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This study explores the innovative use of 3D robotic spray for applying self-sensing cementitious coating, emphasising its potential for multifunctional smart concrete applications. The effects of spray parameters on the performance of self-sensing cementitious composites were investigated by systematically examining the impact of nozzle travel speed, air injection pressure, nozzle standoff distance, and spray direction on the self-sensing coating. In-depth analyses were conducted on mechanical strength, coating adhesion properties, and sensing performance. Micro-CT was performed to investigate the coating's inherent porosity. This study evaluated the sensing performance of the coatings by analysing their piezoresistive behaviour under cyclic compression and bending. Furthermore, it demonstrated the coating's capacity for real-time structural health monitoring by evaluating its performance under compressive and bending stresses until failure. This research underscores the significant impact of spray parameters on optimising the sensing capabilities of the self-sensing spray coating, highlighting its potential for advanced real-time structural health monitoring.

Among reinforcement methods for 3D concrete printing (3DCP) structures, steel cable reinforcement and reinforced concrete confined by 3DCP formwork (RC-3DPF) methods offer high design freedom and automation. However, the former lacks reinforcement in directions perpendicular to the printing direction, and the latter cannot satisfy constructional requirements. This paper proposed a hybrid approach: the steel rebar reinforced concrete column confined by the steel cable reinforced 3DCP permanent formwork (RC-SC-3DPF). Axial compression tests and theoretical analysis were conducted to study axial performances. Test results showed steel cables and fibres added to 3DCP formwork benefit RC-SC-3DPF structural performances. With a steel cable confinement ratio above 0.534%, RC-SC-3DPF outperforms the traditional case. Steel fibre, compared to PVA fibre, demonstrates greater potential for RC-SC-3DPF due to improved axial load resistance and reduced ductility loss. A theoretical model, based on experimental results, existing standards, and M&T model, was developed to effectively evaluate RC-SC-3DPF structural behaviour.

Fatty infiltration denotes the anomalous accrual of adipocytes in non-adipose tissue, thereby generating toxic substances with the capacity to impede the ordinary physiological functions of various organs. With aging, the musculoskeletal system undergoes pronounced degenerative alterations, prompting heightened scrutiny regarding the contributory role of fatty infiltration in its pathophysiology. Several studies have demonstrated that fatty infiltration affects the normal metabolism of the musculoskeletal system, leading to substantial tissue damage. Nevertheless, a definitive and universally accepted generalization concerning the comprehensive effects of fatty infiltration on the musculoskeletal system remains elusive. As a result, this review summarizes the characteristics of different types of adipose tissue, the pathological mechanisms associated with fatty infiltration in bone, muscle, and the entirety of the musculoskeletal system, examines relevant clinical diseases, and explores potential therapeutic modalities. This review is intended to give researchers a better understanding of fatty infiltration and to contribute new ideas to the prevention and treatment of clinical musculoskeletal diseases.

IntroductionAccurate detection of potato seedlings is crucial for obtaining information on potato seedlings and ultimately increasing potato yield. This study aims to enhance the detection of potato seedlings in drone-captured images through a novel lightweight model.MethodsWe established a dataset of drone-captured images of potato seedlings and proposed the VBGS-YOLOv8n model, an improved version of YOLOv8n. This model employs a lighter VanillaNet as the backbone network in-stead of the original YOLOv8n model. To address the small target features of potato seedlings, we introduced a weighted bidirectional feature pyramid network to replace the path aggregation network, reducing information loss between network layers, facilitating rapid multi-scale feature fusion, and enhancing detection performance. Additionally, we incorporated GSConv and Slim-neck designs at the Neck section to balance accuracy while reducing model complexity. ResultsThe VBGS-YOLOv8n model, with 1,524,943 parameters and 4.2 billion FLOPs, achieves a precision of 97.1%, a mean average precision of 98.4%, and an inference time of 2.0ms. Comparative tests reveal that VBGS-YOLOv8n strikes a balance between detection accuracy, speed, and model efficiency compared to YOLOv8 and other mainstream networks. Specifically, compared to YOLOv8, the model parameters and FLOPs are reduced by 51.7% and 52.8% respectively, while precision and a mean average precision are improved by 1.4% and 0.8% respectively, and the inference time is reduced by 31.0%.DiscussionComparative tests with mainstream models, including YOLOv7, YOLOv5, RetinaNet, and QueryDet, demonstrate that VBGS-YOLOv8n outperforms these models in terms of detection accuracy, speed, and efficiency. The research highlights the effectiveness of VBGS-YOLOv8n in the efficient detection of potato seedlings in drone remote sensing images, providing a valuable reference for subsequent identification and deployment on mobile devices.

Studies focusing on the fault system in the Jurassic strata of the Sichuan Basin have been limited, restricting the understanding of the hydrocarbon accumulation mode of the Shaximiao Formation and the expansion of exploration. Through interpretation and coherent slice analysis of extensive seismic data, we have newly discovered that normal faults are widely developed in the northern central Sichuan Basin in the Jurassic strata. These faults mainly extend from the Lower to Upper Jurassic strata and are characterized by the continuous arrangement of NEE-trending small faults in the plane, with a few NNE-trending and NNW-trending faults also present. The distribution of Jurassic fault combinations varies within the basin, with normal faults mainly distributed in the low uplift areas of central Sichuan and the north of central Sichuan. Geochemical data comparisons indicate that these normal faults serve as conduits between the Jurassic source rocks and the Shaximiao Formation reservoir in these areas. Furthermore, the newly discovered normal faults are superimposed with the middle and lower Jurassic source rocks in the northern central Sichuan Basin, suggesting the formation of a new hydrocarbon accumulation model involving hydrocarbon generation from the middle and lower Jurassic, facilitated by communication through normal faults. Notably, one of the promising directions for exploration lies in the multi-stage channel superimposed development zone near these normal faults.

AbstractContext Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism.Objective To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes.Materials and methods Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 μg exosomes), Exo-WSTLZT (30 μg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT.Results ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p

Brake friction material reinforced with coconut fiber and dypsis lutescens fiber was designed and prepared in this study. Specimens incorporating 0–8 wt.% of coconut fibers or dypsis lutescens fibers were fabricated. The effect of the content of these reinforcing fibers on the overall properties of brake friction materials was systematically investigated. The results indicate that the inclusion of reinforcing fibers in the formulation of brake friction materials can improve the physical properties and friction and wear properties of brake friction materials. The specimen incorporating 6 wt.% plant fiber obtained the optimal comprehensive performance with excellent fade resistance and recovery properties, and better wear resistance. In order to further investigate their performance, nine hybrid fiber brake friction materials were designed using the golden section method and orthogonal test method. The study indicated that the F-6 hybrid fiber-reinforced brake friction materials have better physical properties, thermal degradation resistance, recovery properties, and abrasion resistance than the single-fiber-reinforced brake friction materials. This study provides new concepts for the preparation of fiber-reinforced brake friction materials as well as formulation optimization.

Mitochondria plays a role in cell differentiation and apoptosis processes. Maintaining mitochondrial function is critical, and this involves various aspects of mitochondrial quality control such as protein homeostasis, biogenesis, dynamics, and mitophagy. Osteoporosis, a metabolic bone disorder, primarily arises from two factors: the dysregulation between lipogenic and osteogenic differentiation of aging bone marrow mesenchymal stem cells, and the imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Mitochondrial quality control has the potential to mitigate or even reverse the effects. Among the Sirtuin family, consisting of seven Sirtuins (SIRT1-7), SIRT1-SIRT6 play a crucial role in maintaining mitochondrial quality control. Additionally, SIRT1, SIRT3, SIRT6, and SIRT7 are directly involved in normal bone development and homeostasis by modulating bone cells. However, the precise mechanism by which these Sirtuins exert their effects remains unclear. This article reviews the impact of various aspects of mitochondrial quality control on osteoporosis, focusing on how SIRT1, SIRT3, and SIRT6 can improve osteoporosis by regulating mitochondrial protein homeostasis, biogenesis, and mitophagy. Furthermore, we provide an overview of the current state of clinical and preclinical drugs that can activate Sirtuins to improve osteoporosis. Specific Sirtuin-activating compounds are effective, but further studies are needed. The findings of this study may offer valuable insights for future research on osteoporosis and the development of clinical prevention and therapeutic target strategies.

Abstract Background Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events. Methods We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets. Results It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors. Conclusion Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.

Abstract Are the sound systems of languages ecologically adaptive like other aspects of human behavior? In previous substantive explorations of the climate–language nexus, the hypothesis that desiccation affects the tone systems of languages was not well supported. The lack of analysis of voice quality data from natural speech undermines the credibility of the following two key premises: the compromised voice quality caused by desiccated ambient air and constrained use of phonemic tone due to a desiccated larynx. Here, the full chain of causation, humidity → voice quality → number of tones, is for the first time strongly supported by direct experimental tests based on a large speech database (China’s Language Resources Protection Project). Voice quality data is sampled from a recording set that includes 997 language varieties in China. Each language is represented by about 1200 sound files, amounting to a total of 1,174,686 recordings. Tonally rich languages are distributed throughout China and vary in their number of tones and in the climatic conditions of their speakers. The results show that, first, the effect of humidity is large enough to influence the voice quality of common speakers in a naturalistic environment; secondly, poorer voice quality is more likely to be observed in speakers of non-tonal languages and languages with fewer tones. Objective measures of phonatory capabilities help to disentangle the humidity effect from the contribution of phylogenetic and areal relatedness to the tone system. The prediction of ecological adaptation of speech is first verified through voice quality analysis. Humidity is observed to be related to synchronic variation in tonality. Concurrently, the findings offer a potential trigger for diachronic changes in tone systems.

Abstract Background Immune inflammatory responses play an important role in spinal cord injury (SCI); however, the beneficial and detrimental effects remain controversial. Many studies have described the role of neutrophils, macrophages, and T lymphocytes in immune inflammatory responses after SCI, although little is known about the role of B lymphocytes, and immunosuppression can easily occur after SCI. Methods A mouse model of SCI was established, and HE staining and Nissl staining were performed to observe the pathological changes. The size and morphology of the spleen were examined, and the effects of SCI on spleen function and B cell levels were detected by flow cytometry and ELISA. To explore the specific mechanism of immunosuppression after SCI, B cells from the spleens of SCI model mice were isolated using magnetic beads and analyzed by 4D label-free quantitative proteomics. The level of inflammatory cytokines and iron ions were measured, and the expression of proteins related to the Tom20 pathway was quantified by western blotting. To clarify the relationship between iron ions and B cell pyroptosis after SCI, we used FeSO4 and CCCP, which induce oxidative stress to stimulate SCI, to interfere with B cell processes. siRNA transfection to knock down Tom20 (Tom20-KD) in B cells and human B lymphocytoma cell was used to verify the key role of Tom20. To further explore the effect of iron ions on SCI, we used deferoxamine (DFO) and iron dextran (ID) to interfere with SCI processes in mice. The level of iron ions in splenic B cells and the expression of proteins related to the Tom20–Bax–caspase–gasdermin E (GSDME) pathway were analyzed. Results SCI could damage spleen function and lead to a decrease in B cell levels; SCI upregulated the expression of Tom20 protein in the mitochondria of B cells; SCI could regulate the concentration of iron ions and activate the Tom20–Bax–caspase–GSDME pathway to induce B cell pyroptosis. Iron ions aggravated CCCP-induced B cell pyroptosis and human B lymphocytoma pyroptosis by activating the Tom20–Bax–caspase–GSDME pathway. DFO could reduce inflammation and promote repair after SCI by inhibiting Tom20–Bax–caspase–GSDME-induced B cell pyroptosis. Conclusions Iron overload activates the Tom20–Bax–caspase–GSDME pathway after SCI, induces B cell pyroptosis, promotes inflammation, and aggravates the changes caused by SCI. This may represent a novel mechanism through which the immune inflammatory response is induced after SCI and may provide a new key target for the treatment of SCI.

Abstract Background Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor in the treatment of CMP. Duloxetine is an effective treatment option for patients with CMP as its antidepressant effect. The purpose of this article is to evaluate the efficacy and safety of duloxetine in treating CMP. Databases and data treatment We searched PubMed, Web of Science, Embase, Cochrane Library from inception to May, 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of duloxetine versus placebo in patients with CMP were included. We identified 13 articles and studied a population of 4201 participants in 4 countries. Results This meta-analysis showed that the duloxetine has statistically significant compared with the placebo control, benefits on 24-hour average pain, living quality, physical function, and global impressions and there was no difference in the incidence of serious adverse event. In general, duloxetine can improve mood and pain level at the same time. Conclusions This review shows a significant contribution of duloxetine to CMP symptom relief. This meta-analysis improved that duloxetine can significantly reduce the pain level of patients, improve depressive symptoms and global impression, and has no obvious serious adverse reactions. However, additional studies are required to confirm the relationship between psychological diseases and chronic pain and explore their internal links.

Introduction: The Muglad basin, located on the southern Central Africa Shear Zone, is an intracontinental passive rift basin. The Fula sag, situated in northeastern of the basin, is a hydrocarbon-rich depression. As exploration advanced, the Fula sag has entered the stage of fine exploration for complex fault blocks. Therefore, studying the characteristics and evolution of faults can aid in deepening the understanding of hydrocarbon accumulation rules in the area, and guide the next steps of oil and gas exploration. Previous studies have primarily focused on the division of fault level and their role in hydrocarbon accumulation, but have not delved into the geometric features and evolution of the fault system across the entire Fula sag.Methods: In this paper, we systematically studied the fault system and its hydrocarbon control within the sag using petroleum seismic reflection profiles, as well as logging data.Results and Discussion: And the conclusions are as followed: 1) tectonic features in diverse areas of the Fula sag vary significantly from a shovel-like half-graben to the asymmetric graben, and faults in the study area can be classified into five combination features. 2) Three complete rift-sag cycles have developed since the early Cretaceous, with continuously active faults controlling the formation of “inherited” sag. 3) The strong activity of faults in the first and second riftting period led to the development of mainly AG-Formation source rocks and middle reservoir-forming assemblages in the Fula sag. Additionally, the formation and distribution of oil and gas reservoirs in the sag were controlled by the faults in the central fault zone and the western steep slope zone. Furthermore, hydrocarbons migrated and formed reservoirs through the main faults in the central fault zone and the western main fault. Our research will provide a valuable insight for understanding the petroleum geological characteristics of basins with a similar genesis mechanism.

Abstract Aim The aim of this study was to examine hope level and its influencing factors in patients with decompensated liver cirrhosis. Design A prospective observational study. Methods We selected 93 patients with decompensated liver cirrhosis from a Chinese university hospital based on the inclusion and exclusion criteria. A general information questionnaire and Herth Hope Index were used, and multiple linear regression identified factors associated with the patients' hope level. Results The participants' average hope level was 32.01 ± 6.14 (moderate). The hope score's highest and lowest dimensions were “interconnectedness” (11.29 ± 2.17) and “temporality and future” (10.12 ± 2.28), respectively. Multiple linear regression showed that education level and monthly per capita income were independent influencing factors (p

The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2–5) named albaphenol A–E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7–16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1–16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC50 45.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC50 2.5–32.8 μM) than the positive control galantamine (IC50 35.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 μM. The structure–activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor–enzyme complex.

Introduction: The southwestern Sichuan fold-thrust belt (SWSB) is a duplex detachment system and features the basal Precambrian detachment at a depth of approximately 15–17 km and the upper Mid-Triassic detachment. Moreover, the SWSB undergoes forward-breaking propagation during the Cenozoic. To date, the mechanism and kinematic evolution governing the SWSB in this thrusting deformation as well as the way the two detachments control the structural deformation pattern of the SWSB remains unknown.Methods: In this work, three discrete-element numerical models with the same strong upper detachment but basal detachments with different mechanical strengths and thicknesses were designed to study the deformation of the SWSB.Results: The results indicate that for the Model I with a strong frictional basal detachment with thickness of 500 m, most deformation and thrust faults concentrate near the mobile backwall. Model I exhibits characteristics such as linearly increasing wedge height and stepwise increasing wedge width and slope angle. For the Model II with a modest frictional basal detachment with thickness of 500 m, the strain and deformation propagate into the foreland quickly and multiple back-thrust and thrust faults form on the upper detachment in the second thrusting period. The first thrusting period in Model II, exhibits similarities with Model I. However, in the second period, the wedge reaches a stable state, and its geometry remains constant. In this stage, the deformation propagates along the shallow detachment into the right side of the model. The geometry and activity of thrust faults in the foreland differ significantly in the model III with a modest frictional basal detachment but a greater thickness. Two additional pop-up structures are generated in the second period in this model. The first half of the first thrusting period is similar to the first two models. In the second half of the first period and the second period, the wedge is in a stable state. In the first stage of the shortening, all models undergo a transition from a subcritical state to entering a supercritical state, which indicates that the deformation is progressing rapidly along the basal detachment towards the right side of the model.Discussion: The results of Model III are consistent with the deformation pattern of the SWSB. The study of the kinematics and interaction between two detachments could help hydrocarbon exploration beneath the upper detachment.

Understanding the structural style, kinematic process, and timing of superimposed structures worldwide is often difficult due to complex structure deformation process. Fortunately, the newly acquired high-quality seismic reflection data and geological observations covering the Tongnanba anticline provide an excellent chance to characterize such structures. Here, we used geological and seismic data from the Tongnanba region to evaluate the structural style and deformation sequence of Tongnanba anticline. In this regard, we propose a new model of the northeastern Sichuan Basin, which are different from the model that deep structures formed earlier than shallow structures demonstrated by previous studies, and we also discussed the implications of this new model for the deep oil and gas exploration. Compressed by Micangshan and Dabashan thrust belts and controlled by three detachment layers, the Tongnanba anticline shows a complex multi-stage, multi-directional, and multi-level superimposed structure. There were three deformation layers vertically, leading to the multi-level detachment thrust structure style. Specifically, the upper and middle deformation layers were mainly controlled by South Dabashan thrust belt in the early stage, forming long-distance detachment thrust structure extended in the NW-SE direction. A series of pop-up structures propagated toward the upper and middle detachment layers. On the other hand, the lower deformation layer was primarily controlled by the Micangshan thrust belt in the late stage, forming complex basement faults extended in the NE-SW direction, which was consistent with Trishear fault-propagation fold. Along the basement detachment developed multiple branch slopes spread from northeast to southwest. The middle and upper deformation layers was transformed by the basement faults, thus forming the complex superimposed structure of north-south zonation and east-west segmentation at present. It was such complex superimposed structure that control the process of hydrocarbon accumulation and adjustment in each deformation layer, and the deep-ultra-deep ancient oil and gas reservoirs may be worth of exploring.

Osteoporosis is a chronic inflammatory disease that severely affects quality of life. Cornus officinalis is a Chinese herbal medicine with various bioactive ingredients, among which morroniside is its signature ingredient. Although anti-bone resorption drugs are the main treatment for bone loss, promoting bone anabolism is more suitable for increasing bone mass. Therefore, identifying changes in bone formation induced by morroniside may be conducive to developing effective intervention methods. In this study, morroniside was found to promote the osteogenic differentiation of bone marrow stem cells (BMSCs) and inhibit inflammation-induced bone loss in an in vivo mouse model of inflammatory bone loss. Morroniside enhanced bone density and bone microstructure, and inhibited the expression of IL6, IL1β, and ALP in serum (p < 0.05). Furthermore, in in vitro experiments, BMSCs exposed to 0–256 μM morroniside did not show cytotoxicity. Morroniside inhibited the expression of IL6 and IL1β and promoted the expression of the osteogenic transcription factors Runx2 and OCN. Furthermore, morroniside promoted osteocalcin and Runx2 expression and inhibited TRAF6-mediated NF-κB and MAPK signaling, as well as osteoblast growth and NF-κB nuclear transposition. Thus, morroniside promoted osteogenic differentiation of BMSCs, slowed the occurrence of the inflammatory response, and inhibited bone loss in mice with inflammatory bone loss.

Background: Few overlaps between prognostic biomarkers are observed among different independently performed genomic studies of esophageal squamous cell carcinoma (ESCC). One of the reasons for this is the insufficient cohort size. How many cases are needed to prognostic genes analysis in ESCC?Methods: Here, based on 387 stage II/III ESCC cases analyzed by whole-genome sequencing from one single center, effects of cohort size on prognostic genes analysis were investigated. Prognostic genes analysis was performed in 100 replicates at each cohort size level using a random resampling method.Results: The number of prognostic genes followed a power-law increase with cohort size in ESCC patients with stage II and stage III, with exponents of 2.27 and 2.25, respectively. Power-law curves with increasing events number were also observed in stage II and III ESCC, respectively, and they almost overlapped. The probability of obtaining statistically significant prognostic genes shows a logistic cumulative distribution function with respect to cohort size. To achieve a 100% probability of obtaining statistically significant prognostic genes, the minimum cohort sizes required in stage II and III ESCC were approximately 95 and 60, respectively, corresponding to a number of outcome events of 33 and 36, respectively.Conclusion: In summary, the number of prognostic genes follows a power-law growth with the cohort size or events number in ESCC. The minimum events number required to achieve a 100% probability of obtaining a statistically significant prognostic gene is approximately 35.

Two undescribed butenolide derivatives, asperteretal J (1) and K (2), together with 13 known ones (3–15) were isolated from an endophytic fungus Aspergillus terreus SGP-1, the fermentation product of which exhibited selective inhibitory activity toward butyrylcholinesterase. The structures of the new compounds were elucidated based on HRMS and NMR data, and the absolute configurations were determined by specific optical rotation comparison. All compounds were evaluated for cholinesterase inhibitory effects with galantamine as a positive control. Compounds 4–8 selectively inhibited butyrylcholinesterase with IC50 values of 18.4–45.8 µM in a competitive manner, with Ki values of 12.3–38.2 µM. The structure-activity relationship was discussed. Molecular docking and dynamic simulation of the inhibitor-enzyme complex were performed to better understand the interactions.

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of non-neoplastic histiocytes that contain intracytoplasmic crystallized immunoglobulins. Although CSH can occur in various organs, gastric CSH is very rare. Therefore, diagnosing gastric CSH remains a challenge. Here, we present the case of a 69-year-old man with localized gastric CSH who presented with positive fecal occult blood for 2 days. Gastroscopy showed that there was a piece of irregular whitish focus in the big bend of the gastric antrum, which was soft and elastic. Histologically, the biopsied gastric mucosa showed chronic inflammation, mild activity with erosion, and numerous eosinophilic mononuclear cells containing fibrillary crystalloid inclusions in the lamina propria. Immunohistochemically, these crystal-containing cells were positive for CD68/PGM1 and Igk, which revealed that the cells were histiocytes harboring kappa light chain-restricted immunoglobulin crystals. Electron microscopic examination showed numerous high-electron-density particles in the cytoplasm of cells, with crystal structures of different sizes and shapes. This case highlights how immunohistochemistry can help with differential diagnosis and classification.

Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.

Ganoderma lucidum has a wide carbon spectrum, while the expression profile of key genes relevant to carbon metabolism on different carbon sources has been seldom studied. Here, the transcriptomes of G. lucidum mycelia cultured on each of 19 carbon sources were conducted. In comparison with glucose, 16 to 1,006 genes were upregulated and 7 to 1,865 genes were downregulated. Significant gene expression dynamics and induced activity were observed in laccase genes when using agricultural and forestry residues (AFRs) as solo carbon sources. Furthermore, study of laccase gene family in two haploids of G. lucidum GL0102 was conducted. Totally, 15 and 16 laccase genes were identified in GL0102_53 and GL0102_8, respectively, among which 15 pairs were allelic genes. Gene structures were conserved between allelic laccase genes, while sequence variations (most were SNPs) existed. Nine laccase genes rarely expressed on all the tested carbon sources, while the other seven genes showed high expression level on AFRs, especially Gllac2 and Gllac7, which showed 5- to 1,149-fold and 4- to 94-fold upregulation in mycelia cultured for 5 days, respectively. The expression of H53lac7 was consistently higher than that of H8lac7_1 on all the carbon sources except XM, exhibiting a case of allelic expression bias. A total of 47 SNPs and 3 insertions/deletions were observed between promoters of H53lac7 and H8lac7_1, which lead to differences in predicted binding sites of zinc fingers. These results provide scientific data for understanding the gene expression profile and regulatory role on different carbon sources and may support further functional research of laccase.

Quercetin, a flavonoid found in natural medicines, has shown a role in disease prevention and health promotion. Moreover, because of its recently identified contribution in regulating bone homeostasis, quercetin may be considered a promising agent for improving bone health. This study aimed to elucidate the role of quercetin in androgen deprivation therapy-induced osteoporosis in mice. C57BL/6 mice were subjected to orchiectomy, followed by quercetin treatment (75 and 150 mg/kg/d) for 8 weeks. Bone microstructure was then assessed by micro-computed tomography, and a three-point bending test was used to evaluate the biomechanical parameters. Hematoxylin and eosin (H&E) staining was used to examine the shape of the distal femur, gastrocnemius muscle, and liver. The balance motion ability in mice was evaluated by gait analysis, and changes in the gastrocnemius muscle were observed via Oil red O and Masson’s staining. ELISA and biochemical analyses were used to assess markers of the bone, glucose, and lipid metabolism. Western blotting analyses of glucose and lipid metabolism-related protein expression was performed, and expression of the GPCR6A/AMPK/mTOR signaling pathway-related proteins was also assessed. After 8 weeks of quercetin intervention, quercetin-treated mice showed increased bone mass, bone strength, and improved bone microstructure. Additionally, gait analysis, including stride length and frequency, were significantly increased, whereas a reduction of the stride length and gait symmetry was observed. H&E staining of the gastrocnemius muscle showed that the cross-sectional area of the myofibers had increased significantly, suggesting that quercetin improves balance, motion ability, and muscle mass. Bone metabolism improvement was defined by a reduction of serum levels of insulin, triglycerides, total cholesterol, and low-density lipoprotein, whereas levels of insulin-like growth factor-1 and high-density lipoprotein were increased after quercetin treatment. Expression of proteins involved in glucose uptake was increased, whereas that of proteins involved in lipid production was decreased. Moreover, the GPRC6A and the phospho-AMPK/AMPK expression ratio was elevated in the liver and tibia tissues. In contrast, the phospho-mTOR/mTOR ratio was reduced in the quercetin group. Our findings indicate that quercetin can reduce the osteoporosis induced by testosterone deficiency, and its beneficial effects might be associated with the regulation of glucose metabolism and inhibition of lipid metabolism via the GPCR6A/AMPK/mTOR signaling pathway.

Allogeneic stem cell transplantation from haplo-identical donors (haplo-HSCT) has become a well-established therapeutic option for hematological malignancies. The fever of unknown origin (haplo-fever) early after the infusion of T cell repleted graft, which returned to normal right after post-transplantation cyclophosphamide (PTCy), is a unique clinical feature in patients undergoing haplo-HSCT. In the current study, the characteristics of haplo-fever and cytokine profiles during haplo-fever were retrospectively analyzed in a cohort of 37 patients undergoing T cell repleted haplo-HSCT with PTCy as graft versus host disease (GvHD) prophylaxis. In total, 33 patients (89.2%) developed haplo-fever from day 0 to day +7. Patients with high peak temperatures tended to have a lower incidence of chronic GvHD (cGvHD) (p = 0.07), moderate to severe cGvHD (p = 0.08), and superior GvHD and relapse-free survival (GRFS, p = 0.04). During the haplo-fever, there were significant increases in multiple cytokines, such as interferon gamma, interleukin (IL) 6, IL2, IL2 receptor, IL8, IL10, IL17, and tumor necrosis factor (TNF). The increases in IL2 receptor (p = 0.037) and TNF (p < 0.001) on day +4 were correlated with the lower risk of cGvHD. Increased TNF > 1.8055-fold on day +4 was the best predictive threshold for cGvHD, and was correlated with a lower incidence of cGvHD (p < 0.001), moderate to severe cGvHD (p = 0.003), and superior GRFS (p < 0.001). These observations may reflect the early reactivation of donor T cells after haplo graft infusion, which would potentially be eliminated by PTCy. Further studies with larger independent cohorts of patients are warranted, to clarify the clinical significance of haplo-fever, and day +4 TNF as a potential biomarker to predict GvHD and GRFS.

Osteoarthritis (OA), a chronic degenerative joint disease, always occurred in the aging population. There is evidence suggests that chondrocytes’ survival, inflammation, and apoptosis play critical roles in OA pathogenesis. LMX1B has been shown to be involved in antiosteogenic function in early patterning of the calvaria. However, the role and mechanism of LMX1B in OA is not unknown. The present study observed that LMX1B was highly expressed in OA patients compared with normal patients. Besides, we found that IL-1β increased LMX1B mRNA and protein expression in SW1353 and C28/I2 chondrocytes. LMX1B knockdown increased IL-1β-induced cell viability and proliferation and suppressed cell apoptosis and inflammation response, including IFN-γ, TNF-α, IL-6, prostaglandin E2 (PGE2), and NO both in SW1353 and C28/I2. Furthermore, LMX1B silence inhibited MMP-3 and MMP-13 expression both in SW1353 and C28/I2 cells. Also, the activation of the NF-κB and NLRP3 signaling pathway was suppressed in LMX1B silence cells by decreasing the p-p65 and NLRP3 protein expressions. Additionally, inhibition of NF-κB by PDTC suppressed NLRP3 expression. Moreover, NLRP3 overexpression reversed the effects of LMX1B silence on chondrocytes’ survival, proliferation, apoptosis, and inflammation. Finally, we confirmed that LMX1B depletion had protective effects in OA rats in vivo.

Based on the latest geological, seismic, drilling and outcrop data, we studied the geological structure, tectonic evolution history and deformation process of the southwestern Sichuan fold-thrust belt to find out the potential hydrocarbon exploration areas in deep layers. During key tectonic periods, the southwestern Sichuan fold-thrust belt developed some characteristic strata and structural deformation features, including the Pre-Sinian multi-row N-S strike rifts, step-shaped platform-margin structures of Sinian Dengying Formation, the western paleo-uplift in the early stage of Late Paleozoic, the Late Paleozoic–Middle Triassic carbonate platform, foreland slope and forebulge during Late Triassic to Cretaceous, and Cenozoic multi-strike rejuvenated fold-thrusting structures. The fold-thrust belt vertically shows a double-layer structural deformation controlled by the salt layer in the Middle Triassic Leikoupo Formation and the base detachment layer at present. The upper deformation layer develops the NE-SW strike thrusts propagating toward basin in long distance, while the deeper deformation layer had near north-south strike basement-involved folds, which deformed the detachment and thrusting structures formed earlier in the upper layer, with the deformation strength high in south part and weak in north part. The southern part of the fold-thrust belt is characterized by basement-involved fold-thrusts formed late, while the central-northern part is dominated by thin-skin thrusts in the shallow layer. The Wuzhongshan anticlinal belt near piedmont is characterized by over-thrust structure above the salt detachment, where the upper over-thrusting nappe consists of a complicated fold core and front limb of a fault-bend fold, while the deep layer has stable subtle in-situ structures. Favorable exploration strata and areas have been identified both in the upper and deeper deformation layers separated by regional salt detachment, wherein multiple anticlinal structures are targets for exploration. Other potential exploration strata and areas in southwestern Sichuan fold-thrust belt include the deep Sinian and Permian in the Wuzhongshan structure, pre-Sinian rifting sequences and related structures, platform-margin belt of Sinian Dengying Formation, and Indosinian paleo-uplift in the east of the Longquanshan structure.

Numerous studies in plants have shown the vital roles of MYB transcription factors in signal transduction, developmental regulation, biotic/abiotic stress responses and secondary metabolism regulation. However, less is known about the functions of MYBs in Ganoderma. In this study, five medicinal macrofungi of genus Ganoderma were subjected to a genome-wide comparative analysis of MYB genes. A total of 75 MYB genes were identified and classified into four types: 1R-MYBs (52), 2R-MYBs (19), 3R-MYBs (2) and 4R-MYBs (2). Gene structure analysis revealed varying exon numbers (3-14) and intron lengths (7-1058 bp), and noncanonical GC-AG introns were detected in G. lucidum and G. sinense. In a phylogenetic analysis, 69 out of 75 MYB genes were clustered into 15 subgroups, and both single-copy orthologous genes and duplicated genes were identified. The promoters of the MYB genes harbored multiple cis-elements, and specific genes were co-expressed with the G. lucidum MYB genes, indicating the potential roles of these MYB genes in stress response, development and metabolism. This comprehensive and systematic study of MYB family members provides a reference and solid foundation for further functional analysis of MYB genes in Ganoderma species.

Abstract Background The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. Methods The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18–80 years old, in stable CKD stages 4–5 (eGFR > 7 ml/min /1.73 m2), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m2 (routine dialysis group) and 5 ml/min/1.73 m2 or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. Discussion This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m2. With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. Trial registration The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.

Abstract Background Phenylalanine ammonia-lyase (PAL, EC 4.3.1.24) is the first key enzyme in the phenylpropanoid pathway. The pal gene has been widely studied in plants and participates in plant growth, development and defense systems. However, in Pleurotus ostreatus, the biological functions of pal during organismal development and exposure to abiotic stress have not been reported. Results In this study, we cloned and characterized the pal1 (2232 bp) and pal2 (2244 bp) genes from the basidiomycete P. ostreatus CCMSSC 00389. The pal1 and pal2 genes are interrupted by 6 and 10 introns, respectively, and encode proteins of 743 and 747 amino acids, respectively. Furthermore, prokaryotic expression experiments showed that PAL enzymes catalyzed the conversion of L-phenylalanine to trans-cinnamic acid. The function of pal1 and pal2 was determined by constructing overexpression (OE) and RNA interference (RNAi) strains. The results showed that the two pal genes had similar expression patterns during different developmental stages. The expression of pal genes was higher in the reproductive growth stage than in the vegetative growth stage. And the interference of pal1 and pal2 delayed the formation of primordia. The results of heat stress assays showed that the RNAi-pal1 strains had enhanced mycelial tolerance to high temperature, while the RNAi-pal2 strains had enhanced mycelial resistance to H2O2. Conclusions These results indicate that two pal genes may play a similar role in the development of P. ostreatus fruiting bodies, but may alleviate stress through different regulatory pathways under heat stress.

ABSTRACT Coriolopsis trogii is a typical thermotolerant basidiomycete fungus, but its thermotolerance mechanisms are currently unknown. In this study, two monokaryons of C. trogii strain Ct001 were assembled: Ct001_29 had a genome assembly size of 38.85 Mb and encoded 13,113 genes, while Ct001_31 was 40.19 Mb in length and encoded 13,309 genes. Comparative intra- and interstrain genomic analysis revealed the rich genetic diversity of C. trogii, which included more than 315,194 single-nucleotide polymorphisms (SNPs), 30,387 insertion/deletions (indels), and 1,460 structural variations. Gene family analysis showed that the expanded families of C. trogii were functionally enriched in lignocellulose degradation activities. Furthermore, a total of 14 allelic pairs of heat shock protein 20 (HSP20) genes were identified in the C. trogii genome. The expression profile obtained from RNA sequencing (RNA-Seq) showed that four tandem-duplicated allelic pairs, HSP20.5 to HSP20.8, had more than 5-fold higher expression at 35°C than at 25°C. In particular, HSP20.5 and HSP20.8 were the most highly expressed HSP20 genes. Allelic expression bias was found for HSP20.5 and HSP20.8; the expression of Ct29HSP20.8 was at least 1.34-fold higher than that of Ct31HSP20.8, and that of Ct31HSP20.5 was at least 1.5-fold higher than that of Ct29HSP20.5. The unique structural and expression profiles of the HSP20 genes revealed by these haplotype-resolved genomes provide insight into the molecular mechanisms of high-temperature adaptation in C. trogii. IMPORTANCE Heat stress is one of the most frequently encountered environmental stresses for most mushroom-forming fungi. Currently available fungal genomes are mostly haploid because high heterozygosity hinders diploid genome assembly. Here, two haplotype genomes of C. trogii, a thermotolerant basidiomycete, were assembled separately. A conserved tandem cluster of four HSP20 genes showing allele-specific expression was found to be closely related to high-temperature adaptation in C. trogii. The obtained haploid genomes and their comparison offer a more thorough understanding of the genetic background of C. trogii. In addition, the responses of HSP20 genes at 35°C, which may contribute to the growth and survival of C. trogii at high temperatures, could inform the selection and breeding of elite strains in the future.

(1) Background: Few studies have investigated the association between eating styles and IBS. This study aimed to explore the association between abnormal eating styles and irritable bowel syndrome (IBS). (2) Methods: This cross-sectional study investigated students in China Medical University and Shenyang Medical College. Eating styles were evaluated by the Dutch Eating Behavior Questionnaire (DEBQ), and IBS was diagnosed according to Rome III criteria. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). (3) Results: A total of 335 students were diagnosed with IBS. Students with the total scores in tertile 2 and 3 had 1.29 times and 2.75 times higher risk of IBS than students with the total scores in tertile 1, respectively. Simultaneously, the risk of IBS in the tertile 3 of external eating, emotional eating, and restraint eating trends was 3.87 times, 2.71 times, and 3.82 times higher than that of tertile 1, respectively. (4) Conclusions: this study showed that a high score in both total eating styles and each eating style was associated with the odds of having IBS and suggested that the psychological factors behind eating styles may play a critical role in controlling the IBS.

Abstract Background MiR-221, acting as onco-miR or oncosuppressor-miR, plays an important role in tumor progression; however, the prognostic value of miR-221 in human carcinomas is controversial and inconclusive. The objective of our study was to conducted a systematic review and meta-analysis of miR-221 in various types of human cancers. Methods An online search of up-to-date electronic databases, including PubMed and Embase, was conducted to identify as many relevant papers as possible. 32 papers involving 3041 patients with different carcinomas were included in the analysis. Hazard ratios (HRs) of miR-221 were used to evaluate prognostic values. Results Thirty-two papers involving 15 cancers were included. MiR-221 was associated with a worse overall survival (OS) in patients, and a combined HR was 1.93 (95% CI of 1.43–2.60, 2080 patients, 22 studies, I-squared = 80.4%, P = 0.000); however, the combined HR for relapse-free survival (RFS) was 1.37 (95% CI of 0.75–2.48, 625 patients, 7 studies, I-squared = 78.8%, P = 0.000), and disease-free survival (DFS) was 1.24 (95% CI of 0.60–2.56, 539 patients, 5 studies, I-squared = 81.8%, P = 0.000). Conclusion MiR-221 was shown to be associated with a poor OS in human carcinomas, and thus may serve as a useful predictor of clinical outcomes.

The northwestern Sichuan region has experienced multi-stage tectonic evolution including marine cratonic basin from the Sinian to the Middle Triassic and intra-continental basin from the Late Triassic to the Cenozoic. Several regional tectonic activities caused complicated stratigraphic distribution and structural deformations in the deep-buried layers. During the key tectonic periods, some characteristic sedimentary and deformation structures were formed, including the step-shaped marginal carbonate platform of Dengying Formation, the western paleo-high at the end of Silurian, and the passive continental margin of the Late Paleozoic–Middle Triassic. The Meso-Cenozoic intra-continental compressional tectonic processes since the Late Triassic controlled the formation of complex thrusting structures surrounding and inside the northwestern basin. The northern Longmenshan fold-thrust belt has a footwall in-situ thrust structure, which is controlled by two sets of detachments in the Lower Triassic and Lower Cambrian and presents as a multi-level deformation structure with the shallow folds, the middle thin-skin thrusts and the deeper basement-involved folds. The thrust belt in front of the Micangshan Mountain shows a double-layer deformation controlled by the Lower Triassic salt detachment, which is composed by the upper monocline and deep-buried imbricate thrust structures. The interior of the basin is characterized by several rows of large-scale basement-involved folds with NEE strike direction. From the perspective of structural geology, the favorable exploration reservoirs and belts in northwestern Sichuan have obvious zoning characteristics. The favorable exploration layers of Dengying Formation of Upper Sinian are mainly distributed in the eastern and northern areas of the northwestern Sichuan Basin, in which the Jiulongshan structural belt, Zitong syncline and Yanting slope are the most favorable. The Lower Paleozoic was transformed by Caledonian paleo-uplift and late Cenozoic folding, and the midwest area such as the Zitong syncline is a potential area for hydrocarbon exploration. The favorable part of the Upper Paleozoic is mainly distributed in the northern Longmenshan belt and its frontal area, where the deep-buried thin-skin thrust structures in the footwall are the key exploration targets. Key Words: northwestern Sichuan Basin, fold-thrust belt, multi-level detachment, Sinian, Paleozoic, platform margin, paleohigh, structural deformation, tectonic evolution, hydrocarbon exploration

Busulfan (BU) is widely used in conditioning regimens prior to hematopoietic stem cell transplantation (HSCT). The exposure-escalated BU directed by therapeutic drug monitoring (TDM) is extremely necessary for the patients with high-risk hematologic malignancies in order to diminish relapse, but it increases the risk of drug-induced toxicity. BU exposure, involved in the glutathione- (GSH-) glutathione S-transferases (GSTs) pathway and proinflammatory response, is associated with clinical outcomes after HSCT. However, the expression of genes in the GSH-GSTs pathway is regulated by NF-E2-related factor 2 (Nrf2) that can also alleviate inflammation. In this study, we evaluated the influence of NRF2 polymorphisms on BU exposure, proinflammatory cytokine levels, and clinical outcomes in HSCT patients. A total of 87 Chinese adult patients receiving twice-daily intravenous BU were enrolled. Compared with the patients carrying wild genotypes, those with NRF2 -617 CA/AA genotypes showed higher plasma interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α levels, poorer overall survival (OS; RR = 3.91), and increased transplant-related mortality (TRM; HR = 4.17). High BU exposure [area under the concentration-time curve (AUC) > 9.27 mg/L × h)] was related to BU toxicities. Furthermore, NRF2 -617 CA/AA genotypes could significantly impact TRM (HR = 4.04; p = 0.0142) and OS (HR = 3.69; p = 0.0272) in the patients with high BU AUC. In vitro, we found that high exposure of endothelial cell (EC) to BU, in the absence of Nrf2, elicited the hyperstimulation of NF-κB-p65, accompanied with the elevated secretion of proinflammatory cytokines, and led to EC death. These results showed that NRF2 -617 CA/AA genotypes, correlated with high proinflammatory cytokine levels, could predict inferior outcomes in HSCT patients with high BU AUC. Thus, NRF2 -617 CA/AA genotyping combined with TDM would further optimize personalized BU dosing for sufficient efficacy and safety endpoint.

Based on forward modeling of detachment fold, this study presents a method to analyze multi-level detachment structures and identify the authenticity of deep-seated anticlines using time-domain seismic section. The steps include the conversion of the time-migrated seismic image into depth domain image using a constant velocity field, structural interpretation of the depth seismic image, measurement of each structural relief area and each height above reference level, plotting of area-height relationship chart with piecewise fitting etc. The area-depth correlation can help the division of structural sequences, the definition of detachment levels, the calculation of the tectonic shortening, and the identification of deep-seated structure. The segment area-height relationship is a feature of multi-level detachment structures, while little or no linear correlation between area and height is an indicator of non-deformation or pseudo-anticline. Regardless of the uncertainty of area-height relationship, the segment slopes will correspond to the differential shortenings of multi-level detachments, the intersection between adjacent segments will give the height of detachment surface above reference level and then help define the detachment level in original time-domain seismic section. This method can make use of time-domain seismic data to determine the geologic structure of complicated structure areas and assess risks of deep exploration targets. It has achieved good results in southern Junggar and eastern Sichuan areas. Key words: multi-level detachments, anticline, time-domain seismic section, area-height relationship, complicated structure, southern Junggar Basin, eastern Sichuan fold belt

Circular RNAs (circRNAs) participate in the pathogenesis of various diseases by sponging microRNAs (miRs). However, the roles of circRNAs remain unreported in glomerular diseases. We previously reported that miR-150 positively correlated with renal chronicity index in patients with lupus nephritis (LN). We aimed to investigate renal circRNA profiling and the interaction between circRNAs and miR-150 in LN patients. Six renal biopsies from untreated female patients with LN class IV and five normal kidney tissues from urology patients were used for circRNA sequencing. 171 circRNAs with 2-fold differential expression were identified in LN compared with normal control. Ten selected circRNAs were validated by real-time qPCR, and seven circRNAs showed the same significant increases as the sequencing results. circHLA-C positively correlated with proteinuria (R = 0.92, p

Abstract Background This study aimed to assess the association between 14 single nucleotide polymorphisms (SNPs) in six genes (IRF8, TMEM39A, IKZF3, ORMDL3, GSDMB, and ZPBP2) and systemic lupus erythematosus (SLE) in a Chinese Han population sample. Methods We carried out a case-control study of 415 patients with SLE and 470 healthy controls without autoimmune disease or cancer. DNA for genetic analysis was isolated from the blood of all subjects using standard phenol-chloroform method. TagSNPs were identified using genotype data from the panel (Han Chinese in Beijing) of the HapMap Project and were selected using the Haploview program. Genotyping assay was conducted using the Sequenom MassARRAY iPLEX Gold platform. The frequencies of the alleles and genotypes were calculated and analyzed. Association studies and haplotype analysis were also performed. Results The genotypic frequencies of rs12493175 and rs13062955 were significantly different between the SLE patients and the healthy controls. Compared with the common homozygous genotype, the CT and CT + TT genotypes in rs12493175 and the AC and AC + AA genotypes in rs13062955 was observed to significantly reduce the risk of SLE. The haplotype analysis of TMEM39A polymorphisms showed that the CGTA haplotype frequency was significantly low in the SLE patients. Conclusion Our findings identified three novel associations in SNPs located in the TMEM39A gene associated with SLE susceptibility in a Chinese Han population.

Abstract Background To determine the prevalence of depressive symptoms and to explore related factors of depressive symptoms in hemodialysis (HD) patients in northern China. Methods We used a cross-sectional research design to recruit 227 chronic kidney disease (CKD) patients who were undergoing HD treatment in northern China during December, 2012 to March, 2013. The Chinese edition of the Center for Epidemiologic Studies Depression (CES-D) was used to measure depressive symptoms. Information on quality of life (QOL), activities of daily living (ADL), social support status, coping style, self-efficacy, ego resiliency and demographic characteristics was all collected by face to face interview. Multivariate logistic regression analysis was used to explore related factors of depressive symptoms. Results The prevalence of depressive symptoms among HD patients was 29.1%. Patients with a lower mood have worse ADL and QOL than patients with better mood. Patients with a lower mood have got less social support than patients with better mood, including both family support and outside family support. For coping style, patients with a lower mood were more inclined to choose “acceptance-resignation” coping style than patients with better mood, while the result is opposite in “avoidance” coping style. And patients with a better mood have better self-efficacy and ego resiliency than patients with lower mood. Multivariate logistic regression analyses revealed that ADL (OR = 1.124, p = 0.002), family support (OR = 0.867, p = 0.021), “acceptance-resignation” coping style (OR = 1.228, p = 0.022), and ego resiliency (OR = 0.944, p = 0.021) were associated with low mood independently. Conclusions The prevalence of depressive symptoms is high in CKD patients on HD in northern China. activities of daily living, family support, “acceptance-resignation” coping style and ego resiliency were independently associated with depressive symptoms.

Erythroderma is occasionally associated with lung cancer. Here we report a 69-year-old male who has history of melanoma from 8 years ago presented with erythroderma associated with skin, soft tissue and pulmonary infection. CT chest showed a single enlarging right upper lobe lung nodule. Biopsy showed evidence of adenocarcinoma, and eventually proven to be metastatic melanoma. The patient improved after antibiotics and antifungal treatment. To our knowledge, this is the first case of melanoma metastasis presented as erythroderma as paraneoplastic syndrome. Keywords: Melanoma, Erythroderma, Sepsis, Lung cancer

Aims: We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. Methods: Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. Results: 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p

Background/Aims: Pioglitazone is a type of peroxisome proliferator-activated receptor γ agonist and is capable of alleviating renal ischemia-reperfusion injury. Methods: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. Results: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. Conclusion: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.

Based on the latest data from oil and gas exploration, the structural geometry features of the northern Longmenshan fold-thrust belt and its forming process were examined, and then favorable hydrocarbon prospecting areas were predicted. Two major orogenic events occurred in the Longmenshan belt since the Mesozoic: thrusts and folds were formed by a late Triassic compressional event, and later transformed by the late Cenozoic deformation featuring base-involved large folds. Due to the influence of the two events, thrust nappes, autochthonous thrusts and in-situ blind thrusts developed from the orogen to the foreland basin sequentially, and these structural units show different profile combination from the north to south. Among these structural units, the autochthonous thrusts and folds under lower allochthonous nappes have high potential for oil and gas exploration. Key words: Longmenshan, fold-thrust belt, structural analysis, favorable target

Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx) rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats. Renal fibrosis and enhanced expressions of profibrotic proteins TGF-β1, fibronectin and collagen I caused by Nx were significantly alleviated by pioglitazone. In addition, pioglitazone protected mitochondrial functions by stabilizing the mitochondrial membrane potential, inhibiting ROS generation, maintaining ATP production and the activities of complexes I and III, and preventing cytochrome C leakage from mitochondria. Pioglitazone also upregulated the expression levels of ATP synthase β, COX I and NDUFB8, which were downregulated in the kidney of Nx rats and TGF-β1-exposed HK-2 cells. Furthermore, pioglitazone increased fusion proteins Opa-1 and Mfn2 expressions and decreased fission protein Drp1 expression. The results imply that pioglitazone may exert the renoprotective effects through modulating mitochondrial electron transport chain and mitochondrial dynamics in CKD. Finally, these recoveries were completely or partly inhibited by GW9662, which suggests that these effects at least partly PPARγ dependent. This study provides evidence for the pharmacological mechanism of pioglitazone in the treatment of CKD.

The purpose of this study is to assess the efficacy and safety of nocturnal hemodialysis on end-stage renal disease (ESRD) patients.We searched Medline, EmBase, and the Cochrance Central Register of Controlled Trials for studies up to January 2016. Analysis was done to compare variant outcomes of different hemodialysis schedules, including mortality, cardiovascular-associated variables, uremia-associated variables, quality of life (QOL), side-effects, and drug usage.We collected and analyzed the results of 28 studies involving 22,508 patients in our meta-analysis. The mortality results in this meta-analysis indicated that the nocturnal hemodialysis (NHD) group was not significantly different from conventional hemodialysis (CHD) group (Mortality: OR: 0.75; 95% confidence intervals (CIs): 0.52 to 1.10; p = 0.145), but the CHD group had significantly fewer number of hospitalizations than the NHD group (OR: 1.54; 95%CI: 1.32 to 1.79; p

Biomass is a crucial option of substituting fossil fuels to reduce emissions, and bioenergy with carbon capture and storage (BECCS) allows for obtaining net-negative emissions. We explore the role of biomass in China’s long-term mitigation toward the Paris climate goals in light of three narratives and five mitigation scenarios, modeling by a refined Global Change Assessment Model. While presenting a limited contribution to achieving China’s Nationally Determined Contribution (NDC), biomass plays an important role in China’s post-NDC mitigation toward the Paris climate goals. All the assessed scenarios call for extensive biomass use, accounting for 6.5%–28% of China’s 2100 primary energy in our three 2 °C scenarios and 15%–30% in our two 1.5 °C scenarios. The exact biomass deployment trajectories tend to depend greatly on how China envisages national mitigation paces and BECCS strategies. For either 2 °C or 1.5 °C, a smaller negative-emission narrative, which means a more rapid immediate decarbonization of the energy system toward mid-century, depends on larger bioenergy in medium-to-long-term. Delaying short- and medium-term ambition delays bioenergy applications but requires far more in the second half of the century to create greater negative emissions via BECCS. Moving from 2 °C toward 1.5 °C features higher and earlier bioenergy deployments and meaningfully increasing BECCS volumes and biofuel shares in China’s energy system. Consequently, the Chinese stockholders might be ready to make a decision on to what degree biomass and BECCS enter the sphere of China’s energy and climate policies, which will greatly influence not only national biomass roadmap but also mid-century mitigation targets.

Catalases are ubiquitous hydrogen peroxide-detoxifying enzymes. They participate in fungal growth and development, such as mycelial growth and cellular differentiation, and in protecting fungi from oxidative damage under stressful conditions. To investigate the potential functions of catalases in Pleurotus ostreatus, we obtained two catalase genes from a draft genome sequence of P. ostreatus, and cloned and characterized them (Po-cat1 and Po-cat2). Po-cat1 (group II) and Po-cat2 (group III) encoded putative peptides of 745 and 528 amino acids, respectively. Furthermore, the gene structures were variant between Po-cat1 and Po-cat2. Further research revealed that these two catalase genes have divergent expression patterns during different developmental stages. Po-cat1/Po-cat1 was at a barely detectable level in mycelia, accumulated gradually during reproductive growth, and was maximal in separated spores. But no catalase activity of Po-cat1 was detected by native-PAGE during any part of the developmental stages. In contrast, high Po-cat2/Po-cat2 expression and Po-cat2 activity found in mycelia were gradually lost during reproductive growth, and at a minimal level in separated spores. In addition, these two genes responded differentially under 32 °C and 40 °C heat stresses. Po-cat1 was up-regulated under both temperature conditions, while Po-cat2 was up-regulated at 32 °C but down-regulated at 40 °C. The accumulation of catalase proteins correlated with gene expression. These results indicate that the two divergent catalases in P. ostreatus may play different roles during development and under heat stress.

To investigate the effect of ursolic acid on autophagy mediated through the miRNA-21-targeted phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in rat mesangial cells cultured under high glucose (HG) conditions.Rat glomerular mesangial cells were cultured under normal glucose, HG, HG with the PI3K inhibitor LY294002 or HG with ursolic acid conditions. Cell proliferation and hypertrophy were assayed using an MTT assay and the ratio of total protein to cell number, respectively. The miRNA-21 expression was detected using RT-qPCR. The expression of phosphatase and tensin homolog (PTEN)/AKT/mTOR signaling signatures, autophagy-associated protein and collagen I was detected by western blotting and RT-qPCR. Autophagosomes were observed using electron microscopy.Compared with mesangial cells cultured under normal glucose conditions, the cells exposed to HG showed up-regulated miRNA-21 expression, down-regulated PTEN protein and mRNA expression, up-regulated p85PI3K, pAkt, pmTOR, p62/SQSTMI, and collagen I expression and down-regulated LC3II expression. Ursolic acid and LY294002 inhibited HG-induced mesangial cell hypertrophy and proliferation, down-regulated p85PI3K, pAkt, pmTOR, p62/SQSTMI, and collagen I expression and up-regulated LC3II expression. However, LY294002 did not affect the expression of miRNA-21 and PTEN. Ursolic acid down-regulated miRNA-21 expression and up-regulated PTEN protein and mRNA expression.Ursolic acid inhibits the glucose-induced up-regulation of mesangial cell miRNA-21 expression, up-regulates PTEN expression, inhibits the activation of PI3K/Akt/mTOR signaling pathway, and enhances autophagy to reduce the accumulation of the extracellular matrix and ameliorate cell hypertrophy and proliferation.

Given that integrin β1 is an important component of the connection to maintain glomerular structural integrity, by binding with multiple extracellular matrix proteins and mediating intracellular signaling. Focal adhesion kinase (FAK) is the most essential intracellular integrator in the integrin β1-FAK signalling pathway. Here, we investigated the changes of the two molecules and visualized the possible interaction between them under various hemodynamic conditions in podocytes. Mice kidney tissues were prepared using in vivo cryotechnique (IVCT) and then were stained and observed using light microscopy, confocal laser scanning microscopy and immunoelectron microscopy. The expression of these molecules were examined by western blot. Under the normal condition, integrin β1 stained continually and evenly at the membrane, and FAK was located in the cytoplasm and nuclei of the podocytes. There were significant colocalized plaques of two molecules. But under acute hypertensive and cardiac arrest conditions, integrin β1 decreased and stained intermittently. Similarly, FAK decreased and appeared uneven. Additionally, FAK translocated to the nuclei of the podocytes. As a result, the colocalization of integrin β1 and FAK reduced obviously under these conditions. Western blot assay showed a consistent result with the immunostaining. Collectively, the abnormal redistribution and decreased expressions of integrin β1 and FAK are important molecular events in regulating the functions of podocytes under abnormal hemodynamic conditions. IVCT could offer considerable advantages for morphological analysis when researching renal diseases.