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Abstract The cable bracket is one of the crucial components of high-speed Electric Multiple Units (EMUs), which is fixed to the axle box by bolts to support the cable. As an important parameter of the joint surface, contact stiffness significantly affects the dynamic response and service life of the cable bracket. However, it is difficult to directly measure the contact stiffness of the joint surface. As a result, an identification method is proposed in this investigation to identify the contact stiffness. A finite element model incorporating both normal and tangential stiffness parameters is developed. According to the finite element model and modal testing results, an improved particle swarm optimization algorithm is employed to identify the contact stiffness of the joint surface. The effect of the contact stiffness on the vibrations of the cable bracket is investigated. The findings indicate that pre-tightening torque significantly influences the contact stiffness of the cable bracket. The contact stiffness has a great effect on the vibrations of the cable bracket. Optimal contact stiffness notably reduces vibrations of the cable bracket, thereby extending its service life.

Objective To study the quality comparability of human coagulation factor Ⅷ (FⅧ) produced before and after the change of factory site. Methods A comparative study was carried out on quality quantitative indexes, related impurities and stability data of FⅧ produced before and after the change of factory site. Results The FⅧ quantitative quality before and after the change of factory site all met the quality standard, and the related impurities including aluminum residue, tributyl phosphate residue, polysorbate 80 residue and PEG residue all met the quality standard. Other impurities including human fibrinogen, fibronectin, plasminogen, IgA, IgM and IgG were extremely low in content and equivalent in quality. The content of VWF (von Willebrand factor) had no obvious change before and after the change of factory site, but was significantly higher than that of other domestic manufacturers’ commercial products. The results of accelerated stability and long-term stability tests showed that the titer of FⅧ fluctuated within the methodological error range, and the results all met the quality standard. Conclusion The change of factory site of FⅧ has no effect on the quality.

Abstract Methods Web of Science, Cochrane library and PubMed were systematically searched up to January 2024 to identify studies examining the impact of financial incentives on diabetes management in patients. Studies were evaluated based on the robustness of their methodology, participant numbers, and quality scores. The Cochrane risk-of-bias tool was applied for randomized controlled trials, while the Newcastle–Ottawa Scale was used for non-randomized controlled trials to assess study quality. Due to the heterogeneity of the included studies, a narrative synthesis approach was utilized. Results In the study, we included 12 published research studies. Five studies investigated the influence of financial incentives on patient behavior, all demonstrating a significant positive impact on behaviors such as blood glucose monitoring, medication adherence, and physical activity. 10 studies analyzed the impact of financial incentives on HbA1c levels in diabetes patients. Among them, 5 studies reported that financial incentives could improve HbA1c levels through longitudinal historical comparisons. The other 5 studies did not find significant improvements compared to the control group. Three studies explored long-term effects, two studies targeting the adolescent population had no impact, and one study targeting adults had a positive impact. Conclusions In summary, this review found that financial incentives can positively influence patient behavior and enhance compliance, but their impact on HbA1c levels is inconsistent. Financial incentives may help adult patients maintain behavior even after the withdrawal of incentives.

Abstract Background China’s family planning policies have experienced stages of one-child policy, partial two-child policy, and universal two-child policy. However, the impact of these policy shifts on the spatial accessibility to maternal and child health (MCH) services for women and children remains uncertain. This study aimed to evaluate the spatiotemporal trends and geographic disparities in spatial accessibility to MCH services in the context of two-child polices. Methods This study was conducted in Nanning prefecture, China, from 2013 to 2019. Data on the transportation networks, MCH institutes, the annual number of newborns, and the annual number of pregnant women in Nanning prefecture were collected. Gaussian two-step floating catchment area (Ga2SFCA) method was employed to measure the spatial accessibility to MCH services at county, township, and village levels. Temporal trends in spatial accessibility were analyzed using Joinpoint regression analysis. Geographic disparities in spatial accessibility were identified using geographic information system (GIS) mapping techniques. Results Overall, the spatial accessibility to MCH services showed an upward trend from 2013 to 2019 at county, town, and village levels, with the average annual percent change (AAPC) being 5.04, 4.73, and 5.39, respectively. Specifically, the spatial accessibility experienced a slight downward trend during the period of partial two-child policy for both parents only children (i.e., 2013–2014), a slight upward trend during the period of partial two-child policy for either parent only child (i.e., 2014–2016) and the early stages of universal two-child policy (i.e., 2016–2018), and a large upward trend in the later stages of universal two-child policy (i.e., 2018–2019). Spatial accessibility to MCH services gradually decreased from central urban areas to surrounding rural areas. Regions with low spatial accessibility were predominantly located in remote rural areas. Conclusion With the gradual opening of the two-child policies, the spatial accessibility to MCH services for women and children has generally improved. However, significant geographic disparities have persisted throughout the stages of the two-child policies. Comprehensive measures should be considered to improve equity in MCH services for women and children.

Abstract Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results.

BackgroundA newly developed technique, the Triglyceride-glucose (TyG) index, supplies a more straightforward method to identify IR than the HOMA-IR (Homeostasis Model Assessment of Insulin Resistance). Yet no methodical analysis has looked into the link involving the TyG index and low muscle mass (LMM), low muscle strength (LMS), and sarcopenia within the US. Thus, this study intended to find any connection concerning the TyG index and LMM, LMS, and sarcopenia.MethodsBetween 2011 to 2014, data from the NHANES were used to conduct a nationally representative study involving 2,504 participants. LMM, LMS, and sarcopenia were the outcome variables. Moreover, this positive correlation persists irrespective of age and gender.ResultsThe TyG index revealed a significant correlation with the prevalence of developing LMM (OR = 1.63(1.26–2.11), p=0.001), LMS (OR = 1.61(1.36–1.91), p

A single nucleotide variant in mitochondrial DNA (mtDNA) 1555A>G is associated with drug-induced hearing loss. For the 1555A>G mutation site, 1555A wild-type and 1555G mutant-type plasmids were constructed, respectively. In this study, a PCR method based on the TaqMan amplification refractory mutation system was proposed to detect mtDNA 1555A>G. A common upstream primer, a common TaqMan probe, and two downstream allele-specific primers with mismatched bases were designed. One-step amplification and detection of the wild-type and mutant type at the 1555 site were realized for the deafness-related gene through two reactions. Based on this detection method, the minimum detection limit of the wild-type and mutant type detection systems for plasmids was 50 copies/μL. The minimum sensitivity for the detection of nucleic acids in real dried blood spot (DBS) samples was 0.1 ng/μL. In the normal DBS DNA sample, the detection limit of the mutation abundance reached 0.78%. The specificity of the detection method was 100%, and the coefficient of variation was less than 3.36%. This approach was validated using clinical DNA extracted from 113 DBS samples of newborns. Additionally, it showed 100% agreement with bi-directional Sanger sequencing. It can be used as an optional method for the clinical detection of deafness-related genes.

Introduction This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. Methods This was an in vivo and in vitro study. In vitro, PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action. And the impact of nicotine on mitochondrial Ca2+ levels and Ca2+ transport-related proteins in PSCs was analyzed. The changes in nicotine effects were observed after the knockdown of the mitochondrial calcium uniporter (MCU) in PSCs. In vivo experiments were conducted using a mouse model of CP to assess the effects of nicotine on pancreatic fibrosis and oxidative stress in mice. The alterations in nicotine effects were observed after treatment with the MCU inhibitor Ru360. Results In vitro experiments demonstrated that nicotine promoted PSCs activation, characterized by increased cell proliferation, elevated α-SMA and collagen expression. Nicotine also increased the production of reactive oxygen species (ROS) and cellular malondialdehyde (MDA), exacerbating oxidative stress damage. Transcriptome sequencing revealed that nicotine may exert its effects through the calcium signaling pathway, and it was verified that nicotine elevated mitochondrial Ca2+ levels and upregulated MCU expression. Knockdown of MCU reversed the effects of nicotine on mitochondrial calcium homeostasis, improved mitochondrial oxidative stress damage and structural dysfunction, thereby alleviating the activation of PSCs. In vivo validation experiments showed that nicotine significantly aggravated pancreatic fibrosis in CP mice, promoted PSCs activation, exacerbated pancreatic tissue oxidative stress, and increased MCU expression. However, treatment with Ru360 significantly mitigated these effects. Conclusions This study confirms that nicotine upregulates the expression of MCU, leading to mitochondrial calcium overload and exacerbating oxidative stress in PSCs, and ultimately promoting PSCs activation and exacerbating pancreatic fibrosis in CP.

This study evaluated the nutrients, flavour and antioxidant capacity in the embryo, colloid and fruiting body of Dictyophora rubrovalvata. The embryo had the highest protein [2.91 ± 0.39 g.(100 g)-1] and polysaccharides (17.44 ± 1.49 mg.g-1), the fruiting body had the highest total phenol content (0.87 ± 0.17 mg.g-1), the colloid was rich in minerals [1.57 ± 0.16 g.(100 g)-1]. The antioxidant capacity of the embryo was higher than that of the other parts, in terms of different solvents, the antioxidant capacity of D. rubrovalvata extracted with ethanol was higher than that of water. 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing capacity were positively correlated with polysaccharides, proteins and polyphenols. The free amino acid content ranged from 7.44 to 11.52 mg.g-1, the distribution was fruiting body > embryo > colloid, of which glutamic acid content was the highest, and the flavour characteristics were mainly umami and sweetness. The nucleotide content of fruiting body and embryo was higher than in the colloid. In addition, the compositions of volatile flavour compounds were identified by headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), mainly alcohols, aldehydes and ketones, their distributions varied greatly among the three samples. These results indicated that different parts of D. rubrovalvata have different nutritional characteristics, the fruiting body has a high content of volatile and non-volatile components, the embryo and the colloid have good functional activity, laying a foundation for the functional development and comprehensive utilisation of D. rubrovalvata.

Radiation-induced intestinal injury is a common complication of radiotherapy for abdominal and pelvic malignancies. Due to its rapid proliferation, the small intestine is particularly sensitive to radiation, making it a critical factor limiting treatment. Ferulic acid (FA), a derivative of cinnamic acid, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we established a mouse model of radiation-induced intestinal injury using a dose of 11 Gy at a rate of 96.62 cGy/min. Our findings indicate that FA’s protective effects against radiation-induced intestinal injury may be mediated through the parkinsonism-associated deglycase (DJ-1) nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homolog 1 (Sirt1) nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) NOD-like receptor family, pyrin domain containing 3 (NLRP3). FA was found to mitigate changes in oxidative stress indices and inflammatory factors induced by radiation, as well as to attenuate radiation-induced pathological alterations in the small intestine. Furthermore, FA enhanced the expression of DJ-1 and Nrf2 at both the transcriptional and protein levels, inhibited NLRP3 protein fluorescence intensity, and reduced the expression of NLRP3, interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). Additionally, FA suppressed the transcription and translation of NF-κB, NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), IL-18, and IL-1β by upregulating Sirt1, thereby alleviating radiation-induced inflammatory injury in the small intestine. Thus, FA holds promise as an effective therapeutic agent for ameliorating radiation-induced intestinal injury.

The disruption of hematopoietic and immune functions is a significant consequence of the long-term effects of radiation exposure. This study investigated the potential mechanisms by which ferulic acid (FA) acts as a radioprotective agent in mitigating radiation-induced immune damage. C57BL/6J mice were exposed to a dose of 6.0 Gy of 60Co γ irradiation. FA was administered at doses of 25, 50, and 100 mg/kg/d for 7 days before and 30 days following irradiation. We evaluated changes in peripheral blood cells, T and B lymphocytes, natural killer cells in the spleen, and hematopoietic stem/progenitor cells in the bone marrow (BM). Whole-genome transcriptome sequencing of BM was performed to explore potential mechanisms. FA administration resulted in a significant reduction in malonaldehyde levels (p < 0.0001), an increase in catalase and beta-nicotinamide adenine dinucleotide levels in serum (p < 0.05), and enhanced multipotent progenitors (p < 0.01) and common lymphoid progenitors (p < 0.05) in the BM. Additionally, there was an elevation in white blood cell levels, red blood cell levels, and hemoglobin levels in peripheral blood (p < 0.01). Transcriptome analysis indicated that FA reversed the radiation-induced expression of genes related to immunity and inflammation. Enzyme-linked immunosorbent assay experiments further demonstrated that FA reduced interleukin-6 levels in the BM and decreased JAK1, JAK2, and STAT3 protein content (p < 0.01). In conclusion, FA might mitigate hematopoietic and immune damage by modulating the JAK/STAT signaling pathway.

ObjectiveTo analyze the effect of different types of disinfectants for perineum and urethral meatus cleaning in preventing catheter-associated asymptomatic bacteriuria and catheter-associated urinary tract infection (CAUTI).MethodsChinese and English databases were searched to collect randomized controlled trials (RCTs) of different disinfectants for perineum and urethral meatus cleaning to prevent CAUTI, and the positive rates of urine culture with different cleaning methods were contrasted by network meta-analysis.ResultsA total of 18 RCTs were included in this study to analyze the effect of 10 disinfectants in preventing CAUTI. The disinfectants were 0.1% chlorhexidine (CHG), 0.5% CHG, 2% CHG, 0.1% benzalkonium bromide (DBDAB), 0.05% iodophor, 0.5% iodophor, acidic oxidizing potential water (EOW), normal saline (NS), Shehuang lotion, and sterile water. Meta-analysis showed that the positive rates of urine culture in the 0.5% CHG cluster, EOW cluster, 0.5% iodophor cluster, and Shehuang lotion cluster were remarkably lower than that in the 0.1% DBDAB cluster (P < 0.05). The positive rate of urine culture in the 0.5% CHG cluster was remarkably lower than that in the 0.05% iodophor cluster (P < 0.05), whereas the positive rates of urine culture in the 0.5% CHG cluster, 0.5% iodophor cluster, Shehuang lotion cluster, and EOW were remarkably lower than that in the normal saline cluster (P < 0.05). The positive rate of urine culture in the 0.5% CHG cluster and EOW cluster were remarkably lower than those in the sterile water cluster (P < 0.05). The results of the area under the cumulative ranking probability plot (SUCRA) analysis showed that the probability ranking of the preventive effect of different disinfectants was as follows: 0.5% CHG > Shehuang lotion > EOW > 0.5% Iodophor > 2% CHG > 0.1% CHG > 0.05% Iodophor > Sterile Water > 0.1% DBDAB > Saline. Conclusion0.5% CHG, Shehuang lotion, EOW, and 0.5% iodophor can be used to clean the perineum and urethral meatus in patients with indwelling catheters.Systematic review registrationChinese Clinical Trial Registry (ChiCTR), identifier ChiCTR2100052260.

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

Abstract Background Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics. Methods This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software. Results The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway. Conclusions Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.

Breast cancer (BC) is the most prevalent malignant tumor, surpassing lung cancer as the most frequent malignancy in women. Drug resistance, metastasis, and immune escape are the major factors affecting patient survival and represent a huge challenge in BC treatment in clinic. The cell- and subcellular organelle-targeting nanoparticles-mediated targeted BC therapy may be an effective modality for immune evasion, metastasis, and drug resistance. Nanocarriers, efficiently delivering small molecules and macromolecules, are used to target subcellular apparatuses with excellent targeting, controlled delivery, and fewer side effects. This study summarizes and critically analyzes the latest organic nanoparticle-mediated subcellular targeted therapeutic based on chemotherapy, gene therapy, immunotherapy, and combination therapy in detail, and discusses the challenges and opportunities of nanoparticle therapy.

Abstract Epigenetic alterations and metabolic dysfunction are two hallmarks of aging. However, the mechanism of how their interaction regulates aging, particularly in mammals, remains largely unknown. Here we show ELOVL fatty acid elongase 2 (Elovl2), a gene whose epigenetic alterations are most highly correlated with age prediction, contributes to aging by regulating lipid metabolism. We applied artificial intelligence to predict the protein structure of ELOVL2 and the interaction with its substrate. Impaired Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction, leading to key aging phenotypes at both cellular and physiological level. Furthermore, restoration of mitochondrial activity can rescue age-related macular degeneration (AMD) phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial (RPE) cells; this indicates a conservative mechanism in both human and mouse. Taken together, we revealed an epigenetic-metabolism axis contributing to aging and illustrate the power of an AI-based approach in structure-function studies.

Capsaicinoids, mostly from chili peppers, are widely used in daily life. Capsaicinoids are considered to be markers for the identification of illegal cooking oil (ICO), which is a serious threat to public health. The identification of capsaicinoids can help reveal food-related fraud, thereby safeguarding consumers’ health. Here, a novel and ultrasensitive method was established with a signal amplification strategy for the detection of capsaicinoids. AuNPs@Fe3O4 nanocomposites were functionalized with 4-aminothiophenol (4-atp). After diazotization, 4-atp on AuNPs@Fe3O4 reacted with capsaicinoids and formed capsaicinoids-azo-atp-AuNPs@Fe3O4. Ultimately, capsaicinoids-azo-atp-AuNPs@Fe3O4 was dropped onto the surface of a screen-printed carbon electrode (SPCE) and detected via the differential pulse voltammetry (DPV) method. AuNPs@Fe3O4 nanocomposites increased the specific surface area of the electrode. Moreover, the diazotization–coupling reaction enriched the analytes on the electrode surface. Liquid–liquid extraction was used for sample pretreatment. Under a pH value of 9.0 and concentration of 0.20 mol/L for the supporting electrolyte, the linearity of capsaicinoids in ICO is from 0.10 to 10.00 ng/mL, and the limit of detection (S/N = 3) is 0.05 ng/mL. This method is ultra-sensitive, reliable, and cost-effective for the detection of capsaicinoids. Herein, this method provides a promising tool for the identification of ICO.

The development of tantalum capacitor (TC) industry is associated with the production of one technology metal-tantalum (Ta). The recycling of waste tantalum capacitors (WTCs) is an important strategy for the sustainable development of tantalum related industries. A cryogenic crushing-alkaline calcination-leaching process has been proposed and experimentally studied in the present work, and main results showed: 1) after the refrigeration treatment with liquid nitrogen, WTCs got discharged and became brittle. Three groups of materials could be produced after the milling - magnetic separation - screening treatment, and portions of collected iron-nickel alloy, tantalum wire, and Ta bearing powder were 6.94%, 1.50%, and 91.56%, respectively; 2) organic components in Ta-bearing powder could be efficiently removed in the alkaline calcination process, and Si converted to Na2O·mSiO2 (m = 1, 2), which could be easily leached with water; 3) NaOH was selected to be the alkaline for calcination reactions, and the optimized temperature was 700 °C, the reacting time was 300 min, and the NaOH excess coefficient was 1.0; 4) water leaching residue was treated with nitric acid, and Ag, Fe and Ni could be enriched in the leaching liquor, and the overall recovery of Ta was 96.72% at optimized conditions.

Urbanization and cultivated land use coordination is the key to urban‒rural coordinated development, especially in the major grain-producing areas in China, but it is rarely examined. A coordination framework of urbanization and cultivated land use efficiency systematically clarified how to achieve Urbanization and cultivated land use coordination. Taking Hunan Province as an example, this study explored the spatiotemporal evolution of the level of Urbanization and cultivated land use coordination from 2000 to 2018 at the county level, identified current types of Urbanization and cultivated land use coordination and discussed the key optimization measures for different types. The results showed that 1) urban‒rural coordinated development, abstractly represented by the Urbanization and cultivated land use coordination in major grain-producing areas, depends on the intensity of interactions and the level of integration of urbanization and cultivated land use systems. 2) From 2000 to 2018, the level of Urbanization and cultivated land use coordination in Hunan changed from serious maladjustment to great maladjustment to coordination. 3) The current Urbanization and cultivated land use coordination pattern in Hunan Province has a strong spatial differentiation, which can be divided into eight subregions. The key to the coordinated development of each type is to accelerate the flow of elements through deepening reform and innovation mechanisms to complement the shortcomings of development. This study will provide a scientific reference for the effective implementation of regional coordinated development strategies in major food-producing regions.

Abstract Mitochondrial retrograde signaling (mito-RTG) triggered by mitochondrial dysfunction plays a potential role in regulating tumor metabolic reprogramming and cellular sensitivity to radiation. Our previous studies showed phos-pyruvate dehydrogenase (p-PDH) and PDK1, which involved in aerobic glycolysis, were positively correlated with radioresistance, but how they initiate and work in the mito-RTG pathway is still unknown. Our further genomics analysis revealed that complex I components were widely downregulated in mitochondrial dysfunction model. In the present study, high expression of p-PDH was found in the complex I deficient cells and induced radioresistance. Mechanistically, complex I defects led to a decreased PDH both in cytoplasm and nucleus through [Ca2+]m-PDP1-PDH axis, and decreased PDH in nucleus promote DNA damage repair (DDR) response via reducing histone acetylation. Meanwhile, NDUFS1 (an important component of the complex I) overexpression could enhance the complex I activity, reverse glycolysis and resensitize cancer cells to radiation in vivo and in vitro. Furthermore, low NDUFS1 and PDH expression were validated to be correlated with poor tumor regression grading (TRG) in local advanced colorectal cancer (CRC) patients underwent neoadjuvant radiotherapy. Here, we propose that the [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling activated by mitochondrial complex I defects contribute to cancer cell radioresistance, which provides new insight in the understanding of the mito-RTG. For the first time, we reveal that NDUFS1 could be served as a promising predictor of radiosensitivity and modification of complex I function may improve clinical benefits of radiotherapy in CRC.

Glycosylation is an important post-translational modification of proteins, contributing to protein function, stability and subcellular localization. Fungal immunomodulatory proteins (FIPs) are a group of small proteins with notable immunomodulatory activity, some of which are glycoproteins. In this study, the impact of glycosylation on the bioactivity and biochemical characteristics of FIP-nha (from Nectria haematococca) is described. Three rFIP-nha glycan mutants (N5A, N39A, N5+39A) were constructed and expressed in Pichia pastoris to study the functionality of the specific N-glycosylation on amino acid N5 and N39. Their protein characteristics, structure, stability and activity were tested. WT and mutants all formed tetramers, with no obvious difference in crystal structures. Their melting temperatures were 82.2 °C (WT), 81.4 °C (N5A), 80.7 °C (N39A) and 80.1 °C (N5+39A), indicating that glycosylation improves thermostability of rFIP-nha. Digestion assays showed that glycosylation on either site improved pepsin resistance, while 39N-glycosylation was important for trypsin resistance. Based on the 3D structure and analysis of enzyme cleavage sites, we conclude that glycosylation might interfere with hydrolysis via increasing steric hindrance. WT and mutants exerted similar bioactivity on tumor cell metabolism and red blood cells hemagglutination. Taken together, these findings indicate that glycosylation of FIP-nha impacts its thermostability and digestion resistance.

The copolymers of cycloolefin (COC), a type of thermoplastic material, have been widely used for the large-scale industrial fabrication of droplet microfluidic devices, which is often performed using hot-embossing or injection-molding techniques. The generation of droplets and the uniformity of droplet sizes are significantly affected by the surface wettability of COC during fabrication and the pressure stability of the employed fluid pump during operation. In order to alleviate the effects of undesirable surface wettability and pressure variation on the generation of droplets in COC-based devices, a simple surface modification procedure was applied to hydrophobically modify the surfaces of COC-based microchannels for large-scale industrial production. The surface modification procedure consisted of an oxygen plasma treatment of the polymer surface followed by a solution-phase reaction in fluorocarbon solvent. The experimental results demonstrate that following the proposed surface modification, the COC droplet microfluidic devices could stably generate microvolume water droplets with a small coefficient of variation, even if the pressure of the dispersed phase (water) fluctuated. The durability test results regarding the modified surfaces show that the hydrophobicity of the modified COC surfaces could be sustained for up to four months, deteriorating with time thereafter. Our study can provide a potential solution useful in and guidance for the large-scale industrial production of droplet microfluidic devices for various applications, including polymerase chain reaction and single-cell analysis.

Since the Mesozoic, the convergence of the Tethys ocean plate and the Paleo-Pacific plate on the South China block has resulted in the multi-sequence tectonic deformation as well as the multi-stage magmatic and metallogenic events, and has formed many important polymetallic metallogenic belts in South China. In this context, mineralization stages, distribution of ore bodies and metallogenic mechanisms of typical skarn deposits in metallogenic areas were sorted out. And then the mineralization processes and genetic mechanisms of typical deposits are completed using the sequence of tectonic deformation and its rock/ore-control regularity. A structural deformation analysis was made on the southwestern Fe polymetallic metallogenic belt, the northeastern Jiangxi Taqian-fuchun W-Cu metallogenic belt and the Laojunshan W-Sn ore concentration area to set up three relatively complete periods of deformation sequence during the Indosinian period, the middle-late Jurassic and the Cretaceous, combined with previous research results; however, the three deformation sequences differ in duration of tectonics, structural property, scale and strength, and deformation style. The analysis of rock-control by tectonics together with the existing isotope chronology data both revealed that the magmatic or metamorphic thermal events were consistent with the deformation sequence occurred in each mineralization zone, and then the multi-stage magmatic events related to the Makeng-type Fe polymetallic deposit, the Zhuxi W-Cu deposit and the Nanyangtian W deposit were clarified using the corresponding laws between deformation sequence and magmatic stage. On this basis, we identified the multi-stage mineralization events and supposed that multi-stage superposition occurred in the mineralization process of all three typical deposits. From the point of view of structural control over the emplacement mechanism of the ore deposit, this paper analyzed the mechanism of the decentralized polymorphic orebody of the Makeng-type deposit, the vertical large-span mineralization and deep giant orebody of the Zhuxi deposit, and the stratiform-vein superposition orebody of the Nanyangtian deposit, which are controlled by the folding detachment of the ore-bearing strata, the large-scale thrust duplex and the two-stage tectonic compounding respectively. The dynamic background of tectonic deformation and magmatic mineralization in the important metallogenic belts of South China at different stages were discussed.

The human gut microbiota play essential roles in metabolism and human health, especially by enzymatically utilizing dietary fiber that the host cannot directly digest and releasing functional components including short-chain fatty acids (SCFAs) and hydroxycinnamic acids (e.g., ferulic acid). In our previous study, seven potential feruloyl esterase (FAE) genes were identified from the gut microbiota. In the current work, one of the genes encoding a novel FAE (DfFAE) from Dorea formicigenerans of Firmicutes was bacterially expressed, purified and characterized. The 30.5 kDa type-A DfFAE has an optimum pH and temperature of 8.4 and 40 °C, respectively, exhibiting a higher substrate specificity toward short-chain acyl-ester substrate (pNPA). The AlphaFold2 based ab initio structural modeling revealed a five α-helices cap domain that shaped an unusually narrow and deep active site pocket containing a specific substrate access tunnel in DfFAE. Furthermore, rational design strategy was subjected to the active site pocket in an aim of improving its enzymatic activities. The mutants V252A, N156A, W255A, P149A, and P186A showed 1.8 to 5.7-fold increase in catalytic efficiency toward pNPA, while W255A also exhibited altered substrate preference toward long-chain substrate pNPO (45.5-fold). This study highlighted an unusual active site architecture in DfFAE that influenced its substrate selectivity and illustrated the applicability of rational design for enhanced enzymatic properties.

Abstract Background To describe the diagnostic criteria used and their application accuracy in the practice of polycystic ovary syndrome (PCOS) caring among obstetricians and gynaecologists across China. Methods This was an Online cross-sectional survey of Obstetricians and gynecologists involved in PCOS caring conducted via the largest continuing education platform of obstetrics and gynecology across China from September 2019 to November 2019. Results A total of 2,328 respondents were eligible for the final analysis. Of these, 94.5 % were general obstetricians and gynaecologists (Ge-ObGyn), and 5.5 % were reproductive endocrinologists (Re-ObGyn). Overall, the most frequently used criteria were the Androgen Excess and Polycystic Ovary Syndrome Society (AE-PCOS) criteria (48.2 %), followed by the Rotterdam criteria (35.7 %) and NIH criteria (12.1 %). Of the respondents, 31.3 % used their diagnostic criteria in their clinical practice. More respondents who chose the Rotterdam criteria could accurately apply the diagnostic criteria than those who chose the AE-PCOS criteria (41.2 % vs. 32.1 %, P

Numerical weather prediction technology plays an increasingly important role in improving accuracy and service level of modern weather forecast. With the development of observation system and higher resolution and complexity of the numerical weather prediction model, the products of numerical weather forecast have been greatly improved in quantity and quality, and can offer rich information at high spatial-temporal frequency. However, such a large amount of prediction data are not fully explored. Artificial intelligence has achieved great success in many fields, such as pattern recognition and natural language processing, which provides an opportunity for further improving numerical weather prediction. It's also employed in initialization, numerical model and production of weather forecast service, involving observation system, data assimilation, model integration, ensemble forecast and high-performance computing methods. Both the accuracy of forecast results and computational efficiency have been improved by using error correction, parameter estimation, local surrogate model and so on. In addition, some end-to-end neural network models also show the potential of pure data-driven weather forecast. These models use spatial-temporal observation data as input and directly output the prediction results in terms of deterministic results or probabilities. Some of them perform well in short-term severe convective weather, precipitation, and long-term climate forecast. Existing works employ various artificial intelligence technology methods, mainly including large-scale calculation of neural network, feature analysis, interpretability, and customized loss function. However, there are still some challenges, the potential of artificial intelligence needs to be further explored. Some issues should be carefully considered, including weak interpretability, uncertainty analysis and the coupling with conventional numerical models, and how to use physical knowledge to guide the design of artificial intelligence model is also worth addressing. To deal with these challenges, some promising suggestions are proposed. Bayesian network and causal network will help to establish more comprehensive and profound feature engineering. Using Bayesian inference to generate distribution characteristics of current meteorological states may be an alternative to efficient and effective uncertainty quantification. The development of some standard workflow and framework will contribute to the coupling of conventional numerical model and artificial intelligence module. Successful artificial intelligence applications in weather forecast require deep cooperation between meteorological experts and computer experts who focus on artificial intelligence and high-performance computing.

Abstract Background To evaluate different stages of liver fibrosis in cynomolgus monkeys by comparing magnetic resonance-perfusion weighted imaging (MR-PWI) quantitative and semi-quantitative parameters, and confirm the best detection indicators for diagnosis of liver fibrosis. Methods A liver fibrosis model of different stages (S0–S4) was established in cynomolgus monkeys. The changes in MR-PWI quantitative and semi-quantitative parameters with the progression of liver fibrosis were investigated. Results MR-PWI quantitative parameters gradually decreased with the progression of liver fibrosis. Hepatic arterial perfusion index (HPI) was found to increase with the progression of liver fibrosis and significant differences of HPI between each group were observed. There was a highly positive correlation between HPI and the stages of liver fibrosis. Receiver operating characteristic (ROC) curve analysis showed that HPI had the highest efficacy of the MR-PWI quantitative parameters for the diagnosis of liver fibrosis. The MR-PW semi-quantitative parameters gradually reduced with the progression of liver fibrosis, and the differences were statistically significant between stages S3–S4 and S0–S2. Time to peak (TPP) gradually extended and showed a positive correlation with the stages of liver fibrosis. TTP had the highest efficacy of the semi-quantitative parameters for diagnosis of liver fibrosis. Conclusions Both the MR-PWI quantitative and semi-quantitative parameters of the liver fibrosis model in cynomolgus monkeys varied at different stages of liver fibrosis, and HPI and TTP were the best detection indices for quantitative and semi-quantitative evaluation of liver fibrosis, respectively.

Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes ‘magnification’ of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact-deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies.

Objective To explore the clinicopathological features, immunophenotype, molecular genetics, differential diagnosis and prognosis of diffuse midline glioma, H3 K27M mutant. Methods and Results A 21⁃ year⁃ old male patient suffered from polydipsia and polyuria. Physical examination showed that the visual sensitivity on both sides was weakened, the visual field was complete, and other signs were negative. Brain MRI showed that T 1WI iso ⁃low signal and T2WI iso ⁃ high signal occupied the suprasellar space, and enhanced unevenly. The patient underwent surgical treatment, with a greyish⁃red colour, soft texture and abundant blood supply. The tumor was partially resection. Histological findings showed the tumor was mainly composed of spindle shaped and ellipsoidal cells with occasionally typical mitotic activity, which were arranged in fascicularis, swirly or perivascular pseudorosettes patterns, with the moderate ⁃ to high ⁃ density. Small focal areas of necrosis and proliferation of microvessel also could be seen. Immunohistochemical staining showed the nuclei of tumor cells was diffusely positive for histone H3 K27M mutant protein (H3 K27M), oligodendrocytes transcription factor⁃2 (Olig⁃2) and P53, cytoplasm was positive for glial fibrillary acidic protein (GFAP), vimentin (Vim), microtubule ⁃ associated protein ⁃ 2 (MAP ⁃ 2), synaptophysin (Syn) and nestin (Nes), cytoplasm and nuclei were positive for S ⁃100 protein (S ⁃ 100). Ki ⁃ 67 labeling index was 10%-20% . Whole genome sequencing (WGS) revealed the presence of H3 K27M and BRAF V600E gene mutations. Integrational diagnosis was diffuse midline glioma, H3 K27M mutant (WHO Ⅳ) lied in saddle area. The patient died 11 months after surgery. Conclusions Diffuse midline glioma, H3 K27M mutant is a group of primary brain neoplasm of recent acquisition in the 2016 WHO classification of central nervous system tumors, with the diverse histological appearance (WHO Ⅱ-Ⅳgrade), which was misdiagnosed easily. The most important clues for diagnosis were age (mostly in child), location (midline of the brain), diffusely growth pattern, and harbored histone H3 K27M mutation. DOI：10.3969/j.issn.1672⁃6731.2020.04.012

Objective To explore the correlation between multimodal magnetic resonance imaging (MRI) and expression of tissue factor (TF) in glioblastoma (GBM), and investigate the values of MRI parameters as imaging markers for TF. Methods The preoperative routine and functional MRI data of 60 patients with GBM confirmed by surgery and pathology in our hospital from August 2014 to November 2018 were retrospectively collected and analyzed for the parameters, including necrosis ratio, surface regularity, enhanced area volume, edema area volume, volume transfer constant Ktrans, relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) by post-processing. The expression of TF in the GBM tissue was detected with immunohistochemical staining, and then the correlation between above each parameter and TF expression was analyzed. Receiver operating characteristic (ROC) curve analysis was used to obtain the optimal threshold values, sensitivity and specificity of various imaging parameters in differentiation between GBM with TF of high expression and of low expression. Results The necrosis ratio, and Ktrans, rCBV and rCBF values were positively correlated with TF expression level (r=0.665, r=0.631, r=0.661, r=0.619, all P < 0.001). The necrosis ratio and Ktrans, rCBV and rCBF values were significantly higher in the highly-expressed TF group than the lowly-expressed TF group (P < 0.01). ROC analysis showed that all these MRI parameters presented TF level well, with area under curve (AUC) of rCBF reaching 0.907 (0.889, 0.857), that of necrosis ratio 0.869 (0.846, 0.676), that of Ktrans 0.854 (0.813, 0.833), and that of rCBV 0.804 (0.944, 0.571). The combination of conventional magnetic resonance and perfusion magnetic resonance parameters showed even better presention for TF expression level, with the AUC of necrosis ratio combined with Ktrans 0.982 (1, 0.875), necrosis ratio with rCBV 0.939 (0.889, 0.905), and necrosis ratio with rCBF 0.971 (0.944, 0.857). Conclusion Various magnetic resonance parameters (necrosis ratio, Ktrans, rCBV and rCBF) can better reflect TF expression in GBM patients, and can be used as imaging markers for TF expression in GBM.

Recurrent spontaneous abortion (RSA) is a highly heterogeneous complication of pregnancy with the underlying mechanisms remaining uncharacterized. Dysregulated decidualization is a critical contributor to the phenotypic alterations related to pregnancy complications. To understand the molecular factors underlying RSA, we explored the role of longnoncoding RNAs (lncRNAs) in the decidual microenvironment where the crosstalk at the fetal–maternal interface occurs. By exploring RNA-seq data from RSA patients, we identified H19, a noncoding RNA that exhibits maternal monoallelic expression, as one of the most upregulated lncRNAs associated with RSA. The paternally expressed fetal mitogen IGF2, which is reciprocally coregulated with H19 within the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as H19 and IGF2 were actively transcribed from both parental alleles in some decidual tissues. This loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 repressive histone marker in the IGF2 promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR), and the loss of CTCF-mediated intrachromosomal looping. These data suggest that dysregulation of the H19/IGF2 imprinting pathway may be an important epigenetic factor in the decidual microenvironment related to poor decidualization.