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Abstract Challenges in enabling next-generation rechargeable batteries with lower cost, higher energy density, and longer cycling life stem not only from combining appropriate materials, but from optimally using cell components. One-size-fits-all approaches to operational cycling and monitoring are limited in improving sustainability if they cannot utilize and capture essential chemical dynamics and states of electrodes and electrolytes. Herein we describe and show how the use of tilted fiber Bragg grating (TFBG) sensors to track, via the monitoring of both temperature and refractive index metrics, electrolyte-electrode coupled changes that fundamentally control lithium sulfur batteries. Through quantitative sensing of the sulfur concentration in the electrolyte, we demonstrate that the nucleation pathway and crystallization of Li2S and sulfur govern the cycling performance. With this technique, a critical milestone is achieved, not only towards developing chemistry-wise cells (in terms of smart battery sensing leading to improved safety and health diagnostics), but further towards demonstrating that the coupling of sensing and cycling can revitalize known cell chemistries and break open new directions for their development.

Lithium–sulfur batteries are considered as promising candidates for next‐generation energy storage devices for grid applications due to their high theoretical energy density. However, the inevitable shuttle effect of lithium polysulfides and/or dendrite growth of Li metal anodes hinder their commercial viability. Herein, the microporous Zr fumarate metal–organic framework (MOF)‐801(Zr) is considered to produce thin (≈15.6 μm, ≈1 mg cm2) mixed‐matrix membranes (MMM) as a novel interlayer for Li–S batteries. It is found that the MOF‐801(Zr)/C/PVDF‐HFP composite interlayer facilitates Li+ ions diffusion, and anchors polysulfides while promoting their redox conversion effectively. It is demonstrated that MOF‐801 effectively trapped polysulfides at the cathode side, and confirmed for the first time the nature of the interaction between the adsorbed polysulfides and the host framework, through a combination of solid‐state nuclear magnetic resonance and molecular dynamics simulations. The incorporation of MOF‐801(Zr)/C/PVDF‐HFP MMM interlayer results in a notable enhancement in the initial capacity of Li–S batteries up to 1110 mA h g−1. Moreover, even after 50 cycles, a specific capacity of 880 mA h g−1 is delivered.

BackgroundNeoadjuvant immunotherapy with anti-programmed death-1 (neo-antiPD1) has revolutionized perioperative methods for improvement of overall survival (OS), while approaches for major pathologic response patients’ (MPR) recognition along with methods for overcoming non-MPR resistance are still in urgent need.MethodsWe utilized and integrated publicly-available immune checkpoint inhibitors regimens (ICIs) single-cell (sc) data as the discovery datasets, and innovatively developed a cell-communication analysis pipeline, along with a VIPER-based-SCENIC process, to thoroughly dissect MPR-responding subsets. Besides, we further employed our own non-small cell lung cancer (NSCLC) ICIs cohort’s sc data for validation in-silico. Afterward, we resorted to ICIs-resistant murine models developed by us with multimodal investigation, including bulk-RNA-sequencing, Chip-sequencing and high-dimensional cytometry by time of flight (CYTOF) to consolidate our findings in-vivo. To comprehensively explore mechanisms, we adopted 3D ex-vivo hydrogel models for analysis. Furthermore, we constructed an ADGRE5-centered Tsurv model from our discovery dataset by machine learning (ML) algorithms for a wide range of tumor types (NSCLC, melanoma, urothelial cancer, etc.) and verified it in peripheral blood mononuclear cells (PBMCs) sc datasets.ResultsThrough a meta-analysis of multimodal sequential sc sequencing data from pre-ICIs and post-ICIs, we identified an MPR-expanding T cells meta-cluster (MPR-E) in the tumor microenvironment (TME), characterized by a stem-like CD8+ T cluster (survT) with STAT5-ADGRE5 axis enhancement compared to non-MPR or pre-ICIs TME. Through multi-omics analysis of murine TME, we further confirmed the existence of survT with silenced function and immune checkpoints (ICs) in MPR-E. After verification of the STAT5-ADGRE5 axis of survT in independent ICIs cohorts, an ADGRE5-centered Tsurv model was then developed through ML for identification of MPR patients pre-ICIs and post-ICIs, both in TME and PBMCs, which was further verified in pan-cancer immunotherapy cohorts. Mechanistically, we unveiled ICIs stimulated ADGRE5 upregulation in a STAT5-IL32 dependent manner in a 3D ex-vivo system (3D-HYGTIC) developed by us previously, which marked Tsurv with better survival flexibility, enhanced stemness and potential cytotoxicity within TME.ConclusionOur research provides insights into mechanisms underlying MPR in neo-antiPD1 and a well-performed model for the identification of non-MPR.

Abstract Background Some clinical researchers have reported that patients with cCR (clinical complete response) status after neoadjuvant chemoradiotherapy (nCRT) could adopt the watch-and-wait (W&W) strategy. Compared with total mesorectal excision (TME) surgery, the W&W strategy could achieve a similar overall survival. Could the W&W strategy replace TME surgery as the main treatment option for the cCR patients? By using the meta-analysis method, we evaluated the safety and efficacy of the W&W strategy and TME surgery for rectal cancer exhibiting cCR after nCRT. Methods We evaluated two treatment strategies for rectal cancer with cCR after nCRT up to July 2021 by searching the Cochrane Library, PubMed, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Clinical data for primary outcomes (local recurrence, cancer-related death and distant metastasis), and secondary outcomes (disease-free survival (DFS) and overall survival (OS)) were collected to evaluate the efficacy and safety in the two groups. Results We included nine studies with 818 patients in the meta-analysis, and there were five moderate-quality studies and four high-quality studies. A total of 339 patients were in the W&W group and 479 patients were in the TME group. The local recurrence rate in the W&W group was greater than that in the TME group in the fixed-effects model (OR 8.54, 95% CI 3.52 to 20.71, P < 0.001). The results of other outcomes were similar in the two groups. Conclusion The local recurrence rate of the W&W group was greater than that in the TME group, but other results were similar in the two groups. With the help of physical examination and salvage therapy, the W&W strategy could achieve similar treatment effects with the TME approach. Trial registration Protocol registration number: CRD42021244032 .

Providing equal geographical access to hospitals, either in the public or private healthcare sector, is vital and will benefit public health in general. Against the background of the partial privatization of the healthcare sector, the impact of private hospitals on equal healthcare access has been a highly neglected issue. We have applied an assessment methodology to study this situation by comparing the status quo scenario with one without private hospitals, based on accessibility analysis and spatial equality measurements. The case study of Beijing, China revealed a double-sided impact. With the presence of private hospitals, the Gini coefficient of spatial accessibility in urban districts was reduced from 0.03391 to 0.03211, while it increased from 0.1734 to 0.1914 in suburban districts. Thus, private hospitals improved spatial equality in urban districts in Beijing but jeopardized it in suburban districts. These research findings should enlighten policymakers to promote healthcare equality but would also need to be repeated in some other big cities.

Background. Osteoarthritis (OA) is a common chronic disease with numerous and interacting influencing factors, and current inadequate patient perceptions and behaviors in access to care contribute to the difficulties in the diagnosis, treatment, and management of osteoarthritis. Objective. The purpose of this study was to investigate the influencing factors of osteoarthritis (OA) in a southern Chinese population and to provide a scientific basis for the prevention and treatment of OA. Methods. A 1 : 2 matched case-control study was used to select 160 patients with OA from three hospitals in southern China as a case group. Three hundred and twenty cases of the same sex and similar age (within ± 2 years) were selected as the control group, and relevant data were collected for univariate and multivariate conditional logistic regression analysis. Results. There were no significant differences between the two groups of participants in terms of age, sex, and education (P>0.05). Logistic regression statistical analysis showed that genetic factors (OR = 4.52, 95% CI = 1.56–7.83), body mass index (OR = 2.57, 95% CI = 1.16–5.84), alcohol consumption (OR = 3.81, 95% CI = 1.53–5.87), and a history of external joint limb injury (OR = 3.37, 95% CI = 1.67–5.24) would increase the risk of OA. In contrast, eating more fresh vegetables (OR = 0.08, 95% CI = 0.03–0.31), more fresh fruits (OR = 0.34, 95% CI = 0.12–0.96), more soy products (OR = 0.11, 95% CI = 0.04–0.45), and exposure to sunlight (OR = 0.31, 95% CI = 0.14–0.71) would reduce the OA risk of OA. Conclusion. Obesity, alcohol consumption, and a history of joint trauma all increase the risk of OA in a southern Chinese population, whereas a diet rich in fresh vegetables, fresh fruit, soy products, and sun exposure would reduce the risk of OA. In the future, we should focus on improving patients’ awareness of medical care and developing their self-management skills, improving GPs’ treatment skills, improving negative attitudes of both doctors and patients, and promoting positive patient care.

This study presents a new approach to the optimal placement of voltage sag monitors considering the uncertainties associated with transition resistance. The influence of transition resistance on the magnitude of voltage sags triggered by symmetrical and unsymmetrical faults is analyzed. Then the transition resistance interval set array for voltage sags is established, on the basis of which, a random vector model on voltage sag observability is proposed and related observability indices are defined in the form of conditional probability. The optimal placement model is established by taking the available number of monitors as the constraint condition and the maximum sag global observability index as the objective function. Binary particle swarm optimization (BPSO) is implemented to obtain the optimal placement results. Finally, simulation is carried out on IEEE 30-bus system, and it is shown that the proposed optimal monitor placement method is more applicable compared with the traditional MRA method.

Abnormal RNA m6A methylation is known to lead to the occurrence and progression of multiple cancers including gastric cancer (GC). However, the integrative effects of all m6A methylation regulators on GC prognosis are unclear. Our research aimed to globally analyze the prognosis values of all 33 m6A RNA methylation regulators in GC by univariate and multivariate Cox regression analyses. Among all 33 m6A RNA methylation regulators, fat mass and obesity-associated protein (FTO), an m6A demethylase, was identified as a key prognostic risk factor on overall survival (OS) of GC patients. It was found that FTO could promote GC cell migration and invasion abilities, and we predicted that ITGB1 was a demethylated target of FTO. Knockdown (KD) of FTO significantly down-regulated ITGB1 expression at both mRNA and protein levels and augmented ITGB1 mRNA m6A modification level. Moreover, overexpression (OE) of ITGB1 could partially reverse FTO-KD-inhibited migration and invasion of GC cells. Our study found that FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin β1(ITGB1) via decreasing its m6A level. These results indicated that FTO can be a potent GC biomarker for prognosis prediction as well as a potential target in GC treatment.

Patients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent need to explore the key genes that affect the prognosis and develop potentially effective drugs in EGFR-WT NSCLC patients. In this study, we clustered functional modules related to the survival traits of EGFR-WT patients using weighted gene co-expression network analysis (WGCNA). We used these data to establish a two-gene prognostic signature based on the expression of CYP11B1 and DNALI1 by combining the least absolute shrinkage and selection operator (LASSO) algorithms and Cox proportional hazards regression analysis. Following the calculation of risk score (RS) based on the two-gene signature, patients with high RSs showed a worse prognosis. We further explored targeted drugs that could be effective in patients with a high RS by the connectivity map (CMap). Surprisingly, multiple HDAC inhibitors (HDACis) such as trichostatin A (TSA) and vorinostat (SAHA) that may have efficacy were identified. Also, we proved that HDACis could inhibit the proliferation and metastasis of NSCLC cells in vitro. Taken together, our study identified prognostic biomarkers for patients with EGFR-WT NSCLC and confirmed a novel potential role for HDACis in the clinical management of EGFR-WT patients.

Succinylation is a newly discovered and multienzyme-regulated post-translational modification (PTM) that is associated with the initiation and progression of cancer. Currently, no systematic analyses on the role of succinylation regulators in tumors have been reported. In this study, we performed a comprehensive pan-cancer analysis on four well-known succinylation regulators (CPT1A, KAT2A, SIRT5, and SIRT7). We found that these regulators played specific and critical roles in the prognosis of clear cell renal cell carcinoma (ccRCC). We constructed a risk score (RS) based on two independent prognostic prediction factors, CPT1A and KAT2A, and subsequently developed a nomogram model containing the RS, which showed good accuracy in the prediction of overall survival (OS) in ccRCC patients. Furthermore, we used the similar expression pattern of four succinylation regulators according to consensus clustering analysis to divide the patients into three clusters that exhibited prominently different OS as well as clinicopathological characteristics. Differently expressed genes (DEGs) and pathway enrichment analyses of three clusters indicated that succinylation regulators might promote malignant progression of ccRCC by regulating the infiltration of immune cells and RNA N6-methyladenosine (m6A) methylation. Importantly, our data suggest that CPT1A and SIRT5 might up-regulate and down-regulate the expression of LRPPRC and EIF3B, respectively. Our study systematically analyzed the prognostic predictive values of four succinylation regulators and revealed their potential mechanisms in ccRCC aggressiveness. These data provide new insight into the understanding of succinylation modification and present clinical evidence for its role in ccRCC treatments.

As a vital feature of the microenvironment, hypoxia, especially long-term hypoxia, is known to promote metastasis and lead to poor prognosis in solid tumors. Circular RNAs (circRNAs) participate in important processes of cell proliferation and metastasis in cancers. However, the contribution of circRNAs to metastasis under long-term hypoxia is obscure. In this study, we aim to explore specific functions of circHIPK3 in long-term hypoxia-promoting metastasis of gastric cancer (GC). The hypoxic resistant gastric cancer (HRGC) cell lines we established previously, which were tolerant to 2% O2 conditions, were used as the long-term hypoxia model. We found that circHIPK3 was upregulated by HIF-2α in HRGC cells, and circHIPK3 facilitated the migration and invasion ability of HRGC cells. Further investigation proved that circHIPK3 promoted metastasis of HRGC cells directly by interacting with miR-653-5p and miR-338-3p to relieve the suppression of neuropilin 1 (NRP1), resulting in the activation of downstream ERK and AKT pathways. Our study identified oncogene functions of circHIPK3 under a long-term hypoxic microenvironment and the possibility of using circHIPK3 as a potential biomarker of long-term hypoxia in GC. In conclusion, circHIPK3 could promote GC metastasis via the miR-653-5p/miR-338-3p-NRP1 axis under a long-term hypoxic microenvironment.

Variable frequency drives (VFDs) are the types of power electronic device commonly used to drive motors with a wide range of industrial and practical applications, especially in power systems. VFDs are sensitive to voltage sag, thereby limiting their application. However, the difficulty in determining the detailed voltage sag tolerance characteristics of VFDs is due to various influencing factors, and the tolerance curve obtained from test results is updated as mainstream low-voltage VFDs change. This paper is the first to perform an in-depth analysis on the influence and operation mechanism of voltage sags on VFDs. Voltage sag types, which are regarded as the important influencing factors, are explored for their different impacts on VFDs from the perspective of energy. Then, eight commonly used low-voltage VFDs with small and medium powers (7.5 and 18.5 kW) are selected as the test objects. The influence of voltage sags on VFDs is tested, and the equipment parameters (protection modes and control modes of VFDs, and load torque and speed) and voltage sag characteristics factors (sag types, voltage magnitude before voltage sag, and harmonics) are considered. Finally, the general tolerance curves of the low-voltage VFDs under different sag types are extracted via comprehensive analyses and processing of more than 13 000 sets of test data. Based on the test data, this paper further explores the influence of voltage sag on the motor by using the permanent magnet synchronous motor (PMSM) as an example, which is used as the load during the tolerance test. Operation performance of the PMSM driven by different VFDs is also discussed.

Coronavirus disease 2019 (COVID-19) has spread rapidly and led to over 5 million deaths to date globally. Due to the successively emerging mutant strains, therapeutics and prevention against the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are urgently needed. Prevention of SARS-CoV-2 infection in public and hospital areas is essential to reduce the frequency of infections. Silver nanoparticles (AgNPs) with virucidal effects have been reported. Therefore, we investigated the virucidal activity and safety of ten types of AgNPs with different surface modifications and particle sizes, in cells exposed to SARS-CoV-2 in vitro. The AgNPs could effectively inhibit the activity of SARS-CoV-2, and different surface modifications and particle sizes conferred different virucidal effects, of which 50-nm BPEI showed the strongest antiviral effect. We concluded that the efficacy of each type of AgNP type was positively correlated with the corresponding potential difference (R2 = 0.82). These in vitro experimental data provide scientific support for the development of therapeutics against COVID-19, as well as a research basis for the development of broad-spectrum virucides. Given the increasing acquired resistance of pathogens against conventional chemical and antibody-based drugs, AgNPs may well be a possible solution for cutting off the route of transmission, either as an external material or a potential medicine.

The effects of dietary lipid source (corn germ vs. corn oil) on digestible energy (DE) and apparent total tract digestibility (ATTD) of various chemical constituents were evaluated in diets fed to growing pigs. Thirty barrows were allotted to one of five treatments with six replicates per treatment. The five diets were comprised of a corn-based basal diet with 15.64 MJ/kg of GE, LCO and LCG diets (containing 1% extracted corn oil or 2% corn germ, respectively) were formulated to maintain 16.00 MJ/kg of GE, as well as HCO and HCG diets (containing 2% extracted corn oil or 12% corn germ, respectively) were formulated to maintain 16.94 MJ/kg of GE. The differences in ATTD of NDF and ADF were neither observed between the LCO and LCG diet nor between the HCO and HCG diet. LCO diet had greater DE and ATTD of GE and EE (p

Genome engineering is a powerful approach to study how chromosomal architecture impacts phenotypes. However, quantifying the fitness impact of translocations independently from the confounding effect of base substitutions has so far remained challenging. We report a novel application of the CRISPR/Cas9 technology allowing to generate with high efficiency both uniquely targeted and multiple concomitant reciprocal translocations in the yeast genome. Targeted translocations are constructed by inducing two double-strand breaks on different chromosomes and forcing the trans-chromosomal repair through homologous recombination by chimerical donor DNAs. Multiple translocations are generated from the induction of several DSBs in LTR repeated sequences and promoting repair using endogenous uncut LTR copies as template. All engineered translocations are markerless and scarless. Targeted translocations are produced at base pair resolution and can be sequentially generated one after the other. Multiple translocations result in a large diversity of karyotypes and are associated in many instances with the formation of unanticipated segmental duplications. To test the phenotypic impact of translocations, we first recapitulated in a lab strain the SSU1/ECM34 translocation providing increased sulphite resistance to wine isolates. Surprisingly, the same translocation in a laboratory strain resulted in decreased sulphite resistance. However, adding the repeated sequences that are present in the SSU1 promoter of the resistant wine strain induced sulphite resistance in the lab strain, yet to a lower level than that of the wine isolate, implying that additional polymorphisms also contribute to the phenotype. These findings illustrate the advantage brought by our technique to untangle the phenotypic impacts of structural variations from confounding effects of base substitutions. Secondly, we showed that strains with multiple translocations, even those devoid of unanticipated segmental duplications, display large phenotypic diversity in a wide range of environmental conditions, showing that simply reconfiguring chromosome architecture is sufficient to provide fitness advantages in stressful growth conditions.

Corn bran (CB) has been used as an ingredient for pigs, but the underlying mechanisms that improve gut health is less clear. This study was conducted to investigate effects of dietary CB on growth performance, nutrient digestibility, plasma indices related to gut hormones and immunity, gut microbiota composition, and fermentation products in weaned pigs. A total of 60 weaned pigs were allocated to two dietary treatments, and piglets in each group received control (CON) diet or 5% CB diet for 28 days. Growth performance, nutrient digestibility, indices of gut hormones and immunity in plasma were evaluated. Microbiota composition in feces was determined using 16S rRNA amplicon sequencing, and fermentation products were measured by high-performance ion chromatography. The results showed that dietary CB did not affect growth performance, nutrient digestibility, gut hormones, or fermentation products in the trial (P > 0.05). There was an increased response to CB inclusion on interleukin-10 production (P < 0.05). On day 28, piglets fed dietary CB had a higher shannon index (P < 0.05). The population of the Firmicutes in CB treatment were decreased (P < 0.05), while the percentage of the Bacteroidetes were increased (P < 0.05). In particular, the populations of Eubacterium corprostanoligenes, Pevotella, and Fibrobacter related to polysaccharide fermentation of cereal bran were increased (P < 0.05). In conclusion, a post-weaning diet containing 5% CB increased intestinal microbial diversity, especially higher richness of fibrolytic bacteria, and promoted anti-inflammatory response to some extent in piglets, these changes should facilitate the adaptation of the digestive system of piglets in the subsequent growing phases.

Abstract The X‐linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology. Here, we identify a family with hemophilia B carrying a novel mutation, Y371D, in the human F9 gene. The CRISPR/Cas9 system was used to generate distinct genetically modified mouse models and confirmed that the novel Y371D mutation resulted in a more severe hemophilia B phenotype than the previously identified Y371S mutation. To develop therapeutic strategies targeting this mutation, we subsequently compared naked DNA constructs versus adenoviral vectors to deliver Cas9 components targeting the F9 Y371D mutation in adult mice. After treatment, hemophilia B mice receiving naked DNA constructs exhibited correction of over 0.56% of F9 alleles in hepatocytes, which was sufficient to restore hemostasis. In contrast, the adenoviral delivery system resulted in a higher corrective efficiency but no therapeutic effects due to severe hepatic toxicity. Our studies suggest that CRISPR/Cas‐mediated in situ genome editing could be a feasible therapeutic strategy for human hereditary diseases, although an efficient and clinically relevant delivery system is required for further clinical studies.

Solid-state fermentation of feedstuffs by Bacillus subtilis MA139 can reduce insoluble dietary fiber content in vitro and improve growth performance in pigs. This study was conducted to investigate the effects of dietary corn bran (CB) fermented by B. subtilis on growth performance and gut microbiota composition in finishing pigs. A total of 60 finishing pigs were allocated to 3 dietary treatments consisting of a control (CON) diet, a 10% CB diet, and a 10% fermented CB (FCB) diet in a 21 d feeding trial. Growth performance and nutrient digestibility were evaluated. Fecal samples were determined for bacterial community diversity by 16S rRNA gene amplicon sequencing. The dietary CB and FCB did not affect growth performance of finishing pigs. The digestibility of organic matter was decreased in both CB and FCB treatments compared with CON group (P < 0.05). The α-diversity for bacterial community analysis of Chao 1 in FCB treatment was lower than CON treatment (P < 0.05). The Fibrobacteres phylum belongs to cellulolytic bacteria was isolated, and their relative abundance in CB group showed no difference between CON and FCB treatments. The abundance of Lachnospiraceae_NK4A136_group in CB treatment was higher than CON and FCB groups (P < 0.05), whereas the population of norank_f_Prevotellaceae was higher in FCB group compared to CON and CB groups (P < 0.05). In conclusion, dietary FCB decreased the abundance of bacterial communities, particularly the population of bacteria related to cellulolytic degradation.

Rocuronium is an acceptable alternative when succinylcholine is contraindicated for facilitating the endotracheal intubation. However, the onset time of rocuronium for good intubation condition is still slower than that condition of succinylcholine. This study systematically investigated the most efficacious pharmacological interventions for accelerating the onset time of rocuronium.Medline, Embase, Cochrane Library databases, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers were searched for randomized controlled trials comparing drug interventions with placebo or another drug to shorten the onset time of rocuronium. Statistical analyses were performed using RevMan5.2 and ADDIS 1.16.5 softwares. Mean differences (MDs) with their 95% confidence intervals (95% CIs) were used to analyze the effects of drug interventions on the onset time of rocuronium.43 randomized controlled trials with 2,465 patients were analyzed. The average onset time of rocuronium was 102.4±24.9 s. Priming with rocuronium [Mean difference (MD) -21.0 s, 95% confidence interval (95% CI) (-27.6 to -14.3 s)], pretreatment with ephedrine [-22.3 s (-29.1 to -15.5 s)], pretreatment with magnesium sulphate [-28.2 s (-50.9 to -5.6 s)] were all effective in reducing the onset time of rocuronium. Statistical testing of indirect comparisons showed that rocuronium priming, pretreatment with ephedrine, and pretreatment with magnesium sulphate had the similar efficacy.Rocuronium priming, pretreatment with ephedrine, and pretreatment with magnesium sulphate were all effective in accelerating the onset time of rocuronium, and furthermore their efficacies were similar. Considering the convenience and efficacy, priming with rocuronium is recommended for accelerating the onset time of rocuronium. However, more strict clinical trials are still needed to reach a more solid conclusion due to the large heterogeneities exist among different studies.

Abstract Background Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. Methods The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. Results TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. Conclusions TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

The International Convention for the Safety of Life at Sea (SOLAS) stipulates that all ships must be equipped with lifesaving devices. The freefall lifeboat has the advantages of simple operation, fast release speed, and good safety performance, so it is widely used. The interaction between the hull and the water body of the freefall lifeboat during the water entry process is a complex fluid–structure interaction process that has great influence on the motion characteristics and structural force of the lifeboat. In order to improve the safety of lifeboats used in the lifesaving process, this paper establishes a 3D, full-scale model of a lifeboat and the fluid area, uses the ALE method to deal with the fluid–structure interaction problem, and numerically simulates the water entry of a lifeboat. Key information such as the hull motion trajectory, motion speed, and impact load are obtained, and three typical modes of lifeboat movement are summarized. At the same time, the influence of different skid angles, skid heights, and skid lengths on the lifeboat launch process is explored. The results show that increasing the angle, height, and length of the skid to a certain extent is conducive to the rapid escape of the lifeboat from a danger zone. The research results of this paper can provide a reference for the design of lifesaving systems for offshore floating facilities such as ships, which is of great significance for ensuring the safety of marine personnel.

After the merger of China’s Ministry of Culture and the National Tourism Administration into the Ministry of Culture and Tourism in 2018, there was a strong push to advance the strategy of culture–tourism integration, which has shown significant effects on the economy and society. Building on this success, the Chinese government proposed the strategy of agriculture–culture–tourism integration in 2023. However, its impact on the agricultural sector remains unclear. This study employs field theory to explain the impact of culture–tourism integration on the agricultural sector. Drawing from the relevant literature, we construct and statistically analyze the Culture–Tourism Coupling Coordination Degree (CTCCD). Utilizing provincial panel data from China from 2000 to 2022, we employ two-way fixed-effects panel regression to empirically estimate and analyze the effects of the CTCCD on the agricultural GDP, Total Factor Productivity (TFP), and various aspects of crop farming. Our findings reveal several key insights: (i) the CTCCD exhibits a significant negative impact on both agricultural GDP and TFP; (ii) the CTCCD negatively affects the proportion of crop farming within the agricultural sector, suggesting that culture–tourism integration results in weaker development of crop farming compared to forestry, animal husbandry, and fisheries; (iii) the CTCCD demonstrates significant negative effects on the sown area, yield per unit area, and total production of food crops, while positively influencing the per capita income of agricultural workers. These empirical results highlight the complex relationship between culture–tourism integration and agricultural development. Our analysis provides quantitative evidence of the trade-offs involved in pursuing integrated development strategies, adding to the existing research on rural development. The findings indicate that promoting agriculture–culture–tourism integration should be balanced with efforts to accelerate agricultural technological progress.

In ocean engineering, interactions between ocean currents and risers lead to regular vortex shedding on both sides of the riser, causing structural deformation. When the frequency of vortex shedding approaches the natural frequency of the structure, resonance occurs, significantly increasing deformation. This phenomenon is a critical cause of riser failure. Therefore, the dynamic response of flexible risers to vortex-induced vibrations (VIV) is crucial for their structural safety. This paper employs the finite-volume method to integrate over control volumes to solve for forces, such as pressure and shear stress, on the surface of the riser, while the finite-element method discretizes the continuous structural body into elements and nodes to solve for structural displacements and stresses. A strongly coupled method is utilized at each timestep to iteratively transfer load-displacement data between the fluid and structural fields, updating the boundary conditions of the fluid domain to achieve a bidirectional fluid–structure interaction simulation of vortex-induced vibrations in a seawater environment for flexible risers. The study finds that the three-dimensional flexible riser exhibits multi-frequency vibration phenomena and broadband vibration response characteristics under high flow velocity conditions. As the flow velocity increases, the vortex-shedding mode is observed to transition from the simple two single (2S) mode to the more complex pair + single (P + S) and two pair (2P) modes. In addition, the stiffness at the ends is enhanced by the fixed boundary conditions, and the coupling between the natural frequency of the ends and the vortex-shedding frequency triggers complex vortex-shedding phenomena in these regions. At higher flow velocities, these boundary effects result in more complex vortex-shedding modes and stronger vibration responses at both ends of the riser.

This study conducted numerical simulations of three-dimensional vortex-induced vibrations (VIV) on cylindrical bodies with various surface protrusion coverage rates, systematically investigating the impact of coverage and protrusion height on the vibrational response of flexible cylinders. The fluid forces on the surface of the riser were resolved using the finite volume method, while the structural forces were solved with the finite element method. A strongly coupled approach was employed for iterative updates between the flow field and structural field data, achieving a bidirectional flow–structure coupling simulation of VIV in a marine environment. The study further explored the performance of surface protrusions in suppressing VIV and considered protrusion heights of 0.1 times the cylinder diameter (0.1D) under coverage rates (CR) of 0%, 10%, 20%, 30%, and 40%, as well as seven different protrusion heights of 0.05D, 0.1D, and 0.15D at a 20% coverage rate. The mechanism of VIV suppression by surface protrusions was identified as altering the separation point of the shear layer and the frequency of vortex shedding through the vortices formed between the surface protrusions. It was found that a 20% coverage rate with a protrusion height of 0.01D (CR20) effectively suppressed the VIV of the cylinder, showing the best performance in VIV suppression, with an efficiency of 30.04%. These results provide a theoretical basis for designing more efficient VIV suppression devices and contribute to enhancing the resistance of marine structures against vortex-induced vibrations.

Abstract. Background:. High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. Methods:. Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. Results:. Fourteen DEGs, ADIPOQ, ALPK2, BARX1, CD37, CNR2, COL5A3, FABP4, FAP, GPR68, ITGBL1, MOXD1, PODNL1, SFRP2, and TRAF3IP3, were upregulated in metastatic tumors in every database while CADPS, GATA4, STAR, and TSPAN8 were downregulated. ALPK2, FAP, SFRP2, GATA4, STAR, and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC (P = 0.0002 and P = 0.0001, respectively). Conclusions:. This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2, which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.

It is a primary task to distinguish whether the groundwater is affected by shallow material recharge or deep medium activity for the research of subsurface fluid. In this paper, the data of water chemical composition and hydrogen and oxygen stable isotope were obtained by collecting and testing several samples from Yongqing well and its surrounding areas. Through the comparison of groundwater sample data, water chemical composition, stable isotopes of hydrogen and oxygen and precipitation line, water temperature and water level data analysis, it is concluded that the repeated abnormal changes of water temperature in Yongqing well are not interference effects. According to the corresponding relationship between the abnormal change of water temperature and earthquake, it is founded that the abnormal water temperature in Yongqing well may be related to three earthquakes.

Taking the abnormal observation data of water temperature instrument in Yongqing seismic observation well as an example, the reliability of water temperature observation data is analyzed in detail by means of comparative observation of water temperature instrument in the same layer, power failure experiment and water injection experiment. The work flow and solution of abnormal verification of fluid observation well are put forward. It provides a reliable and effective method for verifying the anomalies of observation data in seismic stations, and finally finds the real reason of anomalies.

BackgroundThe purpose of this study was to investigate the predictive value of the modified systemic inflammation score (mSIS) in postoperative unplanned admission to the intensive care unit (ICU) in patients with non-small-cell lung cancer (NSCLC).MethodsThe clinical data of 1,321 patients with NSCLC treated with thoracic surgery in our hospital from August 2019 to June 2021 were analyzed retrospectively. The preoperative mSIS, which takes into account the serum albumin (ALB) level and lymphocyte-to-monocyte ratio (LMR), was recorded as 0, 1 or 2 and then was used to identify high-risk patients with unplanned admission to the ICU. The independent risk factors for unplanned admission to the ICU in patients with NSCLC after surgery were identified by multivariate logistic regression analysis.ResultsA total of 1,321 patients, including 549 (41.6%) males and 772 (58.4%) females, were included. The median age was 57 years (range 16–95 years). The incidence of unplanned admission to the ICU in patients with mSIS = 2 was significantly higher than that in those with mSIS = 0 and mSIS = 1. The multivariate analysis showed that an mSIS of 2 (OR = 3.728; P = 0.004; 95% CI, 1.520–9.143), an alcohol consumption history (OR = 2.791, P = 0.011; 95% CI, 1.262–6.171), intraoperative infusion volume (OR = 1.001, P = 0.021; 95% CI, 1.000–1.001) and preoperative underlying diseases (OR = 3. 57, P = 0.004; 95% CI, 1.497–8.552) were independent risk factors for unplanned admission to the ICU after lung cancer surgery. In addition, the multivariate logistic regression model showed that the C-statistic value was 0.799 (95% CI: 0.726∼0.872, P

Abstract Background Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC. Methods Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays. Results Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4. Conclusions PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

Abstract The female inflorescence of hops is traditionally used in the brewing industry to impart bitterness, aroma, flavour and longer shelf life to beer, where the bittering acids are the main compounds that enhance the quality of the beer. In recent years, a wide variety of bioactive compounds have been reported to be present in female flowers. Due to the growing consumer interests in natural ingredients, a great deal of research has been carried out in the last few years to find new sources of functional biomolecules. This paper reviews the recent applications of hops in the food, pharmaceutical and cosmetic industries and provides an overview of the bioactive potential of hops. In addition, the analytical techniques of hops compound are reviewed. The biological activities of hops compound such as antibacterial, antifungal, cardioprotective, antioxidant, anti‐inflammatory and anticancer are reviewed and the recent effects of hop bittering derivatives on beer‐related microbial activity are also presented. It is thus clear that hops have a high potential as bioactive components for use as preservatives in fresh foods to extend shelf life and as cosmetic formulations for skin care products as well as nutraceutical and health implications.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13048-020-00723-7.

In order to solve the problem that the gradient information can’t propagate backward due to the non-differentiability of resampling process in the end-to-end training of Differentiable Particle Filters (DPFs) network model, a particle filter network with gradient propagation is proposed in this article. It uses a differentiable resampling process in the network and is called Gradient Propagation Particle Filter Network(GPPFN). Firstly, an auxiliary noise vector is added to approximate the particle distribution in the resampling process, so that it can be represented by a certain differentiable function. Then, the method is applied to GPPFN model to make the gradient information generated in the training process can be propagated. It can provide the information of previous prediction and update steps for the next step prediction, so as to improve the accuracy of robot localization. In this article, experiments are carried out in the simulation environment of Deepmind lab. GPPFN is used to train the motion model and measurement model respectively, and the training effect is expressed by likelihood degree. The lower the likelihood degree is, the more consistent the training results are. The experiments show that the likelihood loss of motion model and measurement model are reduced by using GPPFN. Finally, The GPPFN model is compared with other methods. The training results showed that compared with the others, the training results of GPPFN has lower error rate and better robustness.

Abstract Background Epithelial ovarian cancer (EOC) is the most lethal cancer in female genital tumors. New disease markers and novel therapeutic strategies are urgent to identify considering the current status of treatment. Receptor tyrosine kinases family plays critical roles in embryo development and disease progression. However, ambivalent research conclusions of ROR2 make its role in tumor confused and the underlying mechanism is far from being understood. In this study, we sought to clarify the effects of ROR2 on high-grade serous ovarian carcinoma (HGSOC) cells and reveal the mechanism. Methods Immunohistochemistry assay and western-blot assay were used to detect proteins expression. ROR2 overexpression adenovirus and Lentivirus were used to create ROR2 overexpression model in vitro and in vivo, respectively. MTT assay, colony formation assay and transwell assay were used to measure the proliferation, invasion and migration ability of cancer cells. Flow cytometry assay was used to detect cell apoptosis rate. Whole transcriptome analysis was used to explore the differentially expressed genes between ROR2 overexpression group and negative control group. SiRNA targeted IRE1α was used to knockdown IRE1α. Kira6 was used to inhibit phosphorylation of IRE1α. Results Expression of ROR2 was significantly lower in HGSOC tissues compared to normal fallopian tube epithelium or ovarian surface epithelium tissues. In HGSOC cohort, patients with advanced stages or positive lymph nodes were prone to express lower ROR2. Overexpression of ROR2 could repress the proliferation of HGSOC cells and induce cell apoptosis. RNA sequencing analysis indicated that ROR2 overexpression could induce unfold protein response. The results were also confirmed by upregulation of BIP and phosphorylated IRE1α. Furthermore, pro-death factors like CHOP, phosphorylated JNK and phosphorylated c-Jun were also upregulated. IRE1α knockdown or Kira6 treatment could reverse the apoptosis induced by ROR2 overexpression. Finally, tumor xenograft experiment showed ROR2 overexpression could significantly repress the growth rate and volume of transplanted tumors. Conclusions Taken together, ROR2 downregulation was associated with HGSOC development and progression. ROR2 overexpression could repress cell proliferation and induce cell apoptosis in HGSOC cells. And the underlying mechanism might be the activation of IRE1α/JNK/CHOP pathway induced by ROR2.

Embryonic stem (ES) cells have immortality for self-renewal and pluripotency. Differentiated human cells undergo replicative senescence. In human, the telomerase reverse transcriptase (Tert), namely the catalytic subunit of telomerase, exhibits differential expression to regulate telomerase activity governing cellular immortality or senescence, and telomerase activity or tert expression is a routine marker of pluripotent ES cells. Here we have identified the medaka tert gene and determined its expression and telomerase activity in vivo and in vitro. We found that the medaka tert locus produces five variants called terta to terte encoding isoforms TertA to TertE. The longest TertA consists of 1090 amino acid residues and displays a maximum of 34% identity to the human TERT and all the signature motifs of the Tert family. TertB to TertE are novel isoforms and have considerable truncation due to alternative splicing. The terta RNA is ubiquitous in embryos, adult tissues and cell lines, and accompanies ubiquitous telomerase activity in vivo and in vitro as revealed by TRAP assays. The tertb RNA was restricted to the testis, absent in embryos before gastrulation and barely detectable in various cell lines The tertc transcript was absent in undifferentiated ES cells but became evident upon ES cell differentiation, in vivo it was barely detectable in early embryos and became evident when embryogenesis proceeds. Therefore, ubiquitous terta expression correlates with ubiquitous telomerase activity in medaka, and expression of other tert variants appears to delineate cell differentiation in vitro and in vivo.