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Dalbergia cultrata Pierre Graham ex Benth (D. cultrata) is a precious rosewood tree species that grows in the tropical and subtropical regions of Asia. In this study, we used PacBio long-reading sequencing technology and Hi-C assistance to sequence and assemble the reference genome of D. cultrata. We generated 171.47 Gb PacBio long reads and 72.43 Gb Hi-C data and yielded an assembly of 10 pseudochromosomes with a total size of 690.99 Mb and Scaffold N50 of 65.76 Mb. The analysis of specific genes revealed that the triterpenoids represented by lupeol may play an important role in D. cultrata’s potential medicinal value. Using the new reference genome, we analyzed the resequencing of 19 Dalbergia accessions and found that D. cultrata and D. cochinchinensis have the latest genetic relationship. Transcriptome sequencing of D. cultrata leaves grown under cold stress revealed that MYB transcription factor and E3 ubiquitin ligase may be playing an important role in the cold response of D. cultrata. Genome resources and identified genetic variation, especially those genes related to the biosynthesis of phytochemicals and cold stress response, will be helpful for the introduction, domestication, utilization, and further breeding of Dalbergia species.

Aegilops tauschii (Coss.) is a highly deleterious, rapidly proliferating weed within the wheat, and its DD genome composition exhibits adaptability toward diverse abiotic stresses and demonstrates heightened efficacy in nutrient utilization. Current study investigated different variegated impacts of distinct nitrogen concentrations with varied plant densities, scrutinizing the behavior of Ae. tauschii under various salinity and drought stress levels through multiple physiological, biochemical, and molecular pathways. Different physiological parameters attaining high growth with different plant density and different nitrogen availability levels increased Ae. tauschii dominancy. Conversely, under the duress of salinity and drought, Ae. tauschii showcased an enhanced performance through a comprehensive array of physiological and biochemical parameters, including catalase, peroxidase, malondialdehyde, and proline content. Notably, salinity-associated traits such as sodium, potassium, and the sodium–potassium ratio exhibited significant variations and demonstrated remarkable tolerance capabilities. In the domain of molecular pathways, the HKT and DREB genes have displayed a remarkable upregulation, showcasing a comparatively elevated expression profile in reaction to different levels of salinity and drought-induced stress. Without a doubt, this information will make a substantial contribution to the understanding of the fundamental behavioral tendencies and the efficiency of nutrient utilization in Ae. tauschii. Moreover, it will offer innovative viewpoints for integrated management, thereby enabling the enhancement of strategies for adept control and alleviation.

Abstract Renal cell carcinoma (RCC) is the second lethal urogenital malignancy with the increasing incidence and mortality in the world. Clear cell renal cell carcinoma (ccRCC) is one major subtype of RCC, which accounts for about 70 to 80% of all RCC cases. Although many innovative therapeutic options have emerged during the last few decades, the efficacy of these treatments for ccRCC patients is very limited. To date, the prognosis of patients with advanced or metastatic ccRCC is still poor. The 5-year survival rate of these patients remains less than 10%, which mainly attributes to the complexity and heterogeneity of the tumor microenvironment (TME). It has been demonstrated that long non-coding RNAs (lncRNAs) perform an indispensable role in the initiation and progression of various tumors. They mostly function as sponges for microRNAs (miRNAs) to regulate the expression of target genes, finally influence the growth, metastasis, apoptosis, drug resistance and TME of tumor cells. However, the role of lncRNA/miRNA/mRNA axis in the TME of ccRCC remains poorly understood. In this review, we summarized the biological function of lncRNA/miRNA/mRNA axis in the pathogenesis of ccRCC, then discussed how lncRNA/miRNA/mRNA axis regulate the TME, finally highlighted their potential application as novel biomarkers and therapeutic targets for ccRCC.

AimsCircular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.MethodsMinus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.ResultsTensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice.ConclusionTaken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA.Cite this article: Bone Joint Res 2023;12(1):33–45.

Abstract Background In mice, liver fibrosis is the most serious pathologic change during Schistosoma japonicum (S. japonicum) infection. Schistosomiasis is mainly characterized by schistosome egg-induced granulomatous fibrosis. Hepatic stellate cells (HSCs) are mainly responsible for the net accumulation of collagens and fibrosis formation in the liver. Activated HSCs regulated by transforming growth factor-β1 (TGF-β1)/Smad signaling have emerged as the critical regulatory pathway in hepatitis virus or carbon tetrachloride-induced liver fibrosis. However, the detailed mechanism of HSC activation in schistosome-induced liver fibrosis is poorly understood. Methods Schistosoma japonicum-induced murine models and a control group were generated by abdominal infection with 15 (± 1) cercariae. The purity of cultured primary HSCs was evaluated by immunocytochemistry. The histopathological changes in the livers of infected mice were estimated by hematoxylin–eosin and Masson staining. Dynamic expression of pro-fibrotic molecules and microRNAs was detected by real-time quantitative PCR (RT-qPCR). Mainly members involved in the TGF-β1/Smad signaling pathway were examined via RT-qPCR and Western blot. Results The egg-induced granulomatous inflammation formed at 4 weeks post-infection (wpi) and developed progressively. Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, TGF-β1, Smad2, Smad3, and Smad4 showed a significant increase in mitochondrial RNA (mRNA) and protein expression compared with the control group at 7 and 9 weeks post-infection (wpi), while an opposite effect on Smad7 was observed. In addition, the mRNA expression of microRNA-21 (miRNA-21) was significantly increased at 7 wpi, and the mRNA expression of miRNA-454 was decreased starting from 4 wpi. Conclusion Our present findings revealed that HSCs regulated by the TGF-β1/Smad signaling pathway play an important role in liver fibrosis in S. japonicum-infected mice, which may provide proof of concept for liver fibrosis in schistosomiasis. Graphical Abstract

Abstract Appropriate overtaking can improve the safety and efficiency of driving. Practically, overtaking consists of two asymmetric lane‐changes: firstly to the left lane and then return back. Existing literatures treated the two lane‐changes as the same behaviour, which may result in frequent and unnecessary lane‐changes. For the more complex first lane‐change, discretionary lane‐change strategies have been developed to gain speed advantage with least deceleration. Most of them, however, described vehicles' dynamics with rough simplifications different from actual execution (e.g. constant speed and constant acceleration), which may fail them in practical applications. This paper presents an event‐triggered overtaking decision‐making strategy for autonomous vehicles to make the overtaking meet the driver's expectations. Firstly, the difference between the left‐lane change and right‐lane change is analysed. Left‐lane change is mainly concerned with the efficiency, whereas driving safety is the main target of the right‐lane change. Secondly, an event‐triggering condition covering the speed difference between the ego vehicle and its preceding vehicle is set. Afterwards, based on quantified speed advantage, considering surrounding vehicles' changes in both speed and acceleration, an optimisation of overtaking decision‐making strategy is proposed. During right‐lane change in an overtaking, safety is ensured by predicting whether the ego vehicle will collide with surrounding vehicles. Finally, several scenarios are defined in the combination of SCANeR studio and Simulink, which are used to test and demonstrate the effectiveness and applicability of the overtaking decision‐making strategy. The results show that the proposed overtaking decision‐making strategy, by mathematical quantification of speed advantage, performs well in measuring the motivation of lane‐change and avoiding frequent lane changes, which correspond to driver habits.

Abstract Background Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. Methods The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. Results Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7−Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7−Hs and CK7+Hs (2 +) (P

In order to improve the comprehensive utilization rate of V2O5 form vanadium titanomagnetite concentrates, the direct leaching and the roasting-leaching tests were carried out using titanium white waste acid byorthogonal experiment method. The results of direct leaching experiment show that the liquid-solid ratio is the most important factor affecting the leaching rate of V2O5, and the concentration of titanium white waste acid is the least. The 71.05% vanadium can be leached under the experimental condition of 20% of titanium white waste acid, 90℃ for 90 min with a liquid-to-solid ratio of 5. The results of roasting-leaching experiment show that the effects of roasting temperature, K2CO3 ratio, Na2CO3 ratio and roasting time on the leaching rate of V2O5 are from large to small. When the conditions of roasting time of 2 h, roasting temperature of 1000℃, Na2CO3 ratio of 10%, and K2CO3 ratio of 10%, and the leaching rate of V2O5 can reach 84.48%.

Abstract Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC. Graphical Abstract

Fish viscera are one of the main by-products of fish processing, and often considered a low value resource, so they are mostly discarded. Fish viscera contain high levels of protein, and fish protein hydrolysates (FPH) have functional activities such as antioxidant, hypoglycemic, anti-inflammatory, and blood pressure reduction, and can be used as a potential functional ingredient and food additive. This paper reviews the research status of the preparation process and physiological activity of the hydrolysates of fish viscera protein in order to provide reference for the deep processing and utilization of fish viscera.

Abstract As a kind of promising drug carriers, smart polymers have attracted much attention due to the effective and controlled drug release in target cells. Herein, a reactive oxygen species (ROS)‐responsive thioether‐containing amphiphilic hyperbranched polymer prepared from MTPA and TMPTGE (HBPMT) is synthesized from 3‐(methylthio)propylamine (MTPA) and trimethylolpropane triglycidyl ether (TMPTGE) by the amine‐epoxy click reaction via A2 + B3 one‐pot approach. Benefiting from its inherent amphiphilic nature, HBPMT can self‐assemble into stable micelles in water. Triggered by H2O2, these micelles can be dissociated rapidly because hydrophobic thioether segments in their cores are oxidized into hydrophilic sulfoxide or sulfone groups. Additionally, the ROS produced by photosensitizer under light irradiation can also play the same role of H2O2. Such HBPMT micelles can be utilized to encapsulate anticancer drug paclitaxel (PTX) and photosensitizer chlorin e6 (Ce6) simultaneously for drug delivery and control release. The methyl thiazolyl tetrazolium assay toward MCF‐7 tumor cells (a human breast adenocarcinoma cell line) indicates that these micelles encapsulated with PTX and Ce6 exhibit a significant combinational efficacy of cell proliferation inhibition, which means the promising potential for synergistic chemo‐photodynamic cancer therapy. Such a novel nanocarrier based on amphiphilic to hydrophilic transition would provide a candidate for controlled drug release and cancer combination therapy.

Abstract Equilibrium climate sensitivity (ECS) refers to the total global warming caused by an instantaneous doubling of CO2 from the preindustrial level. It is mainly estimated through the linear fit between the changes in global-mean surface temperature and top-of-atmosphere net radiative flux, due to the high costs of millennial-length simulations for reaching a stable climate. However, the accuracy can be influenced by the response’s nonlinearity and the internal noise, especially when using a limited-length simulation. Here, we propose a new method that derives a new series using an exponential-interval sampling (EIS) method for the original simulation to reduce the noise and estimate the ECS more accurately. Utilizing the millennial-length simulations of LongRunMIP, we prove that the EIS method can effectively reduce the influence of internal variability, and the estimated ECS based on the first 150 years of simulation is closer to the final ECS in the millennial-length simulations than previous estimations with the deviation rate decreased by around 1/3. The ECS in CMIP6 models estimated by the EIS method ranges from 1.93 to 6.78 K, and suggests that the multimodel mean ECS derived from the original series with previous methods could be underestimated.

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. Vaccines are one of the efficient ways to prevent the viral infection. After COVID-19 vaccination, the monitoring of the dynamic change in neutralizing antibodies is necessary to determine booster requirements.MethodsWe estimated the effectiveness of the inactivated vaccines by monitoring dynamic SARS-CoV-2 neutralizing antibodies for over 2 years. Additionally, we also investigated the activation of T lymphocytes (CD3+ T cells) after three doses of the inactivated vaccine.ResultThe results showed that the rate of reduction of SARS-CoV-2 neutralizing antibody levels gradually showed after each booster dose. The IgG/IgM level at 9 months after the third vaccination were significantly higher than those at 6 months after the second dose (p

ABSTRACT: Introduction and Objectives: Hepatocellular carcinoma (HCC) may be diagnosed using the GAAP and ASAP models; our goal was to verify and evaluate their diagnostic effectiveness compared to alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and AFP & DCP for both HCC and HCC caused by the hepatitis B virus (HBV). Patients and Methods: GAAP and ASAP models were validated and compared using a retrospective investigation of 938 patients from our hospital between July 2020 and July 2021. Results: Both the GAAP and ASAP models had better diagnostic efficacy than AFP, DCP, AFP & DCP. The GAAP model achieved better performance in section A for the detection of HCC and in section C for the detection of HBV-HCC than the ASAP model. The Hosmer-Lemeshow test showed that the GAAP and ASAP models were well-calibrated for the diagnoses of these two groups. To be more specific, the area under curve (AUC) of the GAAP model for HCC detection in section A was 0.862 [95% confidence interval (CI): 0.838-0.883], and that of the ASAP model was 0.850 [95% CI: 0.826-0.872]. The AUC of the GAAP model for HBV-HCC detection in section C was 0.897 [95% CI: 0.872-0.918], and that of the ASAP model was 0.878 [95% CI: 0.852-0.902]. Conclusions: The GAAP model was more accurate and reliable than the AFP, DCP, AFP and DCP, as well as the ASAP model in section A for the detection of HCC and in section C for the detection of HBV-HCC.

Cisplatin is a first-line chemotherapeutic agent in the treatment of malignant tumors with remarkable clinical effects and low cost. However, the ototoxicity and neurotoxicity of cisplatin greatly limit its clinical application. This article reviews the possible pathways and molecular mechanisms of cisplatin trafficking from peripheral blood into the inner ear, the toxic response of cisplatin to inner ear cells, as well as the cascade reactions leading to cell death. Moreover, this article highlights the latest research progress in cisplatin resistance mechanism and cisplatin ototoxicity. Two effective protective mechanisms, anti-apoptosis and mitophagy activation, and their interaction in the inner ear are discussed. Additionally, the current clinical preventive measures and novel therapeutic agents for cisplatin ototoxicity are described. Finally, this article also forecasts the prospect of possible drug targets for mitigating cisplatin-induced ototoxicity. These include the use of antioxidants, inhibitors of transporter proteins, inhibitors of cellular pathways, combination drug delivery methods, and other mechanisms that have shown promise in preclinical studies. Further research is needed to evaluate the efficacy and safety of these approaches.

In order to put students in the spotlight and make it simpler for them to understand and master the teaching topics, public tennis classes in colleges and universities used a combination of targeted teaching techniques and a staged evaluation method. A random sampling was used to select 200 students from public physical education classes at Zhuhai University of Science and Technology as the study population. They were divided into a control group and an experimental group of 100 students each (50 male and 50 female). The study found significant differences between the experimental and control groups in terms of forehand stroke, backhand stroke, technical movements, physical fitness, interest in learning, and motivation to learn. The use of the goal-based teaching technique in combination with the phased evaluation method has been shown to improve students' fundamental tennis skills, as well as their interest and motivation in learning. These results suggest that this teaching method could be effective in the instruction of public sports classes at universities.

Summary: Interactions between microglia and macroglia play important roles in the neurodegeneration of the central nervous system and so is the situation between microglia and Müller cells in retina neurodegenerations like glaucoma. This study focuses on the roles of microglia-derived osteopontin (OPN) in impacting Müller cells and retinal ganglion cells (RGCs). Rat model and cell pressurization culture were used to simulate glaucoma scenarios. Animals were differently treated with anti-OPN, suppressors of OPN receptors (Itgαvβ3/CD44) or microglia inhibitor minocycline, while isolated retinal Müller cells were accordingly treated with conditioned media from microglia culture pretreated with pressuring, overexpression-OPN, SiR-OPN, or minocycline. SB203580 was introduced to explore the role of p38 MAPK signaling pathway. Results revealed microglia may secret OPN to impact Müller cells’ autophagy and RGCs survival via binding to Itgαvβ3/CD44 receptors in glaucomatous neurodegeneration with involvement of p38 MAPK pathway. This discovery may benefit understanding neurodegenerative disorders and exploring therapeutics.

Drought-induced metabolic dysregulation significantly enhances the production of reactive oxygen species (ROS), which, in turn, exerts a substantial influence on the oxidation–reduction regulatory status of cells. These ROS, under conditions of drought stress, become highly reactive entities capable of targeting various plant organelles, metabolites, and molecules. Consequently, disruption affects a wide array of metabolic pathways and eventually leads to the demise of the cells. Given this understanding, this study aimed to investigate the effects of different drought stress levels on the growth and development of the invasive weed Wedelia trilobata and its co-responding native counterpart Wedelia chinensis. Both plants evolved their defense mechanisms to increase their antioxidants and hormone contents to detoxify ROS to avoid oxidative damage. Still, the chlorophyll content fluctuated and increased in a polyethylene-glycol-simulated drought. The proline content also rose in the plants, but W. chinensis showed a significant negative correlation between proline and malondialdehyde in different plant parts. Thus, W. trilobata and W. chinensis exhibited diverse or unlike endogenous hormone regulation patterns under drought conditions. Meanwhile, W. trilobata and W. chinensis pointedly increased the content of indole acetic acid and gibberellic acid in a different drought stress environment. A positive correlation was found between endogenous hormones in other plant parts, including in the roots and leaves. Both simulated and natural drought conditions exerted a significant influence on both plant species, with W. trilobata displaying superior adaptation characterized by enhanced growth, bolstered antioxidant defense mechanisms, and heightened hormonal activities.

Airborne speech enhancement is always a major challenge for the security of airborne systems. Recently, multi-objective learning technology has become one of the mainstream methods of monaural speech enhancement. In this paper, we propose a novel multi-objective method for airborne speech enhancement, called the stacked multiscale densely connected temporal convolutional attention network (SMDTANet). More specifically, the core of SMDTANet includes three parts, namely a stacked multiscale feature extractor, a triple-attention-based temporal convolutional neural network (TA-TCNN), and a densely connected prediction module. The stacked multiscale feature extractor is leveraged to capture comprehensive feature information from noisy log-power spectra (LPS) inputs. Then, the TA-TCNN adopts a combination of these multiscale features and noisy amplitude modulation spectrogram (AMS) features as inputs to improve its powerful temporal modeling capability. In TA-TCNN, we integrate the advantages of channel attention, spatial attention, and T-F attention to design a novel triple-attention module, which can guide the network to suppress irrelevant information and emphasize informative features of different views. The densely connected prediction module is used to reliably control the flow of the information to provide an accurate estimation of clean LPS and the ideal ratio mask (IRM). Moreover, a new joint-weighted (JW) loss function is constructed to further improve the performance without adding to the model complexity. Extensive experiments on real-world airborne conditions show that our SMDTANet can obtain an on-par or better performance compared to other reference methods in terms of all the objective metrics of speech quality and intelligibility.

Integer Aperture Bootstrapping (IAB) is a crucial method for testing ambiguity acceptance in carrier-phase differential global navigation satellite system (CDGNSS) positioning. It has the advantage that integrity parameters, such as the failure rate, can be analytically calculated, which is essential in safety-of-life applications. Although the IAB methods have been extensively studied, their threshold-determining method is still not well explained, theoretically. In this study, a new method, named Analytical Integer Aperture Bootstrapping (AIAB), is theoretically derived to determine the optimal IAB threshold. AIAB is novel in that: (1) a precise and easy-to-compute expression has been developed to describe the relationship between the IAB threshold and the failure rate, (2) an analytical function model has been derived from the expression to determine the IAB threshold; moreover, the function model is simplified, and (3) a data-constraint approach has been proposed to reduce the complexity of IAB. In the global CDGNSS simulations, AIAB is shown to outperform the existing IAB methods under both strong and weak models, particularly at low fix rates, which are 23% to 40% higher than the basic IAB method. The Monte Carlo simulation results show that AIAB can obtain almost theoretically the same performance as Optimal Integer Aperture (OIA).

Abstract The increasing complexity of interconnected power system has brought challenges to detailed dynamic simulation in terms of computational effort. Therefore, for transient stability assessment, dynamic equivalents of parts of large‐scale system are required to capture the electromagnetic transients. This paper presents a review of past research on dynamic equivalencing using coherency‐based methods and system identification methods. Future topics are discussed to improve the state‐of‐art approaches.

Abstract Background Salvia-Nelumbinis naturalis (SNN), the extract of Chinese herbal medicine, has shown effects on NAFLD. This study aims to explore the underlying mechanism of SNN for regulating the lipid metabolism disorder in NAFLD based on the SIRT1/AMPK signaling pathway. Methods Male C57BL/6J mice fed with a high-fat diet (HFD) were used to establish the NAFLD model. Dynamic changes of mice including body weight, liver weight, serological biochemical indexes, liver histopathological changes, and protein level of AMPK and SIRT1 were monitored. After18 weeks, SNN treatment was administrated to the NAFLD mice for another 4 weeks. Besides the aforementioned indices, TC and TG of liver tissues were also measured. Western blot and quantitative RT-PCR were used to detect the expression and/or activation of SIRT1 and AMPK, as well as the molecules associated with lipid synthesis and β-oxidation. Furthermore, AML12 cells with lipid accumulation induced by fatty acids were treated with LZG and EX527 (SIRT1 inhibitor) or Compound C (AMPK inhibitor ) to confirm the potential pharmacological mechanism. Results Dynamic observation found the mice induced by HFD with gradually increased body and liver weight, elevated serum cholesterol, hepatic lipid accumulation, and liver injury. After 16 weeks, these indicators have shown obvious changes. Additionally, the hepatic level of SIRT1 and AMPK activation was identified gradually decreased with NAFLD progress. The mice with SNN administration had lower body weight, liver weight, and serum level of LDL-c and ALT than those of the NAFLD model. Hepatosteatosis and hepatic TG content in the liver tissues of the SNN group were significantly reduced. When compared with control mice, the NAFLD mice had significantly decreased hepatic expression of SIRT1, p-AMPK, p-ACC, ACOX1, and increased total Acetylated-lysine, SUV39H2, and SREBP-1c. The administration of SNN reversed the expression of these molecules. In vitro experiments showed the effect of SNN in ameliorating hepatosteatosis and regulating the expression of lipid metabolism-related genes in AML12 cells, which were diminished by EX527 or Compound C co-incubation. Conclusions Taken together, the SIRT1/AMPK signaling pathway, involved in hepatic lipid synthesis and degradation, plays a pivotal role in the pathogenesis of NAFLD development. The regulation of SIRT1/AMPK signaling greatly contributes to the underlying therapeutic mechanism of SNN for NAFLD.

Background Fatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM). Methods A total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity. Results FABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 μg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 μg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014). Conclusion FABP4 may be used as a serum biomarker for the diagnosis of DR.

Tumour-associated angiogenesis facilitates the growth of tumours. Here the authors show that integrin α3β1 promotes blood vessel formation in glioblastoma through calcium-mediated macropinocytosis and lysosomal exocytosis.

Load dumping overvoltage has a significant effect on insulation coordination of direct current (DC) transmission system. Based on the PSCAD/EMTDC electromagnetic transient simulation programs, this paper has built the electromagnetic transient calculation model of ultra high-voltage direct current (UHVDC) transmission system. Respectively, we have done comparative research on the overvoltage during load dumping under three rated-load operations, which are the bipolar operation with ground return, unipolar operation with metal return, unipolar operation with ground return, concluding that alternating current (AC) load dumping on the inverter side under these three operations can result in overvoltage no less than 50% on the DC polar line, DC valve top, as well as both ends of the converter transformer valve and the upper six pulses bridge also produce a large overvoltage. Besides, we observed a similar overvoltage level between unipolar ground return operation and unipolar metal return operation. These conclusions can provide suggestions for insulation coordination in various operations.

A chemical ignition mathematical model was established based on the analysis of the process of chemical ignition and thermal ignition theory . Then, the model was solved by the method of nets on a computer to explore the mechanism for in-situ combustion ignition with chemical additives. Also, the development course of in-situ combustion ignition was reviewed. In addition, the ignition process by chemical methods was analysed. It was shown that the mathematical model was able to calculate some parameters such as the critical duration of the outer source action and critical energy for ignition. The heat flux that ignites an oil layer is greater than 2.35, when its dimensionless initial activation energy ɛ and initial temperature θ0are 0.026 and 11. Moreover, the ignition process and temperature distribution of oil sands were described with the model. The results are of great theoretical significance for understanding chemically assisted ignition mechanism in-depth, controlling ignition parameters and guiding chemical additives formulation design and optimization, etc.

Accurately predicting the overvoltage level under typical faults and operating condition in the UHVDC (Ultra High Voltage DC) transmission project is not only beneficial to the insulation coordination design of the system, improving the security and reliability of the system, but also helping to reduce the project cost. Based on the circuit transient simulation platform, this paper builds a UHVDC transmission system simulation model, analyzes the typical overvoltage sources, compares the overvoltage characteristics of the system under 3 types and 12 typical operating faults including the inverter side, rectifier side, and DC line side, and analyzes the operation of the arrester under fault conditions. Results show that when the midpoint of the line is ground faulty, an overvoltage of 1791kV will appear at the midpoint of the non-faulty DC line, which is the most serious overvoltage of the DC line, and when a ground fault occurs at the outlet of the DC line on the rectifier side or the inverter side, the overvoltage amplitude of the DC valve top on the corresponding side is the highest, which respectively are 1324kV and 1190kV. The research results provide a reference for the insulation coordination of the UHVDC transmission project.

Abstract Lean NAFLD is a special phenotypic closely correlated with metabolic syndrome (MS). The aim of this study is to investigate the MS development and the gender differences in lean NAFLD population. Participants were divided into 4 groups by BMI and NAFLD status. Descriptive analysis was performed to characterize baseline information. A total of 18,395 subjects were participated, and 1524 incident cases of MS were documented. Then, Kaplan–Meier curves were used to present the MS outcomes in different groups, and the NAFLD was found to be a riskier factor than obesity for MS. Subgroup analysis showed significantly higher MS incidence in female than male among lean NAFLD group, which is different from other groups. Although with higher prevalence in male, lean NAFLD seems to be a more harmful phenotype for females according to the TG, ALT and GGT levels. The logistic regressive analysis was performed to show the impact of NAFLD status and BMI changes on MS risk. Lean non-NAFLD subjects merely developed to NAFLD with no BMI status changes exhibited highest MS risk (ORs = 1.879, 95% CI 1.610–2.292) than that with both BMI increase and NAFLD development (ORs = 1.669, 95% CI 1.325–2.104). It also suggests the metabolic specificity of this population.

The long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) acts as an oncogene in several cancers, and is highly expressed in ovarian cancer. MiR-543, a tumor suppressor, was expressed lowly in ovarian cancer. However, whether SNHG6 performed its oncogenic role via miR-543 in ovarian cancer, as well as the underlying mechanism is still not clear. In this study, we showed that the levels of SNHG6 and Yes-associated protein 1 (YAP1) were significantly elevated, while the level of miR-543 was significantly decreased, in ovarian cancer tissues compared with adjacent normal samples. We demonstrated that overexpression of SNHG6 significantly promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ovarian cancer cells SKOV3 and A2780. Knockdown of SNHG6 showed the opposite effects. MiR-543 level was negatively correlated with the SNHG6 level in ovarian cancer tissues. SHNG6 overexpression significantly inhibited the expression of miR-543, and SHNG6 knockdown significantly elevated the expression of miR-543 in ovarian cancer cells. The effects of SNHG6 on ovarian cancer cells were abrogated by miR-543 mimic, and strengthened by anti-miR-543. YAP1 was identified as a target of miR-543. Forced expression of miR-543 significantly inhibited the expression of YAP1. Moreover, YAP1 overexpression could reverse the effects of SNHG6 downregulation on the malignant phenotypes of ovarian cancer cells. In summary, our study showed that SNHG6 promoted the malignant phenotypes of ovarian cancer cells via miR-543/YAP1 pathway.

Abstract Endothelial dysfunction is considered a predominant driver for pulmonary vascular remodeling in pulmonary hypertension (PH). SOX17, a key regulator of vascular homoeostasis, has been found to harbor mutations in PH patients, which are associated with PH susceptibility. Here, this study explores whether SOX17 mediates the autocrine activity of pulmonary artery ECs to maintain endothelial function and vascular homeostasis in PH and its underlying mechanism. It is found that SOX17 expression is downregulated in the endothelium of remodeled pulmonary arteries in IPH patients and SU5416/hypoxia (Su/hypo)‐induced PH mice as well as dysfunctional HPAECs. Endothelial knockdown of SOX17 accelerates the progression of Su/hypo‐induced PH in mice. SOX17 overexpression in the pulmonary endothelium of mice attenuates Su/hypo‐induced PH. SOX17‐associated exosomes block the proliferation, apoptosis, and inflammation of HPAECs, preventing pulmonary arterial remodeling and Su/hypo‐induced PH. Mechanistic analyses demonstrates that overexpressing SOX17 promotes the exosome‐mediated release of miR‐224‐5p and miR‐361‐3p, which are internalized by injured HPAECs in an autocrine manner, ultimately repressing the upregulation of NR4A3 and PCSK9 genes and improving endothelial function. These results suggest that SOX17 is a key gene in maintaining endothelial function and vascular homeostasis in PH through regulating exosomal miRNAs in an autocrine manner.

Changes in the water regime are among the crucial factors controlling soil carbon dynamics. However, at the aggregate scale, the microbial mechanisms that regulate soil respiration under flooding and drying conditions are obscure. In this research, we investigated how the shift from flooding to drying changes the microbial respiration of soil aggregates by affecting microbial community composition and their co-occurrence patterns. Soils collected from a riparian zone of the Three Gorges Reservoir, China, were subjected to a wet-and-dry incubation experiment. Our data illustrated that the shift from flooding to drying substantially enhanced soil respiration for all sizes of aggregate fractions. Moreover, soil respiration declined with aggregate size in both flooding and drying treatments. The keystone taxa in bacterial networks were found to be Acidobacteriales, Gemmatimonadales, Anaerolineales, and Cytophagales during the flooding treatment, and Rhizobiales, Gemmatimonadales, Sphingomonadales, and Solirubrobacterales during the drying treatment. For fungal networks, Hypocreales and Agaricalesin were the keystone taxa in the flooding and drying treatments, respectively. Furthermore, the shift from flooding to drying enhanced the microbial respiration of soil aggregates by changing keystone taxa. Notably, fungal community composition and network properties dominated the changes in the microbial respiration of soil aggregates during the shift from flooding to drying. Thus, our study highlighted that the shift from flooding to drying changes keystone taxa, hence increasing aggregate-scale soil respiration.

Tectonically induced liquefaction and the resulting soft-sediment deformation structure (SSDS) can provide useful information on paleo-earthquakes, which is vital for the assessment of geohazard susceptibility in tectonically active regions. In this study, we combined sedimentary and chronological methods to the reveal detailed characteristics of the mottled clay in the Huizhou Quaternary Basin. The dating results suggest that mottled clay usually developed during the late Pleistocene, overlying the fluvial deposit or embedding homogeneous aeolian yellow silt. Mottled clay has a typical bimodal frequency distribution with modal sizes at 5 and 80–90 μm, which are identical to those of the yellow silt and the underlying fluvial sand, respectively. Micro-X-ray fluorescence mapping revealed high concentrations of Fe and Si in the red and white fraction, respectively. In addition, the red fraction of mottled clay has a high hematite content, similar to loess-like yellow silt, whereas the white fraction and the underlying fluvial sediments are dominated by goethite. This sedimentary evidence together suggests that the mottled clay could be an admixture of aeolian yellow silt and the underlying fluvial sand. Furthermore, diverse deformed structures (e.g., fragmented structures, sand veins, sand dykes and flame structures) were observed in mottled clay. Therefore, we suggest that the mottled clay structure in the Huizhou Basin is a product of liquefaction-induced SSDS. Tectonic activity was considered to have triggered the liquefaction and SSDS, which is supported by the close spatial relationship between the mottled clay and regional faults. We propose that the SSDS of mottled clay could be a potential indicator of paleo-earthquakes in the coastal Quaternary basins of the northern South China Sea.

The PANK2 gene, which encodes mitochondrial pantothenate kinase 2 protein, is the disease-causing gene for pantothenate kinase-associated neurodegeneration (PKAN). We report a case of atypical PKAN with autism-like symptoms presenting with speech difficulties, psychiatric symptoms, and mild developmental retardation. Magnetic resonance imaging (MRI) of the brain showed the typical “eye-of-the-tiger” sign. Whole-exon sequencing revealed PANK2 p.Ile501Asn/p.Thr498Ser compound heterozygous variants. Our study highlights the phenotypic heterogeneity of PKAN, which can be confused with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) and requires careful clinical identification.

Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.

ObjectiveTo determine the genetic etiology of a family pedigree with two patients affected by differences of sex development (DSD).MethodsAssess the clinical characteristics of the patients and achieve exome sequencing results and in vitro functional studies.ResultsThe 15-year-old proband, raised as female, presented with delayed puberty and short stature associated with atypical genitalia. Hormonal profile showed hypergonadotrophic hypogonadism. Imaging studies revealed the absence of a uterus and ovaries. The karyotype confirmed a 46, XY pattern. Her younger brother presented with a micropenis and hypoplastic scrotum with non-palpable testis and hypospadias. Laparoscopic exploration was performed on the younger brother. Streak gonads were found and removed due to the risk of neoplastic transformation. Post-operative histopathology showed the co-existence of Wolffian and Müllerian derivatives. Whole-exome sequencing identified a novel mutation (c.1223C>T, p. Ser408Leu) in the Asp-Glu-Ala-His-box helicase 37 gene, which was found to be deleterious by in silico analysis. Segregation analysis of the variant displayed a sex-limited, autosomal dominant, maternal inheritance pattern. In vitro experiments revealed that the substitution of 408Ser by Leu caused decreased DHX37 expression both at the mRNA and protein levels. Moreover, the β-catenin protein was upregulated, and the p53 protein was unaltered by mutant DHX37.ConclusionsWe described a novel mutation (c.1223C>T, p. Ser408Leu) of the DHX37 gene associated with a Chinese pedigree consisting of two 46, XY DSD patients. We speculated that the underlying molecular mechanism might involve upregulation of the β-catenin protein.

Objective: To explore the clinical efficacy and metabolic mechanism of Tongdu Huoxue Decoction (THD) in treating lumbar spinal stenosis (LSS).Methods: A total of 40 LSS patients and 20 healthy participants were recruited from January 2022 to June 2022. The patients’ pre- and post-treatment visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) scores were recorded. ELISA kits were used to assess pre- and post-treatment levels of serum Interleukin-1beta (IL-1β), Alpha tumour necrosis factor (TNF-α) and prostaglandin E2 (PGE2). Finally, the patients’ pre- and post-treatment and healthy human sera were subjected to extensively targeted metabolomics using Ultra Performance Liquid Chromatography (UPLC) to identify potential differential metabolites and metabolic pathways using multivariate statistical analysis.Results: Compared to the pre-treatment (group A), the patients’ VAS scores decreased significantly (p < 0.05), while JOA scores increased significantly (p < 0.05) post-treatment (group B), indicating that THD could effectively improve the pain and lumbar spine function of LSS patients. Moreover, THD could effectively inhibit the expression of IL-1β, TNF-α and PGE2-associated inflammatory factors in serum. Regarding metabolomics, the levels of 41 differential metabolites were significantly different in the normal group (group NC) compared to group A, and those were significantly restored after treatment with THD, including chenodeoxycholic acid 3-sulfate, taurohyodeoxycholic acid, 3,5-Dihydroxy-4-methoxybenzoic acid, pinocembrin. These biomarkers are mainly involved in purine metabolism, steroid hormone biosynthesis and amino acid metabolism.Conclusion: This clinical trial demonstrated that THD is effective in improving pain, lumbar spine function and serum levels of inflammation in patients with LSS. Moreover, its mechanism of action is related to the regulation of purine metabolism, steroid hormone biosynthesis and the expression of key biomarkers in the metabolic pathway of amino acid metabolism.

Bacterial loading aggravates the harm of particulate matter (PM) to public health and ecological systems, especially in operations of concentrated animal production. This study aimed to explore the characteristics and influencing factors of bacterial components of inhalable particles at a piggery. The morphology and elemental composition of coarse particles (PM10, aerodynamic diameter ≤ 10 µm) and fine particles (PM2.5, aerodynamic diameter ≤ 2.5 µm) were analyzed. Full-length 16 S rRNA sequencing technology was used to identify bacterial components according to breeding stage, particle size, and diurnal rhythm. Machine learning (ML) algorithms were used to further explore the relationship between bacteria and the environment. The results showed that the morphology of particles in the piggery differed, and the morphologies of the suspected bacterial components were elliptical deposited particles. Full-length 16 S rRNA indicated that most of the airborne bacteria in the fattening and gestation houses were bacilli. The analysis of beta diversity and difference between samples showed that the relative abundance of some bacteria in PM2.5 was significantly higher than that in PM10 at the same pig house (P

Fire emissions in South America consistently decreased in 2003–2019, although anthropogenic forcing could exacerbate drought and fire risks. Here the authors find that the decreasing fires were associated with climatic conditions unfavorable for intensifying and spreading fires, led by the phase transition of the Atlantic Multidecadal Oscillation.

The comprehensive utilization of metallurgical mineral solid waste is an important part of building a green and low-carbon circular economy system. In this paper, the vanadium-extracted and discarded slag is used as raw material, and the vanadium-extracted and discarded slag solar thermal collector coating is prepared by iron removal, ball milling, beating, and spraying. As the medium, the heat collection performance at different inclination angles was studied. The results show that when the inclination angle is 30°, the heat collection efficiency of the vanadium-extracted spoil coated heat collector plate is the best, which can reach 84.69%. The heat collection efficiency of the titanium film-coated collector plate is 6.81% lower. It shows that the vanadium-extracted waste slag used as a solar collector coating has a feasible technology, low price and important significance for solid waste reuse.

Bispecific antibodies (BsAbs) are a class of promising anticancer immunotherapies. Among them, the US Food and Drug Administration (FDA)-approved blinatumomab (BLI) is very effective in eliminating the minimum residual disease (MRD) of acute lymphoblastic leukemia (ALL), resulting in long-term remission in many individuals. However, the need for months-long intravenous delivery and high cost limit its clinical acceptance. Here we demonstrate that these problems can be solved by a BsAb expressed by one intramuscular (i.m.) dose of a minicircle DNA vector (MC). In a human B lymphoma xenograft mouse model, when microcancers became detectable in bone marrow, the mice received an i.m. dose of the MC encoding the BsAb anti-CD3/CD20 (BsAb.CD20), followed by 8 subsequent intravenous (i.v.) doses, one every other day (q2d), of human T cells to serve as effectors. The treatment resulted in persistent expression of a therapeutic level of serum BsAb.CD20 and complete regression or growth retardation of the cancers in the mice. These results suggest that the i.m. MC technology can eliminate the physical and financial burdens of i.v. delivered BLI without compromising anticancer efficacy and that cancer can be treated as easily as injecting a vaccine. This, together with other superior MC features, such as safety and affordability, suggests that the i.m. MC BsAb technology has great clinical application potential.

Creating new insecticide lead compounds based on the design and modification of natural products is a novel process, of which chlorfenapyr is a typical successful example. Chlorfenapyr is an arylpyrrole derivative that has high biological activity, a wide insecticidal spectrum, and a unique mode of action. For decades, a series of chlorfenapyr derivatives were designed and synthesized continuously, of which many highly active insecticidal compounds were discovered sequentially. However, due to the widespread application of chlorfenapyr and its degradation properties, some adverse effects, including pest resistance and environmental toxicity, occurred. In this review, a brief history of the discovery and development of chlorfenapyr is first introduced. Then, the synthesis, structural modification, structure activity relationship, and action mechanism of arylpyrroles are summarized. However, challenges and limitations still exist, especially in regard to the connection with pest resistance and environmental toxicology, which is discussed at the end of this review. This comprehensive summary of chlorfenapyr further promotes its progress and sensible application for pest management.

Osteoarthritis (OA) is a worldwide joint disease. However, the precise mechanism causing OA remains unclear. Our primary aim was to identify vital biomarkers associated with the mechano-inflammatory aspect of OA, providing potential diagnostic and therapeutic targets for OA. Thirty OA patients who underwent total knee arthroplasty were recruited, and cartilage samples were obtained from both the lateral tibial plateau (LTP) and medial tibial plateau (MTP). GO and KEGG enrichment analyses were performed, and the protein–protein interaction (PPI) assessment was conducted for hub genes. The effect of PSD95 inhibition on cartilage degeneration was also conducted and analyzed. A total of 1247 upregulated and 244 downregulated DEGs were identified. Significant differences were observed between MTP and LTP in mechanical stress-related genes and activated sensory neurons based on a self-contrast model of human knee OA. Cluster analysis identified DLG4 as the hub gene. Cyclic loading stress increased PSD95 (encoded by DLG4) expression in LTP cartilage, and PSD95 inhibitors could alleviate OA progression. This study suggests that inhibiting PSD95 could be a potential therapeutic strategy for preventing articular cartilage degradation.

We propose a DeiT (Data-Efficient Image Transformer) feature encoder-based algorithm for identifying disease types and generating relevant descriptions of diseased crops. It solves the scarcity problem of the image description algorithm applied in agriculture. We divided the original image into a sequence of image patches to fit the input form of the DeiT encoder, which was distilled by RegNet. Then, we used the Transformer decoder to generate descriptions. Compared to “CNN + LSTM” models, our proposed model is entirely convolution-free and has high training efficiency. On the Rice2k dataset created by us, the model achieved a 47.3 BLEU-4 score, 65.0 ROUGE_L score, and 177.1 CIDEr score. The extensive experiments demonstrate the effectiveness and the strong robustness of our model. It can be better applied to automatically generate descriptions of similar crop disease characteristics.

This study investigates the heat and mass transfer characteristics of a binary mixture (R134a/R245fa) evaporated in a porous medium. The Eulerian model coupled with the multiphase VOF model and species transport equations is employed to establish a multi-component evaporation model. The effects of heat flux ranging from 200 kW/m2 to 500 kW/m2, porosity ranging from 0.4 to 0.6, and mass fraction ratios (R134a/R245fa) of 3:7, 5:5, and 7:3 are explored. The results indicate that an increase in heat flux contributes to an increase in the evaporation rate. For the overall evaporation rate, the evaporation rates of R134a and R245fa improve by 11.3%, 6.9%, and 16.3%, respectively, while the maximum improvement in heat transfer coefficient is only 1.4%. The maximum evaporation rate is achieved at intermediate porosity in the porous medium, and the highest heat transfer coefficient is obtained at a porosity of 0.4. With the increase in mass fraction, the evaporation rate of the corresponding species also increases, while the overall evaporation rate and heat transfer coefficient remain almost unchanged.

Abstract Background Tai Chi has been shown to improve motor symptoms in Parkinson’s disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms. Methods Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction. Results Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training. Conclusions Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020).

3,4-Dihydroxy-2,2-dimethyl-chroman derivatives have diverse physiological properties. A polyketone (3S,4S)-3,4-Dihydroxy-6-methoxy-2,2-dimethylchromom (3S,4S-DMD) with antibacterial activity was isolated from the solid culture of rare edible fungus Panus lecomtei. However, the yield of 3S,4S-DMD in solid culture of P. lecomtei is very low and the production period are too long. In this work, efficient accumulation of 3S,4S-DMD in P. lecomtei by submerged fermentation is studied. The key fermentation factors of P. lecomtei for 3S,4S-DMD production were optimised by single-factor experiment successively, and then a Box-Behnken design (BBD) experiment was carried out to further enhance 3S,4S-DMD production. A maximum 3S,4S-DMD yield of 196.3 mg/L was obtained at 25.78 g/L glucose, 1.67 g/L MgSO4 · 7H2O, 40°C and 197 r/min, respectively, which increased by 1.3-fold in comparison with that in the non-optimised fermentation conditions. Furthermore, an enhanced yield of 3S,4S-DMD (261.6 mg/L) was obtained in 5-L agitated fermenter. The 3S,4S-DMD productivity in flask and fermenter reached to 7.26 and 8.07 mg/g per day, respectively, which considerably increased by over 121-fold in comparison with that in the solid fermentation (0.06 mg/g per day). This study presents a potential method for the production of 3S,4S-DMD by submerged fermentation.

The problem of resistance reduction has always been the key and difficult point of lightning protection. However, the problem of reducing the grounding resistance efficiently has not been solved. A method is introduced in this paper to solve this problem from the lightning current attenuation. The lightning discharge shock wave mechanism, shock overpressure reflection mechanism, and arc truncation mechanism are included to theoretically analyze the lightning current attenuation mechanism. The overpressure of the lightning discharge is much higher than the cut-off arc radial tolerance pressure, which contributes to the temporarily closing of discharge channel. Moreover, a lightning discharge model is established in COMSOL to simulate the process of discharge in lightning current. The results show that the pressure in the tube reaches up to $4\times 10$ 8 Pa rapidly, and the velocity in the mouth of the tube could reach as high as 4200 m/s. Finally, the current attenuation experiments are designed to validate the lightning current attenuation effect. The results show that the current is attenuated by the action of the prototype, the amplitude of the impulse current decreased from 66.95 kA to 35.10 kA, and the steepness of the impulse current decreased from 18.49 kA/ $\mu \text{s}$ to 4.14 kA/ $\mu \text{s}$ . All of the results show that this method could efficiently attenuate lightning currents.

Liquidambar formosana is important for its ornamental value in China; it is increasingly used for landscaping and gardening trees due to its diverse leaf colors and seasonal changes. Varieties including either a fixed leaf color, the purplish ‘Fuluzifeng’ (ZF), or seasonal changes in leaf color, the reddish ‘Nanlinhong’ (NLH) have been bred and registered as new plant varieties under the International Union for the Protection of New Plant Varieties (UPOV) system. To gain practical insights into the anthocyanin biosynthetic process, transcriptome sequencing (Illumina) was performed to clarify the metabolic pathways present in the three seasonal changes in leaf colors in NLH and in the springtime purple-red color of ZF. qRT-PCR was used to verify the speculation. Based on the differentially expressed genes and flavonoids analyses, the spring, summer, and autumn leaves of NLH were compared to study the seasonal differences. NLH and ZF were compared to study the formation mechanism of the two leaf colors in spring. Transcriptome sequencing produced a total of 121,216 unigenes from all samples, where 48 unigenes were differentially expressed and associated with the anthocyanidin pathway. The expression levels of LfDFR and LfANS genes corresponded to the accumulation of concentrations of cyanidins in spring (NLHC) and autumn leaves (NLHQ), respectively, with different shades of red. Moreover, the LfF3′5′H gene corresponded to the accumulation of flavonols and delphinidins in purple-red leaves (ZFC). Cyanidin and peonidin were the key pigments in red and dark-red leaves, and purple-red leaves were co-pigmented by cyanidins, pelargonidins, and delphinidins.