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Abstract Background The health effects of different weight loss strategies vary greatly, and the relationship between weight loss strategies, especially the combination of multiple strategies, and death is still unclear. We aimed to examine the associations of various numbers and combinations of weight loss strategies with all-cause and specific-cause mortality and to further evaluate the associations of different total weight loss volumes with mortality. Methods Using data from NHANES (1999–2018) with 48,430 participants aged 20 and above, we collected fourteen self-reported weight loss strategies and identified five clusters using latent class analysis. Cox proportional hazards models were used to examine the association between the amounts and clusters of weight loss strategies and mortality. Results During a median follow-up of 9.1 years of 48,430 participants, 7,539 deaths were recorded (including 1,941 CVDs and 1,714 cancer). Participants who adopted 2, 3–4, and ≥ 5 weight loss strategies had a lower risk of all-cause mortality, with HRs of 0.88 (95% CI, 0.81 to 0.97), 0.89 (95% CI, 0.81 to 0.96) and 0.71 (95% CI, 0.61 to 0.82). Regardless of weight loss or weight gain categories, there was a significant trend toward reduced mortality as the number of weight loss strategies increased (P trend

Abstract Megalurothrips usitatus (Bagnall) (Thysanoptera: Thripidae) is an important pest in Vigna unguiculata (L.) Walp. Neoseiulus barkeri (Hughes) (Acari: Phytoseiidae) is widely used for control of pest mites and insects worldwide. We evaluated its effect on M. usitatus when predators (N. barkeri) or insecticides (Spinetoram) were applied in the fields. Neoseiulus barkeri Hughes consumed 80% of M. usitatus prey offered within 6 h, and predation showed Type III functional response with prey density. The maximum consumption of N. barkeri was 27.29 ± 1.02 individuals per d per arena (1.5 cm diameter), while the optimal prey density for the predatory mite was 10.35 ± 0.68 individuals per d per arena (1.5 cm diameter). The developmental duration of N. barkeri fed with M. usitatus was significantly shorter than those fed with the dried fruit mite, Carpoglyphus lactis (L.) (Acari: Astigmata). In field trials, the efficiency of N. barkeri against M. usitatus was not significantly different from that of applications of the insecticide spinetoram. Biodiversity of other insects in treated fields was assessed, and there were 21 insect species in garden plots treated with N. barkeri releases. The total abundance (N), Shannon’s diversity index (H), Pielou’s evenness index (J) and Simpson’s diversity index (D) of the garden plots treated with predatory mites were all significantly higher than that in the garden plots treated with spinetoram, where we found no species of predators or parasitoids and 7 herbivores. Our results show that N. barkeri is a potential means to control M. usitatus while preserving arthropod diversity at the level of treated gardens.

Abstract Lacking effective therapeutic targets heavily restricts the improvement of clinical prognosis for patients diagnosed with esophageal squamous cell carcinoma (ESCC). Ubiquitin Specific Peptidase 21 (USP21) is dysregulated in plenty of human cancers, however, its potential function and relevant molecular mechanisms in ESCC malignant progression as well as its value in clinical translation remain largely unknown. Here, in vitro and in vivo experiments revealed that aberrant upregulation of USP21 accelerated the proliferation and metastasis of ESCC in a deubiquitinase-dependent manner. Mechanistically, we found that USP21 binds to, deubiquitinates, and stabilizes the G3BP Stress Granule Assembly Factor 1 (G3BP1) protein, which is required for USP21-mediated ESCC progression. Further molecular studies demonstrated that the USP21/G3BP1 axis played a tumor-promoting role in ESCC progression by activating the Wnt/β-Catenin signaling pathway. Additionally, disulfiram (DSF), an inhibitor against USP21 deubiquitylation activity, markedly abolished the USP21-mediated stability of G3BP1 protein and significantly displayed an anti-tumor effect on USP21-driving ESCC progression. Finally, the regulatory axis of USP21/G3BP1 was demonstrated to be aberrantly activated in ESCC tumor tissues and closely associated with advanced clinical stages and unfavorable prognoses, which provides a promising therapeutic strategy targeting USP21/G3BP1 axis for ESCC patients.

Introduction: Although inguinal hernia (IH) is prevalent in elderly males, research on its specific diagnostic biomarkers is limited. Protein N-glycosylation is one of the most important and ubiquitous post-translational modifications and often results in a remarkable heterogeneity of protein glycoforms. Protein N-glycosylation often changes in a disease and holds great potential for discovering non-invasive biomarkers. This study aimed to gain insights into total serum protein N-glycosylation of IH to identify candidate non-invasive biomarkers for diagnosis and subtype classification of IH. Methods: Linkage-specific sialylation derivatization combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry detection was used to analyze serum protein N-glycosylation patterns in IH patients and healthy controls. Results: IH patients had abnormal glycan fucosylation and sialylation compared to healthy controls (HC), of which two glycan traits representing linkage-specific sialylation within monoantennary glycans showed high potential as diagnostic biomarkers for IH with an area under the curve (AUC) of 0.75. Additionally, serum N-glycans were different between indirect IH and direct IH in glycosylation features, namely complexity, fucosylation, galactosylation, sialylation, and α2,6‐linked sialylation. Four distinctive glycans between the two subtypes showed good performance with AUC >0.8, suggesting that these glycan traits have potential as biomarkers for subtype classification. Conclusions: We first reported the serum N-glycomic features of IH patients. Furthermore, we identified several potential biomarkers for the diagnosis and subtype classification of IH. These findings can deepen the understanding of IH.

Recent advances in artificial intelligence (AI) have sparked a surge in the application of computer vision (CV) in surgical video analysis. Laparoscopic surgery produces a large number of surgical videos, which provides a new opportunity for improving of CV technology in laparoscopic surgery. AI-based CV techniques may leverage these surgical video data to develop real-time automated decision support tools and surgeon training systems, which shows a new direction in dealing with the shortcomings of laparoscopic surgery. The effectiveness of CV applications in surgical procedures is still under early evaluation, so it is necessary to discuss challenges and obstacles. The review introduced the commonly used deep learning algorithms in CV and described their usage in detail in four application scenes, including phase recognition, anatomy detection, instrument detection and action recognition in laparoscopic surgery. The currently described applications of CV in laparoscopic surgery are limited. Most of the current research focuses on the identification of workflow and anatomical structure, while the identification of instruments and surgical actions is still awaiting further breakthroughs. Future research on the use of CV in laparoscopic surgery should focus on applications in more scenarios, such as surgeon skill assessment and the development of more efficient models.

The internal flow of a pump turbine is unstable in part-load pump mode for small guide-vane openings, and the strong vibration caused by pressure pulsation is related to the safe and stable operation of the unit. A pump turbine with a six-splitter-blade runner was chosen for unsteady simulation analyses. A standard k-epsilon turbulence model was adopted to study the unsteady flow and pressure pulsation in part-load pump mode. The predicted results show that the flow in the draft tube and the runner with splitter blades was relatively stable and the flow of the blade-to-blade channel was symmetrical. When the inlet and outlet velocity distribution of the vanes was not uniform, a vortex began to form in the stay-vane domain. The reason for this vortex formation is explained, and it is pointed out that the existence of the vortex and backflow leads to uneven velocity distribution. The unsteady calculation results showed that the pressure-pulsation peak-to-peak amplitudes in the vaneless area and guide vanes were much higher than those of other monitor points because of rotor–stator interference between the rotating runner and the vanes. In addition, the pulsation characteristics of the monitor points at different circumferential positions in the vaneless region were quite different. In the vaneless area, the velocity gradient along the circumferential direction was very large, and there was a phenomenon of backflow. Also, the pressure pulsation was 0.2 times that of the runner rotational frequency, and the blade-passing frequency was a third-order frequency. At the outlet of the guide vane, the pressure pulsation was mainly of a low frequency with a complex vortex flow. Finally, the pressure pulsation began to decrease rapidly in the stay-vane region.

Abstract The most common kind of acute leukemia in adults is acute myeloid leukemia (AML), which is often treated with induction chemotherapy regimens followed by consolidation or allogeneic hematopoietic stem cell transplantation (HSCT). However, some patients continue to develop relapsed or refractory AML (R/R-AML). Small molecular targeted drugs require long-time administration. Not all the patients hold molecular targets. Novel medicines are therefore needed to enhance treatment outcomes. T cells and natural killer (NK) cells engineered with chimeric antigen receptors (CARs) that target antigens associated with AML have recently been produced and are currently being tested in both pre-clinical and clinical settings. This review provides an overview of CAR-T/NK treatments for AML.

With the great advantages and continuous innovations, prolific research efforts have been devoted to the Stirling engine (SE) domain driven by the sustainability development. In this study, a bibliometric analysis is conducted to explore the research tend and hotspots of SE. The country co-authorship, institute co-authorship and keyword networks are engendered from the visual map using VOSviewer, showing China ranks the first with the total number of published articles and the majority publications are presented by Chinese Academy of Sciences. Owing to the highest node centrality, the research findings in USA can be considered the most influential and greatly worthy being referred, particularly represented by the early contribution for thermo-acoustic SE. The total 7 keyword clusters are classified through the top terms in Citespace and 4 of them are related to its energy supply system, demonstrating the typical application of SE-based combined heat and power (CHP) and integrated multi-energy complementary system have gained much attention. Based on this, a detailed review of SE-based energy supply systems is further conducted through the system forms, 4E performance evaluation and soft model combing optimization solutions. Several relevant issues hindering the improvement of these terms are summarized, providing the potential guides to help develop the SE-based energy supply system.

The sediment erosion of Pelton turbine components is a major challenge in the operation and development of high-head water resources, especially in mountainous areas with high sediment yield. In this paper, a study using numerical simulation was conducted with different sediment particle sizes in the fine sand range. And the erosion mechanism of the Pelton turbine injector was analyzed. The Eulerian Lagrange method was adopted to simulate the gas–liquid–solid flow. The Mansouri’s model was applied to estimate the injector erosion. The predicted erosion results were in accord with field erosion photographs. In particular, the asymmetrical erosion distribution on the needle surface was physically reproduced. With the sediment particle size increasing from 0.05 mm, the needle erosion rate decreased, while the nozzle casing erosion rate increased dramatically. In order to clarify this tendency, the characteristics of the three-phase flow were analyzed. Interestingly, the results show that with the rise in particle size, the separation of particles and water streamlines became more serious in the contraction section of the nozzle mouth. Consequently, it caused the enhancement of erosion of the nozzle surfaces and weakened the erosion of the needle surfaces. Significant engineering insights may be provided for weakening Pelton injector erosion with needle guides in the current study.

Abstract Background ABO blood group incompatibility, neonatal sepsis, G-6-PD deficiency, thyroid dysfunction, and hereditary spherocytosis are all probable causes of neonatal hyperbilirubinemia. However, the etiology of some hyperbilirubinemia is extremely complicated, which may be caused by multiple factors, resulting in severe jaundice. We report a case of severe jaundice due to three causes, showing the significance for the investigation of the etiology of neonatal hyperbilirubinemia. Case presentation At 96 h of life, a full-term and vaginal delivery male infant with yellowish discoloration of body was transferred to our hospital. When he entered neonatal intensive care unit on the fourth day after birth, he developed jaundice and the transcutaneous bilirubin was 28 mg/dl. Total bilirubin was 540.2 μmol/L, while the indirect bilirubin was 516.7 μmol/L. Both parents and the baby’s blood types were O Rh(D +), and direct coomb’s test was negative. But mother’s indirect coomb’s test was positive. Investigating for minor blood group revealed that the father’s blood type of Rh was CCDee, the mather’s was ccDEE, and CcDEe for the baby. After intensive phototherapy and double volume exchange transfusion, the total bilirubin remained at 303 μmol/L. At day 10, the bilirubin level was 303.5 μmol/L, intensive phototherapy was continued, and intravenous immunoglobulin was used again. The test for thyroid hormones at day 10, the TSH was 13.334mIU/L. And the screening for congenital hypothyroidism showed the TSH was 33mIU/L. Because of the palpable abdominal mass, ultrasound and MRI was done, showed a huge mass in the right adrenal gland. Brainstem auditory evoked potential was performed at day 7, which indicated hearing impairment (65db for left ear and 70db for the right). Euthyrox and intermittent phototherapy were given as following treatment. The jaundice did not subside until the 12th day. Conclusion Even if their parents' ABO blood group and Rh (d) are consistent, a Coomb test is required for newborns with hyperbilirubinemia since they may have minor blood group incompatibilities. When bilirubin rises rapidly or the clinical treatment effect is inadequate, additional causes should be aggressively screened. Adrenal ultrasound should be performed on newborns with palpable abdominal mass, anemia and jaundice to determine whether there is adrenal hemorrhage.

BackgroundRectal cancer has a high risk of recurrence and metastasis, with median survival ranging from 24 months to 36 months. K-RAS mutation is a predictor of poor prognosis in rectal cancer. Advanced rectal cancer can be stopped in its tracks by pelvic exenteration.Case summaryA 51-year-old woman was diagnosed with advanced rectal cancer (pT4bN2aM1b, stage IV) with the KRAS G12D mutation due to a change in bowel habits. The patient had experienced repeated recurrences of rectal cancer after initial radical resection, and the tumor had invaded the ovaries, sacrum, bladder, vagina and anus. Since the onset of the disease, the patient had undergone a total of seven surgeries and long-term FOLFIRI- or XELOX-based chemotherapy regimens, with the targeted agents bevacizumab and regorafenib. Fortunately, the patient was able to achieve intraoperative R0 resection in almost all surgical procedures and achieve tumor-free survival after pelvic exenteration. The patient has been alive for 86 months since her diagnosis.ConclusionsPatients with advanced rectal cancer can achieve long-term survival through active multidisciplinary management and R0 surgery.

BackgroundLeft subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method.MethodsIn this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients.ResultsThe treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P

A 10-year-old girl presented with obvious cyanosis, and the saturation of arterial blood oxygen (SpO2) was decreased to 60.5% in the outpatient examination. Computed tomography angiography (CTA) and echocardiography suggested congenitally corrected transposition of the great arteries (ccTGAs), membranous ventricular septal aneurysm (MVSA), atrial septal defect (ASD), severe pulmonary stenosis (PS), and severe tricuspid regurgitation (TR). Due to the complex pathological anatomical structures, the three-dimensional printed model was used for preoperative assessment. After a comprehensive evaluation was completed, the operation was performed by physiological correction under cardiopulmonary bypass, including the resection of MVSA, repair using the bovine pericardial patch for ASD, and linear valvuloplasty of the tricuspid valve. Due to the special anatomical structures of ccTGA, PS was treated by extracardiac pipe technique. After the operation, the patient recovered well, cyanosis disappeared, SpO2 was up to 96%, and the extracardiac pipe was well-functioning without regurgitation or obstruction.

Bacteriophages, which are viruses infecting bacteria, are the most ubiquitous and diverse entities in the biosphere. There is accumulating evidence revealing their important roles in shaping the structure of various microbiomes. Thanks to (viral) metagenomic sequencing, a large number of new bacteriophages have been discovered. However, lacking a standard and automatic virus classification pipeline, the taxonomic characterization of new viruses seriously lag behind the sequencing efforts. In particular, according to the latest version of ICTV, several large phage families in the previous classification system are removed. Therefore, a comprehensive review and comparison of taxonomic classification tools under the new standard are needed to establish the state-of-the-art. In this work, we retrained and tested four recently published tools on newly labeled databases. We demonstrated their utilities and tested them on multiple datasets, including the RefSeq, short contigs, simulated metagenomic datasets, and low-similarity datasets. This study provides a comprehensive review of phage family classification in different scenarios and a practical guidance for choosing appropriate taxonomic classification pipelines. To our best knowledge, this is the first review conducted under the new ICTV classification framework. The results show that the new family classification framework overall leads to better conserved groups and thus makes family-level classification more feasible.

BackgroundLumbar intervertebral disc degeneration (IVDD) is an important cause of low back pain or sciatica, and metabolic factors play an important role. However, little is known about the relationship of dyslipidemia to the risk of intervertebral disc degeneration (IVDD). This study aimed to assess the impact of serum lipid levels on the severity of lumbar disc degeneration and to investigate its association with endplate inflammation.MethodsWe conducted a case retrospective study in which a total of 302 hospitalized Chinese patients were recruited, of whom 188 (112 males and 76 females; mean age: 51.66 years) were without underlying disease, while the remaining 114 patients (51 males and 63 females; mean age: 62.75 years) had underlying diseases. We examined fasting serum lipid levels for total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Magnetic resonance imaging (MRI) was used to determine endplate inflammation. Pfirrmann grading and Weishaupt grading were used to evaluate the severity of intervertebral disc degeneration and facet joint degeneration, respectively.ResultsThere was no difference in age, gender, and general BMI between the two groups (P > 0.05), but there were significantly high levels in TC, LDL-C, and LDL-C/HDL-C (P = 0.04, P = 0.013, P = 0.01, respectively). TG and HDL-C showed no significant difference (P = 0.064, P = 0.336, respectively). The multivariate logistic regression model showed that age was a risk factor for the occurrence of endplate inflammation. In the group without underlying diseases, age, but not other indicators, was a risk factor for the occurrence of endplate inflammation (P < 0.01), In the group with underlying diseases, none of the patient indicators was directly related to the occurrence of endplate inflammation (P > 0.05). A nonlinear machine learning model was used to measure the contribution of each factor to the disease outcome and to analyze the effect between the top three contributing factors and the outcome variables. In patients without underlying diseases, the top three factors contributing to the severity grading of intervertebral disc degeneration were age (32.9%), high-density lipoproteins (20.7%), and triglycerides (11.8%). For the severity grading of facet joint degeneration, the top three contributing factors were age (27.7%), high-density lipoproteins (19.4%), and triglycerides (14.6%). For patients with underlying diseases, the top three factors contributing to intervertebral disc degeneration were age (25.4%), BMI (15.3%), and low-density lipoprotein/high-density lipoprotein ratio (13.9%). In terms of degree classification for facet joint degeneration, the top three contributing factors were age (17.5%), BMI (17.2%), and total cholesterol (16.7%).ConclusionThis study shows that age, high-density lipoprotein, and triglycerides affect the degree of degeneration in patients with symptomatic lumbar degeneration without underlying diseases. Age and BMI are two major factors affecting the severity of degeneration in patients with underlying diseases, and dyslipidemia is a secondary factor. However, there is no clear association between dyslipidemia and the occurrence of endplate inflammation in either group.

BackgroundAarskog–Scott syndrome, a rare X-linked genetic disorder, is identified by combined clinical manifestations of short stature, facial, skeletal, and genital anomalies. Annually, two or three new cases are diagnosed with Aarskog–Scott syndrome, which is associated with FGD1 variants. However, there is no specific treatment for Aarskog–Scott syndrome due to its unclear mechanism.MethodsClinical data were collected when the patient first visited the hospital. Trio whole-exome sequencing and Sanger sequencing were performed for the genetic cause of disease. To evaluate the pathogenicity of the variants in vitro, stable cell lines were constructed using lentivirus infection in 143B cell. Furthermore, Western blot was used to verify the expression of signaling pathway-related proteins, and the transcription levels of osteogenic-related genes were verified by luciferase reporter gene assay.ResultsA 7-year-old boy was manifested with facial abnormalities, intellectual disability, and short stature (−3.98 SDS) while the growth hormone level of stimulation test was normal. Trio whole-exome sequencing and Sanger sequencing identified a variant (c.1270A>G, p.Asn424Asp) in FGD1 gene. The Asn424 residue was highly conserved and the hydrogen bond in the FGD1 variant protein has changed, which led to decrease in the interaction with CDC42 protein. In vitro study showed that the Asn424Asp variant significantly decreased the transcription levels of OCN, COL1A1, and ALP activity, and it activated the phosphorylation of JNK1.ConclusionMolecular biological mechanisms between abnormal expression of FGD1and Aarskog–Scott syndrome remain poorly understood. In our study, c.1270A>G variant of FGD1 resulted in Aarskog–Scott syndrome, and the analysis of pathogenicity supports the deleterious effect of the variant. Furthermore, we demonstrated the weakened affinity of the mutant FGD1 and CDC42. Decreased expression of osteogenic-related gene and abnormal activation of JNK1 were also shown in this work.

With the strong advancement of the global carbon reduction strategy and the rapid development of renewable energy, compressed air energy storage (CAES) technology has received more and more attention for its key role in large-scale renewable energy access. This paper summarizes the coupling systems of CAES and wind, solar, and biomass energies from the perspective of system topology, and points out the advantages and limitations of each system. It is shown that the coupling of wind energy and CAES is mainly combined in series and in parallel, and sometimes part of the wind power can be converted into thermal energy when coupled to CAES. The coupling between solar heat and CAES is an important form of coupling between solar energy and CAES. Solar-heat-coupled CAES mainly uses solar energy to heat expander inlet air. The coupling forms of solar energy and CAES are based on various CAES forms, various heat heating sequences, reheating, bottom cycle, and other factors. The combination of biomass and CAES is generally based on biomass gasification power generation technology. In the future, a wind–solar–CAES multiple coupling system is expected to become a promising large-scale form for the utilization of renewable energy, and this integrated system has great potential as a system configuration, but has some technical challenges.

Land cover mapping plays a pivotal role in global resource monitoring, sustainable development research, and effective management. However, the complexity of the mapping process, coupled with significant computational and data storage requirements, often leads to delays between data processing and product publication, thereby bringing challenges to creating multi-timesteps large-area products for monitoring dynamic land cover. Therefore, improving the efficiency of each stage in land cover mapping and automating the mapping process is currently an urgent issue to be addressed. This study proposes a high-performance automated large-area land cover mapping framework (HALF). By leveraging Docker and workflow technologies, the HALF effectively tackles model heterogeneity in complex land cover mapping processes, thereby simplifying model deployment and achieving a high degree of decoupling between production models. It optimizes key processes by incorporating high-performance computing techniques. To validate these methods, this study utilized Landsat imagery data and extracted samples using GLC_FCS and FROM_GLC, all of which were acquired at a spatial resolution of 30 m. Several 10° × 10° regions were chosen globally to illustrate the viability of generating large-area land cover using the HALF. In the sample collection phase, the HALF introduced an automated method for generating samples, which overlayed multiple prior products to generate a substantial number of samples, thus saving valuable manpower resources. Additionally, the HALF utilized high-performance computing technology to enhance the efficiency of the sample–image matching phase, thereby achieving a speed that was ten times faster than traditional matching methods. In the mapping stage, the HALF employed adaptive classification models to train the data in each region separately. Moreover, to address the challenge of handling a large number of classification results in a large area, the HALF utilized a parallel mosaicking method for classification results based on the concept of grid division, and the average processing time for a single image was approximately 6.5 s.

Abstract Background Preperitoneal herniation is a rare complication after transabdominal preperitoneal patch plasty (TAPP) and may be caused by inadequate peritoneal closure. We herein report two cases of postoperative small bowel obstruction due to preperitoneal herniation through a disrupted peritoneum. Case presentation Two men in their 70s were admitted to our center because of small bowel obstruction after TAPP. After examinations and unsuccessful conservative treatment, emergency laparoscopic exploration was performed. Preperitoneal herniation through the disrupted peritoneum was found. The herniated small bowel was reduced and the peritoneum was properly reclosed. The patients recovered and were discharged with normal bowel function. Conclusions Inadequate peritoneal closure may cause preperitoneal herniation and lead to postoperative small bowel obstruction and even death. Hernia surgeons can avoid this complication by improving their suture technique and paying attention to the procedure details.

Estimating crop yield in large areas is essential for ensuring food security and sustainable development. Accounting for variations in the temporal cumulative growth of crops across regions (i.e., spatial heterogeneity of crop growth) can improve the accuracy of yield estimation in large areas. However, current spatial heterogeneity learning methods have limitations such as cutting off inherent correlations among regions, difficulty obtaining accurate prior knowledge, and high subjectivity. Therefore, this study proposed a novel deep learning adaptive crop model (DACM) to accomplish adaptive high-precision yield estimation in large areas, which emphasizes adaptive learning of the spatial heterogeneity of crop growth based on fully extracting crop growth information. Results showed that the DACM achieved an average root mean squared error (RMSE) of 4.406 bushels·acre−1 (296.304 kg ha−1), with an average coefficient of determination (R2) of 0.805. Compared with other state-of-the-art machine learning and deep learning methods, DACM improves the large-area yield estimation accuracy and performs more robustly in space. The analyses on attention values and estimation stability demonstrate that DACM can learn the spatial heterogeneity of crop growth and adopt adaptive strategies to optimize yield estimation. Considering both performance stability and interpretability, DACM provides a practical approach for estimating large-area crop yields by adaptively learning the spatial heterogeneity patterns of crop growth.

At present, the theory and application of fractional-order neural networks remain in the exploratory stage. We study the asymptotic stability of fractional-order neural networks with Riemann-Liouville (R-L) derivatives. For non-delayed and delayed systems, we propose an asymptotic stability criterion based on the combination of the Lyapunov method and linear matrix inequality (LMI) method. The highlights include the following: (1) for fractional-order neural networks with time delay, the existence and uniqueness of solutions are proven by using matrix analysis theory and contraction mapping theorem, and (2) based on the unique solution, a suitable Lyapunov functional is constructed. Based on the inequality theorem and LMI method, two sets of asymptotic stability criteria for fractional-order neural networks are proven, which avoids the difficulty of solving the fractional derivative by the Leibniz law. Finally, the results are verified using numerical simulations.

Spatial downscaling is an important approach to obtain high-resolution land surface temperature (LST) for thermal environment research. However, existing downscaling methods are unable to sufficiently address both spatial heterogeneity and complex nonlinearity, especially in high-resolution scenes (2 of 0.974 and minimum RMSE of 0.896 °C) compared to widely used methods in four test areas with large differences in topography, landforms, and seasons. We also achieved the best extracted and most detailed spatial textures. Our findings suggest that GNNWR is a practical method for surface temperature downscaling considering its high accuracy and model performance.

Objective: To assess the clinical value of the laparoscopic transabdominal preperitoneal (TAPP) technique in recurrent inguinal hernia repair. Methods: The clinical data of 354 patients with recurrent inguinal hernia who underwent TAPP surgery from June 2010 to June 2016 at the Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University, were retrospectively analyzed. Results: Laparoscopic surgery was successfully completed in all 360 patients. Among them TAPP were finished in 354 patients, while TAPP repair were attempted but finally converted to open or TAPE repair in 6 patients. The mean operation time was 54.7 ± 19.4 min (range 30–90 min), mean duration of hospitalization was 4.7 ± 2.1 days (range 2–14 days), and mean duration of follow-up was 37.7 ± 12.4 months (range 12–60 months). The rate of intraoperative injury was 4.5% (16/354), and the rate of postoperative complications was 13.6% (48/354). No patient developed a foreign body sensation, wound infection, intestinal obstruction, mesh infection, or chronic pain. Two patients (0.6%) developed re-recurrence requiring reoperation, with no further recurrence. Conclusion: When performed by an experienced surgeon with excellent technique, the TAPP technique is safe and effective for recurrent hernia after surgical treatment via the anterior repair, and maybe a good alternative for recurrent hernia after surgical treatment via the posterior repair.

Background: 46,XY disorders/differences of sex development (46,XY DSD) are congenital conditions that result from abnormal gonadal development (gonadal dysgenesis) or abnormalities in androgen synthesis or action. During early embryonic development, several genes are involved in regulating the initiation and maintenance of testicular or ovarian-specific pathways. Recent reports have shown that MAP3K1 genes mediate the development of the 46,XY DSD, which present as complete or partial gonadal dysgenesis. Previous functional studies have demonstrated that some MAP3K1 variants result in the gain of protein function. However, data on possible mechanisms of MAP3K1 genes in modulating protein functions remain scant.Methods: This study identified a Han Chinese family with the 46,XY DSD. To assess the history and clinical manifestations for the 46,XY DSD patients, the physical, operational, ultra-sonographical, pathological, and other examinations were performed for family members. Variant analysis was conducted using both trio whole-exome sequencing (trio WES) and Sanger sequencing. On the other hand, we generated transiently transfected testicular teratoma cells (NT2/D1) and ovary-derived granular cells (KGN), with mutant or wild-type MAP3K1 gene. We then performed functional assays such as determination of steady-state levels of gender related factors, protein interaction and luciferase assay system.Results: Two affected siblings were diagnosed with 46,XY DSD. Our analysis showed a missense c.556A > G/p.R186G variant in the MAP3K1 gene. Functional assays demonstrated that the MAP3K1R186G variant was associated with significantly decreased affinity to ubiquitin (Ub; 43–49%) and increased affinity to RhoA, which was 3.19 ± 0.18 fold, compared to MAP3K1. The MAP3K1R186G led to hyperphosphorylation of p38 and GSK3β, and promoted hyperactivation of the Wnt4/β-catenin signaling. In addition, there was increased recruitment of β-catenin into the nucleus, which enhanced the expression of pro-ovarian transcription factor FOXL2 gene, thus contributing to the 46,XY DSD.Conclusion: Our study identified a missense MAP3K1 variant associated with 46,XY DSD. We demonstrated that MAP3K1R186G variant enhances binding to the RhoA and improves its own stability, resulting in the activation of the Wnt4/β-catenin/FOXL2 pathway. Taken together, these findings provide novel insights into the molecular mechanisms of 46,XY DSD and promotes better clinical evaluation.

Abstract Background Peritoneal fibrosis (PF) is a frequent complication caused by peritoneal dialysis (PD). Peritoneal mesothelial cells (PMCs), the first barrier of the peritoneum, play an important role in maintaining structure and function in the peritoneum during PD. Mesothelial-mesenchymal transition (MMT) and oxidative stress of PMCs are two key processes of PF. Purpose To elucidate the efficacy and possible mechanism of asiaticoside inhibition of MMT and ROS generation in TGF-β1-induced PF in human peritoneal mesothelial cells (HPMCs). Methods MMT and ROS generation of HPMCs were induced by TGF-β1. To explain the anti-MMT and antioxidant role of asiaticoside, varied doses of asiaticoside, oxygen radical scavenger (NAC), TGF-β receptor kinase inhibitor (LY2109761) and Nrf2 inhibitor (ML385) were used separately. Immunoblots were used to detect the expression of signaling associated proteins. DCFH-DA was used to detect the generation of ROS. Transwell migration assay and wound healing assay were used to verify the capacity of asiaticoside to inhibit MMT. Immunofluorescence assay was performed to observe the subcellular translocation of Nrf2 and expression of HO-1. Results Asiaticoside inhibited TGF-β1-induced MMT and suppressed Smad signaling in a dose-dependent manner. Migration and invasion activities of HPMCs were decreased by asiaticoside. Asiaticoside decreased TGF-β1-induced ROS, especially in a high dose (150 μM) for 6 h. Furthermore, ML385 partly abolished the inhibitory effect of asiaticoside on MMT, ROS and p-Smad2/3. Conclusions Asiaticoside inhibited the TGF-β1-induced MMT and ROS via Nrf2 activation, thus protecting the peritoneal membrane and preventing PF.

Objective: The objective of this study was to assess the efficacy and safety of denosumab therapy in osteoporotic postmenopausal women who were previously treated with bisphosphonates. Methods: Meta-analyses of four available randomised controlled trials that compared osteoporotic patients who switched to denosumab from bisphosphonates (n ​= ​1416) and those who continued bisphosphonates therapy (n ​= ​1411) were included. Results: The increase in bone mineral density (BMD) of both the spine and hip was significantly higher in patients who shifted to denosumab than in those who continued bisphosphonates. Despite the incidence of adverse events (AEs) and fractures being comparable, treatment withdrawal owing to AEs was significantly less frequent in the denosumab group. Conclusion: The outcomes and treatment compliance were improved in postmenopausal osteoporotic women who shifted to denosumab from bisphosphonates. The translational potential of this article: The replacement of bisphosphonates with denosumab may lead to better therapeutic efficacy and fewer adherence barriers ​than those with continued usage of bisphosphonates, which in the future may guide the choice of drug therapy in clinics.

BackgroundKidney involvement is common in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It tends to be aggressive, and in some patients, the kidney involvement may reach the criteria of acute kidney injury (AKI). Here, we aim to describe the clinical characteristics of these patients and find risk factors for poor outcomes.MethodsPatients diagnosed with AAV in our hospital from February 2003 to February 2017 were included. Those who reached the KDIGO AKI criteria were reclassified according to the KDIGO AKI stage. The clinical features of these patients were analyzed. Also, according to the variation of serum creatinine 3 months after AKI episode, patients were further divided into two groups: patients whose serum creatinine (Scr) level at the third month decreased by 30% or more from the peak Scr level was classified into G1 and others were classified into G2. Long-term renal and survival outcomes of these patients were analyzed with a Cox model. The renal endpoint was reaching end-stage renal disease (ESRD), and the survival endpoint was death. Nomograms were built based on cox models.ResultsOf 141 AAV patients included, during the median follow-up period of 64.0 (IQR 34.8, 85.4) months, 36 (25.5%) patients reached renal endpoints, and 22 (15.6%) patients died. The median renal survival time was 35.9 (IQR 21.3, 72.6) months and the median survival time was 48.4 (IQR 26.8, 82.8) months. Multivariate analysis showed that poor recovery of Scr level at 90 days (P < 0.001, RR = 9.150, 95%CI 4.163–20.113), BVAS score (P = 0.014, RR = 1.110, 95% CI1.021–1.207), and AKI stage 3 (P = 0.012 RR = 3.116, 95%CI 1.278–7.598) were independent risk factors for renal endpoints; poor recovery of Scr level at 90 days (P = 0.010, RR = 3.264, 95%CI 1.326–8.035), BVAS score (P = 0.010, RR = 1.171, 95%CI 1.038–1.320) and age (P = 0.017, RR = 1.046, 95%CI 1.008–1.086) were independent risk factors for all-cause death. The c-index of nomograms is 0.830 for the renal outcome and 0.763 for the survival outcome.ConclusionKDIGO AKI stage 3 is the risk factor for ESRD in AAV patients with AKI. The BVAS score and level of kidney function recovery at 90 days are the independent risk factors for both ESRD and all-cause death and are of predictive value for the outcome.

Background/Aims: The epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a crucial event in the induction of peritoneal fibrosis (PF), in which canonical Wnt/β-catenin signaling participates. Smads signaling is reported to interact with β-catenin and synergistically regulates EMT. This study was aimed to reveal the effect of Astragalus on β-catenin in EMT of PMCs. Methods: To obtain the role of β-catenin in EMT, gene transfer into HMrSV5 cell line and rats has been achieved. After Astragalus treatment, EMT markers and signaling pathway-related indicators were detected by western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and real time-PCR. Results: β-catenin knockdown suppressed EMT of HMrSV5 cells. Astragalus alleviated EMT of PMCs characterized by increased E-cadherin and decreased α-SMA and Vimentin. In rat model of peritoneal dialysis (PD), Astragalus attenuated peritoneal thickening and fibrosis. Astragalus down-regulated β-catenin by stabilizing the Glycogen synthase kinase-3β (GSK-3β)/β-catenin complex and further inhibited the nuclear translocation of β-catenin. Meanwhile, Astragalus down-regulated β-catenin by enhancing Smad7 expression. Silencing Smad7 antagonized the EMT-inhibitory effect of Astragalus. Conclusion: Astragalus inhibits EMT of PMCs by down-regulating β-catenin. The modulation of β-catenin in peritoneum can be a novel tool to prevent PF.

Electroacupuncture (EA) can effectively modulate pain perception and pain-related negative affect; however, we do not know whether the effect of EA on sensation and affect is parallel, or dissociated, interactional. In this study, we observed the effects of the anterior cingulate cortex (ACC) lesion and the primary somatosensory cortex (S1) activation on pain perception, pain-related affection, and neural oscillation in S1. ACC lesions did not affect pain perception but relieved pain-paired aversion. S1 activation increased pain perception and anxious behavior. EA can mitigate pain perception regardless of whether there is an ACC lesion. Chronic pain may increase the delta and theta band oscillatory activity in the S1 brain region and decrease the oscillatory activity in the alpha, beta, and gamma bands. EA intervention may inhibit the oscillatory activity of the alpha and beta bands. These results suggest that EA may mitigate chronic pain by relieving pain perception and reducing pain-related affection through different mechanisms. This evidence builds upon findings from previous studies of chronic pain and EA treatment.

Background: Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive diseases characterized by enzyme deficiencies, within steroid hormone anabolism, which lead to disorders in cortisol synthesis. The 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is an uncommon form of CAH caused by variants in the CYP17A1 gene.Aims: We report a novel compound heterozygous CYP17A1 variant and its association with the pathogenesis of 17-OHD.Methods: The patient was assessed for medical history, clinical manifestations, physical examination, laboratory examination, karyotype analysis, and adrenal computed tomography. Mutation screening was conducted using whole-exome sequencing (WES) and Sanger sequencing. The wild-type and mutant CYP17A1 complementary DNAs (cDNAs) were amplified and cloned into a pcDNA3.1(+) vector. These plasmids were transfected transiently into HEK-293T cells. Quantitative PCR and Western blotting analysis were performed to measure the expression level of P450c17. An enzymatic activity assay was conducted to measure the content of 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone (DHEA) in medium using liquid chromatography–tandem mass spectrometry (LC-MS/MS).Results: The proband was characterized by 17-OHD with rhabdomyolysis, hypokalemia, and adrenal insufficiency. Novel compound heterozygous variants of the CYP17A1 gene (c.1304T > C/p.Phe435Ser and c.1228delG/p.Asp410Ilefs*9) were identified. The enzymatic activity assay revealed that this variant resulted in a complete deficiency of 17α-hydroxylase and 17,20-lyase activity. This was consistent with the hormonal characteristics of the proband’s blood.Conclusions: These results suggest that the compound heterozygous variant of c.1304T > C and c.1228delG of the CYP17A1 gene can lead to 17-OHD. Our findings thus provide a novel insight into the clinical evaluations and molecular basis of 17-OHD.

The goal of this study was to identify and compare the main biomarkers of Taxillus chinensis from different hosts. A metabolomics approach utilizing ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS), including cluster analysis, sample correlation analysis and orthogonal partial least squares discriminant analysis, was used to explore the flavonoid metabolites of Taxillus chinensis growing on different hosts. Results: The total flavonoids content (up to 30.08 mg/g) in Taxillus chinensis from Morus alba (CSG) was significantly higher than that from growth on Liquidambar formosana (CFG) or Clausena lansium (CHG) (p < 0.01). There were 23 different metabolites between CSG and CHG, 23 different metabolites between CSG and CFG, and 19 different metabolites between CHG and CFG. The results demonstrated that different hosts exerted a large influence on the metabolites of Taxillus chinensis; it was found that CSG differed from CFG and CHG in eleven metabolic compounds, ten of which were upregulated and one of which was downregulated. Most of these metabolites derive from compounds contained in the host plant, white mulberry (Morus alba); many feature potent anti-cancer effects. Differences in host can influence the type and abundance of flavonoids in parasitic plants such as Taxillus chinensis, which is of great significance to researchers seeking to understand the formation mechanism of Taxillus chinensis metabolites. Therefore, attention should be paid to the species of host plant when studying the Taxillus chinensis metabolome. Plants grown on Morus alba offer the greatest potential for the development of new anti-cancer drugs.

Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-deficient (ApoE−/−) mice.Methods: Male ApoE−/− mice (6 weeks) were fed with a high-fat diet for 13 weeks and then randomized to the model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or the atorvastatin group (5 mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber, and foam cells to the plaque. The expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum levels of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array.Results: Tan IIA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15 ± 1.2%, HT: 12.2 ± 1.64%, MT: 13.93 ± 1.59%, MOD: 18.84 ± 1.46%, P < 0.05) or foam cells (ATO: 16.05 ± 1.26%, HT: 14.88 ± 1.79%, MT: 16.61 ± 1.47%, MOD: 22.08 ± 1.69%, P < 0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22 ± 1.91%, HT: 17.58 ± 1.33%, MT: 15.71 ± 2.26%, LT:14.92 ± 1.65%, MOD: 9.61 ± 0.7%, P < 0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88, and NF-κB p65, and serum level of MCP-1 and TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL, or TG levels between ApoE–/– mice and those treated with atorvastatin.Conclusions: These results suggest that Tan IIA could stabilize vulnerable AS plaque in ApoE−/− mice, and this anti-inflammatory and immune-regulating effect may be achieved via the TLR4/MyD88/NF-κB signaling pathway.

This paper focuses on a systematic isogeometric design approach for the optimal petal form and size characterization of tetra-petals auxetics, considering both plane stress and plane strain conditions. The underlying deformation mechanism of a tetra-petals auxetic is analyzed numerically with respect to several key parameters. Design optimizations are performed systematically to give bounding graphs for the minimum Poisson's ratio achievable with different stiffness constraints. Tunable design studies with targeted effective Poisson's ratio, shear modulus and stiffness are demonstrated. Potential application for functionally graded lattice structures is presented. Numerical and experimental verifications are provided to verify the designs. The out-of-plane buckling phenomenon in tension for thin auxetics with re-entrant features is illustrated experimentally to draw caution to results obtained using plane stress formulations for designing such structures. Keywords: Negative Poisson's ratio, Petal auxetic, Computational homogenization, Shape form optimization, Isogeometric analysis

3' downstream inhibitory stem plays a crucial role in locking rpoS mRNA 5' untranslated region in a self-inhibitory state. Here, we used optical tweezers to study the unfolding/refolding of rpoS inhibitory stem in the absence and presence of Mg2+. We found adding Mg2+ decreased the free energy of the RNA junction without re-arranging its secondary structure, through confirming that this RNA formed a canonical RNA three-way junction. We suspected increased free energy might change the relative orientation of different stems of rpoS and confirmed this by small angle X-ray scattering. Such changed conformation may improve Hfq-bridged annealing between sRNA and rpoS RNA inhibitory stem. We established a convenient route to analyze the changes of RNA conformation and folding dynamics by combining optical tweezers with X-ray scattering methods. This route can be easily applied in the studies of other RNA structure and ligand-RNA.

Our previous studies have confirmed that electroacupuncture (EA) can effectively intervene in pain memory, but the neural mechanism involved remains unclear. In this study, we observed the effects of EA in regulating pain memory-related behaviors and synchronous neural oscillations in the rostral anterior cingulate cortex (rACC). During nociceptive behavioral testing, pain memory induced a nonpain stimulus that spurred a neural oscillatory reaction similar to that caused by pain stimuli in the rACC. After EA, nonpain stimuli did not induce decreased neural oscillatory activity in the rACC until the presentation of pain stimuli. During aversive behavioral testing, EA, through the downregulation of theta power, inhibited the retrieval of aversive memory and relieved pain memory-induced aversive behaviors. These changes of oscillatory activity may be the hallmarks of EA therapy for pain memory.

The technical feasibility of using calcium oxide (CaO) as a sorbent for CO2 and Fe-Cr as a catalyst for the water-gas shift (WGS) reaction using syngas for the steam gasification of biomass was investigated. The effects of temperature, steam to biomass mass ratio, CaO to biomass molar ratio, and Fe-Cr WGS catalyst on gas composition were studied. Within a temperature range of 250 C to 550 C, the H2 concentration increased from 1.2% to 17.1%, with a total increase of 16%. As the steam rate increased within the range of 0 kg/h to 0.12 kg/h, the maximum value of H2 concentration increased from 12.1% to 17.13%, with a total increase of 5%. As the CaO to biomass molar ratio was increased from 0 to 2, the CO2 concentration demonstrated a minimum value of 1.3%, and the H2 concentration exhibited a maximum value of 53.1%. A catalyst to biomass mass ratio of 1 resulted in the minimum value of CO2 concentration, which decreased from 7.9%, in the absence of CaO, to 1.6%. A CaO to biomass molar ratio of 1.5 resulted in the maximum value of H2 concentration, which increased from 27.6%, in the absence of CaO, to 63%.