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In this study, the effects of hydrogen blending ratios and high CO2 content on hydrogen embrittlement (HE) of offshore natural gas X65 pipeline steel were investigated. In high-pressure hydrogen gas, the impact of hydrogen content on yield strength and tensile strength was minimal. However, the effect on elongation was more significant, with the area decreasing and the HE index increasing until the hydrogen-blended ratio approached 30%, at which point the HE index reached 8.94%. Introducing CO2 into high-pressure hydrogen-rich gas further increased the HE index with high CO2 content. At 40% CO2, the HE index was 2.42 times higher than in high-pressure hydrogen-blended mixtures (30% H2). Additionally, the local fracture morphology transitions from ductile to quasi-cleavage fracture with the addition of CO2 and H2.

The Da'anzhai Member of the Lower Jurassic in northern Sichuan Basin is one of the major oil-bearing formations in the basin. In recent years, with the development of unconventional exploration theories, exploration efforts have shifted towards the shale reservoirs in the Da'anzhai Member, enhancing the understanding of the exploration directions for continental shale oil in northern Sichuan. Based on the data from shale oil exploration wells LY1 and YY2, including core samples, experiments, drilling, and fracturing data, a reassessment of the oil and gas formation conditions, resource potential, and engineering geological conditions was conducted. The results indicate that: (1) The second submember of the Da'anzhai Member in Langzhong has a good resource base and formation conditions, indicating great exploration potential. The second submember mainly develops three lithologies: shale, shell limestone, and shale interbedded with shell limestone. The shale exhibits good hydro- carbon source quality and is generally in a middle to high-mature stage. Its hydrocarbon production intensity is (20-90)×104 t/km2, and the retained hydrocarbon accounts for 66% to 78% of the total hydrocarbon production, with a shale oil resource amounting to 3.26×108 t. (2) The shale samples from the second submember in the study area have poorly developed fracture networks, characterized by poor permeability conditions, difficult drilling and compressibility conditions. The matrix-type shale oil has high crude oil viscosity and high wax content. The coupling configuration relationship between the permeability of the shale samples and the fluidity of the shale oil is key to achieving high production in target layers. (3) Given the current poor production results in matrix-type shale exploration, it is recommended to adopt a combined conventional and unconventional exploration method to study the formation system of the shale and limestone interlayer reservoirs in the research area, considering high-quality shale and fracture-porosity type limestone as favorable exploration targets. Through the integration of geological and engineering research methods, efforts should be made to tackle technical challenges related to drillability, compressibility, and production, thereby improving engineering and technological levels.

Acetic acid is a common inhibitor present in lignocellulose hydrolysate, which inhibits the ethanol production by yeast strains. Therefore, the cellulosic ethanol industry requires yeast strains that can tolerate acetic acid stress. Here we demonstrate that overexpressing a yeast native arginase-encoding gene, CAR1, renders Saccharomyces cerevisiae acetic acid tolerance. Specifically, ethanol yield increased by 27.3% in the CAR1-overexpressing strain compared to the control strain under 5.0 g/L acetic acid stress. The global intracellular amino acid level and compositions were further analyzed, and we found that CAR1 overexpression reduced the total amino acid content in response to acetic acid stress. Moreover, the CAR1 overexpressing strain showed increased ATP level and improved cell membrane integrity. Notably, we demonstrated that the effect of CAR1 overexpression was independent of the spermidine and proline metabolism, which indicates novel mechanisms for enhancing yeast stress tolerance. Our studies also suggest that CAR1 is a novel genetic element to be used in synthetic biology of yeast for efficient production of fuel ethanol.

Accurate pneumoconiosis staging is key to early intervention and treatment planning for pneumoconiosis patients. The staging process relies on assessing the profusion level of small opacities, which are dispersed throughout the entire lung field and manifest as fine textures. While conventional convolutional neural networks (CNNs) have achieved significant success in tasks such as image classification and object recognition, they are less effective for classifying fine-grained medical images due to the need for global, orderless feature representation. This limitation often results in inaccurate staging outcomes for pneumoconiosis. In this study, we propose a deep texture encoding scheme with a suppression strategy designed to capture the global, orderless characteristics of pneumoconiosis lesions while suppressing prominent regions such as the ribs and clavicles within the lung field. To further enhance staging accuracy, we incorporate an ordinal label distribution to capture the ordinal information among profusion levels of opacities. Additionally, we employ supervised contrastive learning to develop a more discriminative feature space for downstream classification tasks. Finally, in accordance with standard practices, we evaluate the profusion levels of opacities in each subregion of the lung, rather than relying on the entire chest X-ray image. Experimental results on the pneumoconiosis dataset demonstrate the superior performance of the proposed method confirming its effectiveness for accurate pneumoconiosis staging.

The acid water-soluble fraction of the 95% EtOH extract of Leonurus japonicus exhibited significant anti-inflammatory activity by suppressing the p-ERK/ERK ratio and iNOS expression. A further phytochemical investigation of this acid water-soluble fraction led to the isolation of three previously undescribed sesquineolignan glycosides, leolignosides A–C (1–3), and their planar structures were elucidated using HR-ESI-MS and 1D and 2D NMR. To determine the complicated absolute configuration of sesquineolignan glycosides, coupling constants, NOESY data, empirical rules, enzymatic hydrolysis, and ECD data were comprehensively used. These isolated compounds were also screened for anti-inflammatory activity. Encouragingly, leolignosides A–C all suppressed LPS-induced NO overproduction in RAW 264.7 macrophages. The aglycone (3a) of leolignoside C was chosen for further investigation for its activity and the available amount. Similar to the acid water-soluble fraction, compound 3a inhibited NO overproduction and decreased the p-ERK/ERK and p-NF-κB/NF-κB ratios, indicating that 3a may exert anti-inflammatory effects through the ERK/NF-κB signaling pathway.

Abstract Background The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. Results In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-β1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. Conclusions Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

BackgroundThe relationship between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is widely known; however, causal evidence of this link is lacking. Here, we aimed to determine the causal effect of peripheral immune cells, specifically total white blood cells, lymphocytes, monocytes, basophils, eosinophils, and neutrophils, as well as lymphocyte subset traits, on the IgAN risk using a Mendelian randomization (MR) analysis.MethodsThe inverse-variance weighted (IVW) method was used for the primary analysis. We applied three complementary methods, including the weighted median, MR-Egger regression, and MR-PRESSO, to detect and correct for the effect of horizontal pleiotropy. Additionally, we performed a multivariable MR (MVMR) analysis, adjusting for the effects of C-reactive protein (CRP) levels. The roles of specific lymphocyte subtypes and their significance have garnered interest. Bidirectional two-sample MR analysis was performed to test the potential causal relationships between immune traits, including median fluorescence intensities (MFIs) and the relative cell count (AC), and IgAN.ResultsThe IVW-MR analysis suggested a potential causal relationship between lymphocyte counts and IgAN in Europe (OR per 1-SD increase: 1.43, 95% CI: 1.08–1.88, P = 0.0123). The risk effect of lymphocytes remained even after adjusting for CRP levels using the MVMR method (OR per 1-SD increase: 1.44, 95% CI: 1.05–1.96, P = 0.0210). The other sensitivity analyses showed a consistent trend. The largest GWAS published to date was used for peripheral blood immunophenotyping to explore the potential causal relationship between peripheral immune cell subsets and IgAN. Six AC–IgAN and 14 MFI–IgAN pairs that reached statistical significance (P < 0.05) were detected. Notably, CD3, expressed in eight subsets of T cells, consistently showed a positive correlation with IgAN. The bidirectional MR analysis did not reveal any evidence of reverse causality. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates.ConclusionsGenetically determined high lymphocyte counts were associated with IgAN, supporting that high lymphocyte counts is causal risk factor for IgAN.

Sesquiterpenoids are integral constituents of terpenoid-bearing plants, comprising a diverse and abundant class of natural compounds, among which eudesmane-type sesquiterpenoids have bicyclic structures that feature the fusion of two six-membered carbon rings, thereby attracting considerable attention. They are widespread in nature, with multifaceted biological activities such as anti-inflammatory, anticancer, antimicrobial, antimalarial, and insecticidal activities, thus gaining focus in life science research. The discovery and identification of these active compounds have laid a foundation for unraveling their potential medicinal value. In this review, we comprehensively explore the natural eudesmane-type sesquiterpenoids isolated (totaling 391 compounds) between 2016 and 2022, elucidating their chemical structures, plant distribution patterns, and pertinent biological properties. Accordingly, the study serves not only as a framework for researchers to thoroughly comprehend these compounds but also as a robust reference for future endeavors aimed at exploring the pharmaceutical potential and prospective applications of these molecules.

Rice is one of the important cereal crops in the world, and its yield and quality have always been the focus of breeders, which are related to global food security and human health. Rice grain type, mainly includes grain length, grain width and grain thickness, is an important quantitative trait controlled by multiple genes, and it not only directly affects rice yield, but is also closely related to rice quality. A good understanding of the formation and regulation mechanism of grain type will help to further increase rice yield per plant and improve rice quality. The development of molecular biology and the study of genomics have brought new changes to the exploration of the internal regulation mechanism of rice. A large number of quantitative trait locus (QTL) of rice grain type have been successfully identified and analyzed, and the functions of genes related to them have been verified. So far, several pathways regulating grain type have been identified, such as ubiquitin-proteasome degradation pathway, G protein signaling pathway, mitogen-activated protein kinase (MAPK) pathway, transcription factor regulation pathway, plant hormone pathway and MiRNA-related pathways. However, the regulatory network of grain type is extremely complex, and the mechanisms of the upstream and downstream regulatory components of many genes are still unclear, and there are even some cross interactions among the pathways that affect grain type. This review discussed the research progress of genes related to different signaling pathways affecting rice grain type and the interaction between key grain type genes, summarized the application of grain type genes in breeding in recent years, and proposed to analyze the regulation mechanism of rice grain type with multi-omics, with an aim to better serve the molecular design and breeding and provide support for the development of new high-yield and high-quality rice breeding.

Abstract Patients who receive heart valve surgery need anticoagulation prophylaxis to reduce the risk of thrombosis. Warfarin often is a choice but its dosage varies due to gene and clinical factors. We aim to study, among them, if there is an interaction between acute kidney injury and two gene polymorphisms from this study. We extracted data of heart valve surgery recipients from the electronic health record (EHR) system of a medical center. The primary outcome is about the average daily dose of warfarin, measured as an additive interaction effect (INTadd) between acute kidney injury (AKI) and warfarin-related gene polymorphisms. The confounders, including age, sex, body surface area (BSA), comorbidities (i.e., atrial fibrillation [AF], hypertension [HTN], congestive heart failure [CHF]), serum albumin level, warfarin-relevant gene polymorphism (i.e., CYP2C9, VKORC1), prosthetic valve type (i.e., metal, bio), and warfarin history were controlled via a multivariate-linear regression model. The study included 200 patients, among whom 108 (54.00%) are female. Further, the mean age is 54.45 years, 31 (15.50%) have CHF, and 40 (20.00%) patients were prescribed concomitant amiodarone, which potentially overlays with the warfarin prophylaxis period. During the follow-up, AKI occurred in 30 (15.00%) patients. VKORC1 mutation (1639G>A) occurred in 25 (12.50%) patients and CYPC29 *2 or *3 mutations presented in 20 patients (10.00%). We found a significant additive interaction effect between AKI and VKORC1 (− 1.17, 95% CI − 1.82 to − 0.53, p = 0.0004). This result suggests it is probable that there is an interaction between acute kidney injury and the VKORC1 polymorphism for the warfarin dose during the initial period of anticoagulation prophylaxis.

Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3–5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca2+ in uterine tissues by promoting extracellular Ca2+ influx and intracellular Ca2+ release, which were related to the activation of L-type Ca2+ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca2+ in uterine tissues via inhibition of extracellular Ca2+ influx and intracellular Ca2+ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage.

The Lower Cambrian Qiongzhusi Formation in Sichuan Basin and on its periphery is rich in shale gas resources, and it has become one of the important shale gas development intervals in Sichuan Basin. Controlled by complex sedimentary setting, the silty shale reservoir in Qiongzhusi Formation has various lithofacies and strong heterogeneity longitudinally, which restricts the exploration and development of shale gas. Therefore, it is urgent to study the sedimentary characteristics, sedimentary facies and sedimentary models. Based on the previous understanding of tectonic setting and sequence stratigraphy, and through detailed analysis of rock data, well logging data, geochemistry data and paleontology data, this paper clarifies the Early Cambrian sedimentary background of combined ocean-paleoland influence, moderate water depth and widespread reduction of Sichuan Basin and its periphery. The paper also believes that the Qiongzhusi Formation is mainly deposited in shore facies and continental shelf facies. The continental shelf facies are dominated, including shallow water continental shelf subfacies and deep water continental shelf subfacies. Based on the analysis of the combined action of wave and tide, seawater evaporation, suspension, rising ocean current, sedimentary paleogeomorphology and other fine-grained sedimentary influencing factors, and combined with the spatial distribution characteristics of sediments, the fine-grained sedimentary model of the Lower Cambrian Qiongzhusi Formation in Sichuan Basin and on its periphery is established, i.e., in the early stage of sedimentation, the effect of differential sedimentation is significant, the sequence thickness varies greatly, and the sedimentary characteristics and influencing factors differ greatly in different regions. In the middle stage of sedimentation, the effect of differential sedimentation is diminished and the difference of sequence thickness decreases continuously. In the late stage of sedimentation, with steady sedimentation, it enters the "open basin" stage, and the sequence thickness tends to be consistent.

Abstract Objective To determine the efficacy of cataract surgeries in blindness prevention programs in Chongqing. Methods During February–December 2019, we prospectively enrolled 487 patients (592 eyes) undergoing cataract surgery during blindness prevention programs in 6 Chongqing district/county hospitals (experimental group) and 481 patients (609 eyes) undergoing cataract surgery in the First Affiliated Hospital of Chongqing Medical University (controls). Uncorrected visual acuity (UCVA), refractive status, best corrected visual acuity (BCVA), slit lamp examination, and visual function/quality of life (VF-QOL) questionnaire scores were evaluated preoperatively, and at 1 and 6 months postoperatively. Results In the experimental group, UCVA, BCVA, and VF-QOL scores at 1 and 6 months were better than the preoperative values (P 0.5 logMAR) in the experimental group were uncorrected refractive errors (33.0%), PCO (29.5%), and fundus diseases (33.9%). Conclusion Cataract surgeries in blindness prevention programs in Chongqing significantly improved visual acuity, VF, and QOL, but underperformed compared to surgeries in the tertiary teaching hospital.

Diarylheptanoids, potential therapeutic agents and dietary supplements, are the main active compounds in the genus Curcuma, however, determination of the absolute configurations of the flexible polyhydric main chains in linear diarylheptanoids is still a challenge. In this study, an exploration of the phytochemical constituents of Curcuma phaeocaulis led to the isolation of eight novel linear diarylheptanoids (1–8). Enzymatic hydrolysis, preparation of acetonide derivatives, preparation of MTPA esters, and electronic circular dichroism calculations were comprehensively performed in order to determine their absolute configurations. In in vitro assays, compounds 2, 3, and 6 exhibited anti-angiogenic activities, and compounds 2, 3, and their aglycones inhibited the proliferation of HepG2 cells. These findings suggest that diarylheptanoid glucosides of C. phaeocaulis may be useful for suppression of hepatoma growth and metastasis.

Background: Extensive bone loss on femur and acetabulum posed a big challenge to orthopedists in total hip revision surgeries. Impaction bone grafting (IBG) as a valuable bone preservation technique could effectively address this problem. Either IBG revision on the femoral or acetabular side was well studied, while its use on both sides in one operation was not. The aim of this study is to present the outcomes of IBG on both femoral and acetabular sides at first-time hip revision. Methods: We retrospectively reviewed 8 patients (mean follow-up of 5.8 years) undergoing first-time revision with IBG on both acetabular and femoral sides at our institution. The Paprosky classification system was used to classify bone defects. Freeze-dried allografts and cemented prostheses were used in all patients. Postoperative complications and rerevision rates were reported. Results: Five patients presented a Paprosky type IIC acetabular defect, 3 with a type IIIB, IIIA, and IIC defect, respectively. Three patients presented with a type IV femoral defect, 3 with a type IIIB defect, and 2 with a type II defect. Two patients developed complications, while one had an intraoperative femoral fracture and one had delayed wound healing. At the latest follow-up, no patient had rerevisions or operations related to the prosthesis. Conclusions: IBG in combination with cemented prosthesis is a profitable biological reconstruction revision technique that could provide satisfying midterm outcomes. We first propose the use of blood clots mixed with bone grafts for potential bone incorporation enhancement, while its specific effects need to be verified in further studies.

Curcumae Rhizoma, a traditional Chinese medicine with a wide range of pharmacological activities, is obtained from the dried rhizomes of Curcuma phaeocaulis VaL., Curcuma kwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling. Sesquiterpenoids and curcuminoids are found to be the main constituents of Curcumae Rhizoma. Sesquiterpenoids are composed of three isoprene units and are susceptible to complex transformations, such as cyclization, rearrangement, and oxidation. They are the most structurally diverse class of plant-based natural products with a wide range of biological activities and are widely found in nature. In recent years, scholars have conducted abundant studies on the structures and pharmacological properties of components of Curcumae Rhizoma. This article elucidates the chemical structures, medicinal properties, and biological properties of the sesquiterpenoids (a total of 274 compounds) isolated from Curcumae Rhizoma. We summarized extraction and isolation methods for sesquiterpenoids, established a chemical component library of sesquiterpenoids in Curcumae Rhizoma, and analyzed structural variances among sesquiterpenoids sourced from Curcumae Rhizoma of diverse botanical origins. Furthermore, our investigation reveals a diverse array of sesquiterpenoid types, encompassing guaiane-type, germacrane-type, eudesmane-type, elemane-type, cadinane-type, carane-type, bisabolane-type, humulane-type, and other types, emphasizing the relationship between structural diversity and activity. We hope to provide a valuable reference for further research and exploitation and pave the way for the development of new drugs derived from medicinal plants.

Background: Uncemented short stems have been shown to optimize load distribution on the proximal femur, reducing stress shielding and preserving bone mass. However, they may adversely affect the initial stability of the stems. To date, most research conducted on short stems has predominantly centered on uncemented stems, leaving a notable dearth of investigations encompassing cemented stems. Therefore, this study aimed to investigate the length of cemented stems on the transmission of femoral load patterns and assess the initial stability of cemented short stems.Method: A series of finite element models were created by gradient truncation on identical cemented stem. The impact of varying lengths of the cemented stem on both the peak stress of the femur and the stress distribution in the proximal femur (specifically Gruen zones 1 and 7) were assessed. In addition, an experimental biomechanical model for cemented short stem was established, and the initial stability was measured by evaluating the axial irreversible displacement of the stem relative to the cement.Result: The maximum von-Mises stress of the femur was 58.170 MPa. Spearman correlation analysis on the shortened length and von-Mises stress of all nodes in each region showed that the p-values for all regions were less than 0.0001, and the correlation coefficients (r) for each region were 0.092 (Gruen Zone 1) and 0.366 (Gruen Zone 7). The result of the biomechanical experiment showed that the irreversible axial displacement of the stem relative to cement was −870 μm (SD 430 μm).Conclusion: Reducing the length of a cemented stem can effectively enhance the proximal load of the femur without posing additional fracture risk. Moreover, the biomechanical experiment demonstrated favorable initial stabilities of cemented short stems.

Pogocablanols A–G (1–7), seven new compounds with an unprecedented sesquiterpenoid skeleton, were isolated from the aerial parts of Pogostemon cablin. This novel type of sesquiterpenoids, named pogocablane-type sesquiterpenoids, possesses a bicyclic nonisoprenoid system, including a five-membered carbocycle with a methyl group, a six-membered carbocycle with two methyl groups, and a methylene connecting the two carbocycles. Particularly, three isomers have an interesting 1-oxaspiro[4,4]nonane moiety. Their structures and absolute configurations were determined using extensive spectroscopic evidence, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Pogocablanols A–D (1–4) exhibited a concentration-dependent inhibitory effect on rat jejunum smooth muscle contraction induced by acetylcholine, with Emax values varying from 48.87 ± 4.01% to 69.02 ± 7.54%. Preliminary structure–activity relationship analysis suggested that the oxaspirocycle and the pyran ring in pogocablanols are important structural features for the relaxing effects on jejunum smooth muscle. This study offered crucial support for more investigation and development of P. cablin by showing that these pogocablane-type sesquiterpenoids had the potential to be applied in pharmaceutical and functional food formulations.

Eleven alkaloids, including five previously undescribed indolizidine alkaloids (1, 2a, 2b, 3a, and 3b) and four new pyrrolidine alkaloids (5−8), were isolated from the roots of Anisodus tanguticus. Of these, two new pairs of enantiomeric alkaloids (2a/2b and 3a/3b) are the first examples of alkaloids containing both indolizidine and pyrrolidine structural fragments. The one-carbon bridge connections with two pyrrolidine rings (6) or with a pyrrolidine ring and a pyridine ring (8) are the first reported from nature. Extensive spectroscopic techniques were used to elucidate their structures, and NMR and ECD calculations were used to determine the absolute configurations. The viability of human umbilical vein endothelial cells (HUVECs) was inhibited by compounds 2a, 2b, 3a, 4b, and 5, and compound 2b exhibited a potential anti-angiogenic effect by inhibiting the proliferation, migration, and tube formation of HUVECs. A chorioallantoic membrane assay also demonstrated the anti-angiogenic activity of 2b. In addition, compounds 2a, 2b, 3a, and 4b exhibited moderate cytotoxicity against A2780 cells.

The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc− axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms.

Abstract Background Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. Results In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. Conclusions Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Graphic abstract Video Abstract

Unconventional gas in the Sichuan Basin mainly includes shale gas and tight gas. The development of shale gas is mainly concentrated in the Ordovician Wufeng Formation–Silurian Longmaxi Formation, but has not made any significant breakthrough in the Cambrian Qiongzhusi Formation marine shale regardless of exploration efforts for years. The commercial development of tight sandstone gas is mainly concentrated in the Jurassic Shaximiao Formation, but has not been realized in the widespread and thick Triassic Xujiahe Formation. Depending on the geological characteristics of the Qiongzhusi Formation and Xujiahe Formation, the feedback of old wells was analyzed. Then, combining with the accumulation mechanisms of conventional gas and shale gas, as well as the oil/gas shows during drilling, changes in production and pressure during development, and other characteristics, it was proposed to change the exploration and development strategy from source and reservoir exploration to carrier beds exploration. With the combination of effective source rock, effective carrier beds and effective sandstone or shale as the exploration target, a model of unconventional gas accumulation and enrichment in carrier beds was built. Under the guidance of this study, two significant results have been achieved in practice. First, great breakthrough was made in exploration of the silty shale with low organic matter abundance in the Qiongzhusi Formation, which breaks the traditional approach to prospect shale gas only in organic-rich black shales and realizes a breakthrough in new areas, new layers and new types of shale gas and a transformation of exploration and development of shale gas from single-layer system, Longmaxi Formation, to multi-layer system in the Sichuan Basin. Second, exploration breakthrough and high-efficient development were realized for difficult-to-produce tight sandstone gas reserves in the Xujiahe Formation, which helps address the challenges of low production and unstable production of fracture zones in the Xujiahe Formation, promote the transformation of tight sandstone gas from reserves without production to effective production, and enhance the exploration and development potential of tight sandstone gas.

In this work, the Permian Longtan marine-continental transitional shale in the southeast of Sichuan Basin was taken as study object. Through petrology and geochemical analysis, lithofacies types of the marine-continental transitional shale were classified, key controlling factors of physical properties and gas content of the different shale lithofacies were analyzed. The research results show that the Longtan Formation marine-continental transitional shale in the study area has four types of lithofacies, namely, organic-lean calcareous shale, organic-lean mixed shale, organic-lean argillaceous shale, and organic-rich argillaceous shale, among which the organic-rich argillaceous shale is the most favorable lithofacies of the study area. The pore types of different lithofacies vary significantly and the clay mineral-related pore is the dominant type of the pore system in the study area. The main controlling factor of the physical properties is clay mineral content, and the most important factor affecting gas content is TOC content. Compared with marine shale, the marine-continental transitional shale has low average values, wide distribution range, and strong heterogeneity in TOC content, porosity, and pore structure parameters, but still contains some favorable layers with high physical properties and gas contents. The organic-rich clay shale deposited in tidal flat-lagoon system is most likely to form shale gas sweet spots, so it should be paid more attention in shale gas exploration.

Abstract Background Intrauterine growth retardation (IUGR) is associated with severely impaired nutrient metabolism and intestinal development of pigs. Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon. However, the consequences of IUGR on bile acid metabolism in pigs remained unclear. The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of growing pigs with IUGR using bile acid targeted metabolomics. Furthermore, we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight (NBW) pigs at different growth stages that were 7, 21, and 28-day-old, and the average body weight (BW) of 25, 50, and 100 kg of the NBW pigs. Results The results showed that the plasma total bile acid concentration was higher (P

Deep shales refer to the shales with buried depth greater than 3500 m. Yields of shale gases depend on the form of their occurrence at the depth, but the major controlling factors on shale gas occurrence state in deep high-over mature shales are poorly understood. Using the Longmaxi Formation as an example, the shale gas occurrence characteristics of deep high-over mature shales were quantitatively characterized, and the effects of temperature, pressure, pore structure, and organic matter abundance on the occurrence characteristics of shale gas were studied by using the control variable method. The results show that the Longmaxi shale is mainly organic-rich argillaceous shale, with an average porosity of 7.54%. The pore volumes are mainly contributed by mesopores, whereas the total specific surface areas are primarily by micropores. The Longmaxi shale has high gas contents, with total gas contents of 3.82∼7.89 m3/t rock, in which the proportion of free gas varies from 71% to 83%, with an average of 77%. The high proportion of free gas depends on the particular geological conditions in the Longmaxi Formation. High temperature is not conducive to shale gas storage, and its negative effect on adsorbed gas is greater than that on free gas. High pressure is beneficial to shale gas storage, and its positive influence on free gas is greater than that on adsorbed gas. The large pore volume dominated by mesopores provides sufficient storage place for free gas. High organic matter content is beneficial for shale gas enrichment but reduce the proportion of free gas. In conclusion, high pressure and large pore volume are the major factors for the high proportion of free gas.

Diabetes mellitus (DM) is one of the main chronic diseases severely threatening human health, of which type 2 DM (T2DM) is the most common type. Traditional Chinese medicine has unique advantages in the treatment of T2DM. Mulberry (Morus alba L.) is a medicinal and edible plant that is well known for its rich nutrition and medicinal values. The medicinal parts of mulberry include leaf, twig, root bark, and fruit, all of which have remarkable hypoglycemic effects. In this paper, the extracts and compounds with hypoglycemic effects from four medicinal parts of mulberry are reviewed. It is found that the hypoglycemic compounds in mulberry are mainly flavonoids, polysaccharides, alkaloids, stilbenes, and Diels-Alder compounds. Their mechanisms of action are mainly related to the regulation of lipid profiles and glucose metabolism, protection of pancreatic β-cells, promotion of insulin secretion, antioxidation, inhibition of protein tyrosine phosphatase 1B and α-glycosidase activities. In addition, mulberry treatment could change intestinal microbiota of mice, which are associated with insulin resistance and diabetes. This review provides reference for further research and development of different medicinal parts of mulberry for the treatment of DM.

Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different growth stages of pigs are still unclear. Therefore, this study explored through multi-omics analyses whether the IUGR damages the intestinal barrier function and alters the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs. Seventy-two piglets (36 IUGR and 36 NBW) were allocated for this trial to analyze physiological and plasma biochemical parameters, as well as oxidative damage and inflammatory response in the colon. Moreover, the colonic microbiota communities and metabolome were examined using 16s rRNA sequencing and metabolomics technologies to reveal the intestinal characteristics of IUGR pigs at different growth stages (25, 50, and 100 kg). IUGR altered the concentrations of plasma glucose, total protein, triglycerides, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels and colonic SOD-1, SOD-2, and GPX-4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased colonic IL-1β and TNF-α levels while reducing IL-10, possibly through activating the TLR4-NF-κB/ERK pathway. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFA concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbiota community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Moreover, colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.

This study evaluated the effects of maternal selenium-enriched yeast (SeY) supplementation during late gestation and lactation on sow performance, transfer of selenium (Se) and redox status, and gut microbiota community, as well as on the gut health of offspring. Seventy pregnant sows on day 85 of gestation were randomly allocated to the following two treatments: (1) sows who were fed a basal diet (basal diet contained 0.3 mg/kg Se as Na2SeO3, n = 35); (2) and sows who were fed a SeY-supplemented diet (basal diet with 0.2 mg/kg Se as SeY, n = 35). The offspring piglets were only cross-fostered within the group on day 3 of lactation (L3) according to the pig farm epidemic prevention policy. The plasma, milk, and feces samples from 10 sows, as well as plasma and intestinal samples per treatment, were collected on L1 and L21, respectively. Our results showed that maternal SeY supplementation increased the first week average weight and ADG of piglets (p < 0.05). Compared with the CON group, the SeY supplementation increased the Se content in the plasma and milk of sows and the plasma of piglets on L1 and L21 (p < 0.05). In addition, in sows, the levels of fat in the milk on L21, the level of IgA, T-AOC, and GSH-Px in the plasma on L21, and the level of T-AOC and GSH-Px in the colostrum were increased, while the MDA content was decreased in the plasma on L1 and in the colostrum and milk on L14 (p < 0.05). In the piglet plasma, the levels of IgA on L1 and L21, GSH-Px on L1, and GSH on L21 were increased, while the MDA content was decreased on L1 (p < 0.05). Maternal SeY supplementation up-regulated the small intestinal protein abundances of MUC1, E-cadherin, ZO-1, occludin, and claudin and activated the Nrf2/Keap1 signaling pathway in weaned offspring piglets. The 16S rRNA sequencing results showed that fecal microbiota had distinct separations during lactation, and the relative abundances of unclassified_f_Lachnospiraceae, Prevotaceae_UCG-001, and Lachnospiraceae_NK4A136_group were increased on L1. Collectively, the current findings suggest that maternal SeY supplementation during late gestation and lactation could improve the piglet’s growth performance, Se status, antioxidant capacity and immunoglobulins transfer at the first week of lactation, as well as alter the fecal microbiota composition by increasing antioxidative-related and SCFA-producing microbiota in sows. These changes contributed to enhancing the small intestinal barrier function and activating the Nrf2/Keap1 pathway in offspring.

Abstract Gas-bearing property evaluation and main controlling factor analysis have remained a concern in shale gas research. The application of principal component analysis, an important mathematical statistical method, in gas-bearing property evaluation and main controlling factor analysis of the Longmaxi shale in the Weirong area, Sichuan Basin, was examined. The Longmaxi shale exhibits high heterogeneity, manifested in the organic matter abundance, mineral composition, and pore structure. Seven geological factors, including the temperature, pressure, TOC content, clay content, brittle mineral content, pore volume, and specific surface area (SSA), were selected in principal component analysis. Four principal components with geological significance, such as mineral composition, formation condition, pore structure, and organic matter abundance, were extracted through principal component analysis, and further constituted a comprehensive factor. Shale gas-bearing properties were evaluated according to the score of the comprehensive factor. The Longmaxi shale could be identified as exhibiting good, medium, and poor gas-bearing properties based on the comprehensive factor scores of these samples. According to each geological factor’s contribution to the comprehensive factor, combined with geological analysis, it could be considered that gas-bearing properties are primarily controlled by pore volume, SSA, and clay content, followed by TOC content, brittle mineral content, temperature and pressure.

Three pairs of new enantiomeric adenine alkaloids, (+)/(−)-liguadenines A–C [(+)/(−)-1–3], were isolated from the rhizome of Ligusticum chuanxiong Hort. The structures and absolute configurations of these compounds were determined using spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism analyses. To the best of our knowledge, compounds (+)-1 and (−)-1 are the first hybrid phthalide–adenines to be ever reported. The linkage between the phthalide and adenine units in these compounds forms a rare 5-oxa-1-azaspiro[3,4]octane moiety. Analyses of the anti-inflammatory activities of the isolated compounds show that (+)/(−)-1 and (+)-3 exhibit significant inhibitory activity against LPS-induced TNF-α and IL-6 production in RAW264.7 cells. RT-qPCR analysis confirms that the most active compound, (+)-3, exerts anti-inflammatory activity by downregulating the mRNA expressions of TNF-α and IL-6 in the cells.

Background Apolipoprotein E (ApoE) is involved in lipid transformation and metabolism. Although some studies have examined the association between ApoE polymorphisms and the risk of type 2 diabetes mellitus (T2DM), the findings differ depending on the location and population. Methods A total of 1,738 participants, including 743 patients with T2DM and 995 controls without T2DM, were enrolled from central China, and ApoE polymorphisms, 388T > C (rs429358) and 526C > T (rs7412), were genotyped. The association between ApoE alleles and T2DM and blood lipid levels was analyzed. Logistic regression analysis was performed to evaluate the interactions between ApoE polymorphisms and various factors, such as age, sex, and prevalence of hypertension in patients with T2DM. Results The genotype ɛ3/ɛ4 and ɛ4 alleles of ApoE were associated with T2DM risk in the Chinese Han population in central China. Moreover, in patients with T2DM, participants in the E4 (ɛ3/ɛ4, ɛ4/ɛ4) group had significantly higher lipid profiles than those in the E3 (ɛ3/ɛ3) group, whereas participants in the E2 group (ɛ2/ɛ2, ɛ2/ɛ3) showed lower total cholesterol, low-density lipoprotein cholesterol, and ApoE-A1 levels than those in the E3 (ɛ3/ɛ3) group. The results from the current study may help in understanding ApoE polymorphisms and lipid profiles in the Chinese Han population.

This study evaluated the effects of betaine supplementation in sows and/or their offspring’s diets on the redox status, immune and inflammatory levels, colonic barrier function, and colonic microbial community of offspring piglets. Thirty-six Bama mini-sows on day 3 of gestation and their weaned offspring piglets (28 d of age) were randomly allocated to the following treatments: (1) sows and their weaned offspring fed the basal diet (control group, Con group); (2) sows fed the basal diet with 3.50 kg/t betaine, and their weaned offspring fed the basal diet (sows betaine group, SB group); (3) sows fed the basal diet with 3.50 kg/t betaine, and their weaned offspring fed the basal diet with 2.50 kg/t betaine (sow-offspring betaine group, S-OB group). Six offspring piglets from each group were selected to collect plasma and colon samples on d 30, 60, and 90 after weaning. Compared with the Con group, the plasma levels of IgA, IgM, GSH-Px, and SOD during d 30–90 after weaning, IFN-α, T-AOC, and GSH on d 30 and 60 after weaning were increased, while MDA during d 30–90 after weaning was decreased in the SB and S-OB groups (p < 0.05). In addition, the plasma levels of IFN-γ on d 60 and T-AOC on d 30 after weaning were higher in the S-OB group than those in the Con group (p < 0.05). In the colon, betaine supplementation increased plasma T-AOC, GSH, and SOD levels while decreasing MDA concentration (p < 0.05). Betaine supplementation improved the colonic protein abundances of ZO-1, occludin, and claudin in offspring and activated the Nrf2/Keap1 signaling pathway while inhibiting the TLR4-NF-κB/MAPK signaling pathway on d 90 after weaning. The 16S rRNA sequencing results showed that betaine supplementation altered colonic microbiota composition by increasing the relative abundances of Verrucomicrobia and Actinobacteria in the SB group while decreasing proinflammatory-associated microbiota abundances (Tenericutes, Prevotella, and Parabacteroides) (p < 0.05). Collectively, these findings suggest that dietary betaine supplementation in sows and/or their offspring could improve offspring piglets’ redox status and immune and anti-inflammatory levels and enhance the colonic barrier function by activating Nrf2/Keap1 and inhibiting TLR4-NF-κB/MAPK signaling pathways.

Abstract Rice varieties are required to have high yield and good grain quality. Grain chalkiness and grain shape are two important traits of rice grain quality. Low chalkiness slender grains are preferred by most rice consumers. Here, we dissected two closely linked quantitative trait loci (QTLs) controlling grain chalkiness and grain shape on rice chromosome 8 by substitution mapping. Two closely linked QTLs controlling grain chalkiness and grain shape were identified using single-segment substitution lines (SSSLs). The two QTLs were then dissected on rice chromosome 8 by secondary substitution mapping. qPGC8.1 was located in an interval of 1382.6 kb and qPGC8.2 was mapped in a 2057.1 kb region. The maximum distance of the two QTLs was 4.37 Mb and the space distance of two QTL intervals was 0.72 Mb. qPGC8.1 controlled grain chalkiness and grain width. qPGC8.2 was responsible for grain chalkiness, grain length and width. The additive effects of qPGC8.1 and qPGC8.2 on grain chalkiness were not affected by higher temperature. Two closely linked QTLs qPGC8.1 and qPGC8.2 were dissected on rice chromosome 8. They controlled the phenotypes of grain chalkiness and grain shape. The two QTLs were insensitive to higher temperature.

ObjectivesTo investigate myopia progression and associated factors of refractive status among children and adolescents in Tibet and Chongqing in China during the COVID-19 pandemic.MethodsA population-based cross-sectional study was conducted to compare rates of myopia and high myopia, axial length (AL), spherical equivalent (SE), outdoor activity time, digital device use, and frequency of visual examinations for children and adolescents affected by myopia in Chongqing and Tibet in 2021.ResultsA total of 2,303 students from Chongqing and 1,687 students from Tibet were examined. The overall prevalence of myopia and high myopia in these two groups were 53.80 and 7.04% vs. 43.86 and 1.30%, respectively in each case. The Chongqing students had a longer AL than the group from Tibet (23.95 vs. 23.40 mm, respectively; p < 0.001). The mean SE of the students with myopic parents in Tibet was lower than that of the students in Chongqing with myopic parents (−2.57 ± 2.38 diopters (D) vs. −2.30 ± 2.34 D, respectively) (p < 0.001). Conversely, the mean SE of the students from urban areas in Chongqing was lower than that of the students in Tibet (−2.26 ± 2.25 D vs. −1.75 ± 1.96 D, respectively; p < 0.001). The Chongqing students exhibited lower SE (−2.44 ± 2.22 D) than their Tibetan counterparts (mean SE: −1.78 ± 1.65 D (p = 0.0001) when spending more than 2.5 h outdoors. For example, 61.35% of the students in Tibet spent more than 2.5 h outdoors daily, compared with 43.04% of the students in Chongqing. Correspondingly, the proportion of students using digital devices in Tibet (64.43%) was lower than that in Chongqing (100%). For the latter, 38.62% of the students in Chongqing spent more than 2.5 h online using digital devices compared to 10.49% of the students in Tibet. Greater monitoring of visual status was observed for the Chongqing students (mean SE: −1.90 ± 1.98 D) compared with students in Tibet (mean SE: −2.68 ± 1.85 D) (p = 0.0448), with the frequency of optimal examinations being every 6 months. Outdoor activity time was identified as a common risk factor for myopia in both of the populations examined, with odds ratios (ORs) of 1.84 (95% CI: 1.79–1.90) in Chongqing and 0.84 (95% CI: 0.73–0.96) in Tibet. Digital screen time was associated with myopia and high myopia in Chongqing, with ORs of 1.15 (95% CI: 1.08–1.22) and 1.06 (95% CI: 0.94–1.77), respectively. Digital screen time was also found to be a risk factor for high myopia in Tibet (OR: 1.21, 95% CI: 0.77–1.61). The type of digital devices used was also associated with myopia and high myopia in Tibet (OR: 1.33, 95% CI: 1.06–1.68 and OR: 1.49, 95% CI: 0.84–2.58, respectively). Finally, examination frequency was found to correlate with high myopia in the Tibet group (OR: 1.79, 95% CI: 0.66–2.71).ConclusionBased on our data, we observed that the prevalence of refractive errors in children and adolescents was significantly lower in Tibet than in Chongqing. These results are potentially due to prolonged outdoor activity time, and the type and time of use for digital devices that characterize the group of children and adolescents from Tibet. It is recommended that parents and children in Chongqing would benefit from increased awareness regarding myopia progression and its prevention.

In this literature, we are concerned with the necessary condition for classicality and separability of the spin states by virtue of Cauthy tensors. The classicality and separability of the spin-j states are identified with the positive semidefiniteness of the 2j order associated tensor under tensor representation of quantum states. According to the properties of Bloch vector and trρ=1, we present necessary condition for classicality (separability) and entanglement of the spin-j states by virtue of Cauthy tensors with the positive generating vector c. This necessary condition not only perfectly maintains the physical properties of the quantum system, but also depends only on spin-j and the generating vector c. In addition, we show that Cauchy tensor method has a wider detection range and is easy to verify compared with the existing smallest tensor eigenvalue method.

In the interests of more flexible and less stiff bridge constructs to stimulate bone healing, the technique of far cortical locking has been designed to improve locked plating constructs in terms of stress concentration, stress shielding, and inhibition of issues around fracture healing. However, far cortical locking screws currently lack objective designs and anti-fatigue designs. This study investigates an optimization algorithm to form a special locking screw composed of various metals, which can theoretically achieve the maintenance of the excellent mechanical properties of far cortical locking constructs in terms of fracture internal fixation, while maintaining the biomechanical safety and fatigue resistance of the structure. The numerical results of our study indicate that the maximum von Mises stress of the optimized construct is less than the allowable stress of the material under each working condition while still achieving sufficient parallel interfragmentary motion. Numerical analysis of high cycle fatigue indicates that the optimized construct increases the safety factor to five. A high cycle fatigue test and defect analysis indicates that the sandwich locking constructs have better fatigue resistance. We conclude that the sandwich locking construct theoretically maintains its biomechanical safety and fatigue resistance while also maintaining excellent mechanical properties for fracture internal fixation.

Two new sesquiterpenoids, curcumanes E (1) and F (2), were isolated from the rhizome of Curcuma longa, and their structures and absolute configurations were examined using extensive spectroscopic analyses and ECD calculations. Interestingly, compounds 1 and 2 are diastereoisomers possessing a rare sesquiterpenoid skeleton that has been reported only once before. Both curcumanes E and F exhibit significant vasorelaxant effects against KCl-induced contraction of rat aortic rings, with EC50 values of 5.10 ± 0.79 and 5.58 ± 1.77 μM, respectively. These findings enrich the data concerning this rare type of sesquiterpenoids and further indicate that these rare sesquiterpenoids can effectively reduce blood pressure.

Tight sandstone reservoir is characterized by ultra-low porosity, complex microporous structure and water residues, which shows different gas storage and transport mechanism from conventional reservoirs. Therefore, effective development of tight sandstone gas reservoirs is faced with technical challenges. Microporous structures, distribution mechanism of fluid is a basic issue in gas reservoir evaluation. In this work, we take gas reservoir in the 2nd member of Xujiahe Formation in Yuanba area as an example to analyze the microscopic feature of pore structure and fluid distribution. The three-dimensional digital core has been applied to represent the real microporous structure. Specifically, a digital core reconstruction method based on SEM and casting slice images has been proposed. Ultimately, the mechanism of distribution, mode of occurrence of water residues in tight sandstone reservoirs has been simulated and quantitatively analyzed. The results show that the water residues could been visualized and categorized into three modes, water mass in corner, water film on surface, and water column in throat. The water residues could cause dramatic influence on pore structures, active pore size could be decreased with rising residual water saturation, the magnitude falls by over 50%. In addition, grain size would affect the distribution of water residues, which shows different percentage in medium and fine sand. Pore connectivity is another characteristic factor to describe the microporous structures. In this study, cluster marking algorithm has been applied to obtain the pore connectivity in tight sandstone with different grain size. In medium sand, the pore connectivity is dramatically decreased with rising water saturation, the downward trend become slower when water saturation reaches to 60%. Compared to fine sand, the tendency variation appears when water saturation reaches to 40%. This paper provides an applicable method to reveal the micro-scale reservoir properties and fluid distribution mechanisms in tight sandstone gas reservoirs.

PurposeThe purpose of this study is to analyze clinical information and combine significant parameters to generate a predictive model and achieve a better prognosis prediction of dermatomyositis-associated interstitial lung disease with positive melanoma differentiation-associated gene 5 antibody (MDA5+ DM-ILD) and stratify patients according to prognostic risk factors appropriately.MethodsWe retrospectively reviewed 63 patients MDA5+ DM-ILD who were treated in our hospital from January 2018 to January 2021. Our study incorporated most clinical characteristics in clinical practice to explore the associations and predictive functions of clinical characteristics and prognosis. Student's t-test, Mann-Whitney U-test, chi-squared test, Pearson correlation analysis, Cox regression analysis, R, receiver operating characteristic curves (ROC curves), and Kaplan-Meier survival curves were performed to identify independent predictors for the prognosis of MDA5+DM-ILD.ResultsIn all the 63 patients with MDA5+DM-ILD, 44 improved but 19 did not. Poor prognosis was found more frequently in patients who were older, clinically amyopathic variant of dermatomyositis (CADM), and/or with short duration, short interval of DM and ILD, long length of stay, fever, dyspnea, non-arthralgia, pulmonary infection, pleural effusion (PE), high total computed tomography scores (TCTs), ground-glass opacity (GGO), consolidation score, reticular score and fibrosis score, decreased forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), albumin, A/G, glomerular filtration rate (GFR) and tumor necrosis factor α (TNFα), high titer of anti-MDA5, proteinuria, high levels of monocyte, lactate dehydrogenase (LDH), ferritin (FER), neuron specific enolase (NSE) and glucocorticoid, antibiotic, antiviral, and non-invasive positive pressure ventilation (NPPV). The multivariate Cox regression analysis demonstrated that duration, fever, PE, TCTs and aspartate transaminase (AST) were independent predictors of poor prognosis in patients with MDA5+DM-ILD. The nomogram model quantified the risk of 400-day death as: duration ≤ 4 months (5 points), fever (88 points), PE (21 points), TCTs ≥10 points (22 points), and AST ≥200 U/L (100 points) with high predictive accuracy and convenience. The ROC curves possessed good discriminative ability for combination of fever, PE, TCTs, and AST, as reflected by the area under curve (AUC) being.954, 95% CI 0.902–1.000, and sensitivity and specificity being 84.2 and 94.6%, respectively.ConclusionWe demonstrated that duration, fever, PE, TCTs, and AST could be integrated together to be independent predictors of poor prognosis in MDA5+ DM-ILD with highly predictive accuracy.

Asian cultivated rice is a self-pollinating crop, which has already lost some traits of natural outcrossing in the process of domestication. However, male sterility lines (MSLs) need to have a strong outcrossing ability to produce hybrid seeds by outcrossing with restorer lines of male parents in hybrid rice seed production. Stigma exsertion rate (SER) is a trait related to outcrossing ability. Reconstruction of the high-SER trait is essential in the MSL breeding of rice. In previous studies, we detected eighteen quantitative trait loci (QTLs) for SER from Oryza sativa, Oryza glaberrima, and Oryza glumaepatula using single-segment substitution lines (SSSLs) in the genetic background of Huajingxian 74 (HJX74). In this study, eleven of the QTLs were used to develop pyramiding lines. A total of 29 pyramiding lines with 2–6 QTLs were developed from 10 SSSLs carrying QTLs for SER in the HJX74 genetic background. The results showed that the SER increased with increasing QTLs in the pyramiding lines. The SER in the lines with 5–6 QTLs was as high as wild rice with strong outcrossing ability. The epistasis of additive by additive interaction between QTLs in the pyramiding lines was less-than-additive or negative effect. One QTL, qSER3a-sat, showed minor-effect epistasis and increased higher SER than other QTLs in pyramiding lines. The detection of epistasis of QTLs on SER uncovered the genetic architecture of SER, which provides a basis for using these QTLs to improve SER levels in MSL breeding. The reconstruction of the high-SER trait will help to develop the MSLs with strong outcrossing ability in rice.

Abstract Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

Abstract Background Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is an irreversible pathologic condition of unknown cause, commonly involving the joint and the lung with variable amounts of fibrotic change. In contrast to rheumatoid arthritis or other chronic interstitial lung diseases such as interstitial pulmonary fibrosis, there is so far no extensively accepted or implemented animal model for this disease. Aims To provide guidance for those who are investigating the pathogenesis of RA‐ILD with animal models. Materials and Methods An analysis of papers from PubMed during 1978‐2020. Results We outline the present status quo for animal models of RA‐ILD about their modeling methods and pathogenesis, compare their pros and cons with respect to their ability to mimic the clinical and histological features of human disease and discuss their applicability for future research. Discussion There is no doubt that these animal models do provide valuable information relating to the pathogenesis of RA‐ILD and the development of effective therapeutic drugs. Nevertheless, these animal models can not entirely recapitulate clinical pathology and have some limitations in experimental research application. Therefore, it should be emphasized that we should improve and explore animal models in more accordance with the pathogenesis and clinical characteristics of human RA‐ILD. Conclusion These established animal models of the disease can significantly progress our understanding of the etiology of RA‐ILD, the fundamental mechanisms of its pathogenesis and the identification of new bio‐markers, and can contribute to the development and implementation of novel treatment strategies.

Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC50 values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor.

To explore the sesquiterpenoids in Curcuma longa L. and their activity related to anti-atherosclerosis. The chemical compounds of the rhizomes of C. longa were separated and purified by multiple chromatography techniques. Their structures were established by a variety of spectroscopic experiments. The absolute configurations were determined by comparing experimental and calculated NMR chemical shifts and electronic circular dichroism (ECD) spectra. Their anti-inflammatory effects and inhibitory activity against macrophage-derived foam cell formation were evaluated by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (ox-LDL)-injured RAW264.7 macrophages, respectively. This study resulted in the isolation of 10 bisabolane-type sesquiterpenoids (1–10) from C. longa, including two pairs of new epimers (curbisabolanones A–D, 1–4). Compound 4 significantly inhibited LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) production in RAW264.7 cells. Furthermore, compound 4 showed inhibitory activity against macrophage-derived foam cell formation, which was represented by markedly reducing ox-LDL-induced intracellular lipid accumulation as well as total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) contents in RAW264.7 cells. These findings suggest that bisabolane-type sesquiterpenoids, one of the main types of components in C. longa, have the potential to alleviate the atherosclerosis process by preventing inflammation and inhibiting macrophage foaming.

Since the development of indica hybrid rice in the 1970s, great success has been achieved in hybrid rice production in China and around the world. The utilization of inter-subspecific indica–japonica hybrid rice has always been considered due to its stronger heterosis characteristics. However, indica–japonica hybrids face a serious problem of sterility, which hinders the exploitation of their heterosis. In the past decades, the genetic basis of indica–japonica hybrid sterility has been well studied. It was found that in sterile indica–japonica hybrids, female sterility was mainly controlled by the S5 locus and male sterility by the Sa, Sb, Sc, Sd, and Se loci. In this study, we developed wide-compatible indica lines (WCILs) by pyramiding multiple neutral (n) alleles of the hybrid sterility loci. First, we identified Sn alleles of the loci in single-segment substitution lines (SSSLs) in the genetic background of indica Huajingxian 74 (HJX74). Then, the Sn alleles of S5, Sb, Sc, Sd, and Se loci in SSSLs were pyramided in the HJX74 genetic background. The WCILs carrying Sn alleles at the S5, Sb, Sc, Sd, and Se loci showed wide compatibility with indica and japonica rice varieties. Therefore, the WCILs will be used to develop inter-subspecific indica–japonica hybrid rice with normal fertility.

Breast cancer ranks as the leading cause of death in lethal malignancies among women worldwide, with a sharp increase of incidence since 2008. Triple negative breast cancer (TNBC) gives rise to the largest proportion in breast cancer-related deaths because of its aggressive growth and rapid metastasis. Hence, searching for promising targets and innovative approaches is indispensable for the TNBC treatment. Maackiain (MA), a natural compound with multiple biological activities, could be isolated from different Chinese herbs, such as Spatholobus suberectus and Sophora flavescens. It was the first time to report the anti-cancer effect of MA in TNBC. MA could suppress TNBC cell proliferation, foci formation, migration, and invasion. MA also exerted a significant inhibitory effect on tumor growth of TNBC. Furthermore, MA could induce apoptosis with an increase of GADD45α and a decrease of miR-374a. In contrast, overexpressing miR-374a would result in at least partly affecting the proapoptotic effect of MA and suppressing GADD45α stimulated by MA. These results reveal the anti-TNBC effect of MA in vitro and in vivo, providing evidence for its potential as a drug candidate utilized in TNBC therapy.

Artemisia annua L., which is known for its antimalarial compound artemisinin, has commonly been used for its anti-inflammatory and antibacterial functions. Enzymatically treating Artemisia annua L. can improve its bioavailability. The purpose of this study was to investigate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation in late gestation and lactation diets on sow performance, serum hormone, inflammatory cytokines, and immunoglobulin level of heat-stressed sows. A total of 135 multiparous sows (Large White × Landrace) on day 85 of gestation were selected and randomly distributed into 3 groups with 45 replicates per group. The control group was reared under standard conditions (temperature: 27.12 ± 0.18°C, THI (temperature-humidity index): 70.90 ± 0.80) and fed with basal diet. The heat stress (HS) and HS + EA groups were raised in heat-stressed conditions (temperature: 30.11 ± 0.16°C, THI: 72.70 ± 0.60) and fed with basal diets supplemented with 0 or 1.0 g/kg EA, respectively. This trial lasted for 50 consecutive days until day 21 of lactation. Compared with the control group, HS increased the concentrations of serum endotoxin and heat shock protein 70 (HSP-70), and inflammatory cytokines in serum, colostrum, and 14 day milk of sows. Meanwhile, the EA supplementation decreased levels of serum endotoxin, HSP-70, and inflammatory cytokines in both sows and offspring and increased serum triiodothyronine (T3) level and average daily feed intake (ADFI) of sows. In addition, EA significantly improved average daily gain (ADG) and altered intestinal morphology with an increased villus height in the duodenum and ileum of piglets. Collectively, EA supplementation at 1.0 g/kg in late gestation and lactation diets alleviated the adverse effects of HS, which were reflected by enhancing ADFI and decreasing endotoxin as well as inflammatory cytokine levels in the serum and colostrum of heat-stressed sows, while promoting ADG and gut development of their offspring.

Deltaic areas are among the most promising regions in the world. Their strategic location and superior quality of their soils are core factors supporting both human development and the rise of these regions as global economic hubs. At the same time, however, deltas are extremely vulnerable to multiple threats from both climate change and the rush to urbanization. These include an increased flood risk combined with the resulting loss of ecological and social-cultural values. The urbanization of deltas can be understood as a set of complex social-ecological systems (and subsystems), each with its own dynamics and speed of change. To ensure a more sustainable future for these areas, spatial strategies are needed to strengthen resilience, i.e. help the systems to cope with their vulnerabilities as well as enhance their capacity to overcome natural and artificial threats. In this article we elaborate a landscape-based regional design approach for the adaptive urban transformation of urbanizing deltas, taking the Pearl River Delta as a case study. Based on an assessment of the dynamics of change regarding the transformational cycles of natural and urban landscape elements, eco-dynamic regional design strategies are explored to reveal greater opportunities for the exploitation of natural and social-cultural factors within the processes of urban development. Furthermore, adaptive transformational perspectives are identified toensure reduced flood risk and inclusive socio-ecological design.