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Resveratrol, a valuable plant-derived polyphenolic compound with various bioactivities, has been widely used in nutraceutical industries. Microbial production of resveratrol suffers from metabolic burden and low malonyl-CoA availability, which is a big challenge for synthetic biology. Herein, we took advantage of coculture engineering and divided the biosynthetic pathway of resveratrol into the upstream and downstream strains. By enhancing the supply of malonyl-CoA via CRISPRi system and fine-tuning the expression intensity of the synthetic pathway genes, we significantly improved the resveratrol productivity of the downstream strain. Furthermore, we developed a resveratrol addiction circuit that coupled the growth of the upstream strain and the resveratrol production of the downstream strain. The bidirectional interaction stabilized the coculture system and increased the production of resveratrol by 74%. Moreover, co-utilization of glucose and arabinose by the coculture system maintained the growth advantage of the downstream strain for production of resveratrol throughout the fermentation process. Under optimized conditions, the engineered E. coli coculture system produced 204.80 mg/L of resveratrol, 12.8-fold improvement over monoculture system. This study demonstrates the promising potential of coculture engineering for efficient production of natural products from biomass.

Hybrid neural networks combine advantages of spiking and artificial neural networks in the context of computing and biological motivation. The authors propose a design framework with hybrid units for improved flexibility and efficiency of hybrid neural networks, and modulation of hybrid information flows.

Abstract We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, ν 3 decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on τ 3/m 3 in the ν 3 decay model, the width of the neutrino wave packet σ x , and the intrinsic relative dispersion of neutrino momentum σ rel.

Abstract Background Due to the extensive development of assisted reproductive technology, the number of twin pregnancies has increased significantly over recent decades. Twin pregnancy is the most representative type of multiple pregnancies and is associated with high infant morbidity and mortality. Perinatal complications of twin pregnancy are also markedly increased compared with those of single pregnancy. Transabdominal selective reduction (SR) is a remedial intervention. This study aimed to research the adverse outcomes of transabdominal selective reduction of twin pregnancy and the correlation between the reduction week and pregnancy outcomes. Objective The purpose of this study was to examine the adverse outcomes of the transabdominal selective reduction of twin pregnancy and the correlation between the reduction week and pregnancy outcomes. Methods A retrospective cohort study of the transabdominal reduction of twin pregnancy was conducted in a single prenatal diagnosis medical centre from September 2012 to October 2020. According to chorionicity, women with twin pregnancies were divided into 2 groups: dichorionic (DC) twin pregnancies and monochorionic (MC) twin pregnancies. Women with DC twin pregnancies underwent potassium chloride reduction, and those with MC twin pregnancies underwent radiofrequency ablation (RFA). The reduction indications included pregnancy complications, foetal abnormalities, and maternal factors. The perinatal outcomes of different chorionic twins after reduction were analysed. Each foetus with an adverse outcome was included. The relative relationship between the reduction weeks and delivery weeks of twins was examined by correlation analysis. Results A total of 161 women were included in this study. A total of 112 women had DC twin pregnancies, and 49 women had MC twin pregnancies. Preterm delivery rates were significantly higher in the MC twin reduction group than in the DC twin reduction group prior to 37 weeks (53.1% vs. 29.5%, P = 0.004). The mean gestational age at delivery of the foetuses in the DC twin group that underwent SR was significantly older than that of those in the MC twin group that underwent SR (36.9 ± 4.0 vs. 33.5 ± 6.6 weeks, P = 0.001). The number of DC twins that underwent SR and were delivered after 37 weeks was obviously greater than that of the MC twins that underwent SR (70.5% vs. 46.9%, P = 0.004). The foetal survival rate was 95.5% in the DC twin reduction group and 77.6% in the MC twin reduction group. If the indication of TTTS was not included, there was no significant difference in the foetal survival rate of the DC and MC twin reduction groups (95.5% vs. 86.2%, P = 0.160). Cotwin death 1 week after reduction was greater in the MC group (6.1% vs. 0%, P = 0.027). Compared to other indications, this finding indicated that a significantly lower proportion of women remained undelivered after selective reduction with the indication of TTTS. There was a significant negative correlation between the reduction weeks and delivery weeks of the two groups (P

Abstract Background The prevalence of idiopathic membranous nephropathy (IMN) is increasing worldwide and the gut microbiota is recognized to play a role in its pathology. The aim of this study was to understand the involvement of the gut–kidney axis in IMN by analyzing the composition of the gut microbiota of biopsy-proven IMN patients compared with healthy controls (HC). Methods Fecal samples from 30 patients with IMN diagnosed by renal biopsy and 30 healthy co-residents (control group) were collected for analysis in the Nephrology Department of the Second Affiliated Hospital of Harbin Medical University. The microbiota composition was analyzed by a 16S rRNA microbial profiling approach. Results The results indicated that the α- and β-diversity of IMN patients differed significantly from those of the HC groups (P 2). Abundant bacterial functions related to lipid metabolism were observed among IMN group. Conclusion Patients with IMN appear to have an altered gut microbiome, which could provide reference for future research on the interaction mechanism between the intestinal flora and IMN.

Dengue fever (DF) is one of the most rapidly spreading mosquito-borne viral diseases in the world. It can impose an enormous socioeconomic and disease burden on the world's population. The spatial and temporal distribution patterns of DF cases in China are heterogeneous. It is evident that further research is necessary to identify the high-risk areas of dengue occurrence and associated risk factors at a fine spatiotemporal scale. This will facilitate the prevention and control of DF transmission. With the rapid development of remote sensing (RS) and geographic information system (GIS) technology, RS and GIS technology have played an important role in monitoring, forecasting, and identifying influencing factors and formulating prevention and control strategies for DF. In China, the majority of dengue cases were clustered in Guangdong and Yunnan Provinces. In this study, Bayesian spatiotemporal models were fitted at the county level in order to quantify the relationships between environmental and socioeconomic factors and DF. Our findings indicate that both environmental and socioeconomic factors can affect the transmission of DF in Guangdong and Yunnan Provinces. However, the underlying drivers and the spatially clustered patterns observed in the two provinces appear to be different. The results indicate that elevated temperatures facilitate the transmission of DF, but it was found that the risk of DF begins to decrease when the temperature exceeds 27.6 oC in Guangdong Province. There was a positive correlation between temperature and the incidence of DF, although no statistical significance was found in Yunnan Province. In Guangdong Province, the amount of precipitation did not significantly affect the incidence of DF. In Yunnan Province, the relationship between precipitation and DF is nonlinear. As the amount of precipitation increases, the risk of DF epidemics increases. In addition, vegetation cover can significantly affect the DF transmission, but the nonlinear relationships between vegetation cover and DF are diverse and complex in these two provinces. The incidence of DF was found to be positively correlated with the level of urbanization at the county level. The findings may prove beneficial to the governments of both provinces in the development of targeted strategies for the control of DF outbreaks at the county level. [ABSTRACT FROM AUTHOR]

In classical Fourier optics, an optical imaging system is regarded as a linear space-invariant system, which is only an approximation. Especially in digital holography, the space-variance effect has a great impact on the image quality and cannot be ignored. Therefore, it is comprehensively investigated in this article. Theoretical analyses indicate that the space-variance effect is caused by linear frequency modulation and ideal low-pass filtering, and it can be divided into three states: the approximate space-invariance state, the high-frequency distortion state, and the boundary-diffraction state. Classical Fourier optics analysis of optical imaging systems only considers the first. Regarding the high-frequency distortion state, the closer the image field is to the edge, the more severe the distortion of high-frequency information is. As for the boundary-diffraction state, in addition to the distortion of high-frequency information in the margin, a prominent boundary-diffraction phenomenon is observed. If the space-variance effect of the imaging lens is ignored, we predict that no space-variance effect in image holography will occur when the hologram is recorded at the back focal plane of the imaging lens. Simulation and experimental results are presented to validate our theoretical prediction.

Laser absorption spectroscopy tomography is an effective combustion diagnostic method for obtaining simultaneous two-dimensional distribution measurements of temperature and gas molar concentrations. For the reconstruction process of complex combustion flames, a new algorithm named ‘multi-iterative adaptive optimization regularization’ (MIARO) is proposed. This algorithm is a further development of another algorithm known as the ‘modified adaptive algebraic reconstruction technique’ (MAART) with the improvement of the initial value and adaptive regularization parameter selections. In MIARO, the problem of the MAART’s initial value sensitivity is compensated for, and in addition, reconstruction parameters are also introduced into the regularization so that both the quality of reconstruction and the convergence of regularization are guaranteed. In butane burner experiments, an average relative error of 1.82% was achieved with MIARO, compared to 2.44% with MAART, which is a significant reduction of 25.1%. The simulation and experimental results clearly demonstrate that the MIARO algorithm can be used to reconstruct dynamic combustion fields and eliminate boundary artifacts with improved measurement accuracy and robustness.

Little is known regarding the ability of protozoans to transfer phosphates and improve maize growth. The objective of this study was to determine whether Colpoda cucullus could improve the maize phosphorus (P) level by transferring phosphate. In this three-compartment root box study, the soil in the outer compartment was inoculated with the common ciliate, C. cucullus, together with the addition of either KH232PO4, rock phosphate (RP), super phosphate (SP) or ammonium phosphate (AP), and then maize was grown in the inner compartment. The results showed that the maize plants grown in the soil inoculated with C. cucullus had much higher 32P radioactivity than the control. Colpoda cucullus inoculation resulted in significant increases in dry matter by up to 25.07%, and nitrogen (N), P and potassium (K) absorption by 1–36% (P

Abstract Background Metastasis is critical for endometrial cancer (EC) progression and prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) can operate as independent functional entities. However, the functional regulatory mechanisms of circRNAs in EC remain unclear. Methods The levels of circESRP1, miR-874-3p, and CPEB4 mRNA in EC tissues and cells were determined by qRT-PCR. Sanger sequencing, PCR with divergent primers, an actinomycin D assay, and RNase R treatment were applied to verify the circular properties. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic fractionation were used to determine the localization of circESRP1. CCK-8, EdU incorporation, colony formation, Transwell, and wound healing assays were applied to assess the effects of circESRP1 on cell proliferation, migration, and invasion. The mutual regulatory mechanism of ceRNAs was investigated using dual-luciferase reporter, RNA pulldown, RNA immunoprecipitation (RIP), and Western blot assays. The biological effects were further validated in vivo in nude mouse xenograft models. Results circESRP1 was highly expressed in EC tissues and cells and was mainly localized in the cytoplasm. Silencing circESRP1 inhibited the proliferation, migration, and invasion of EC cells in vitro and in vivo; however, overexpression of circESRP1 had the opposite effects. Mechanistically, circESRP1 sponged miR-874-3p to upregulate CPEB4 expression and ultimately contribute to EC cell proliferation and metastasis. Furthermore, circESRP1 regulated tumour growth in xenograft models. Conclusions CircESRP1 can interact with miR-874-3p to regulate EMT in endometrial cancer via the miR-874-3p/CPEB4 axis. CircESRP1 may serve as a promising therapeutic target for endometrial cancer.

Objective(s): Global cerebral ischemia (GCI), a consequence of cardiac arrest (CA), can significantly damage the neurons located in the vulnerable hippocampus CA1 areas. Clinically, neurological injury after CA contributes to death in most patients. Mastoparan-M extracted from Vespa magnifica (Smith) can be used to treat major neurological disorders. Hence, this study aimed to assess the effects of Mastoparan-M on GCI. Materials and Methods: To evaluate the neurotoxicity and neuroprotective effect of Mastoparan-M, the CCK8 and Annexin V-FITC/PI apoptosis assays were first performed in hippocampal HT22 neuronal cells in vitro. Then, Pulsinelli’s 4-vascular occlusion model was constructed in rats. After treatment with Mastoparan-M (0.05, 0.1, and 0.2 mg/kg, IP) for 3 or 7 days, behavioral tests, H&E staining or Nissl staining, immunohistochemistry, and ELISA were employed to investigate neuroprotective effects of Mastoparan-M on GCI in rats.Results: In vitro, the growth of HT22 neuronal cells was restrained at concentrations of 30-300 µg/ml (at 24 hr, IC50=105.2 µg/ml; at 48 hr, IC50=46.81 µg/ml), and Mastoparan-M treatment (0.1,1 and 5 µg/ml) restrained apoptosis. In vivo, Mastoparan-M improved neurocognitive function and neuronal loss in the hippocampal CA1 area of rats. In addition, these effects were associated with the prevention of neuroinflammation, oxidative stress, and apoptosis. Conclusion: Mastoparan-M acts as a neuroprotective agent to alleviate neuronal death in rats.

Radopholus similis (Cobb 1893) Thorne (1949) is a destructive migratory endoparasitic plant nematode. In this study, the pathogenic process of R. similis infection in Nicotiana benthamiana (tobacco) was studied using quartz sand culture in laboratory. The results showed that R. similis mainly parasitised the root cortex, leading to cortical cell decomposition and tissue decay. We optimised the inoculation conditions to establish a method for determining the pathogenicity of R. similis as follows: (1) a glass culture tube was filled with quartz sand (about 1/3 of the height) and sterilised twice; (2) 20-day-old N. benthamiana seedlings were transplanted into test tubes and cultivated for 10 days at (25±1)°C; (3) R. similis female nematodes were inoculated in the root rhizosphere at a rate of 150 nematodes per plant; (4) the number of nematodes, disease severity, and growth of the plant at 30 days post-inoculation (dpi) were determined. The pathogenicity of eight R. similis populations from different hosts was determined, which proved the feasibility of this method.

Global and local learning represent two distinct approaches to artificial intelligence. In this manuscript, Wu et al present a hybrid learning strategy, drawing from elements of both approaches, and implement it on a co-designed neuromorphic platform.

The recently developed achromatic metalenses have exhibited a significant potential to replace the conventional bulky lenses. However, the numerical aperture (NA) of current broadband achromatic metalenses (BAMs) operated in long-wavelength infrared (LWIR) range is still insufficient for the applications of microscopy or high-resolution imaging. To address the restriction, a BAM with high NA for sub-diffraction focusing in LWIR waves is proposed. Specifically, the multipole decomposition is performed to avoid the undesirable resonances in the operation wavelength from 9 to 11 μm, which ensures the great linearity of the phase profiles from meta-atoms. After elaborately arranging the meta-atoms to compose a high-NA BAM, numerical results demonstrate that the chromatic aberration is well corrected in the operation wavelength and the maximum deviation is only 3.95%. Moreover, the actual NA of proposed BAM reaches up to 0.79 and the transverse sizes of focal spots are beyond the Abbe diffraction limit. The results indicate that the proposed high-NA BAM may have promising potential in the broadband applications of high-resolution imaging and microscopy.

Collaboration proves to be an effective way to facilitate students’ engagement and solve the mostly-mentioned problems of blended learning (BL). For collaborative BL, self-regulated learning (SRL), self-efficacy and engagement are frequently referred to in BL studies and represent key elements of effective BL. Furthermore, the interaction of these elements correlates closely with the performance of students. There have been few research attempts to draw synergies and explore the relationship among these key elements. To address this gap, data were collected through a questionnaire and records on LMS from 125 students in a Chinese university. Descriptive analytics show that students fully recognize the positive effects of collaborative BL. Correlation analysis and regression analysis find that self-regulated learning (SRL) is significantly correlated with all factors except workload. It is also a significant predictor of behavioral engagement. Therefore, SRL proves to be central among the essential BL elements. Emotional engagement is significantly correlated to and interact with multiple key BL factors. Specifically, emotional engagement is a significant predictor of behavioral engagement. The findings offer insight into the interactions of key elements of BL and provide practical implications for improving BL learning design.

We present a facile and economical method for synthesizing aromatic carboxylic acid derivatives through direct electrochemical C(sp2)–H carboxylation of (hetero)arenes with CO2. The reaction is carried out using a graphite felt anode and a nickel foam cathode in a user-friendly undivided cell setup under constant current conditions. Corresponding methyl carboxylates are obtained smoothly with good site-selectivity without the need of harsh chemical reductants or toxic transition metal catalysts. A cyclic voltammetry study was conducted, to distinguish between two potential mechanistic pathways. Additionally, nBu4NI was identified to serve as both electrolyte and anodic mediator. Notably, the methodology allows direct access to the desired product in a scale up manner.

Objectives: This study investigated the knowledge, attitude, and behavior of healthcare workers related to hospital infection in Chinese medicine hospitals in Hunan Province. We analyzed the influencing factors and made rational suggestions to improve the healthcare workers’ ability for hospital infection prevention and control in Chinese medicine hospitals based on knowledge, beliefs, and action models. Methods: The survey participants were selected using multi-stage stratified cluster random sampling. In the first stage, 14 tertiary-level hospitals and 42 tertiary-level hospitals in Hunan Province were selected, and 56 TCM hospitals at provincial, municipal, and county levels were finally covered. In the second stage, 2253 Medical personnel were selected as survey participants from January 2022 to January 2023. The network questionnaire was used to investigate the current knowledge, attitude, and behavior of hospital infection prevention and control by self-compiled questionnaire. Results: According to the self-prepared questionnaire, the survey results show that 2253 Medical personnel scored 35.88 ± 8.96, 98.12 ± 24.61, and 112.27 ± 6.31 on knowledge, attitude, and behavior regarding hospital infection prevention and control, respectively. There was a linear relationship between knowledge and sex, age, working years, education level, job title, and position, with working experience having the greatest influence. There was a linear relationship between attitudes and working years, education level, job title, position, and hospital level, with working experience having the greatest influence. There was a linear relationship between attitudes and sex, age, working years, education level, job title, and hospital level, with education level having the greatest influence. Conclusions: The knowledge reserve of medical staff in TCM hospitals should be improved. The level of awareness of nosocomial infection prevention when using traditional Chinese medicine techniques is low. Therefore, training is required to strengthen and enhance awareness regarding hospital infection prevention and control among healthcare workers in traditional Chinese medicine hospitals. Moreover, there is a need to adopt stratified management training for healthcare workers of different ages and educational levels, especially to regulate the behavior of junior healthcare workers.

IntroductionDue to the superposition of multiple complex socioeconomic environments and the complexity and uncertainty of the agricultural industry chain itself, the agricultural industry chain has become unstable, jeopardizing its long-term sustainability.MethodsThe purpose of this study is to construct and validate a stability mechanism model of cooperative relationships within agricultural industry chains based on the institutional theory. The questionnaire survey method was used for empirical analysis.ResultsThe results show that imitative pressure, mandatory pressure, and normative pressure have significant positive effects on the stability of cooperative relationships in agricultural industrial chains. Besides, perceived benefits, perceived risks, and trust play composite multiple mediating roles between imitative pressure and cooperation stability, and between normative pressure and cooperation stability in agricultural industrial chains. Perceived benefits and trust play partial mediating roles in the stability of cooperative relationships between mandatory pressure and agricultural industrial chains.DiscussionThis study is conducive to further understanding the cooperative psychology of agricultural industry chain operators. And this research can provide a reference for managers to take targeted measures to deal with the instability in the development of agricultural industry chains.

A novel stable laser absorption spectroscopy (LAS) tomographic sensor with enhanced stability and spatial resolution is developed and applied to complex combustion flame diagnosis. The sensor reduces the need for laser collimation and alignment even in extremely harsh environments and improves the stability of the received laser signal. Furthermore, a new miniaturized laser emission module was designed to achieve multi-degree of freedom adjustment. The full optical paths can be sampled by 8 receivers, with such arrangement, the equipment cost can be greatly reduced, at the same time, the spatial resolution is improved. In fact, 100 emitted laser paths are realized in a limited space of 200mm×200 mm with the highest spatial resolution of 1.67mm×1.67 mm. The stability and penetrating spatial resolution of the LAS tomographic sensor were validated by both simulation and field experiments on the afterburner flames. Tests under two representative experiment states, i.e., the main combustion and the afterburner operation states, were conducted. Results show that the error under the main combustion state was about 4.32% and, 5.38% at the afterburner operation state. It has been proven that this proposed sensor can provide better tomographic measurements for combustion diagnosis, as an effective tool for improving performances of afterburners.

Abstract The OSIRIS detector is a subsystem of the liquid scintillator filling chain of the JUNO reactor neutrino experiment. Its purpose is to validate the radiopurity of the scintillator to assure that all components of the JUNO scintillator system work to specifications and only neutrino-grade scintillator is filled into the JUNO Central Detector. The aspired sensitivity level of $$10^{-16}\hbox { g/g}$$ 10 - 16 g/g of $$^{238}\hbox {U}$$ 238 U and $$^{232}\hbox {Th}$$ 232 Th requires a large ( $$\sim 20\,\hbox {m}^3$$ ∼ 20 m 3 ) detection volume and ultralow background levels. The present paper reports on the design and major components of the OSIRIS detector, the detector simulation as well as the measuring strategies foreseen and the sensitivity levels to U/Th that can be reached in this setup.

Abstract JUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day (cpd), therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration to reduce at minimum the impact of natural radioactivity. We describe our efforts for an optimized experimental design, a careful material screening and accurate detector production handling, and a constant control of the expected results through a meticulous Monte Carlo simulation program. We show that all these actions should allow us to keep the background count rate safely below the target value of 10 Hz (i.e. ∼1 cpd accidental background) in the default fiducial volume, above an energy threshold of 0.7 MeV.

Abstract Atmospheric neutrinos are one of the most relevant natural neutrino sources that can be exploited to infer properties about cosmic rays and neutrino oscillations. The Jiangmen Underground Neutrino Observatory (JUNO) experiment, a 20 kton liquid scintillator detector with excellent energy resolution is currently under construction in China. JUNO will be able to detect several atmospheric neutrinos per day given the large volume. A study on the JUNO detection and reconstruction capabilities of atmospheric $$\nu _e$$ ν e and $$\nu _\mu $$ ν μ fluxes is presented in this paper. In this study, a sample of atmospheric neutrino Monte Carlo events has been generated, starting from theoretical models, and then processed by the detector simulation. The excellent timing resolution of the 3” PMT light detection system of JUNO detector and the much higher light yield for scintillation over Cherenkov allow to measure the time structure of the scintillation light with very high precision. Since $$\nu _e$$ ν e and $$\nu _\mu $$ ν μ interactions produce a slightly different light pattern, the different time evolution of light allows to discriminate the flavor of primary neutrinos. A probabilistic unfolding method has been used, in order to infer the primary neutrino energy spectrum from the detector experimental observables. The simulated spectrum has been reconstructed between 100 MeV and 10 GeV, showing a great potential of the detector in the atmospheric low energy region.

Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we discovered that degeneration following synaptic silencing is governed by competition between active and inactive cells, which is a circuit refinement process traditionally thought to end early in postnatal life. Our data suggests that the developmental window for wholesale circuit plasticity may extend into adulthood for specific brain regions. We speculate that this sustained potential for remodeling by entorhinal neurons may support lifelong memory but renders them vulnerable to prolonged activity changes in disease.

Abstract The use of CO2 as a C1 building block to access carboxylic acids is one of the key aspects in the context of carbon capture and utilization (CCU). Herein we report on an electrochemical carboxylation of allyl esters with CO2 at atmospheric pressure. This strategy enabled to the synthesis of diverse carboxylic acids without the need for a transition metal catalyst. Furthermore, the mechanism was studied through ICP‐MS analysis and cyclic voltammetry studies for the cross‐electrophile CO2 coupling.

BackgroundAcupuncture is a widely practiced, convenient, and safe treatment modality within complementary and integrative medicine. Increasing studies have revealed the efficacy of acupuncture for the treatment of osteoporosis in both human and non-human subjects. The aim of the present study was to assess the improvement of osteoporosis after overall adjustment acupuncture (OA) as well as its endocrine-modulating effect in an ovariectomized rat model.MethodsIn total, 32 female Sprague–Dawley (SD) rats were randomly divided into the sham, model, ovariectomy+estrogen (OVX+E), and OVX+OA (OVX+A) groups with eight rats in each group. The postmenopausal osteoporosis (PMOP) rat model was induced by bilateral ovariectomy. At 12 weeks after surgery, rats in the OVX+E group received estradiol (0.2 mg/kg/i.g./qod) for 12 weeks, and rats in the OVX+A group were treated with acupuncture at Zusanli (ST36), Shenshu (BL23), and Dazhu (BL11) points (qod) for 12 weeks. At the end of the treatment, all rats were sacrificed, and the body weight, uterus index, bone mineral density (BMD), bone mineral content (BMC), bone trabeculae structural parameters, femoral biomechanical properties, femoral histomorphology, and several hormone levels were examined.ResultsIn OVX rats, OA abrogated the body weight gain and improved osteoporosis in terms of BMD, BMC, bone trabeculae structural parameters, bone strength, and bone tissue histomorphology. Moreover, OA modulated the serum levels of estradiol, corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT).ConclusionsOA improves osteoporosis and exerts an endocrine-modulating effect in ovariectomized rats.

Abstract Introduction Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons. Accumulating evidence has shown that activation of the NLR family pyrin domain‐containing 3 (NLRP3) inflammasome is an early and cardinal feature in PD progression. Nevertheless, little is known about the effect of NLRP3 in the substantia nigra pars compacta (SNc) on DA neurodegeneration. Methods and results In the present study, we constructed NLRP3 interference sequences wrapped by lentivirus (LV3‐siNlrp3) to facilitate NLRP3 knockdown in the SNc region by intracerebral stereotactic injection. Then, we explored the effects of NLPR3 knockdown on PD pathologies via behavioral monitoring, immunohistochemistry and western blot analysis in acute 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP) mouse model. Moreover, we performed in vitro experiments to investigate the effect of microglial NLRP3 knockdown on DA neuron survival in the context of 1‐methyl‐4‐phenylpyridinium (MPP+) stimulation. Our results demonstrated that NLRP3 knockdown in the SNc region significantly improved MPTP‐induced dyskinesia, DA neuronal loss and microglia activation in vivo. Meanwhile, knockdown of microglial NLRP3 attenuated MPP+‐induced DA neuronal damage in an indirect coculture system in which neurons were cultured in microglial conditional medium. Cumulatively, these data reveal that microglial NLRP3 located in the SNc region is detrimental to DA neurons survival, and knockdown of microglial NLRP3 is a potential strategy to rescue DA neurons in the progression of PD. Conclusions This work demonstrates the role of NLRP3 in PD pathogenesis via microglia‐neuron communication, and sheds light on targeting microglial NLRP3 to develop disease‐modifying therapy for PD.

ObjectivesThis study sought to evaluate the clinical applicability of the Liwen Liu RF™ ablation system for percutaneous intramyocardial septal radiofrequency ablation (PIMSRA).BackgroundData on new cardiac radiofrequency ablation devices for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) are limited.Materials and methodsFrom July 2019 to July 2020, a total of 68 patients with drug-resistant HOCM, who underwent PIMSRA with the Liwen RF™ ablation system, which has an ablation electrode of stepless adjustable length, were prospectively enrolled. Safety endpoints included, amongst others, the occurrence of pericardial effusion and/or hemorrhage, cardiac arrhythmias, device failure and procedural death. The reduction in left ventricular outflow tract (LVOT) gradients at 12 months follow-up were used as a surrogate marker for device efficacy.ResultsAll procedures were technically successful. The total energy output time of the system was 75.8 (IQR: 30.0) min, and the average power was 43.61 ± 13.34 watts. No ablation system error occurred. The incidence of pericardial effusion or hemorrhage, transient arrhythmia and resuscitation was 8.8, 39.7, and 1.5% during procedure, respectively. None of the patients died. During 30-day follow-up, there were no complications with the exception of a pericardial effusion in one patient (1.5%). No further complications were reported after 30 days. The patients’ resting [baseline: 75 (IQR: 48) vs. 12-months: 12 (IQR: 19) mmHg, p < 0.001] and provoked [baseline: 122 (IQR: 53) vs. 12-months: 41 (IQR: 59) mmHg, p < 0.001] LVOT gradients decreased significantly during follow-up.ConclusionIn this study, we demonstrate the safety and feasibility of the Liwen RF™ ablation system to treat HOCM. The system allows for significant and sustainable LVOT gradient reduction during 12-months of follow-up. Hence, the Liwen RF™ ablation system is a promising new device that has the potential to become an alternative to existing septal reduction concepts in HOCM patients.

Endometrial cancer (EC) is one of the most common gynecological cancers. Ferroptosis is a newly identified form of cell death characterized by iron-dependent lipid peroxide accumulation. Circular RNAs (circRNAs) have emerged as critical regulators for cancer development. However, circRNA-mediated modulation of ferroptosis in EC is yet to be clarified. In this study, we found that circRAPGEF5 expression was elevated in EC tissues compared to the normal endometrial tissues. In vitro and in vivo functional analysis demonstrated that circRAPGEF5 facilitates rapid proliferation of EC cells. RNA binding protein fox-1 homolog 2 (RBFOX2), a splicing regulator, was identified as the protein interacts with circRAPGEF5. Further studies revealed that circRAPGEF5 can bind to the Fox-1 C-terminal domain of RBFOX2 and induces specific exon exclusion of TFRC through obstructing the binding of RBFOX2 to pre-mRNA. As a result, elevated levels of circRAPGEF5 lead to ferroptosis resistance via the decreased labile iron pool and attenuated lipid peroxide production in EC cells. Additionally, a series of gain- and loss-of-function experiments demonstrated that knocking down or overexpressing RBFOX2 reversed the effects of knocking down or overexpressing circRAPGEF5 in EC cells. Finally, it is revealed that circRAPGEF5 promote the formation of TFRC with exon-4 skipping and confer ferroptosis resistance in EC cells through the interaction with RBFOX2. Collectively, these findings provide new insight into the molecular mechanism in which circRNAs mediate mediates ferroptosis via modulating alternative splicing, and circRAPGEF5/RBFOX2 splicing axis could be a promising therapeutic target for treating EC.

Interferon epsilon (IFN-ε) is a type I IFN. Some biological properties has been identified in many species, such as antiproliferative, anti-tumor, and antiviral effects, of IFN-ε, which are much weaker than those of IFN-α, have also been revealed. It has been shown to play a role in mucosal immunity and bacterial infection and in the prevention of certain sexually transmitted diseases, such as human immunodeficiency virus (HIV). This paper reviews the known activity of IFN-ε, particularly in some viruses. In general, this review provides a better understanding of effective IFN-ε treatment in the future.

Supercritical carbon-dioxide (SC-CO2) is a promising two-phase technology for flavor components (volatile oil and alkylamides) extract from Zanthoxylum bungeanum pericarp. However, the gastric protective effect of SC-CO2 extract from Z. bungeanum (SZB) have not been systematically investigated. In this study, response surface methodology (RSM) was employed to optimize the yield of SZB, and the average yield of 11.07 % were obtained under optimal parameters (30 MPa, 43 °C and time 75 min). Here, limonene, linalool and hydroxy-α-sanshool were identified as the main compounds of SZB by GC–MS and UPLC-Q-Extractive Orbitrap/MS analysis. When the gastric protective effect of SZB (5, 10 and 20 mg/kg, p.o.) were evaluated, significant increase in body weight and organ indexes of rat, and decreased gastric lesion were observed. Furthermore, nineteen serum metabolites were regarded as the potential biomarkers for the gastric protective effect of SZB. Collectively, this study provides a comprehensive perspective into the chemical composition analysis and gastric protective effect of Z. bungeanum SC-CO2 extract.

The assessment of seismic risk and the prevention of earthquake occurrences during reservoir operation present significant challenges in terms of accurate determination. This study aims to address this issue by developing a numerical model. The primary objective is to estimate the vulnerability of different fault types to reservoir impoundment. This model integrates essential parameters such as fault dip and the relative orientation between the reservoir and potential earthquakes, and it is structured within a risk framework using polar coordinates. Through comprehensive computations, we evaluate the alterations in elastic stress and fluid pore pressure resulting from water impoundment. This is achieved by employing a fully coupled two-dimensional poroelastic approach. Furthermore, our model incorporates relevant seismic data to enhance its accuracy. The findings of our study underscore that the critical factor lies in the fault’s precise positioning with respect to the reservoir. The risk associated with a fault is contingent upon both its location and its orientation, emphasizing the importance of these factors in determining hazardous zones.

The Sentinel-1 imaging radar mission provides a short revisit-time, continuous all-weather, and day-and-night imagery at the C-band, which brings opportunities for the dynamic extraction of lake water areas. For wetland-type lakes, it is difficult to distinguish between the water, submerged plants, and mudflats at the edge of a lake, which leads to difficulty in recognizing the water edge of a lake and affects the accuracy of lake water area extraction. In this paper, a water area extraction and water level prediction algorithm based on Sentinel-1 dual-polarization data decomposition is proposed to solve the problem. We can accurately extract lake water through generalized Stokes polarization decomposition. At the same time, we can verify the accuracy of water area extraction by establishing the water area and in situ water level elevation (A–E) relationship, and predicting the water level according to the calculated water area. In this study, dual-polarization Sentinel-1 time series SAR data covering the Dongting Lake wetland from 2018 to 2022 are used to verify the proposed water area extraction algorithm and establish the A–E relationship of the East Dongting Lake basin. The results show that the generalized Stokes decomposition parameters are very sensitive to the water boundary, and the R2 of the water area and the water level can reach 0.98 by using the piecewise linear function. It confirms the accuracy of the water area inversion, which is of extremely important significance for the high-precision monitoring of the water area of Dongting Lake with long-term Sentinel-1 data. Meanwhile, the predicted lake water level acquired using the A–E relationship established in this paper is compared with the field water level, with an RMSE of 0.4857 m and R2 of 0.9930. This means that the water level derived using the method in this study is quite compatible with the field observations, which provides a good idea for the water level monitoring of lakes lacking hydrological monitoring stations.

Currently, the new space-based laser altimetry mission, Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2), is widely used to obtain terrain information. Photon cloud filtering is a crucial step toward retrieving sub-canopy terrain. However, an unsuccessful photon cloud filtering performance weakens the retrieval of sub-canopy terrain. In addition, sub-canopy terrain retrieval would not be accurate in densely forested areas due to existing sparse ground photons. This paper proposes a photon cloud filtering method and a ground photon extraction method to accurately retrieve sub-canopy terrain from ICESat-2 data. First, signal photon cloud data were derived from ICESat-2 data using the proposed photon cloud filtering method. Second, ground photons were extracted based on a specific percentile range of elevation. Third, erroneous ground photons were identified and corrected to obtain accurate sub-canopy terrain results, assuming that the terrain in the local area with accurate ground photons was continuous and therefore could be fitted appropriately through a straight line. Then, the signal photon cloud data obtained by the proposed method were compared with the reference signal photon cloud data. The results demonstrate that the overall accuracy of the signal photon identification achieved by the proposed filtering method exceeded 96.1% in the study areas. The sub-canopy terrain retrieved by the proposed sub-canopy terrain retrieval method was compared with the airborne LiDAR terrain measurements. The root-mean-squared error (RMSE) values in the two study areas were 1.28 m and 1.19 m, while the corresponding R2 (coefficient of determination) values were 0.999 and 0.999, respectively. We also identified and corrected erroneous ground photons with an RMSE lower than 2.079 m in densely forested areas. Therefore, the results of this study can be used to improve the accuracy of sub-canopy terrain retrieval, thus pioneering the application of ICESat-2 data, such as the generation of global sub-canopy terrain products.

Abstract Tumour metastasis is the main cause of postoperative tumour recurrence and mortality in patients with hepatocellular carcinoma (HCC), but the underlying mechanism remains unclear. Accumulating evidence has demonstrated that programmed cell death 10 (PDCD10) plays an important role in many biological processes. However, the role of PDCD10 in HCC progression is still elusive. In this study, we aimed to explore the clinical significance and molecular function of PDCD10 in HCC. PDCD10 is significantly upregulated in HCC, which also correlates with aggressive clinicopathological characteristics and predicts poor prognosis of HCC patients after liver resection. High PDCD10 expression promotes HCC cell proliferation, migration, and invasion in vitro and tumour growth, metastasis in vivo. In addition, PDCD10 could facilitate epithelial-to-mesenchymal transition (EMT) of HCC cells. In terms of the mechanism, PDCD10 directly binds to the catalytic subunit of protein phosphatase 2A (PP2Ac) and increases its enzymatic activity, leading to the interaction of YAP and dephosphorylation of the YAP protein. This interaction contributes to YAP nuclear translocation and transcriptional activation. PP2Ac is necessary for PDCD10-mediated HCC progression. Knocking down PP2Ac abolished the tumour-promoting role of PDCD10 in the migration, invasion and EMT of HCC. Moreover, a PP2Ac inhibitor (LB100) could restrict tumour growth and metastasis of HCC with high PDCD10 expression. Collectively, PDCD10 promotes EMT and the progression of HCC by interacting with PP2Ac to promote YAP activation, which provides new insight into the mechanism of cancer metastasis. PDCD10 may be a potential prognostic biomarker and therapeutic target for HCC.