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Abstract Background In March 2022, a new outbreak of COVID-19 emerged in Quanzhou, leading to the implementation of strict lockdown management measures in colleges. While existing research has indicated that the pandemic has had a significant impact on sleep quality, the specific effects of containment measures on college students’ sleep patterns remain understudied. Objective This study aimed to understand the sleep quality of college students in Fujian Province during the epidemic and determine sensitive variables, in order to develop an efficient prediction model for the early screening of sleep problems in college students. Methods A cross-sectional survey was conducted April 5–16, 2022 to survey college students in Quanzhou. A total of 4959 college students in Quanzhou were enrolled in this study. Descriptive analysis, univariate analysis, correlation analysis, and multiple regression analysis were used to explore the influencing factors regarding sleep quality. In addition, we constructed eight sleep quality risk prediction models to predict sleep quality. Results A mean PSQI total score of 6.03 ± 3.21 and a sleep disorder rate of 29.4% (PSQI > 7) were obtained. Sleep quality, sleep latency, sleep efficiency, diurnal dysfunction, and PSQI score were all higher than the national norm (P

Abstract It is essential to understand the modification mechanism of hydrophobicity nano-CaCO3 to their potential application in different fields of chemistry. However, the water absorption of hydrophobicity nano-CaCO3 is seldom studied. In this study, Raman, BET and TGA experiments were performed on nano-CaCO3 samples to obtain surfactants contents and microstructure characteristics. SEM, TEM and DSL results showed that the nano-CaCO3 modified by stearic acid and sodium stearate had larger particle size and smaller nanoclusters. In the water vapor adsorption test, the order of saturation adsorption capacity was nano-CaCO3(PCC) > nano-CaCO3 modified by sodium stearate(PCC-Sa-Na) > nano-CaCO3 modified by stearic acid(PCC-Sa), and XPS results showed that PCC-Sa had more hydrophobic groups than PCC-Sa-Na, which also explained that the hydrophobicity of PCC modified by stearic acid and sodium stearate was improved by increasing the hydrophobic bond on the surface of CaCO3 and reducing the hydrophilic groups. Our analysis provides a path for the design and the prediction of hydrophobicity of nano-CaCO3, which is the main focus of our work.

Abstract Background Hepatocellular adenoma (HCA) is a rare benign neoplasm, seldom ascribed as the cause of endocrine and metabolic derangement. We herein report a case of primary amenorrhea, growth arrest and metabolic syndrome. En bloc resection of the tumor normalized all the disturbances. Case presentation A 16-year-old girl complained of primary amenorrhea and growth arrest for the past 2 years. Her height and weight were at the 3rd percentile, whereas waist circumference was at the 90th percentile for chronological age. She was hypertensive on admission. Plasma cholesterol, triglyceride and uric acid were elevated. Evaluation of GH/IGF-1 axis showed extremely low IGF-1 concentration, which was unresponsive to hGH stimulation. Computer tomography identified a huge liver mass (18.2 cm×13.7 cm×21 cm). The patient underwent an uneventful open right hepatic lobectomy. The tumor was en bloc resected. Immunohistochemistry indicated an unclassified HCA, which was confirmed by genetic screening. IGF-1 concentration, blood pressure, lipid profile and ovarian function were all normalized after surgery, and the girl had reduction in waist circumference and gain in height during the follow up. Conclusion We provide evidence that liver-derived IGF-1 has a direct effect on skeletal and pubertal development, blood pressure, visceral adiposity and dyslipidemia independent of insulin resistance and obesity in the circumstance of undernutrition. Though rare, we propose the need to look into HCA cases for the existence of IGF-1 deficiency and its impact on metabolic derangement.

PurposeThis study aims to summarize the characteristics of children under three years old (≤3 years) with central nervous system (CNS) tumors and to investigate the factors that influence their overall survival (OS) time.MethodsWe treated 171 pediatric patients (≤3 years) with CNS tumors at Yuquan Hospital of Tsinghua University from January 2016 to June 2023. Of these, 162 cases were successfully followed up. Kaplan–Meier survival analysis and Cox regression were utilized to evaluate factors potentially influencing OS of malignancies.ResultsThere was a male predominance among the patients. The three most common tumors were embryonal tumors, gliomas, and craniopharyngiomas. Gross total resection (GTR) was achieved in select cases. Patients with high-grade malignancies were advised to undergo chemotherapy and/or radiotherapy after surgery. Optic gliomas and diffuse midline gliomas were partially resected and treated with adjuvant treatments. The median survival time of low-grade malignant tumors was 41.5 months, while that of high-grade malignant tumors was 15 months. Kaplan–Meier survival analysis identified the factors potentially influencing OS of malignancies: extent of resection, CNS WHO grade, grade of malignancies, and Ki-67 labeling index (Ki-67 LI). Subsequent multivariate analysis highlighted the interactive factor (extent of resection × CNS WHO grade) along with Ki-67 LI, as the most significant variables. Factors such as sex, age, tumor location, and onset-to-treatment time appeared not to affect OS.ConclusionsGTR remains the cornerstone of treatment for children (≤3 years) with CNS tumors, except for optic glioma, diffuse midline glioma, and germinoma. The interactive factor (extent of resection × CNS WHO grade) and Ki-67 LI are the most significant factors affecting OS. The implementation of preoperative neoadjuvant chemotherapy and early postoperative chemotherapy may enhance prognosis.

BackgroundNocardiosis poses a diagnostic challenge due to its rarity in clinical practice, non-specific clinical symptoms and imaging features, and the limitations of traditional detection methods. Nocardia aobensis (N. aobensis) is rarely detected in clinical samples. Metagenomic next-generation sequencing (mNGS) offers significant advantages over traditional methods for rapid and accurate diagnosis of infectious diseases, especially for rare pathogens.Case presentationA 52-year-old woman with a history of immune thrombocytopenia for over 2 years was hospitalized for recurrent fever and cough lasting for 10 days. Her initial diagnosis on admission was community-acquired pneumonia, based on chest computed tomography findings of lung inflammation lesion. Empirical treatment with moxifloxacin and trimethoprim-sulfamethoxazole (TMP-SMZ) was initiated. However, her condition failed to improve significantly even after 1 week of treatment. Bronchoalveolar lavage fluid (BALF) subjected to mNGS revealed the presence of N. aobensis, resulting in a diagnosis of pulmonary nocardiosis caused by N. aobensis. This diagnosis was also supported by Sanger sequencing of the BALF. After adjusting the antibiotic regimen to include TMP-SMZ in combination with imipenem, the patient’s condition significantly improved. She was finally discharged with instructions to continue oral treatment with TMP-SMZ and linezolid for 6 months. The patient’s first follow-up 1 month after discharge showed good treatment outcomes but with obvious side effects of the drugs. Consequently, the antibiotic regimen was changed to doxycycline, and the patient continued to improve.ConclusionWe report the first detailed case of pulmonary nocardiosis caused by N. aobensis diagnosed by mNGS. mNGS could be an effective method that facilitates early diagnosis and timely decision-making for the treatment of nocardiosis, especially in cases that involve rare pathogens.

Abstract Pancreatic cancer is a commonly occurring malignant tumor, with pancreatic ductal carcinoma (PDAC) accounting for approximately 95% of cases. According of its poor prognosis, identifying prognostic factors of pancreatic ductal carcinoma can provide physicians with a reliable theoretical foundation when predicting patient survival. This study aimed to analyze the impact of marital status on survival outcomes of PDAC patients using propensity score matching and machine learning. The goal was to develop a prognosis prediction model specific to married patients with PDAC. We extracted a total of 206,968 patient records of pancreatic cancer from the SEER database. To ensure the baseline characteristics of married and unmarried individuals were balanced, we used a 1:1 propensity matching score. We then conducted Kaplan–Meier analysis and Cox proportional-hazards regression to examine the impact of marital status on PDAC survival before and after matching. Additionally, we developed machine learning models to predict 5-year CSS and OS for married patients with PDAC specifically. In total, 24,044 PDAC patients were included in this study. After 1:1 propensity matching, 8043 married patients and 8,043 unmarried patients were successfully enrolled. Multivariate analysis and the Kaplan–Meier curves demonstrated that unmarried individuals had a poorer survival rate than their married counterparts. Among the algorithms tested, the random forest performed the best, with 0.734 5-year CSS and 0.795 5-year OS AUC. This study found a significant association between marital status and survival in PDAC patients. Married patients had the best prognosis, while widowed patients had the worst. The random forest is a reliable model for predicting survival in married patients with PDAC.

A novel elastomer-modified multicomponent, multiphase waste-sourced biocomposites, was prepared for converting waste biomass and plastic into value-added products. The effects of blending elastomer–olefin block copolymer (OBC) and maleic anhydride (MAH), and divinylbenzene (DVB) co-grafting of recycled polypropylene (rPP) matrix on the adhesion interface, structure, and properties of high wood flour-filled (60 wt.%) composites were thoroughly investigated. The results indicated that DVB introduced branched structures into the polymer matrix molecular chain and increased the MAH grafting rate. Co-grafting rPP/OBC blends enhanced the interfacial adhesion among rPP, OBC, and wood flour. Additionally, MAH-grafted OBC was prone to encapsulating rigid wood flour, thereby forming an embedded structure. Notably, the tensile modulus and impact strength of the final three-component composites increased by 60% and 125%, respectively, compared with the unmodified composites. Additionally, dynamic mechanical analysis revealed that DVB-induced branching promoted the formation of microvoids in the OBC shell layer surrounding the wood, which in turn induced significant plastic deformation in the polymer matrix. This work offers a facile and efficient method for preparing high-toughness, high-stiffness, and low-cost waste PP-based composites for automotive interiors, and indoor and outdoor decoration.

This is an essay in the field of process mineralogy. Rare metals such as lithium, beryllium, niobium and tantalum, as national strategic emerging resources, are mainly used in industrial fields such as national defense, aviation and aerospace, and have attracted the attention of geologists in recent years. A niobium tantalite deposit in Hubei Province is a niobium-bearing trachytic volcanic rock and pyroclastic rock deposit. In this paper, a systematic process mineralogical study is carried out on the ore. It is found that the main niobium-containing minerals in the ore are niobium iron ore, niobium iron rutile, hematite and limonite, ilmenite and pyrite. Niobium iron ore is the main recovered mineral for the separation of niobium concentrate. The embedded particle size of most niobium minerals is less than 0.04 mm, and the particle size of niobium iron ore is fine, mostly 0.5 ~ 8 μm. However, at 90% of -0.037 mm, the monomer dissociation can reach 71.11%. Magnetic separation can be considered to separate niobate and gangue minerals; Gangue minerals in the ore are mainly sericite and plagioclase, which are seriously argillized after grinding. Attention should be paid to the influence of mud grade material agglomeration on beneficiation test.

Abstract Background Upregulation of an RNA-binding protein HuR has been implicated in glomerular diseases. Herein, we evaluated whether it is involved in renal tubular fibrosis. Methods HuR was firstly examined in human kidney biopsy tissue with tubular disease. Second, its expression and the effect of HuR inhibition with KH3 on tubular injury were further assessed in a mouse model induced by a unilateral renal ischemia/reperfusion (IR). KH3 (50 mg kg−1) was given daily via intraperitoneal injection from day 3 to 14 after IR. Last, one of HuR-targeted pathways was examined in cultured proximal tubular cells. Results HuR significantly increases at the site of tubular injury both in progressive CKD in patients and in IR-injured kidneys in mice, accompanied by upregulation of HuR targets that are involved in inflammation, profibrotic cytokines, oxidative stress, proliferation, apoptosis, tubular EMT process, matrix remodeling and fibrosis in renal tubulointerstitial fibrosis. KH3 treatment reduces the IR-induced tubular injury and fibrosis, accompanied by the remarkable amelioration in those involved pathways. A panel of mRNA array further revealed that 519 molecules in mouse kidney following IR injury changed their expression and 71.3% of them that are involved in 50 profibrotic pathways, were ameliorated when treated with KH3. In vitro, TGFβ1 induced tubular HuR cytoplasmic translocation and subsequent tubular EMT, which were abrogated by KH3 administration in cultured HK-2 cells. Conclusions These results suggest that excessive upregulation of HuR contributes to renal tubulointerstitial fibrosis by dysregulating genes involved in multiple profibrotic pathways and activating the TGFß1/HuR feedback circuit in tubular cells. Inhibition of HuR may have therapeutic potential for renal tubular fibrosis.

The sugarcane field excitation, the engine excitation and reaction forces acting on cutters constitute complicated excitations of sugarcane harvesters. Axial cutter vibration displacement measuring and sugarcane cutting experiments were done on a self-developed sugarcane harvester experiment platform (SHEP) with complicated excitations simulated through a simulated sugarcane field exciter and an actuating engine. Effects of the sugarcane field excitation, the engine excitation and cutting parameters on the axial cutter vibration, three-directional cutting forces and the sugarcane cutting quality (SCQ) were studied through single-factor and orthogonal experiments. Effects of the axial cutter vibration on three-directional cutting forces and those of these two influence factors on the SCQ were also studied. Significance levels of effects in the sugarcane cutting process form high to low are as follow, the sugarcane field excitation, the cutter rotating speed, the engine excitation, the cutter installing angle, the sugarcane harvester moving speed. The axial cutter vibration has a directly and highly significant monotonic negative correlated effect on the SCQ. For the best SCQ, the cutter rotating speed is 700 r/min, the sugarcane harvester moving speed is 0.6 m/s and the cutter installing angle is 8°, providing a reference for setting cutting parameters of sugarcane harvesters with a good SCQ.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear. Methods Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed. Results A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts

Refractory Mo–10%Nb sputtering targets play a key role in the electronic integrated circuit and flat panel display industries. However, the fabrication of high-performance Mo–10%Nb sputtering targets is a challenging task. In order to improve the sintering densification and homogeneity of Mo–10%Nb targets, activated Mo–10%Nb solid-solution powders were prepared and characterised in our previous study. In this research, the structural stability, deoxidation characteristics, and sintering behaviours of activated Mo–10%Nb solid-solution powders were investigated. The results revealed that the crystal structure and composition of the activated powders had good stability when stored in vacuum at room temperature for 30 days. Further, the oxygen content of the activated powders was mainly concentrated at the surface, as confirmed by electron probe microanalysis and X-ray photoelectron spectrometry. The oxygen content could be significantly decreased from ∼6000 to ∼3000 ppm by a deoxidation process using Mg as the reductant. Finally, the density of the sintered billet increased from 86.19 to 91.36% upon using the Mo–10%Nb solid-solution powder, and the homogeneity of the composition and microstructure was greatly improved. Moreover, the average grain size decreased from 20.89 to 6.69 μm. This research suggests that activated Mo–10%Nb solid-solution powders can effectively improve the quality of sintered Mo–10%Nb targets.

In order to improve the drying efficiency, microwave intermittent drying characteristics of Xilin fire ginger slices were studied and drying kinetics model was established. Using microwave power density, intermittent time, laying density and slice thickness as the factors, the moisture changes in the microwave intermittent drying process of Xilin fire ginger slices under various conditions were measured in real time. By fitting four common drying models, the suitable model for microwave intermittent drying of Xilin fire ginger slices was optimized and its parameters were solved. A model for real time microwave intermittent drying of Xilin fire ginger slices was obtained. The results showed that there were three stages in the microwave intermittent drying process: Acceleration, constant speed and deceleration. The higher the microwave power density, the shorter the batch time, the smaller the laying density and the smaller the thickness, the faster the drying rate, the shorter the drying time required. The optimum microwave power density was 0.9 W/g, the intermittent drying time was 1.0 min, the laying density was 0.6 g/cm2, and the thickness of slices was 6 mm. The Page model was the most suitable for microwave intermittent drying (R2=0.977), and the effective water diffusion coefficient was (0.9727~7.7815)×10-9 m2/s. The drying kinetics model established can objectively and effectively reflect the microwave intermittent drying process of Xilin fire ginger slices, and can provide theoretical reference for microwave drying process of Xilin fire ginger slices.

BackgroundPrimary membranous nephropathy (PMN) is an immune-related disease with increased morbidity and the most common cause of adult nephrotic syndrome (NS). The serum 25-hydroxyvitamin D [25(OH)D)], a biomarker of vitamin D (VD) status, tends to decline in patients with kidney disease. However, the relationship between 25(OH)D and PMN is still unclear. Therefore, this study aims to clarify the association between 25(OH)D and disease severity and therapy response of PMN.MethodsA total of 490 participants diagnosed with PMN by biopsy from January 2017 to April 2022 were recruited at the First Affiliated Hospital of Nanjing Medical University. The correlations between baseline 25(OH)D and manifestations of nephrotic syndrome (NS) or seropositivity of anti-PLA2R Ab were confirmed by univariate and multivariate logistic analyses. Spearman’s correlations were used to examine the associations between baseline 25(OH)D and other clinical parameters. In the follow-up cohort, Kaplan-Meier analysis was used to assess remission outcomes among groups with low, medium, and high levels of 25(OH)D. Furthermore, the independent risk factors for non-remission (NR) were explored by COX regression analysis.ResultsAt baseline, 25(OH)D was negatively related to 24-h urinary protein and serum anti-PLA2R Ab. The lower level of baseline 25(OH)D was associated with an increased risk for the incidence of NS in PMN (model 2, OR 6.8, 95% CI 4.4, 10.7, P < 0.001) and seropositivity of anti-PLA2R Ab (model 2, OR 2.4, 95% CI 1.6, 3.7, P < 0.001). Furthermore, the lower level of 25(OH)D during follow-up was demonstrated as an independent risk factor for NR even after adjusting age, gender, MBP, 24 h UP, serum anti-PLA2R Ab, serum albumin, and serum C3 [25(OH)D (39.2–62.3 nmol/L): HR 4.90, 95% CI 1.02, 23.53 P = 0.047; 25(OH)D < 39.2 nmol/L: HR 17.52, 95% CI 4.04, 76.03 P < 0.001); vs. 25(OH)D ≥ 62.3 nmol/L]. The Kaplan-Meier survival analysis also demonstrated that the higher level of follow-up 25(OH)D had a higher possibility of remission than the lower one (log-rank test, P < 0.001).ConclusionBaseline 25(OH)D was significantly correlated with nephrotic proteinuria and seropositivity of anti-PLA2R Ab in PMN. As an independent risk factor for NR, a low level of 25(OH)D during follow-up might serve as a prognostic tool for sensitively identifying cases with a high probability of poor treatment response.

SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

This study performed in-depth analysis of onsite fatigue damage and stress distribution in pumping rods. Two aspects of fatigue damage were analyzed: macroscopic morphology and chemical properties. In terms of chemical properties, the crystalline phase composition and hardness of the product at fatigue damage were analyzed; the stress distribution was analyzed in term so of the rod-body stress and the connection-section stress. The cross-sectional characteristics of the fatigue crack expansion were summarized, and the types of fatigue fracture and the influencing factors of the pumping rod were obtained from these cross-sectional characteristics. Finally, modeling and stress analysis of the pumping rod were performed using SolidWorks and ABAQUS software. By comparing the stress cloud diagrams of different thread root shapes, the factors that cause fracture in the pumping rod and the locations of stress concentrations and dangerous cross-sections of the rod were determined. The highest principal stresses were obtained at the rod body near the upsetting flange of the pumping rod, and fatigue damage was the most likely to occur at this location. The shoulder of the unloading groove and the upsetting flange area were relatively safe because of their large cross-sectional area and less likelihood to produce stress concentrations. The results of this study can provide scientific guidance and reference for the development of pumping rods for efficient oil production and the improvement of oil and gas production efficiency.

Transgenic animal models with homologous etiology provide a promising way to pursue the neurobiological substrates of the behavioral deficits in autism spectrum disorder (ASD). Gain-of-function mutations of MECP2 cause MECP2 duplication syndrome, a severe neurological disorder with core symptoms of ASD. However, abnormal brain developments underlying the autistic-like behavioral deficits of MECP2 duplication syndrome are rarely investigated. To this end, a human MECP2 duplication (MECP2-DP) rat model was created by the bacterial artificial chromosome transgenic method. Functional and structural magnetic resonance imaging (MRI) with high-field were performed on 16 male MECP2-DP rats and 15 male wildtype rats at postnatal 28 days, 42 days, and 56 days old. Multimodal fusion analyses guided by locomotor-relevant metrics and social novelty time separately were applied to identify abnormal brain networks associated with diverse behavioral deficits induced by MECP2 duplication. Aberrant functional developments of a core network primarily composed of the dorsal medial prefrontal cortex (dmPFC) and retrosplenial cortex (RSP) were detected to associate with diverse behavioral phenotypes in MECP2-DP rats. Altered developments of gray matter volume were detected in the hippocampus and thalamus. We conclude that gain-of-function mutations of MECP2 induce aberrant functional activities in the default-mode-like network and aberrant volumetric changes in the brain, resulting in autistic-like behavioral deficits. Our results gain critical insights into the biomarker of MECP2 duplication syndrome and the neurobiological underpinnings of the behavioral deficits in ASD.

ObjectivesGrowing evidence demonstrated that vitamin D levels had been linked to type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in light of various extraskeletal effects. Therefore, the present study aimed to evaluate the association of 25-hydroxyvitamin D [25(OH)D] level with the clinicopathological features and CKD progression in T2DM.MethodsA total of 182 patients with T2DM with CKD stages 1 through 4 (G1–G4) were retrospectively included. Identification of the serum 25(OH)D level associated with CKD progression was executed by Kaplan–Meier survival analysis and Cox proportional hazards models. We further performed sensitivity analyses with a time-weighted average (TWA) of the serum 25(OH)D level in 75 participants to reinforce the findings.ResultsThe median serum 25(OH)D level was 26 (IQR, 14; 39) nmol/L in the study participants. Median follow-up time was 42 months, during which 70 (38%) patients confronted CKD progression. Cumulative kidney outcomes were significantly higher in the lowest tertile of the serum 25(OH)D level in Kaplan–Meier analyses (P < 0.001). Consistently, the analyses of Cox proportional hazards regression models indicated a significantly greater risk for CKD progression in the lowest tertile of the serum 25(OH)D level compared with the highest tertile of the serum 25(OH)D level (P = 0.03). These relationships remained robust with further sensitivity analysis of data with TWA of the serum 25(OH)D level, showing an independent association between lower TWA of the serum 25(OH)D level and an unfavorable renal outcome in patients with T2DM with CKD.ConclusionsOur findings demonstrated that patients with T2DM with a decreased 25(OH)D level had deteriorated renal function. Both lower levels of baseline and TWA of serum 25(OH)D were associated with an increased risk of CKD progression in patients with T2DM, which suggested that the long-term maintenance of optimal vitamin D levels from early in life might be associated with reduced future risk of CKD development in T2DM.

Abstract Background Mitochondrial dysfunction contributes to the pathogenesis of diabetic nephropathy (DN). Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) play a bottleneck role in the transport of pyruvate into mitochondrial across the mitochondrial inner membrane. A previous study showed that increasing mitochondrial pyruvate carrier content might ameliorate diabetic kidney disease in db/db mice. However, the expression status of MPC1 and MPC2 in patients with DN is unclear. Methods Patients with primary glomerulonephropathy (PGN, n = 30), PGN with diabetes mellitus (PGN-DM, n = 30) and diabetic nephropathy (DN, n = 30) were included. MPC1 and MPC2 protein levels were examined by immunohistochemistry. The expression of MPC in different groups was evaluated by the Kruskal-Wallis test. Spearman’s rank correlation was performed for correlation analysis between MPC levels and clinical factors. Results Both MPC1 and MPC2 were localized in renal tubules. Levels of MPC1 and MPC2 were lower in DN patients than in PGN patients and in PGN patients with DM, whereas there were no differences in MPC1 and MPC2 levels among DN stage II to stage IV. Moreover, both MPC1 and MPC2 levels were significantly correlated with serum creatinine, BUN and eGFR in patients with DN, whereas no analogous trend was observed in nondiabetic kidney disease. Conclusions Our study indicated that MPC localized in renal tubules, which were significantly decreased in DN. MPC was associated with clinical features, especially those representing renal functions.

Abstract Background Both diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM). Methods We used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses. Results A weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P

Abstract Diabetes is directly related to the risk of breast cancer (BC) occurrence and worsened BC prognosis. Currently, there are no specific treatments for diabetes‐associated BC. This paper aims to understand the fundamental mechanisms of diabetes‐induced BC progression and to develop personalized treatments. It reports a metabolic reprogramming strategy (MRS) that pharmaceutical induction of glucose import and glycolysis with metformin and NF‐κB inhibitor (NF‐κBi) while blocking the export of excessive lactate via inhibiting monocarboxylate transporter 4 (MCT4) leads to a metabolic crisis within the cancer cells. It demonstrates that the MRS shifts the metabolism of BC cells toward higher production of lactate, blocks lactate secretion, prompts intracellular acidification and induces significant cytotoxicity. Moreover, a novel MCT4 inhibitor CB‐2 has been identified by structure‐based virtual screening. A triple combination of metformin, CB‐2, and trabectedin, a drug that impedes NF‐κB signaling, strongly inhibits BC cells. Compared to normal glucose condition, MRS elicits more potent cancer cell‐killing effects under high glucose condition. Animal model studies show that diabetic conditions promote the proliferation and progression of BC xenografts in nude mice and that MRS treatment significantly inhibits HG‐induced BC progression. Therefore, inhibition of MCT4 combined with metformin/NF‐κBi is a promising cancer therapy, especially for diabetes‐associated BC.

Background/ObjectivesRenaming non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) suggests a shift of emphasis to the accompanying metabolic disturbance. Controlled attenuation parameter (CAP) measured by FibroScan has been shown to be correlated with hepatic steatosis. We aim to validate its usefulness as a novel surrogate marker for evaluating metabolic derangement.Subjects/MethodsVolunteers were recruited from medical staff at our hospital to undergo CAP measurements. Anthropometrics, CAP, and laboratory assessments for metabolic profiles and insulin resistance were collected. CAP < 238 dB/m denoted no hepatic steatosis, 238 ≤ CAP ≤ 259 dB/m denoted mild, 260 ≤ CAP ≤ 291 dB/m denoted moderate, and CAP > 291 dB/m denoted severe hepatic steatosis according to previous reports.ResultsData of 824 participants were included for analysis. The age was 53.2 ± 15.4 years, body mass index (BMI) was 23.6 ± 3.1 kg/m2, 24.4% were male subjects, and 22.0% met the criteria for metabolic syndrome (MetS). Taking the group with CAP < 238 dB/m as control, subjects with mild, moderate, and severe hepatic steatosis had increased odds of MetS by 3.51-, 3.32-, and 5.12-fold, respectively, after adjusting for multiple confounders (p = 0.020). Metabolic profiles, insulin resistance, and presence of MetS were similar between normal-weight subjects with CAP ≥ 238 dB/m and overweight subjects with CAP < 238 dB/m. Even in subjects with no MetS components, those with CAP ≥ 238 dB/m had higher BMI, waist circumferences, uric acid, triglyceride, white blood cell count, and insulin resistance, whereas lower adiponectin and estimated glomerular filtration rate. Waist circumference [OR 1.11 (1.04, 1.18), p = 0.001] and homeostatic model assessment of insulin resistance (HOMA-IR) [OR 2.39 (1.18, 4.83), p = 0.016] were predictive of hepatic steatosis according to CAP ≥ 238 dB/m.ConclusionsCAP is a convenient, sensitive, and non-invasive indicator for metabolic derangement. Prospective studies are needed to further validate its usefulness as a surrogate marker for the transition of metabolic status over time.

The Sulige is a low-permeability tight gas sandstone field whose natural gas production has gradually declined with continuous development. The primary reason was that most of the wells in the field flew below their critical rates and liquids started to accumulate in the wellbore at different levels, which resulted in the production reduction due to the wellbore pressure decrease and back pressure increase on the produced gas. An artificial lift was required to remove the liquids from those wells. With the advantages such as simple installation and operation, low cost and high liquid-carrying capacity, the plunger lift has been proven effective in the Sulige Gas Field. In this paper, firstly, a series of mathematical models were developed to investigate plunger displacement and velocity in the uplink and downside phases, fluid leakage in the uplink phase, and the characteristics of tubing pressure and casing pressure in the uplink and pressure build-up phases. Then, taking well X1 and well X2 at Su 59 area of the gas field as an example, the established mathematical models were applied to estimate its tubing and casing pressure, plunger moving displacement and speed, fluid leakage during the uplink phase, and gas production during the plunger lift. Hence, the well production cycle operated by the maximum gas rate was optimized. This study provides a theoretical basis for the optimal design of plunger lift parameters and the improvement of gas production.

Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched.Method: Genotypical and phenotypical data from 30 children affected by NPHS1 variants were collected from a multicenter registration system in China and analyzed retrospectively.Results: The patients were divided into two groups: congenital nephrotic syndrome (CNS [n = 24]) and non-CNS (early onset nephrotic syndrome [n = 6]). Renal biopsy was performed on four patients in the non-CNS group, revealing minimal change disease in three and focal segmental glomerulosclerosis in one. A total of 61 NPHS1 variants were detected, involving 25 novel variants. The “recurrent variants” included c.928G>A(p.Asp310Asn) in eight patients with CNS, followed by c.616C>A(p.Pro206Thr) in four, and c.2207T>C (p.Val736Ala) in three. Steroid treatment was applied in 29.2% (7/24)of the patients in the CNS group and 50% (3/6) of the patients in the non-CNS group. One patient in each group experienced complete remission but relapsed subsequently. Immunosuppressants were administered to three patients in the non-CNS group, eliciting an effective response. In the CNS group, three patients underwent renal transplantation and six died mainly from infection.Conclusion: Variants of NPHS1 cause CNS and early childhood-onset nephrotic syndrome. NPHS1 variants in Chinese individuals with nephrotic syndrome (NS) were mainly compound heterozygous variants, and c.928G>A(p.Asp310Asn) in exon 8 may act as a recurrent variant in the Chinese population, followed by c.616C>A(p.Pro206Thr) in exon 6. Steroids and immunosuppressants may be effective in selected patients.

The adhesion of water to the surfaces of unmanned aerial vehicles (UAVs) adversely affects the function. The proposed UAVs will have underwater as well as flight capability, and these aquatic UAVs must shed water to resume flight. The efficient separation of the adhering water from aquatic-UAV surfaces is a challenging problem; we investigated the application of hydrophobic surfaces as a potential solution. Using aquatic-UAV models, one with hydrophilic surfaces and the other with superhydrophobic anisotropic textured surfaces, the antiwetting mechanism of the hydrophobic surfaces was investigated using a simulated-precipitation system and instrumentation to measure the load of the water adhering to the aquatic UAV, and to measure the impact energies. When the model was stationary (passive antiwetting), no adhesion occurred on the superhydrophobic surfaces, while continuous asymmetric thick liquid films were observed on the hydrophilic surfaces. The superhydrophobic surfaces reduced the rain loading by 87.5%. The vibration and movement of the model (dynamic antiwetting, simulating flight motions) accelerated the separation process and reduced the contact time. The observed results were augmented by the use of computational fluid dynamics with lattice Boltzmann methods (LBM) to analyze the particle traces inside the droplets, the liquid phase velocity-field and pressure-field strengths, and the backward bouncing behavior of the derived droplet group induced by the moving surface. The synergy between the superhydrophobic surfaces and the kinetic energy of the droplets promotes the breakup of drops, which avoids the significant lateral unbalance observed with hydrophilic surfaces during simulated flight.

Adrenergic signaling is a well-known input into pancreatic islet function. Specifically, the insulin-secreting islet β cell expresses the Gi/o-linked α2-adrenergic receptor, which upon activation suppresses insulin secretion. The use of the adrenergic agonist epinephrine at micromolar doses may have supraphysiological effects. We found that pretreating β cells with micromolar concentrations of epinephrine differentially inhibited activation of receptor tyrosine kinases. We chose TrkB as an example because of its relative sensitivity to the effects of epinephrine and due to its potential regulatory role in the β cell. Our characterization of brain-derived neurotrophic factor (BDNF)-TrkB signaling in MIN6 β cells showed that TrkB is activated by BDNF as expected, leading to canonical TrkB autophosphorylation and subsequent downstream signaling, as well as chronic effects on β cell growth. Micromolar, but not nanomolar, concentrations of epinephrine blocked BDNF-induced TrkB autophosphorylation and downstream mitogen-activated protein kinase pathway activation, suggesting an inhibitory phenomenon at the receptor level. We determined epinephrine-mediated inhibition of TrkB activation to be Gi/o-dependent using pertussis toxin, arguing against an off-target effect of high-dose epinephrine. Published data suggested that inhibition of potassium channels or phosphoinositide-3-kinase signaling may abrogate the negative effects of epinephrine; however, these did not rescue TrkB signaling in our experiments. Taken together, these results show that (1) TrkB kinase signaling occurs in β cells and (2) use of epinephrine in studies of insulin secretion requires careful consideration of concentration-dependent effects. BDNF-TrkB signaling in β cells may underlie pro-survival or growth signaling and warrants further study.

Objectives: As accumulating data supporting the potential role of the complement system in the pathogenesis of diabetic kidney disease (DKD), the present study aimed to explore the association of glomerular complement C4c deposition with the baseline clinicopathological characteristics and the prognosis of DKD in type 2 diabetes (T2DM) patients.Methods: A total of 79 T2DM patients with biopsy-proven DKD were enrolled. Clinicopathological features and renal outcomes were compared between groups divided by the glomerular C4c deposition patterns and median values of serum C4. Renal outcomes were defined by doubling of serum creatinine level or progression to end-stage renal disease (ESRD). A Cox proportional hazards model was employed to identify the risk factors associated with renal events.Results: Patients with glomerular C4c deposition had worse renal insufficiency than those without C4c deposits, along with higher 24-h urinary protein, triglyceride, but lower serum albumin and higher interstitial inflammation score. Besides, serum C4 levels positively correlated with urinary protein and serum C3 levels. During 21.85 ± 16.32 months of follow-up, Kaplan-Meier curve analysis showed significantly faster deterioration of renal function for patients with positive glomerular C4c deposition as well as higher levels of serum C4. More specifically, more than 50% of the patients with glomerular C4c had co-deposition of C3c or C1q, and patients with glomerular complement complex of C4c and one or two of C3/C1q deposition had more severe proteinuria and a higher rate of DKD progression than those with negative C4c deposits. The univariate Cox regression indicated that factors of combined serum and glomerular C4, urinary protein, serum creatinine, serum C3, combined glomerular C4c and IgM and interstitial inflammation were associated with an increased risk of DKD, but only glomerular C4c intensity (HR 1.584, 95% CI [1.001, 2.508], p = 0.0497), as well as baseline age and diabetic neuropathy, were independent risk factors for renal survival by the multivariate Cox analysis.Conclusions: Glomerular C4c deposition was associated with deteriorated renal function and outcomes in patients with T2DKD. Glomerular C4c deposition was an independent risk factor for DKD progression.

With the deployment of China’s energy strategy in the western regions, complex geological mining conditions such as thin bedrock and ultrathick seams in western China have caused a series of problems such as serious deformation of the surrounding rock at the ends of the working face and the increase in the lead abutment pressure of the roadways; the research on end roof deformation in the resource exploitation in western China has become one of the great demands of the industry. Based on the failure characteristics of rock mass, relying on the actual mining geological conditions of a coal mine in Inner Mongolia, the failure characteristics of the overlying rock strata under the influence of mining were simulated and analyzed using similar material simulation experiment, which intuitively reproduced the failure and deformation processes of the immediate roof, main roof, and key strata and revealed the mechanical mechanism of the directional weakening of the end roof. It is of great significance for the stability control of the surrounding rock at the end of the fully mechanized caving face in the thin bedrocks and ultrathick seams, reducing the abutment pressure of gate roadway and controlling the spontaneous combustion of residual coal in the goaf.

Background. Short-term intensive insulin therapy induces long-term glycemic remission in half of patients with newly diagnosed type 2 diabetes. The concomitant hypoglycemia needs further analysis. Methods. We collected data from three randomized trials conducted with the same inclusion and exclusion criteria at our institution from 2002 to 2015. Continuous subcutaneous insulin infusion (CSII) was provided to achieve the glycemic goals within a week and then maintained for 14 days. Hypoglycemia episodes during short-term treatment and the one-year drug-free glycemic remission were observed. Results. A total of 244 patients were included. The per day episode of mild hypoglycemia (3.0-3.9 mmol/L) was higher in the remission group than in the nonremission group (0.26±0.20 vs. 0.18±0.21, P=0.005). However, a moderate hypoglycemia episode (

Based on the theory of elastic foundation beam, the mechanical model of the backfilling mining support-roof rock beam-gangue filling body under the condition of comprehensive mechanized filling mining is established. The foundation coefficient of each part is determined, and the subsidence of each part of roof rock beam is calculated. It is found that the initial filling height is the decisive factor to control the subsidence and migration stability of each part of the roof rock beam. Properly increasing the pushing force of backfilling-coal mining hydraulic support on the filling body can also effectively control the roof subsidence. The comprehensive mechanized filling mining process was studied by similar simulation experiments, it is found that the influence law of initial filling height on roof rock beam subsidence is the same as that of theoretical analysis, and the experimental measurement values and fitting function relationships are consistent with the theoretical calculation results.