have been developed. Bovine PSCs (bPSCs) are the "seed cells" of regenerative science and have immense potential to advance species propagation, genetic engineering, and disease treatment. Moreover, they can aid in screening new drugs for efficacy and toxicity, model human diseases, and establish a sustainable agricultural system that can cater to the needs of the growing global population. Establishing stable bPSCs in vitro has been a critical scientific challenge, and researchers have made numerous attempts to address this issue. This review primarily delves into the current research progress of bPSCs, the challenges faced, and their potential applications.

As an important organelle in eukaryotic cells, Golgi apparatus is responsible for processing and transporting proteins and lipids in cells. Precise monitoring the status of Golgi apparatus by targeting fluorescence imaging technology is of enormous importance but remains an attractive yet dramatically challenging task. In this study, we report the construction of the first Golgi apparatus targeted sensor with bright near-infrared fluorescence, termed as Golgi-Pdots. As a start point of our investigation, hydrophobic CDs with bright NIR fluorescence at 674 nm (fluorescence quantum yield : 12.18%), narrow emission band of 23 nm, and excellent stability were facilely prepared from Magnolia Denudata flowers through an ultrasonic method. Incorporating the CDs into a polymer matrix modified with Golgi-targeting molecules can produce the water-soluble Golgi-Pdots, which showed high colloidal stability and similar optical properties as compared to CDs. Further studies revealed that the Golgi-Pdots showed good biocompatibility and Golgi-targeting ability. Based on these fascinating properties, Golgi-Pdots have been successfully used for long term bioimaging of Golgi apparatus inside live cells.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that the E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem cell differentiation stimulators, and implantable device components due to their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.

Genome-wide association studies (GWAS) have identified and reproduced thousands of diseases associated loci but many of them are not directly interpretable due to the strong linkage disequilibrium among variants. Transcriptome-wide association studies (TWAS) incorporated expression quantitative trait loci (eQTL) cohorts as reference panel to detect associations with the phenotype at the gene level and were gaining popularity in recent years. For nicotine addiction, several important susceptible genetic variants were identified by GWAS, but TWAS that detected genes associated with nicotine addiction and unveiled the underlying molecular mechanism were still lacking. In this study, we used eQTL data from the Genotype-Tissue Expression (GTEx) consortium as reference panel to conduct tissue specific TWAS on cigarettes per day (CPD) over 13 brain tissues in two large cohorts: UK Biobank (UKBB; N=142,202) and the GWAS &amp; Sequencing Consortium of Alcohol and Nicotine use (GSCAN; N=143,210), and then meta-analyzed the results across tissues while considering the heterogeneity across tissues. We identified three major clusters of genes with different meta-patterns across tissues consistent in both cohorts, including homogenous genes associated with CPD in all brain tissues, partially homogeneous genes associated with CPD in cortex, cerebellum and hippocampus tissues, and lastly the tissue-specific genes associated with CPD in only few specific brain tissues. Downstream enrichment analyses on each gene cluster identified unique biological pathways associated with CPD and provided important biological insights into the regulatory mechanism of nicotine dependence in the brain.

The ergosterol pathway is a prime antifungal target. The minimum inhibitory concentration (MIC) assay is a simple research tool that determines the lowest concentration at which a novel antimicrobial with limited scope to determine the mechanism of action for a drug. In this study, we show that by adding hydrogen peroxide, an oxidative stressor, or glutathione (GSH), an antioxidant, to modify a commonly performed MIC assay allowed us to screen selectively for new antifungal drugs that target ergosterol biosynthesis in fungi. A human pathogen, Microsporum gypseum, was used as a test organism. When exposed to ergosterol targeting drugs, the hydrogen peroxide treatment significantly decreased fungal survival by reducing ergosterol in the cell wall, whereas GSH increased survival of M. gypseum. Further, by performing a series of experiments with M. gypseum, it was determined that the oxidative stress from hydrogen peroxide causes cell death at different developmental stages. These findings allow us to describe a simple, high-throughput method for simultaneously screening new antifungal drugs for activity and effects on the ergosterol pathway. By using this tool, two isoquinoline alkaloids were discovered to be potent inhibitors of ergosterol biosynthesis by reducing the amount of ergosterol without affecting the expression of 1,3-β-glucan.

As symbionts of fungi and algae, lichens produce a variety of secondary products which pharmacological activities. This study aimed to investigate the anti-inflammatory activities of Heterodermia hypoleuca and its main compound, atraric acid. The results confirmed that atraric acid could regulating induced pro-inflammatory cytokine, nitric oxide, induced nitric oxide synthase and cyclooxygenase-2 expression by lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Means while, atraric acid down-regulated expression of phosphorylated IκB, ERK and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results show that atraric acid has an anti-inflammatory effect and its molecular mechanism may be involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its value as a potential therapeutic for inflammatory diseases.

The objective of this study was to synthesize 9-/13-position substituted berberine derivatives and evaluated their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e) and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in compare with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at 9-/13-position of berberine may have facilitated its penetration into test cell and hence enhanced its photocytotoxicity on human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e and 7e induced HepG2 cells to arrest at S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine (1) and its derivatives 5e, 6e and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e and 7e greatly enhanced photocytotoxicity. Taking together, the test data led us to conclude that berberine derivatives with a dodecyl group at 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

It is well known that human activities and climate change have increased steppe habitat loss and fragmentation in Northwest China. Carabid beetles are often used as bioindicators of environmental change because they are extremely sensitive to disturbance. We chose 42 landscapes (18 fragmented and 24 continuous) in both desert and typical steppes of Northwest China to examine the influence of habitat loss and fragmentation on carabid beetle communities. The results showed the largest correlation coefficient between carabid communities and landscape compositions within a 7-km spatial scale in both desert and typical steppes. Further, the response of carabid communities to habitat fragmentation was species-specific in both desert and typical steppes. Habitat fragmentation in the desert steppe had positive effects on the richness and abundance of carabid communities, while in the typical steppe, the effects were negative. Additionally, habitat fragmentation significantly decreased the abundance of two common carabid species in the desert steppe. Therefore, the effects of habitat fragmentation on carabid biodiversity differ with species characteristics and habitat traits, where plant communities, soil structure, and microclimate vary in the different steppe types. The results of this study provide experimental evidence and technical support for biodiversity conservation management in the steppes of Northwest China.

In prostate cancer, p53 maximizes apoptosis in response to severe DNA damage, not DNA replication stress. Here, we examined the apoptotic response of two glioblastoma cells, p53-wild type U87 and a p53-mutated T98G cell, for the same stresses. We ascertained that p53 intensified apoptosis in response to severe DNA damage, not DNA replication stress in glioblastoma. We further asked if p53-mediated apoptosis can be induced by cellular stress other than severe DNA damage. We analyzed two compounds, bortezomib and vorinostat, respective inhibitors of 26S proteasome and histone deacetylase, to evaluate their capacity to activate p53-mediated apoptosis. The cellular stress incited by bortezomib, not vorinostat, activated p53-mediated apoptosis. Next, we asked if the cellular stress generated by combining the two compounds had a synergistic effect on apoptosis. Our results demonstrated that doxorubicin with bortezomib or CFS-1686, or bortezomib with vorinostat have a significant synergistic effect on apoptosis only in p53-wild type cell. Under high stress, p53 translocates from cytosol into the nucleus to cause apoptosis possibly. Together, p53 maximizes apoptosis for cellular stress caused by severe DNA damage, disruption of protein turnover, and for the stress induced by drug combination including doxorubicin with bortezomib or CFS-1686, and bortezomib with vorinostat.

As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl- 2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silybin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40–3.06 µM, a 17- to 52-fold improvement in potency as compared with silybin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.

Water quality monitoring was an important objective in the surroundings. In this study, we investigated the sensing characteristics of the arrayed flexible chloride sensor with XBee wireless sensing system. The sensitivity and linearity of the wireless chloride sensing devices were 91.6 mV/pCl and 0.988, respectively. The hysteresis voltages were 50.14 mV and 36.71 mV during the cycles of 1 M → 10⁻¹ M → 1 M → 10⁻³ M → 1 M and 1 M → 10⁻³ M → 1 M → 10⁻¹ M → 1 M, respectively. The selectivity coefficients of the ClO⁻ ion, ClO₄⁻ ion, NO₃⁻ ion and I⁻ ion for Cl⁻ ion were 5.0 × 10⁻², 1.0 × 10⁻¹, 5.9 × 10⁻³ and 5.6×10⁻¹, respectively. The sensing characteristics of real time measurement were investigated for dynamic microfluidic. The arrayed flexible chloride sensor was integrated with the microfluidic device, syringe pump and wireless sensing system. The sensitivity and linearity were 273.1 mV/pCl and 0.978 at 35 μL/min, respectively.

Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n=7) was significantly lower than C (20.25±1.66 mmHg, n=8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n=7) was higher than C (0.16±0.01 µl/min/mmHg, n=8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P=0.20) or outflow facility (P=0.17) further. Conclusion: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility. Translational Relevance: Microsurgical TM excision over 90° can effectively restore outflow in pigmentary glaucoma.

Herein, we introduce a boron nitride nanosheet (BNNS)-reinforced cellulose nanofiber (CNF) film as a sustainable oxygen barrier film that can potentially be applied in food packaging. Most of commodity plastics are oxygen-permeable. CNF exhibits an ideal oxygen transmittance rate (OTR) of <1 cc/m²/day in highly controlled conditions. A CNF film typically fabricated by the air drying of a CNF aqueous solution reveals an OTR of 19.08 cc/m²/day. The addition of 0-5 wt% BNNS to the CNF dispersion before drying results in a composite film with highly improved OTR, 4.7 cc/m²/day, which is sufficient for meat and cheese packaging. BNNS as a 2D nanomaterial increases the pathway of oxygen gas and reduces the chances of pin-hole formation during film fabrication involving water drying. In addition, BNNS improves the mechanical properties of the CNF films (Young’s modulus and tensile strength) without significant elongation reductions, probably due to the good miscibility of CNF and BNNS in the aqueous solution. BNNS addition also produces negligible color change, which is important for film aesthetics. An in vitro cell experiment was performed to reveal the low cytotoxicity of the CNF/BNNS composite. This composite film has great potential as a sustainable high-performance food packaging material.

Introduction The prevalence of adolescent electronic cigarette (e-cigarette) use has increased in most countries. This study determines the relation between the frequency of e-cigarette use and the frequency and intensity of cigarette smoking. Furthermore, it evaluates the association between the reasons for e-cigarette use and the frequency of its use. Materials and Methods Participants were 68,043 middle and high school students aged 13–18 years from the 2015 Korean Youth Risk Behavior Web-Based Survey. Of the 68,043 participants, we analyzed 6,655 adolescents with an experience of e-cigarette use. Results The prevalence of ever using and current (past 30 days) use of e-cigarettes was 10.1% and 3.9%, respectively. Of the ever e-cigarette users, approximately 40% used e-cigarettes for ≥1/month and 8.1% used e-cigarettes daily. Daily e-cigarettes users were 10 times greater among daily cigarette smokers than among cigarette users for <1/month (18.1% vs. 1.8%) and 16 times more prevalent among those smoking ≥20 cigarettes/day than among those smoking <1 cigarette/month (38.9% vs. 2.4%). The most common reason for e-cigarette use was curiosity (22.9%), followed by less harmful than conventional cigarettes (18.9%), smoking cessation (13.1%), and indoor use (10.7%). Curiosity was the most common reason among less frequent e-cigarette users; however, smoking cessation and indoor use were the most common reasons among more frequent users. Conclusions Results showed a positive relation between frequency or intensity of conventional cigarette smoking and frequency of e-cigarette use among Korean adolescents, and frequency of e-cigarette use differed according to the reason for the use of e-cigarettes.

River estuaries are dynamic and complex ecosystems influenced by various natural processes, including climatic fluctuations and anthropogenic activities. The Pearl River estuary (PRE), one of the largest in China, receives significant land-based pollutants due to its proximity to densely populated areas and urban development. This study aimed to characterize the composition, diversity, and distribution patterns of sediment microbial communities (Bacteria, Archaea, and Eukaryotes) and investigated the connection with environmental parameters within the PRE and adjacent shelf. Physicochemical conditions, such as oxygen levels, nitrogen compounds, and carbon content, were analyzed. The study found that the microbial community structure was mainly influenced by site location and core depth, which together explained approximately 67% of the variation in each kingdom. Sites and core depths varied in sediment properties such as organic matter content and redox conditions, leading to distinct microbial groups associated with specific chemical properties of the sediment, notably C/N ratio and NH4+ concentration. Despite these differences, certain dominant taxonomic groups were consistently present across all sites: Gammaproteobacteria in Bacteria; Bathyarchaeia, Nitrososphaeria, and Thermoplasmata in Archaea; and SAR in Eukaryota. The community diversity index was the highest in the bacteria kingdom, while the lowest values were observed at site P03 across the three kingdoms and were significantly different from all other sites. Overall, this study underscores the critical role of microbial communities in shaping biogeochemical processes in estuarine environments and their sensitivity to environmental changes, providing valuable information for managing and preserving the health of estuaries and coastal ecosystems.

Bone drilling is a common procedure used to create pilot holes for inserting screws to secure implants for fracture fixation. However, dis process can increase bone temperature, teh excessive heat can lead to cell death and thermal osteonecrosis, potentially causing early fixation failure or complications. We conducted a three-dimensional dynamic elastoplastic finite element model to evaluate teh propagation and distribution of heat during bone drilling and assess teh thermally TEMPeffected zone (TAZ) dat may lead to thermal necrosis. dis model investigates teh parameters influencing bone temperature during bone drilling, including drill diameter, rotational speed, feed force, and predrilled hole. Teh results indicate dat our FE model is sufficiently accurate in predicting teh temperature rise TEMPeffect during bone drilling. Teh maximum temperature decreases exponentially wif radial distance. When teh feed forces are 40 and 60 N, teh maximum temperature does not exceed 45 °C. However, wif feed forces of 10 and 20 N, both teh maximum temperature exceeds 45 °C wifin a radial distance of 0.2 mm, indicating a high-risk zone for potential thermal osteonecrosis. Wif teh two-stage drilling procedure, where a 2.5 mm pilot hole is pre-drilled, teh maximum temperature can be reduced by 14 °C. dis suggests dat higher feed force and rotational speed and/or using a two-stage drilling process could mitigate bone temperature elevation and reduce teh risk of thermal osteonecrosis during bone drilling.

Human Epidermal Growth Factor Receptor 2(HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced Non-Small Cell Lung Cancer (NSCLC). In the 2023 NCCN guidelines for NSCLC, Antibody-Drug Conjugate(ADC) Trastuzumab emtansine (T-DM1) is recommended for the treatment of HER2-mutant Lung Cancer (LC). However, this medication is currently not approved in certain regions.So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients.In our study of a patient with HER2 exon 20ins Lung Adenocarcinoma who had previously failed multiple TKI treatments, we discovered that Sunvozertinib could stabilize the patient's condition, achieving a progression-free survival (PFS) of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20ins patients who have failed TKI therapy.