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Objective With obesity a major health concern and call on healthcare resources in China, we explored the preferences and willingness to pay (WTP) for obesity OMC, including the influencing factors behind WTP and preferences. Method We recruited 400 obese participants to undertake a discrete choice experiment (DCE) and the contingent value method (CVM) survey. We used CVM to measure obese participants’ WTP for one-click services (OCS) and used DCE to estimate obesity participants’ preferences and WTP for OMC with different attributes. Results Obese participants were willing to pay more than RMB80 on average for OCS, and more than 50% of participants had a WTP over RMB50 and 5% had a WTP over RMB300, reflecting the strong willingness of Chinese obese patients to pay for OMC. Educational background, income, ethnicity, previous OMC experience and accessibility to offline hospitals with different levels impacted WTP. The relative importance score of attributes in descending order was cost, doctors’ hospital level, doctors’ level, online waiting time, consultation time and consultation form. Obese patients preferred lower cost, doctors from higher-level hospitals, doctors with higher expertise levels, shorter waiting time and consultation duration, and telephone consultation were preferred. 30-min waiting time, 15-min consultation duration and telephone consultation were the most economically efficient set we found. Conclusion To maximize health resources, provincial tertiary and municipal hospitals face different paths to developing obesity OMC platforms. We encouraged young doctors to use OMC. OMC regulators should implement consumer protection policies to optimize OMC pricing and address potential ‘unfair’ pricing.

Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.

As an important oil crop in China and the world, the harvesting problem of Camellia oleifera has attracted much attention. Research is needed on mechanical characteristics of harvesting equipment. Explicit dynamics was used to establish a finite element model under a simulated load response to the branch-pedicel-fruit system of C. oleifera to predict the fracture process at the pedicel junction. The separation mechanism of C. oleifera fruit was determined by measuring the constitutive parameters of fruit branches and pedicels and conducting separation experiments and explicit dynamics simulations on different hanging fruits. The maximum stress at the fruit pedicel was 1.14 MPa, and the goodness of fit between the simulation and experiment was approximately 89.5%, indicating that the branch-pedicel-fruit finite element model could accurately reflect the fruit shedding process and that the pedicel diameter was correlated positively with the separation force. This study provides technical parameters for the optimized design of existing C. oleifera harvesting equipment.

Abstract Signal transducer and activator of transcription 4 (STAT4) is a critical transcription factor for T helper cell differentiation and tumor cells. Although its prognostic role and gene function have been reported in several carcinomas, the role of STAT4 in vitro and in vivo in breast cancer remains poorly understood. The effect of STAT4 in immunotherapy is also unclear. Therefore, we integrated bulk transcriptomics, experiments, and single‐cell transcriptomics to systematically analyze its function in prognosis and signaling pathway. Several clinical breast cancer cohorts confirmed STAT4 as a T‐cell relevant prognostic biomarker. Overexpressed STAT4 increased programmed cell death ligand 1 (PD‐L1) and major histocompatibility complex class II levels in breast cancer cells. In molecular mechanism, transcriptional synergy between STAT4 and STAT3 transactivated interleukin (IL)‐12R and involved a positive feedback loop: STAT4/IL‐12R/JAK2–STAT3–STAT4, which contributed to the upregulation of PD‐L1 expression. The above signaling axis was defined as the STAT4‐related pathway and its score was used to predict T‐cell expansion and anti‐PD1 treatment response. These findings highlight a novel molecular mechanism indirectly regulating PD‐L1 through the STAT4‐related pathway: IL‐12R/JAK2–STAT3–STAT4/PD‐L1, and it has potential application in predicting anti‐PD‐1 immunotherapy response, which may pave the way for stratified immunotherapy in breast cancer.

High-frequency electromagnetic fields refer to electromagnetic waves with frequencies ranging from 100 kHz to 300 MHz. High-frequency medium heating has the advantages of uniform heating, rapid energy consumption, and environmental protection. While it has a wide range of applications, the use of high-frequency dielectric heating in the bamboo industry is rare. Understanding the influence of bamboo temperature rise rate in high-frequency heating could promote bamboo industry development. In this work, curved bamboo was tested with high-temperature energy for continuous heating. The influence of moisture content of bamboo, sample thickness, and high-frequency processing power on temperature rise rate were studied. The results showed that the water content of bamboo affected the temperature rise rate. The effect of high-frequency heating was highest when the moisture content of bamboo was close to 11%. The thickness of sample had little effect on the temperature rise rate, but the high-frequency power had a significant effect on the temperature rise rate. The temperature rise rate of the lower and higher frequency power levels increased slowly and was close to constant. The heating power was 11 kW, and the temperature rise rate was the highest.

Abstract Objectives To investigate whether intravenous thrombolysis (IVT) with alteplase (a recombinant tissue plasminogen activator, rt-PA) before endovascular treatment (EVT) is beneficial for acute ischemic stroke (AIS) patients in different periods. Methods This study enrolled a total of 140 patients hospitalized between 2019 and 2022 with AIS from large vessel occlusion (LVO) in the anterior circulation. Those patients were divided into the EVT alone group and IVT + EVT group, in which EVT was preceded by intravenous rt-PA. According to the time from onset to femoral artery puncture, the above two groups were divided into the following subgroups: 0.05). After adjusting for confounding factors, a lower incidence of intracerebral hemorrhage was observed in the EVT group (P

Abstract Background Osteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA. Methods The OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1β (10 ng/mL) in vitro. Chondrocyte viability and apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative real-time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin–eosin (H&E) staining and safranin O-fast green staining. Results Daphnoretin effectively choked IL-1β-induced chondrocyte apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1β-induced chondrocytes. What’s more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS. Conclusion Daphnoretin alleviated IL-1β-induced chondrocyte apoptosis by hindering ERS and NLRP3 inflammasome. Graphical abstract

In 1971, Folkman proposed that tumors could be limited to very small sizes by blocking angiogenesis. Angiogenesis is the generation of new blood vessels from pre-existing vessels, considered to be one of the important processes in tumor growth and metastasis. Angiogenesis is a complex process regulated by various factors and involves many secreted factors and signaling pathways. Angiogenesis is important in the transport of oxygen and nutrients to the tumor during tumor development. Therefore, inhibition of angiogenesis has become an important strategy in the clinical management of many solid tumors. Combination therapies of angiogenesis inhibitors with radiotherapy and chemotherapy are often used in clinical practice. In this article, we will review common targets against angiogenesis, the most common and up-to-date anti-angiogenic drugs and clinical treatments in recent years, including active ingredients from chemical and herbal medicines.

Pancreatic cancer is one of the most dangerous types of cancer today, notable for its low survival rate and fibrosis. Deciphering the cellular composition and intercellular interactions in the tumor microenvironment (TME) is a necessary prerequisite to combat pancreatic cancer with precision. Cancer-associated fibroblasts (CAFs), as major producers of extracellular matrix (ECM), play a key role in tumor progression. CAFs display significant heterogeneity and perform different roles in tumor progression. Tumor cells turn CAFs into their slaves by inducing their metabolic dysregulation, exacerbating fibrosis to acquire drug resistance and immune evasion. This article reviews the impact of metabolic reprogramming, effect of obesity and cellular crosstalk of CAFs and tumor cells on fibrosis and describes relevant therapies targeting the metabolic reprogramming.

The direction-of-arrival (DOA) tracking of underwater targets is an important research topic in sonar signal processing. Considering that the underwater DOA tracking is a typical multi-target problem under unknown underwater environment with missing detection, false alarm, and uncertain measurement noise, a robust underwater multi-target DOA tracking method for uncertain measurement noise is proposed. First, a kinematic model of the multiple underwater targets and bearing angle measurement model with missing detection and false alarms are established. Then, the multi-target DOA tracking algorithm is derived by using the cardinalized probability hypothesis density (CPHD) filter, the performance of which largely depends on the accuracy of the parameter of measurement noise variance. In addition, the variational Bayesian approach is used to adaptively estimate the uncertain measurement of noise variance for each measurement of target in the real time of tracking. Thus, the robust underwater multi-target DOA tracking is carried out. Finally, comprehensive experimental validations and discussions are made to prove that the proposed algorithm can provide robust DOA tracking in the multi-target tracking scenario with uncertain measurement noise.

Abstract Bearing‐only tracking of an underwater uncooperative target is essential to defend the sea territory. Considering the influences by uncertain underwater environment, the purpose of this work is to estimate 2‐D locations and velocities of an interested underwater target for non‐Gaussian environment. In this work, a fast particle filter (FPF) based on the traditional particle filter (PF) with novel jet transport (JT) technique is proposed to deal with this problem. Aiming to overcome the heavy computation burden of the traditional PF that limits most of its practical applications, the JT technique can dramatically reduce the computation time and complexity in the particle evolution process, which contributes huge computational complexities to the traditional PF. Then, the proposed FPF is tested through simulations in the 2‐D underwater uncooperative target tracking scenario. Finally, the Monte Carlo simulation results demonstrate that the proposed FPF can track the underwater uncooperative target with the similar accuracies as the traditional PF but only occupies less than 20% of the computational resources.

As the urgency for environmental sustainability escalates globally, the exploration of alternative fuels for diesel engines becomes a crucial endeavor. By combining chemical reaction kinetics and three-dimensional simulation software, the combustion and emission characteristics of a diesel engine fueled with two oxygenated fuels, hydrogenated biodiesel and ethanol, and adopting a multi-stage injection strategy were studied. The combustion mechanism of hydrogenated biodiesel ethanol diesel hybrid fuel was established, and the reaction activity of ester alcohol diesel with different mixing ratios was studied through reaction flow analysis at high and low OH temperatures. The established mechanism was coupled with CFD 2021 three-dimensional simulation software to compare the combustion and emission performance of diesel engines fueled with different ratios of ester alcohol diesel. The results show that as the proportion of ester alcohol mixture increases, at low temperatures, the OH generation rate decreases, the consumption rate increases, and the reaction activity decreases, which is not conducive to the promotion of combustion reaction; at high temperatures, the generation rate of OH increases, the consumption rate decreases, and the reaction activity increases, which is conducive to the promotion of combustion reactions. Compared to diesel, the reaction system activity of mixed fuel is enhanced, and the main peak values of cylinder pressure and instantaneous heat release rate are higher than that of diesel. The diffusion of oil and gas in the cylinder is improved. As the proportion of ester alcohol diesel mixture increases, the oxygen content increases, nitrogen oxides emissions increase compared to diesel, and soot emissions decrease compared to diesel. Soot emissions are mainly distributed in areas with a high equivalence ratio and high temperature, which is consistent with the distribution area of C2H2, the precursor of soot generation.

IntroductionIn underwater acoustic applications, the three-dimensional sound speed distribution has a significant impact on signal propagation. However, the traditional sound speed profile (SSP) measurement method requires a lot of manpower and time, and it is difficult to popularize. Satellite remote sensing can collect information on a large ocean surface area, from which the underwater information can be derived.MethodIn this paper, we propose a method for reconstructing the SSP based on an extensible end-to-end tree boosting (XGBoost) model. Combined with satellite remote sensing data and Argo profile data, it extracts the characteristic matrix of the SSP and analyzes the contribution rate of each order matrix to reduce the introduction of noise. The model inverts the SSP above 1000 m in the South China Sea by using the root mean square error (RMSE) as the precision evaluation index.ResultThe results showed that the XGBoost model could better reconstruct the SSP above 1000 m, with a RMSE of 1.75 m/s. Compared with the single empirical orthogonal function regression (sEOF-r) model of the linear regression method, the RMSE of the XGBoost model was reduced by 0.59 m/s.DiscussionFor this model, the RMSE of the inversion results was smaller, the robustness was better, and the regression performance was superior to that of the sEOF-r model at different depths. This study provided an efficient tree boosting model for SSP reconstruction, which could reliably and instantaneously monitor the 3D sound speed distribution.

Single-receiver motion parameter estimation is an effective and economical technology for passive source localization and train-bearing fault diagnosis, in which time-consuming time-frequency analysis (TFA) methods are widely used to suppress noise when extracting the continuous Doppler shift of the overhead pass. Cross-spectrum processing is a potential way to improve the computational efficiency of TFA methods, but its application is overshadowed by the phenomena of unknown Doppler shift offset and power spectrum estimation error. In this paper, conventional cross-spectrum processing is proven to be an approximation trick for power spectrum estimation in a small frequency interval, and the two phenomena are fully explained by the frequency aliasing of bandpass sampling and the approximation error. On this basis, an revised framework for applying the cross-spectrum processing is provided. Processing results of the SWellEx-96 experiment data demonstrate that the computational efficiencies of spectrogram and a parameterized TFA method could be improved up to 85% and 88.2%, respectively, without a noticeable impact on the accuracy of parameter estimates.

Abstract Background Artificial intelligence (AI) assistance has been considered as a promising way to improve colonoscopic polyp detection, but there are limited prospective studies on real‐time use of AI systems. Methods We conducted a prospective, multicenter, randomized controlled trial of patients undergoing colonoscopy at six centers. Eligible patients were randomly assigned to conventional colonoscopy (control group) or AI‐assisted colonoscopy (AI group). AI assistance was our newly developed AI system for real‐time colonoscopic polyp detection. Primary outcome is polyp detection rate (PDR). Secondary outcomes include polyps per positive patient (PPP), polyps per colonoscopy (PPC), and non‐first polyps per colonoscopy (PPC‐Plus). Results A total of 2352 patients were included in the final analysis. Compared with the control, AI group did not show significant increment in PDR (38.8% vs. 36.2%, p = 0.183), but its PPC‐Plus was significantly higher (0.5 vs. 0.4, p

BackgroundDiabetes is an independent risk factor for cognitive impairment. However, little is known about the neuroprotective effects of glucagon-like peptide 1 (GLP-1) analogs on type 2 diabetes mellitus (T2DM). Herein, we assessed the impact of GLP-1 analogs on the general cognitive functioning among patients with T2DM.MethodsRelevant studies were retrieved from PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases from their inception till June 30, 2022, without any language restrictions. For continuous variables, the mean and standard deviation (SD) were extracted. Considering the heterogeneity in general cognitive functioning assessments among the pooled studies, the standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs), were calculated.ResultsFive studies including 7,732 individuals with T2DM were selected for the meta-analysis. The use of GLP-1 analogs exerted no significant effects on the general cognitive functioning in self-controlled studies (SMD 0.33, 95% CI -0.03 to 0.69). Subgroup analyses among the self-controlled studies based on age and history of cardio-cerebrovascular disease showed that GLP-1 analogs significantly improved the general cognitive functioning in T2DM patients younger than 65 years (SMD 0.69, 95% CI 0.31 to 1.08) or those without cardio-cerebrovascular diseases (SMD 0.69, 95% CI 0.31 to 1.08). Similarly, differences in the general cognitive functioning for GLP-1 analogs between treated and non-treated patients with T2DM were significant in subgroups with patients younger than 65 years (SMD 1.04, 95% CI 0.61 to 1.47) or those with no history of cardio-cerebrovascular diseases (SMD 1.04, 95% CI 0.61 to 1.47).ConclusionLimited evidence suggests that the use of GLP-1 analogs exerts no significant effects on general cognitive functioning but may be beneficial for patients with T2DM younger than 65 years or those without a history of cardio-cerebrovascular diseases. Further prospective clinical studies with large sample sizes are needed to validate these findings.Systematic Review Registrationwww.inplasy.com, identifier 202260015.

Background: Cervical cancer (CC), as a serious menace to the health of women, has long been one of the most lethal gynecologic neoplasms throughout the world. Long non-coding RNA (LncRNA) NR2F1-AS1 has been documented to exert crucial functions in many malignant tumors. Nonetheless, the function and molecular mechanism of NR2F1-AS1 in CC remain completely unknown. Objective: This study aimed to explore the function and molecular mechanism of NR2F1-AS1 in CC. Methods: The expression levels of NR2F1-AS1, miR-642a-3p, NR2F1 in CC tissues, and cell lines were examined by reverse transcription real-time quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation and Transwell assays. The protein levels of epithelial-mesenchymal transition markers and NR2F1 in CC cells were assessed by Western blot analysis. The correlations among NR2F1-AS1, miR-642a-3p, and NR2F1 were estimated through luciferase reporter and RNA immunoprecipitation assays. Results: NR2F1-AS1 expression was clearly downregulated in CC tissues and cell lines. Molecular mechanistic experiments showed that NR2F1-AS1 overexpression upregulated NR2F1 expression in CC cells by directly binding to miR-642a-3p, and inhibiting by this way cell viability, proliferation, migration, and invasion in CC. Rescue assays showed that NR2F1 knockdown or miR-642a-3p overexpression offset NR2F1-AS1 upregulation-induced inhibition on CC cell malignant phenotypes. Conclusion: These findings revealed that NR2F1-AS1 played a tumor suppressor role in CC by mediating the miR-642a-3p/NR2F1 axis.

Sclareol, a diterpene alcohol isolated from the herbal and flavor plant clary sage (Salvia sclarea L.), is far-famed as the predominant ingredient in the refined oil of Salvia sclarea (L.). The empirical medicine of Salvia sclarea L. focused on various diseases, such as arthritis, oral inflammation, digestive system diseases, whereas the sclareol possessed more extensive and characteristic bioactivities, including anti-tumor, anti-inflammation and anti-pathogenic microbes, even anti-diabetes and hypertension. However, there is a deficiency of literature to integrate and illuminate the pharmacological attributes of sclareol based on well-documented investigations. Interestingly, sclareol has been recently considered as the potential candidate against COVID-19 and Parkinson’s disease. Accordingly, the bioactive attributes of sclareol in cancer, inflammation, even pharmacochemistry and delivery systems are reviewed for comprehensively dissecting its potential application in medicine.

Tumor angiogenesis is one of the most important processes of cancer deterioration via nurturing an immunosuppressive tumor environment (TME). Targeting tumor angiogenesis has been widely accepted as a cancer intervention approach, which is also synergistically associated with immune therapy. However, drug resistance is the biggest challenge of anti-angiogenesis therapy, which affects the outcomes of anti-angiogeneic agents, and even combined with immunotherapy. Here, emerging targets and representative candidate molecules from ethnopharmacology (including traditional Chinese medicine, TCM) have been focused, and they have been proved to regulate tumor angiogenesis. Further investigations on derivatives and delivery systems of these molecules will provide a comprehensive landscape in preclinical studies. More importantly, the molecule library of ethnopharmacology meets the viability for targeting angiogenesis and TME simultaneously, which is attributed to the pleiotropy of pro-angiogenic factors (such as VEGF) toward cancer cells, endothelial cells, and immune cells. We primarily shed light on the potentiality of ethnopharmacology against tumor angiogenesis, particularly TCM. More research studies concerning the crosstalk between angiogenesis and TME remodeling from the perspective of botanical medicine are awaited.

The bacterium Pseudomonas sp. strain JP233 has been reported to efficiently solubilize sparingly soluble inorganic phosphate, promote plant growth and significantly reduce phosphorus (P) leaching loss from soil. The production of 2-keto gluconic acid (2KGA) by strain JP233 was identified as the main active metabolite responsible for phosphate solubilization. However, the genetic basis of phosphate solubilization and plant-growth promotion remained unclear. As a result, the genome of JP233 was sequenced and analyzed in this study. The JP233 genome consists of a circular chromosome with a size of 5,617,746 bp and a GC content of 62.86%. No plasmids were detected in the genome. There were 5097 protein-coding sequences (CDSs) predicted in the genome. Phylogenetic analyses based on genomes of related Pseudomonas spp. identified strain JP233 as Pseudomonas asiatica. Comparative pangenomic analysis among 9 P. asiatica strains identified 4080 core gene clusters and 111 singleton genes present only in JP233. Genes associated with 2KGA production detected in strain JP233, included those encoding glucose dehydrogenase, pyrroloquinoline quinone and gluoconate dehydrogenase. Genes associated with mechanisms of plant-growth promotion and nutrient acquisition detected in JP233 included those involved in IAA biosynthesis, ethylene catabolism and siderophore production. Numerous genes associated with other properties beneficial to plant growth were also detected in JP233, included those involved in production of acetoin, 2,3-butanediol, trehalose, and resistance to heavy metals. This study provides the genetic basis to elucidate the plant-growth promoting and bio-remediation properties of strain JP233 and its potential applications in agriculture and industry.

Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA.

The intrusive age ranges of Linglong, Guojialing, Weideshan, and Laoshan granites in the Jiaodong Peninsula are 155–154 Ma, 131–130 Ma, 118–111 Ma, and 116 Ma, respectively. Together with the Shidao granite (227–200 Ma), five phases of magmatism can be classified by the time, all of which have different degrees of gold and polymetallic mineralization. The type of granites evolved from A–, S–type to I–, A–type from the Late Triassic to the Early Cretaceous, thus reflects the evolution of geodynamics in the Mesozoic, indicating the switch from North China Craton (NCC)–Yangtze Craton (YC) collision to subduction of the Paleo–Pacific Plate (PPP), with crustal thickening switching to lithospheric thinning and a compressional tectonic setting changing to an extensional setting. It directly leads to a series of extensional structures evolving in the Jiaodong Peninsula and demonstrates affinity for the extensive mineralization in the Early Cretaceous. The key markers of Jiaodong gold and polymetallic mineralization are magmatism, fluid activity and extensional structure. Extensive magmatic uplift and extensional structures in the Early Cretaceous formed the extensional tectonic system. During the formation process, a large proportion of crust and mantle materials exchanged and mixed, and the fluid interaction was highly active, resulting in a magmatic fluid metallogenic system, which provided favorable metallogenic conditions for gold and nonferrous metal hydrothermal deposits. Thus, a large-scale explosive mineralization occurred in Jiaodong in the middle and late Early Cretaceous.

A low molecular weight fucosylated glycosaminoglycan sodium (LFG-Na) is a novel anticoagulant candidate from the sea cucumber Holothuria fuscopunctata that selectively inhibits intrinsic tenase (iXase). The molecular weight, molecular weight distribution and bioactivities are the critical quality attributes of LFG-Na. The determination of these quality attributes of such an oligosaccharides mixture drug is challenging but critical for the quality control process to ensure its safety and efficacy in clinical use. Herein, the molecular weight and molecular weight distribution of LFG-Na were successfully determined using high performance size exclusion chromatography coupled with multi angle laser light scattering and refractive index detector (HPSEC-MALLS-RID). Comparing to the conventional method, HPSEC-MALLS-RID based on the refractive index increment (dn/dc) did not require the reference substances to establish the calibration curve. The acceptance criteria of LFG-Na were established, the weight-average molecular weight (Mw) should be 4000 to 6000 Da, the polydispersity (Mw/Mn) < 1.40, and the fraction with molecular weights of 1500 to 8000 Da should be no less than 80% of the total. HPSEC-MALLS-RID was also utilized for the determination of the starting material native fucosylated glycosaminoglycan (NFG) to choose a better manufacturing process. Furthermore, APTT assay was selected and the potency of anti-iXase, referring to the parallel line assay (PLA) method, was established to clarify the consistency of its biological activities. The results suggest that HPSEC-MALLS-RID and bioactivity assays are critical quality control methods for multi-component glycosaminoglycan LFG-Na. The methods also provide a feasible strategy to control the quality of other polysaccharide medicines.

Algorithms working in mode space instead of directly matching the received complex sound pressure were developed to improve computational efficiency and robustness, but these algorithms may be inconvenient to apply in practice because manual operations are often inevitable when performing modal filtering. Based on a phase-matched filter, an imperfect matching scheme named the modal phase based matched impulse response (MP-MIR) is proposed to estimate the source range rapidly and conveniently with a single hydrophone. The field to be matched is still the received complex sound pressure. The replica field is a sum of several “phase” modes, which can be efficiently and conveniently synthesized merely with the horizontal wavenumbers of normal modes and the source–receiver range. The effectiveness of the proposed MP-MIR was demonstrated in localizing 84 emissions along a weakly range-dependent track at ranges of 2.54–20 km in the South China Sea. Although it was found, from cross-correlation coefficients, that the received signals showed strong variation even between adjacent emissions, MP-MIR outperformed the classical matched impulse response (MIR) with a lower standard deviation in most cases, demonstrating good robustness and potential for practical applications.

The performance of warping transformation in diminishing the error in underwater source-bearing estimation, caused by horizontal refraction effects (also named 3D effects), is studied. First, the capability of warping transformation for separating the normal modes, as well as their direct and horizontally refracted paths, in a standard Acoustical Society of America (ASA) wedge is demonstrated. Second, the error values for source bearing estimation in three different manners, i.e., using the full signal, using its component corresponding to the first mode, and using the component of the latter corresponding only to the direct path are compared for the same wedge case. The results show that the estimation error can be significantly reduced by beamforming, with only the first mode, or using the direct path of the first mode in cases where there exists a horizontally refracted path of the first mode.

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men, respectively, worldwide. Although the antitumor activity of chalcones has been extensively studied, the molecular mechanisms of isoliquiritigenin analog 2', 4', 4-trihydroxychalcone (metochalcone; TEC) against carcinomas remain less well understood. In this study, we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner. TEC induced cell cycle arrest in the S-phase, cell migration inhibition in vitro, and reduced tumor growth in vivo. Moreover, transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways. TEC triggered the senescence-associated secretory phenotype (SASP) by repressing the JAK2/STAT3 axis. The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway, highlighting the potential of chalcone in senescence-inducing therapy against carcinomas. [ABSTRACT FROM AUTHOR]