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PurposeDyslipidemia is a feature of polycystic ovary syndrome (PCOS) that may augment metabolic disturbances. Serum fatty acids are important biomedical indicators of dyslipidemia. The aim of this study was to determine the distinct serum fatty acids in various PCOS subtypes and their association with metabolic risk in women with PCOS.MethodsFatty acids in the serum of 202 women with PCOS were measured using gas chromatography-mass spectrometry. Fatty acids were compared between PCOS subtypes and correlated with glycemic parameters, adipokines, homocysteine, sex hormones, and sex hormone-binding globulin (SHBG).ResultsThe levels of total monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) in the reproductive subtype of PCOS were lower than those in the metabolic subtype. Docosahexaenoic acid, a PUFA, was associated with higher SHBG after correction for multiple comparisons. Eighteen species of fatty acids emerged as potential biomarkers associated with the metabolic risk factors measured, independent of body mass index (BMI). Among them, myristic acid (C14:0), palmitoleic acid (C16:1), oleic acid (C18:1n-9C), cis-vaccenic acid (C18:1n-7), and homo-gamma-linolenic acid (C20:3n-6) were the strongest lipid species that were consistently associated with metabolic risk factors, particularly insulin-related parameters in women with PCOS. As for adipokines, 16 fatty acids were positively associated with serum leptin. Among them, C16:1 and C20:3n-6were significantly associated with leptin levels.ConclusionOur data demonstrated that a distinct fatty acid profile comprising high C14:0, C16:1, C18:1n-9C, C18:1n-7, and C20:3n-6levels is associated with metabolic risk in women with PCOS, independent of BMI.

IntroductionThe lateral habenula (LHb) is a promising deep brain stimulation (DBS) target for treatment-resistant depression (TRD). However, the optimal surgical trajectory and its safety of LHb DBS are lacking.MethodsWe reported surgical trajectories for the LHb in six TRD patients treated with DBS at the General Hospital of the Chinese People's Liberation Army between April 2021 and May 2022. Pre-operative fusions of magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to design the implantation trajectory of DBS electrodes. Fusions of MRI and CT were conducted to assess the safety or precision of LHb DBS surgery or implantable electrodes locations.ResultsResults showed that the optimal entry point was the posterior middle frontal gyrus. The target coordinates (electrode tips) were 3.25 ± 0.82 mm and 3.25 ± 0.82 mm laterally, 12.75 ± 0.42 mm and 13.00 ± 0.71 mm posterior to the midpoint of the anterior commissure–posterior commissure (AC-PC) line, and 1.83 ± 0.68 mm and 1.17 ± 0.75 mm inferior to the AC-PC line in the left and right LHb, respectively. The “Ring” angles (relative to the AC-PC level on the sagittal section plane) of the trajectories to the left and right LHb were 51.87° ± 6.67° and 52.00° ± 7.18°, respectively. The “Arc” angles (relative to the midline of the sagittal plane) were 33.82° ± 3.39° and 33.55° ± 3.72°, respectively. Moreover, there was small deviation of actual from planned target coordinates. No patient had surgery-, disease- or device-related adverse events during the perioperative period.ConclusionOur results suggested that LHb-DBS surgery via frontal trajectory is safe, accurate, and feasible. This is an applicable work to report in detail the target coordinates and surgical path of human LHb-DBS. It has of great clinical reference value to treat more cases of LHb-DBS for TRD.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Rabbit Viral Hemorrhagic Disease (RHD) is a highly contagious and fatal infection, resulting in considerable economic losses to the rabbit industry. Consequently, it is essential to develop a fast and accurate diagnostic method for RHDV GI.1. In this study, a rapid simple reverse transcriptase recombinase polymerase amplification (RTRPA) for RHDV GI.1 was successfully developed using specific primers to RHDV GI.1 VP60 gene. Results indicated that the entire amplification process could be achieved in an isothermal condition at 40°C for 30 minutes, with good specificity and no reaction to other common rabbit disease pathogens, and a high sensitivity of upto 0.1LD50 of RHDV GI.1. Then, RT-RPA method was used to detect 1144 clinical samples, and the positive rates were 0.95%, 1.29% and 2.50% in Zaozhuang, Linyi, and Liaocheng in Shandong Province, respectively (the Fisher's exact test, P = 0.413), suggesting that there is no significant difference in RHDV GI.1 infection among the different regions. In conclusion, this study established a RT-RPA assay which is suitable for quick detection and monitoring of RHDV GI.1, thus making it a viable option for epidemiological surveillance.

Mulberry (Morus alba L.) has a special significance in the history of agriculture and economic plant cultivation. Mulberry has strong environmental adaptability, a wide planting range, and abundant output. It is not only an important resource for silkworm breeding but also a raw ingredient for various foods and has great potential for the development of biological resources. The bioactivities of mulberry in different planting areas are not the same, which is an obstacle to the development of mulberry. This study collected information on the planting conditions of mulberry branches in 12 planting areas, such as altitude, temperature difference, and precipitation. A comparison of the levels of 12 constituents of mulberry branches from mulberry grown in different planting areas was then made. An in vitro model was used to study the bioactivities of mulberry branches in the 12 planting areas, and mathematical analysis was used to explain the possible reasons for the differences in the composition and bioactivities of mulberry branches in different planting areas. After studying mulberry samples from 12 planting areas in China, it was found that a small temperature difference could affect the antiapoptotic effect of mulberry branch on microvascular endothelial cells by changing the levels and proportions of rutin, hyperoside, and morusin. Adequate irrigation can promote the antioxidation of the mulberry branch on microvascular endothelial cells by changing the levels and proportions of scopoletin and quercitrin. The results of the analysis of planting conditions and the levels of active constituents and their correlation with bioactivities support the improvement of mulberry planting conditions and have great significance in the rational development of mulberry resources. This is the first time that a mathematical analysis method was used to analyze the effects of planting conditions on mulberry biological activity.

IntroductionAutophagy can be triggered by oxidative stress and is a double-edged sword involved in the progression of multiple malignancies. However, the precise roles of autophagy on immune response in gastric cancer (GC) remain clarified.MethodsWe endeavor to explore the novel autophagy-related clusters and develop a multi-gene signature for predicting the prognosis and the response to immunotherapy in GC. A total of 1505 patients from eight GC cohorts were categorized into two subtypes using consensus clustering. We compare the differences between clusters by the multi-omics approach. Cox and LASSO regression models were used to construct the prognostic signature.ResultsTwo distinct clusters were identified. Compared with cluster 2, the patients in cluster 1 have favorable survival outcomes and lower scores for epithelial-mesenchymal transition (EMT). The two subtypes are further characterized by high heterogeneity concerning immune cell infiltration, somatic mutation pattern, and pathway activity by gene set enrichment analysis (GSEA). We obtained 21 autophagy-related differential expression genes (DEGs), in which PTK6 amplification and BCL2/CDKN2A deletion were highly prevalent. The four-gene (PEA15, HSPB8, BNIP3, and GABARAPL1) risk signature was further constructed with good predictive performance and validated in 3 independent datasets including our local Tianjin cohort. The risk score was proved to be independent prognostic factor. A prognostic nomogram showed robust validity of GC survival. The risk score was significantly associated with immune cell infiltration status, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint molecules. Furthermore, the model was efficient for predicting the response to tumor-targeted agent and immunotherapy and verified by the IMvigor210 cohort. This model is also capable of discriminating between low and high-risk patients receiving chemotherapy.ConclusionAltogether, our exploratory research on the landscape of autophagy-related patterns may shed light on individualized therapies and prognosis in GC.

The higher proportion of distributed photovoltaic and lower fossil energy integrated into the power network brings huge challenges in power supply reliability and planning. The distributed photovoltaic planning method based on big data is proposed. According to the impact of stochastic photovoltaics and loads on reliability planning, the probability model of distributed photovoltaic and load is analyzed, and the dynamic capacity–load ratios are presented based on big data. The multi-scenario generation and reduction algorithm of stochastic distributed photovoltaic and load planning is studied, and a source–load scenario matching model is proposed based on big data. According to the big data scenario of source–load, the reliability indexes and dynamic capacity–load ratio may be obtained. Finally, the IEEE 33-bus system is used as an example, and the results show that distributed photovoltaic planning methods based on big data can improve photovoltaic utilization and power supply reliability.

Based on the Quick Access Recorder (QAR) data covering over 9000 routes in China, the monthly and intra-day distribution characteristics of aircraft bumpiness at different levels were analyzed, and the relationships between the eddy dissipation rate (EDR) and other aircraft flight status elements during bumpiness occurrence were also analyzed. Afterward, aircraft bumpiness routes were constructed using 19 machine learning models. The analyses show that (1) aircraft bumpiness was mainly concentrated between 0:00 a.m. and 17:00 p.m. Severe aircraft bumpiness occurred more frequently in the early morning in January, especially between 5:00 a.m. and 6:00 a.m., and moderate bumpiness always occurred from 3:00 a.m. to 11:00 a.m. (2) The relationship between the left and right attack angles and aircraft bumpiness on the routes was more symmetrical, with a center at 0 degrees, unlike in the approach area where the hotspots were mainly concentrated in the range of −5 to 0 degrees. In the approach area, the larger the Mach number, the more severe the bumpiness. (3) The performances of the Automatic Relevance Determination Regression (ARD), Partial Least Squares Regression (PLS), Elastic-Net Regression (ENR), Classification and Regression Tree (CART), Passive Aggressive Regression (PAR), Random Forest (RF), Stochastic Gradient Descent Regression (SGD), and Tweedie Regression (TWD) based models were relatively good, while the performances of the Huber Regression (HUB), Least Angle Regression (LAR), Polynomial Regression (PLN), and Ridge Regressor (RR) based models were very poor. The aircraft bumpiness prediction models performed best over the approach area of ZBDT (airport in Datong), ZULS (airport in Lhasa), ZPPP (airport in Kunming), and ZLQY (airport in Qingyang). The model performed best in predicting the ZLLL-ZBDT air route (flight routes for Lanzhou to Datong) with different prediction times.

As a driving force for regional development, innovation holds an increasing position in regional competitiveness, and a reasonable and coordinated innovation network structure can promote high-quality regional development. Utilizing the modified gravity model and social network analysis method, an innovation network composed of 27 cities in the Yangtze River Delta urban agglomeration from 2010 to 2021 was studied. The following conclusions were founded: (1) The innovation development level in the Yangtze River Delta urban agglomeration was constantly improving, and the innovation development level generally showed a spatial pattern of high in the southeast and low in the northwest. (2) The intensity and density of innovation network correlations in urban agglomerations were increasing, and the centrality of network nodes had an obvious hierarchical characteristic. The innovation network had a significant core–periphery spatial structure, with core cities that had higher centrality, such as Shanghai, Nanjing, and Hangzhou, playing the role of “intermediaries” and “bridges”, while cities with lower centrality, such as Anhui and cities in northern Jiangsu, generally played the role of “periphery actors” in the network. (3) The spatial correlation network of innovation of the Yangtze River Delta urban agglomeration could be divided into four blocks, namely, main benefit, broker, two-way spillover, and net spillover, and the spillover effect among them had obvious gradient characteristics of hierarchy.

In a reservoir area, landslides can generate waves that pose a significant threat to bridge piers, endangering both property and human safety. This study utilized three-dimensional water tank experiments to simulate the generation of landslide-induced waves and their impact on bridge piers located on both riverbanks. The analysis focused on the types and distribution patterns of wave pressures on bridge piers. The results reveal the following key findings: (1) The results show that the wave pressures on the piers can be classified into two types: Pulsating pressure (Ppu) and Resonance pressure (Pre). Ppu represents the pressure generated during the wave action process. Ppu closely corresponds to the wave height-time process, with frequencies ranging from 0.2 to 0.5 Hz. Pre occurs prior to Ppu. Pre represents high-frequency vibrational waves generated when bridge piers resonate during wave action. Pre is observed primarily in deep water conditions and on the opposite riverbank, with frequencies ranging from 300 to 900 Hz. (2) On the bridge piers of the opposite riverbank, Ppu exhibits a nearly vertical distribution along the water depth, while on the same side, Ppu exhibits a sawtooth-like decrease along the water depth. Ppu increases with greater landslide volume and steeper landslide angles, and the maximum wave pressure distribution occurs near the water surface. (3) The distribution of Pre/Ppu along the water depth exhibits three forms: multiple-peak, single-peak, and no-peak, with the maximum positions for all conditions of Pre/Ppu occurring at approximately one-third of the water depth from the surface (Y/h=0.3). Finally, predictive formulas for the maximum wave pressures are provided.

Fused LEO navigation systems have been proposed as a low-cost means of supplementing and backing up global navigation satellite system (GNSS) navigation services based on low-earth orbit (LEO) constellations, which means broadcasting navigation signals based on the spectrum and hardware of the currently planned communication constellation. In this paper, we introduce Doppler-aided positioning to fused LEO navigation systems, which can improve the positioning performance and availability of fused LEO navigation systems by addressing insufficient pseudorange measures caused by insufficient navigation resources or the early stages of system construction. Theoretical analysis and simulation results show that Doppler-aided positioning based on the weighted least squares (WLS) method can improve the positioning accuracy of pseudorange positioning and achieve 95% three-dimensional errors within 21 m, even if the number of pseudorange measurements is less than four. Therefore, Doppler-aided positioning can expand the application scenarios of independent navigation services for fused LEO navigation systems.

Diabetic nephropathy (DN) refers to kidney damage caused by diabetes and is one of the major microvascular complications of diabetes. This disease has a certain degree of concealment in the early stage, with clinical symptoms appearing later and a higher mortality rate. Therefore, the detection of early biomarkers for DN is of great importance in reducing kidney function damage. The common biomarkers for DN mainly include glomerular and tubular lesion markers. At present, clinical diagnosis often uses a combination of multiple indicators and symptoms, and the development of a simple, efficient, and sensitive multi-marker detection platform is particularly important for the early diagnosis of DN. In recent years, with the vigorous development of various biomimetic molecular recognition technologies, biomimetic recognition biosensors (BRBS) have many advantages, such as easy preparation, low cost, high stability, and repeatability under harsh environmental conditions, and have great application potential in the analysis of DN biomarkers. This article reviews the research progress of molecularly imprinted polymers (MIPs) construction technology and aptamers assembly technology developed in the field of biomimetic sensor research in recent years, as well as the detection of DN biomarkers based on BRBS, and prospects for their development.

The effect of flume width (b) on overland flow dynamics was investigated in this study. Experiments were conducted with five different flow discharges and five flume widths (0.05–0.30 m, with an interval of 0.05 m). The findings revealed that a narrow flume had a noticeable impact on flow acceleration as the slope length increased. Relative average deviation (RAD) was calculated to evaluate the influence of sidewall effects on flow velocity. The coefficient of variation in the RAD ranged from 1.90% to 3.65%. The RAD has extremely significant differences between different widths when the flow is 0.02–0.08 m2/min. The significant differences in the RAD at different widths decrease as the flow rate increases. The flow regime was evaluated using the ratio of the thickness of the viscous sublayer to the water depth (δ/h), which proved to be a better indicator than the Reynolds number for studying flow regimes in different flume widths. Furthermore, it was observed that the energy variation was smaller in narrow flumes (b = 0.5–0.10 m) compared to wider flumes (b = 0.25–0.30 m). When the flume width ranged from 0.15 to 0.30 m, the specific energy change increased. These results contribute to further understanding of the hydraulic characteristics of overland flow and provide theoretical references for optimizing experimental design.

Researchers have previously investigated the role of Trichopria drosophilae as a pupal parasitoid in the biological control of Drosophila suzukii in China. Here, we investigated the ability of T. drosophilae to parasitize D. suzukii pupae at different temperatures. To do this, we evaluated the functional response of T. drosophilae to D. suzukii pupae at different temperatures and investigated the specific effects of density on parasitism. The results show that the parasitic functional response of T. drosophilae under different high-temperature stimuli is Holling type II. After processing at 29 °C, the instantaneous search rate was 1.1611; the theoretical maximum parasitic value was 20.88 at 31 °C. The parasitic efficiency decreased with increasing stimulation temperature, as the host pupa density increased from 5 to 25, and the strongest search effect occurred at 0.87 at 27 °C. The searching effect of T. drosophilae at each temperature fell gradually with an increase in prey density from 5 to 25. At 31 °C, the theoretical parasitic maximum of T. drosophilae reached a maximum of 20.88 pupae. At this temperature, when a pair of T. drosophilae was placed in a pupa density of 50, its actual total number of parasites was 18.60.

In previous works, inverse design methods have primarily focused on manipulating the optical power to achieve specific design targets. In this paper, we use the inverse design method to enable the precise engineering of the optical phase. As a proof of concept, we present a series of phase shifters (PSs) with varying phase shifts, which are inversely designed and theoretically validated on the silicon-on-insulator (SOI) platform. The designed PSs exhibit remarkable accuracy, with deviations of below 1°. These proposed PSs feature an ultra-compact footprint of 3 µm in length and offer superior fabrication tolerances compared to conventional structures. Over the 1535–1565 nm bandwidth, the discrepancy between the actual and target phase shifts remains below ±1° for all phase shifters, while the insertion loss is consistently below 0.035 dB. Moreover, the feasibility of the designed five PSs is verified using 2 × 2 multimode interference couplers (MMI).

Abstract Background Apoptosis signal-regulating kinase 1-interacting protein 1 (AIP1) participates in inflammatory neovascularization induction. NADPH oxidase 4 (NOX4) produces reactive oxygen species (ROS), leading to an imbalance in nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and NLR family pyrin domain containing 6 (NLRP6) expression. The mechanisms of AIP1, NOX4, ROS and inflammasomes in corneal neovascularization were studied herein. Methods C57BL/6 and AIP1-knockout mice were used in this study. The alkali burn procedure was performed on the right eye. Adenovirus encoding AIP1 plus green fluorescence protein (GFP) (Ad-AIP1-GFP) or GFP alone was injected into the right anterior chamber, GLX351322 was applied as a NOX4 inhibitor, and then corneal neovascularization was scored. The expression of related genes was measured by quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining. 2′,7′-Dichlorofluorescin diacetate staining was used to determine the ROS levels. Results The expression of AIP1 was decreased, while that of cleaved interleukin-1β (clv-IL-1β) and vascular endothelial growth factor A (VEGFa) was increased after alkali burn injury. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. NLRP3/NLRP6 expression was imbalanced after alkali burns. GLX351322 reversed the imbalance in NLRP3/NLRP6 by reducing the ROS levels. This treatment also reduced the expression of clv-IL-1β and VEGFa, suppressing neovascularization. Conclusions AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burn injury. Based on the pathogenesis of corneal neovascularization, these findings are expected to provide new therapeutic strategies for patients. Plain English summary Corneal alkali burn injury is a common type of ocular injury that is difficult to treat in the clinic. The cornea is a clear and avascular tissue. Corneal neovascularization after alkali burn injury is a serious complication; it not only seriously affects the patient’s vision but also is the main reason for failed corneal transplantation. Corneal neovascularization affects approximately 1.4 million patients a year. We show for the first time that AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burns. The expression of AIP1 was decreased, while that of clv-IL-1β and VEGFa was increased after alkali burns. We tried to elucidate the specific molecular mechanisms by which AIP1 regulates corneal neovascularization. NOX4 activation was due to decreased AIP1 expression in murine corneas with alkali burns. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. Additionally, NLRP3/NLRP6 expression was unbalanced, with NLRP3 activation and NLRP6 suppression in the corneal alkali burn murine model. Eye drops containing GLX351322, a NOX4 inhibitor, reversed the imbalance in NLRP3/NLRP6 by reducing ROS expression. This treatment also reduced the expression of clv-IL-1β and VEGFa, reducing neovascularization. Therefore, we provide new gene therapeutic strategies for patients. With the development of neovascularization therapy, we believe that in addition to corneal transplantation, new drug or gene therapies can achieve better results. Video Abstract

Abstract Background In patients with acute hypoxemic respiratory failure whose diagnosis is not established after initial evaluation, obtaining a histopathological diagnosis may improve the patients’ prognosis. This study aims to compare the safety profile and diagnostic yields between transbronchial lung biopsy (TBLB) and transbronchial lung cryobiopsy (TBLC) in these patients. Methods A retrospective comparative study was conducted in a 26-bed intensive care unit over a 5-year period. The consecutive patients with acute hypoxemic respiratory failure who underwent TBLB or TBLC were included to determine the potential etiology. Patients characteristics, procedure related complications, pathological and multidisciplinary discussion (MDD) diagnostic yields, treatment modification and 28-day survival were analyzed. Prognostic factors were identified by Cox regression analysis. Results Forty-five and 25 consecutive patients underwent TBLB and TBLC, respectively. The patients underwent TBLC were more critical. There was no significant difference in overall procedure related complications of patients underwent TBLB and TBLC [15.6% (7/45) vs 28.0% (7/25), p = 0.212]. The rate of pathological diagnostic yield [72.0% (18/25) vs 37.8% (17/45), p = 0.006], MDD diagnostic yield [84.0% (21/25) vs 55.6% (25/45), p = 0.016] and subsequent treatment modification [84.0% (21/25) vs 57.8% (26/45), p = 0.025] in patients underwent TBLC were significantly higher than those in patients underwent TBLB. Multivariate analysis revealed that MDD diagnosis [HR 0.193 (95% CI 0.047–0.792), p = 0.022] and treatment modification [HR 0.204 (95% CI 0.065–0.638), p = 0.006] may be prognostic protective factors. Conclusions TBLC can lead to an increased chance of establishing a diagnosis, which could significantly improve the patients’ prognosis, with an acceptable safety profile.

Polyvinyl alcohol (PVA) embolization particles, currently used in clinical practice, have good expansibility and are capable of permanent embolization. However, the lack of adhesion of embolization particles contributes to facilitated recanalization after embolization, while the lack of visualization facilitates misembolization. At present, embolization materials with good expansion, adhesion, and visualization potential are urgently required in clinical practice. Here, we report the development of PVA/gelatin/iohexol (I) fiber blocks as a novel embolization material for liver embolization in rats. In our work, electrospun PVA/gelatin/I nanofibrous mats were first prepared, homogenized, centrifuged in a gradient manner, and freeze-dried to obtain fiber blocks (fiber diameter ​= ​296.2 ​± ​74.23 ​nm, length 99.6 ​± ​17.0 ​μm ​× ​width 46.9 ​± ​13.3 ​μm). The fiber blocks exhibited excellent cytocompatibility and hemocompatibility. Fiber blocks with a PVA/gelatin/I mass ratio of 8:2:10 were selected due to their excellent expansibility and adhesive properties. The PVA/gelatin/I fiber blocks display excellent liver embolic effects and computed tomography (CT) imaging potential due to a combination of the following characteristics: expansibility of PVA and gelatin, adhesive property of gelatin, and CT imaging potential of I. The developed fiber block material is an embolic material that may potentially be used in interventional medicine.

Abstract This study intended to compare the prevalence of hypertension in adolescents aged 15–17 years in China according to different criteria defined by various guidelines. We included 28 715 adolescents aged 15–17 years from the China Hypertension Survey study (CHS) 2012–2015, and the 2017 American Association of Pediatrics (AAP) Clinical Practice Guideline and 2018 Chinese guidelines for children and adults were used to define hypertension. The prevalence of hypertension among Chinese adolescents aged 15–17 years was 24.4% according to the 2018 Chinese guidelines for children; the corresponding values were 18.6% according to the 2017 AAP Guidelines, and 3.5% according to 2018 Chinese guidelines for adults. The age‐specific prevalence of hypertension in the age of 15, 16, and 17 years in the same population was 26.2%, 24.4%, and 23.3% according to 2018 Chinese guidelines for children; 18.8%, 17.9%, and 19.2% as per the 2017 AAP Guidelines; 3.4%, 3.4%, and 3.6% as per the 2018 Chinese guidelines for adults. A highest prevalence of hypertension was observed according to 2018 Chinese guidelines for children than the other two guidelines. Compared with the 2018 Chinese guidelines for children, a higher 95th percentile BP (systolic and diastolic) was also observed in the present study in each gender‐age‐height‐specific group. And the height, which was key factor to influence blood pressure, was similar between adolescents aged 15–17 and adults, and a paralleled result was seen in the present study. Therefore, the 2018 Chinese guidelines for adults may also be appropriate for adolescents aged 15–17 years.

Abstract Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (

Herein, Ag1-3xSmxNbO3 (0 ≤ x ≤ 0.025) antiferroelectric ceramics were successfully synthesized by solid state methods. The effect of Sm3+ doping on the structure, property and energy storage performance were studied. With the increasing Sm3+ concentrations, the average grain size decreased. Meanwhile, the stability of high temperature M phases (i.e., the structure between Tf and T3) was expanded, which led to low loss for energy storage. Both of structure analysis and ferroelectric tests revealed the existence of weakly polar/AFE-like phase below Tf. The Sm3+ doping tended to suppress the ferroelectric behavior and expand the stability of antiferroelectricity. Consequently, a significantly enhanced energy storage performance (Wrec = 3.8 J/cm3, η = 73 %) could be achieved in Ag0.97Sm0.01NbO3 ceramic, which was almost 1.5 times larger than that in non-doped AgNbO3 (Wrec = 2.4 J/cm3, η = 45 %) under the similar applied field of 1705 kV/cm±. In particular, the performance of the ceramic showed great temperature stability with variation of ±5 % from 25 °C to 125 °C. These results indicated that the Ag0.97Sm0.01NbO3 ceramic could be an ideal lead-free candidate used in the energy storage field.

Abstract It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.

Abstract GNE-493 is a novel PI3K/mTOR dual inhibitor with improved metabolic stability, oral bioavailability, and excellent pharmacokinetic parameters. Here GNE-493 potently inhibited viability, proliferation, and migration in different primary and established (LNCaP and PC-3 lines) prostate cancer cells, and provoking apoptosis. GNE-493 blocked Akt-mTOR activation in primary human prostate cancer cells. A constitutively-active mutant Akt1 restored Akt-mTOR activation but only partially ameliorated GNE-493-induced prostate cancer cell death. Moreover, GNE-493 was still cytotoxic in Akt1/2-silenced primary prostate cancer cells. Significant oxidative stress and programmed necrosis cascade activation were detected in GNE-493-treated prostate cancer cells. Moreover, GNE-493 downregulated Sphingosine Kinase 1 (SphK1), causing ceramide accumulation in primary prostate cancer cells. Daily single dose GNE-493 oral administration robustly inhibited the growth of the prostate cancer xenograft in the nude mice. Akt-mTOR inactivation, SphK1 downregulation, ceramide level increase, and oxidative injury were detected in GNE-493-treated prostate cancer xenograft tissues. Together, GNE-493 inhibited prostate cancer cell growth possibly through the Akt-mTOR-dependent and -independent mechanisms.

When the T-connected transmission line fails, there is a certain relationship between the phases of the three-terminal power frequency fault current, which can be applied to protect the current differential of the T-connected line. In this paper, using the MATLAB/Simulink electric power system simulation software, when the T-connected transmission line is faulty, the power frequency fault current variation law monitored at the installation point is deeply studied, and the judgment method of the T-connected transmission line fault branch based on the power frequency current is proposed.

Summary: The molecular mechanisms mediating the aggregation and transmission of tau in AD remain unclear. Here, we show that the actin-binding protein cofilin is cleaved by a cysteine protease asparagine endopeptidase (AEP) at N138 in the brains of patients with AD. The AEP-generated cofilin 1-138 fragment interacts with tau and promotes its aggregation. The mixed fibrils consisting of cofilin 1-138 and tau are more pathogenic to cells than pure tau fibrils. Furthermore, overexpression of cofilin 1-138 in the brain facilitates the propagation of pathological tau aggregates and promotes AD-like cognitive impairments in tau P301S mice. However, mice infected with adeno-associated viruses (AAVs) encoding an AEP-uncleavable cofilin mutant show attenuated tau pathology and cognitive impairments compared with mice injected with AAVs encoding wild-type cofilin. Together, these observations support the role of the cofilin 1-138 fragment in the aggregation and transmission of tau pathology during the onset and progression of AD.

ObjectivesOlfactory disorder is one of the sensory features that reflects a decline in cognitive function. However, olfactory changes and the discernibility of smell testing in the aging population have yet to be fully elucidated. Therefore, this study aimed to examine the effectiveness of the Chinese Smell Identification Test (CSIT) in distinguishing individuals with cognitive decline from those with normal aging and to determine whether the patients with MCI and AD show changes in their olfactory identification abilities.MethodsThis cross-sectional study included eligible participants aged over 50 years between October 2019 and December 2021. The participants were divided into three groups: individuals with mild cognitive impairment (MCI), individuals with Alzheimer's disease (AD), and cognitively normal controls (NCs). All participants were assessed using neuropsychiatric scales, the Activity of Daily Living scale, and the 16-odor cognitive state test (CSIT) test. The test scores and the severity of olfactory impairment were also recorded for each participant.ResultsIn total, 366 eligible participants were recruited, including 188 participants with MCI, 42 patients with AD, and 136 NCs. Patients with MCI achieved a mean CSIT score of 13.06 ± 2.05, while patients with AD achieved a mean score of 11.38 ± 3.25. These scores were significantly lower than those of the NC group (14.6 ± 1.57; P < 0.001). An analysis showed that 19.9% of NCs exhibited mild olfactory impairment, while 52.7% of patients with MCI and 69% of patients with AD exhibited mild to severe olfactory impairment. The CSIT score was positively correlated with the MoCA and MMSE scores. The CIST score and the severity of olfactory impairment were identified as robust indicators for MCI and AD, even after adjusting for age, gender, and level of education. Age and educational level were identified as two important confounding factors that influence cognitive function. However, no significant interactive effects were observed between these confounders and CIST scores in determining the risk of MCI. The area under the ROC curve (AUC) generated from the ROC analysis was 0.738 and 0.813 in distinguishing patients with MCI and patients with AD from NCs based on the CIST scores, respectively. The optimal cutoff for distinguishing MCI from NCs was 13, and for distinguishing AD from NCs was 11. The AUC for distinguishing AD from MCI was 0.62.ConclusionsThe olfactory identification function is frequently affected in patients with MCI and patients with AD. CSIT is a beneficial tool for the early screening of cognitive impairment among elderly patients with cognitive or memory issues.

In recent years, organic fluorescent probes with tumor microenvironment (TME)-responsive fluorescence turn-on properties have been increasingly used in imaging-guided tumor resection due to their higher signal-to-noise ratio for tumor imaging compared to non-responsive fluorescent probes. However, although researchers have developed many organic fluorescent nanoprobes responsive to pH, GSH, and other TME, few probes that respond to high levels of reactive oxygen species (ROS) in the TME have been reported in imaging-guided surgery applications. In this work, we prepared Amplex® Red (ADHP) with excellent ROS response performance as an ROS-responsive nanoprobe and studied its application in image-guided tumor resection for the first time. To confirm whether the nanoprobe can be used as an effective biological indicator to distinguish tumor sites, we first detected 4T1 cells with the ADHP nanoprobe, demonstrating that the probe can utilize ROS in tumor cells for responsive real-time imaging. Furthermore, we conducted fluorescence imaging in vivo in 4T1 tumor-bearing mice, and the ADHP probe can rapidly oxidize to form resorufin in response to ROS, which can effectively reduce the background fluorescence signal compared with the single resorufin probe. Finally, we successfully carried out image-guided surgery of 4T1 abdominal tumors under the guidance of fluorescence signals. This work provides a new idea for developing more TME-responsive fluorescent probes and exploring their application in image-guided surgery.

Background: A disposable lunch box is an important cause of “white pollution”. Many people consider that the disposable polylactic acid (PLA) lunch box is more environmentally friendly than the disposable paper pulp lunch box and can substitute for the latter. Objective: We can determine whether PLA tableware is more environmentally friendly than paper tableware by analyzing the product life cycle of two tableware types. At the same time, as a continuous compound, carbon dioxide has significant commercial value. Carbon dioxide materials' applications range from beverages to cosmetics and building materials. The future application of carbon dioxide in the field of lunch boxes is discussed in this paper. Methods: In this paper, the production stages of the two types of disposable lunch boxes were compared and surveyed using the life cycle assessment (LCA) method. Conclusion: The results reveal that the main impact of the two types of lunch boxes is resource damage; the PLA lunch box is not better than the paper type; the production stage of the disposable PLA lunch box poses greater damage to the environment in all aspects than the paper type. Discussion: Against the background of carbon neutrality and based on the constantly mature carbon dioxide conversion technology, the author explored the possibility of making products from carbon dioxide and proposed to make product designs based on carbon dioxide.

Redox imbalance can trigger cell dysfunction and damage and plays a vital role in the origin and progression of many diseases. Maintaining the balance between oxidants and antioxidants in vivo is a complicated and arduous task, leading to ongoing research into the construction of redox nanomaterials. Nanodrug platforms with redox characteristics can not only reduce the adverse effects of oxidative stress on tissues by removing excess oxidants from the body but also have multienzyme-like activity, which can play a cytotoxic role in tumor tissues through the catalytic oxidation of their substrates to produce harmful reactive oxygen species such as hydroxyl radicals. In this review, various redox nanomaterials currently used in disease therapy are discussed, emphasizing the treatment methods and their applications in tumors and other human tissues. Finally, the limitations of the current clinical application of redox nanomaterials are considered.

Thrombophilia is an important cause of recurrent spontaneous abortion (RSA). The treatment of thrombophilia is beneficial to the prevention of RSA. Therefore, we explored the clinical effect of Chinese traditional herbs with the effects of invigorating the blood, tonifying the kidney and calming the fetus in the treatment of RSA complicated with thrombophilia. We retrospectively analyzed the clinical outcomes of 190 RSA patients combined with thrombophilia using different treatment methods. The traditional Chinese medicine group was treated with kidney-invigorating, blood-activating and fetus-soothing herbs and the western medicine group was treated with low molecular weight heparin (LMWH), and the traditional Chinese medicine combined with western medicine group was treated with LMWH plus Chinese traditional herbs with the effects of kidney tonifying, blood activating and fetus stabilizing. After treatments, platelet aggregation rate, plasma D-dimer and uterine artery blood flow resistance were significantly reduced in the LMWH plus herbs compared to the simple herbs and LMWH group (P

IntroductionRopivacaine oil delivery depot (RODD) can slowly release ropivacaine and block nerves for a long timejavascript:;. The aim of the present work was to investigate the safety, pharmacokinetics, and preliminary pharmacodynamics of RODD in subcutaneous injection among healthy subjects.MethodsThe abdomens of 3 subjects were subcutaneously administered with a single-needle RODD containing 12~30 mg of ropivacaine. The irritation, nerve blocking range and optimum dose were investigated. Forty-one subjects were divided into RODD groups containing 150, 230, 300, 350 and 400 mg of ropivacaine and a ropivacaine hydrochloride injection (RHI) 150 mg group. Multineedle subcutaneous injection of RODD or RHI was performed in the abdomens of the subjects. The primary endpoint was a safe dose or a maximum dose of ropivacaine (400 mg). Subjects' vital signs were observed; their blood was analyzed; their cardiovascular system and nervous systems were monitored, and their dermatological reactions were observed and scored. Second, the ropivacaine concentrations in plasma were determined, pharmacokinetic parameters were calculated, and the anesthetic effects of RODD were studied, including RODD onset time, duration and intensity of nerve block.ResultsSingle-needle injection of RODD 24 mg was optimal for 3 subjects, and the range of nerve block was 42.5±20.8 mm. Multineedle subcutaneous injection of RODD in the abdomens of subjects was safe, and all adverse events were no more severe than grade II. The incidence rate of grade II adverse events, such as pain, and abnormal ST and ST-T segment changes on electrocardiography, was approximately 1%. The incidence rate of grade I adverse events, including erythema, papules, hypertriglyceridemia, and hypotension was greater than 10%. Erythema and papules were relieved after 24 h and disappeared after 72 h. Other adverse reactions disappeared after 7 days. The curve of ropivacaine concentration-time in plasma presented a bimodal profile. The results showed that ropivacaine was slowly released from the RODD. Compared with the 150 mg RHI group, Tmax was longer in the RODD groups. In particular, Tmax in the 400 mg RODD group was longer than that in the RHI group (11.8±4.6 h vs. 0.77±0.06 h). The Cmax in the 150 mg RODD group was lower than that in the 150 mg RHI group (0.35±0.09 vs. 0.58±0.13 μg·mL-1). In particular, the Cmax increased by 48% when the dose was increased by 2.6 times in the 400 mg group. Cmax, the AUC value and the intensity of the nerve block increased with increasing doses of RODD. Among them, the 400 mg RODD group presented the strongest nerve block (the percentage of level 2 and 3, 42.9%). The corresponding median onset time was 0.42 h, and the duration median was 35.7⁓47.7 h.ConclusionsRODD has a sustained release effect. Compared with the RHI group, Tmax was delayed in the RODD groups, and the duration of nerve block was long. No abnormal reaction was found in the RODD group containing 400 mg of ropivacaine after subcutaneous injection among healthy subjects, suggesting that RODD was adequately safe.Trial registrationChictr.org: CTR2200058122; Chinadrugtrials.org: CTR20192280.

As the most prevalent subtype of aortic aneurysm, abdominal aortic aneurysm (AAA) features the apoptosis, extracellular matrix (ECM) disruption, and inflammation response of vascular smooth muscle cells (VSMCs). Noncoding RNAs (ncRNAs) are crucial factors in AAA progression, while the investigations have not been fully explained. miR-191-5p upregulation is found in aortic aneurysm. However, its role in AAA has not been addressed. This research purposed to excavate the possible and associated molecular axis of miR-191-5p in AAA. In our study, miR-191-5p level was detected to be high in the tissues from AAA patients in comparison with the control group. After miR-191-5p expression was enhanced, cell viability was repressed, cell apoptosis was boosted, and ECM disruption and the inflammation response were fortified. Furthermore, the relationship among MIR503HG, miR-191-5p, and phospholipase C delta 1 (PLCD1) in VSMCs was disclosed via mechanism assays. Decreased MIR503HG lacked the inhibition on miR-191-5p targeting PLCD1, resulting in downregulation of PLCD1, which facilitated the progression of AAA. Thus, targeting MIR503HG/miR-191-5p/PLCD1 pathway will provide an additional method for the cure of AAA patients.

Incentive-based traffic demand management (IBTDM) schemes redistribute traffic demand across space and time. The relationship between IBTDM and traditional tolling programs impacts financial sustainability and decision making of both programs. This study aims to examine if an IBTDM and a tolling program can coexist and should collaborate or compete to establish a financially sustainable mobility ecosystem. We investigate a duopoly case with an IBTDM and a tolling program in a parallel bottleneck model with fixed demand. It is assumed that the IBTDM program has a user acquisition cost and is constrained by a total budget. Then, the collaboration and competition cases between two programs are investigated, respectively. We found that both programs can attract substantial amounts of commuters and thus can coexist with each other, while the IBTDM program could attract more commuters. Overall, the tolling agency will not cooperate with the IBTDM company if its goal is to raise revenue. Additionally, the IBTDM company held an advantage as it can determine an optimal incentive scheme with incomplete information when competing. This study fills the knowledge gap on the coexistence of incentive and tolling programs, which helps to optimize the profiles of incentive and tolling, as well as to make strategic decisions on competition and cooperation.

Background Radiotherapy (RT) combined with chemotherapy is the standard treatment for T1-2N1M0 nasopharyngeal carcinoma (NPC) based on conventional radiotherapy. However, intensity-modulated radiotherapy (IMRT) has narrowed the treatment gap between RT and chemoradiotherapy. Thus, this retrospective study aimed to compare the efficacy of RT and chemoradiotherapy (RT-chemo) in treating T1-2N1M0 NPC in the IMRT era. Materials and methods From January 2008 to December 2016, 343 consecutive patients with T1-2N1M0 NPC in two cancer centers were included. All patients received RT or RT-chemo, chemotherapy including induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT), CCRT, or CCRT + adjuvant chemotherapy (AC). The number of patients who received RT, CCRT, IC + CCRT, and CCRT + AC was 114, 101, 89, and 39. The survival rates were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. Results The median follow-up time for survivors was 93 (range: 55–144) months. The 5-year overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) for the RT-chemo and RT groups were 93.7%, 88.5%, 93.8%, 93.8% and 93.0%, 87.7%, 91.9%, 91.2%, respectively (P>0.05 for all outcomes). No significant survival differences were found between the two groups. The T1N1M0 or T2N1M0 subgroup analysis showed that treatment outcomes had no significant differences between the RT and RT-chemo groups. After adjusting for various factors, treatment mode was not identified as an independent prognostic factor for all survival rates. Conclusions In this study, outcomes of T1-2N1M0 NPC patients treated by IMRT alone were comparable to chemoradiotherapy, supporting the omission or postponement of chemotherapy.

Sustainable business model innovation (SBMI) and green technology innovation (GTI) are keys to creating shared social and business value, and both are essential elements of responsible innovation. However, SBMI or GTI is unable to develop a sustainable business. The main purpose of this study is to analyze sustainable dual innovation as a conceptual framework based on the panel data of 1468 Chinese manufacturing A-share listed companies from 2010 to 2020, and it has obtained three essential findings. First, there is a significant matching effect between SBMI and GTI on sustainable corporate performance (SCP). Companies report higher levels of SCP when there is a higher congruence in SBMI with GTI. Secondly, organizations with high SBMI-low GTI realize superior SCP compared to organizations with low SBMI-high GTI. The high SBMI-low GTI becomes an ideal choice for most companies and avoids the “destructive factors” brought by low SBMI-high GTI. Finally, a highly aggressive corporate strategy has a “magnifying effect” on the impact of the combination of SBMI and GTI on SCP. The research provides a comprehensive understanding and collective impact of SBMI and GTI on SCP. Overall, findings provide a theoretical basis for enterprises to decide on the consistency/inconsistency trade-off between SBMI and GTI. Moreover, it encourages to enterprises must develop an aggressive strategy to balance.

Abstract Sepsis causes multiple organ injuries, among which the heart is one most severely damaged organ. Melatonin (MEL) alleviates septic myocardial injury, although a systematic and comprehensive approach is still lacking to understand the precise protective machinery of MEL. This study aimed to examine the underlying mechanisms of MEL on improvement of septic myocardial injury at a systematic level. This study integrated three analytic modalities including database investigations, RNA‐seq analysis, and weighted gene co‐expression network analysis (WCGNA), in order to acquire a set of genes associated with the pathogenesis of sepsis. The Drugbank database was employed to predict genes that may serve as pharmacological targets for MEL‐elicited benefits, if any. A pharmacological protein–protein interaction network was subsequently constructed, and 66 hub genes were captured which were enriched in a variety of immune response pathways. Notably, PIK3CG, one of the hub genes, displayed high topological characteristic values, strongly suggesting its promise as a novel target for MEL‐evoked treatment of septic myocardial injury. Importantly, molecular docking simulation experiments as well as in vitro and in vivo studies supported an essential role for PIK3CG in MEL‐elicited effect on septic myocardial injury. This study systematically clarified the mechanisms of MEL intervention in septic myocardial injury involved multiple targets and multiple pathways. Moreover, PIK3CG‐governed signaling cascade plays an important role in the etiology of sepsis and septic myocardial injury. Findings from our study provide valuable information on novel intervention targets for the management of septic myocardial injury. More importantly, this study has indicated the utility of combining a series of techniques for disease target discovery and exploration of possible drug targets, which should shed some light on elucidation of experimental and clinical drug action mechanisms systematically.

Hematoma is a life-threatening complication of anterior surgery in cervical spondylosis patients. Herein, we report a cervical spondylosis patient complicated with Huntington’s disease, who developed unexpected neck hematoma after anterior cervical discectomy and fusion (ACDF) surgical treatment. During the debridement, we found no noticeable vessel lesions and concluded that the occurrence of postoperative hematoma might be due to the drainage displacement caused by excessive uncontrolled movements of the neck after the operation. The patient recovered well, and further literature review suggests that chorea secondary to Huntington’s disease likely increases mechanical stress on the cervical spine, indicating an internal relationship between degenerative cervical spondylosis and Huntington’s disease. Cervical spondylotic patients complicated with Huntington’s disease can be treated with surgical intervention but need to be immobilized and under close observation.

Immuno-checkpoint inhibitors (ICIs) bring a promising prospect for patients with cancers, which restrains the growth of tumor cells by enhancing anti-tumor activity. Nevertheless, not all patients benefit from the administration of ICIs monotherapy. The partial response or resistance to ICIs is mainly due to the complex and heterogenous tumor microenvironment (TME). The combined therapy is necessary for improving the efficacy of tumor treatment. Chemotherapy is reported not only to kill tumor cells directly, but also to stimulate effective anti-tumor immune responses. Several combined therapies of ICIs and chemotherapeutic agents have been approved for the first-line treatment of cancers, including PD-1/PD-L1 inhibitors. This review summarizes the potential mechanisms of the combined therapy of ICIs and chemotherapeutic agents in inducing immunogenic cell death (ICD) and reprogramming TME, and elucidates the possible anti-tumor effects of combined therapy from the perspective of metabolic reprogramming and microbiome reprogramming.

BackgroundSepsis associated encephalopathy (SAE) is a common but poorly understood complication during sepsis. Currently, there are no preventive or therapeutic agents available for this neurological disorder. The present study was designed to determine the potential protective effects of β-patchoulene (β-PAE) in a mouse model of SAE and explore the putative mechanisms underpinning the beneficial effects.Materials and methodsSAE was induced in C57BL/6 mice by cecal ligation and puncture(CLP). Mice were administrated with β-PAE or saline by intra-cerebral ventricle(i.c.v) injection immediately after CLP surgery. The inhibitory avoidance tests and open field tests were performed at 24h, 48h and 7days after procedures. Cytokines expression, oxidative parameters, microglia polarization and apoptosis in the brain tissue were assessed. Sirt1, Nrf2, HO-1and cleaved-caspase3 expression in hippocampus was determined by western-blotting. Further, serum cytokines expression and spleen lymphocytes apoptosis were evaluated, and survival study was performed.ResultsSeptic mice suffered severe cognitive decline following CLP as evidenced by decreased memory latency time and lower frequency of line crossing in the behavioral tests. A high dose of β-PAE(1mg/kg) improved the cognitive impairment in SAE mice, which was accompanied by reduced cytokines expression and oxidative stress. Immunofluorescence assay showed that β-PAE inhibited the expression of Iba-1 and iNOS in microglia. The mechanistic study indicated that β-PAE could promote the nuclear expression of Sirt1/Nrf2 and enhance cytoplasmic HO-1 expression. Furthermore, i.c.v administration of β-PAE decreased the expression of serum cytokines and apoptosis in the spleen, thus leading to an improved 7-day survival of septic mice. Finally, blockade of Nrf2 activation with ML385 largely mitigated the protective effects of β-PAE on the cognitive function, neuroinflammation and survival in SAE mice.ConclusionIn this study, we found that β-PAE significantly altered sepsis induced neuroinflammation and microglia activation, thus reversed the cognitive decline and improved the peripheral immune function. The neuroprotective effects were possibly mediated by the activation of Sirt1/Nrf2/HO-1 pathway. β-PAE might serve as a promising therapeutic agent for SAE prevention and treatment.

This study experimentally investigates the condensation performance of moist air on the processed windshield surface. The quantitative results of heat transfer coefficient and condensation rate of three kinds of surfaces under different working conditions are obtained. Under dry conditions, the convective heat transfer coefficients (CHTCs) of the hydrophobic and hydrophilic surfaces are about 20% and 3% higher than that of normal surface. Under wet conditions, the CHTC of hydrophobic surface is superior to that of normal surface by approximately 10%, while the CHTC of hydrophilic surface is inferior to that of normal surface by about 5%. The mean of mass transfer coefficient (kas) for the hydrophobic, hydrophilic and normal surfaces are calculated about 0.0063 m/s, 0.0054 m/s and 0.0054 m/s, respectively. The condensation rate of the hydrophobic surface is higher than that of hydrophilic one about 7–9% due to the dropwise condensation.

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is essential life support in patients with severe acute hypoxaemic respiratory failure. However, biopsies should be considered for some patients with unknown aetiology. This study aims to evaluate the feasibility of transbronchial lung cryobiopsy (TBLC) in such patients. Methods All patients with acute hypoxaemic respiratory failure of unknown aetiology who underwent TBLC with VV-ECMO support were retrospectively reviewed. Patients’ characteristics, ventilation settings, procedure parameters, complications, pathological diagnosis and survival were summarised and analysed. Results Eight female and five male patients with VV-ECMO support underwent TBLC. The median age was 58 (interquartile range (IQR) 38–67) years old. Concurrent diseases were present in 10 of the 13 patients, seven of which were immunosuppressed. The median time between biopsy and VV-ECMO establishment was 2.0 (IQR 0.5–6.5) days. No patient died from the procedure. Neither pneumothorax nor severe bleeding occurred in any of the patients. Five of the 13 patients experienced moderate bleeding, and all bleeding events were successfully controlled with prophylactic balloon blockers. Pathological diagnosis by TBLC was obtained in all patients, and the diagnosis of diffuse alveolar damage was made in nine of them. Conclusions In patients with VV-ECMO support, the TBLC procedure is generally safe when standardised bleeding prophylaxis is in place. TBLC contributes to identifying underlying aetiologies in patients with acute hypoxaemic respiratory failure of unknown aetiology.

Nitrous oxide (N2O) emissions are highly variable due to the complex interaction of climatic and ecological factors. Here, we obtained in-situ annual N2O emission flux data from almost 180 peer-papers to evaluate the dominant drivers of N2O emissions from forests and unfertilized grasslands at a global scale. The average value of N2O emission fluxes from forest (1.389 kg Nha-1yr-1) is almost twice as large as that from grassland (0.675 kg Nha-1yr-1). Soil texture and climate are the primary drivers of global forest and grassland annual N2O emissions. However, the best predictors varied according to land use and region. Soil clay content was the best predictor for N2O emissions from forest soils, especially in moist or wet regions, while soil sand content predicted N2O emissions from dry or moist grasslands in temperate and tropical regions best. Air temperature was important for N2O emission from forest, while precipitation was more efficient in grassland. This study provides an overall understanding of the relationship between natural N2O emissions and climatic and environmental variables. Moreover, the identification of principle factors for different regions will reduce the uncertainty range of N2O flux estimates, and help to identify region specific climate change mitigation and adaptation strategies.

BackgroundGrowing evidence suggests that tumor metastasis necessitates multi-step microenvironmental regulation. Lymph node metastasis (LNM) influences both pre- and post-operative bladder cancer (BLCA) treatment strategies. Given that current LNM diagnosis methods are still insufficient, we intend to investigate the microenvironmental changes in BLCA with and without LNM and develop a prediction model to confirm LNM status.Method"Estimation of Stromal and Immune cells in Malignant Tumors using Expression data" (ESTIMATE) algorithm was used to characterize the tumor microenvironment pattern of TCGA-BLCA cohort, and dimension reduction, feature selection, and StrLNM signature construction were accomplished using least absolute shrinkage and selection operator (LASSO) regression. StrLNM signature was combined with the genomic mutation to establish an LNM nomogram by using multivariable logistic regression. The performance of the nomogram was evaluated in terms of calibration, discrimination, and clinical utility. The testing set from the TCGA-BLCA cohort was used for internal validation. Moreover, three independent cohorts were used for external validation, and BLCA patients from our cohort were also used for further validation.ResultsThe StrLNM signature, consisting of 22 selected features, could accurately predict LNM status in the TCGA-BLCA cohort and several independent cohorts. The nomogram performed well in discriminating LNM status, with the area under curve (AUC) of 75.1% and 65.4% in training and testing datasets from the TCGA-BLCA cohort. Furthermore, the StrLNM nomogram demonstrated good calibration with p >0.05 in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis (DCA) revealed that the StrLNM nomogram had a high potential for clinical utility. Additionally, 14 of 22 stably expressed genes were identified by survival analysis and confirmed by qPCR in BLCA patient samples in our cohort.ConclusionIn summary, we developed a nomogram that included an StrLNM signature and facilitated the preoperative prediction of LNM status in BLCA patients.

IntroductionAnimal intestines are extremely rich in microbial ecosystems. Numerous studies in different fields, such as epidemiology and histology, have revealed that gut microorganisms considerably mediate the survival and reproduction of animals. However, gut microbiology studies of homogeneously distributed wild cranes are still rare. This study aimed to understand the structural composition of the gut microbial community of wild cranes and elucidate the potential roles of the microorganisms.MethodsWe used high-throughput sequencing to analyze the gut microbial community structure of wild cranes in the Zhalong Nature Reserve.ResultsA total of 1,965,683 valid tags and 5248 OTUs were obtained from 32 fecal samples. Twenty-six bacteria phyla and 523 genera were annotated from the intestinal tract of the red-crowned crane. Twenty-five bacteria phyla and 625 genera were annotated from the intestine of the white-naped crane. Firmicutes, Proteobacteria, and Bacteroidetes are the dominant bacterial phyla in the intestinal tract of red-crowned cranes, while Catellicoccus, Lactobacillus, Neisseria, and Streptococcus were the dominant genera. The dominant bacterial phyla in the intestinal tract of white-naped cranes were Firmicutes, Proteobacteria, Bacteroidetes, Epsilonbacteraeota, Actinobacteria, and Fusobacteria. However, the dominant genera were Catellicoccus, Lactobacillus, Neisseria, Campylobacter, Streptococcus, Anaerobiospirillum, Romboutsia, Turicibacter, Haemophilus, and Lautropia. Firmicutes had significantly higher relative abundance in the intestine of the red-crowned than white-naped cranes (P < 0.05). However, the relative abundance of Actinobacteria and Bacteroidetes was significantly higher (P < 0.05) in the intestines of white-naped than red-crowned cranes. The diversity of the intestinal flora between the two crane species was significantly different (P < 0.05). Besides, the alpha diversity of the intestinal flora was higher for white-naped than red-crowned cranes. Eight of the 41 functional pathways differed in the gut of both crane species (P < 0.05).DiscussionBoth species live in the same area and have similar feeding and behavioral characteristics. Therefore, host differences are possibly the main factors influencing the structural and functional differences in the composition of the gut microbial community. This study provides important reference data for constructing a crane gut microbial assessment system. The findings have implications for studying deeper relationships between crane gut microbes and genetics, nutrition, immunity, and disease.

The engineering geological conditions of Lenggu hydropower station located in the middle reaches of Yalong River are very complex, and large-scale landslides are very developed. Taking Xiari landslide of Lenggu hydropower station on Yalong River as an example, the stability development trend of landslide after impoundment is studied by means of test and numerical simulation on the basis of detailed field investigation on the spot. According to the geomorphic morphology, material composition, drilling data and field investigation, the Xiari landslide is divided into three zones, among which the zone II has been deformed and damaged to some extent, and the stability is the worst. The numerical simulation shows that the overall stability of the landslide is fairly good before the impoundment, and the deformation only occurs at the front edge. After the impoundment, the deformation of the landslide is obviously enlarged and the front edge slides along the existing secondary slip zone. It is suggested that lattice anchor and anti-slide pile should be used at the front edge of the Xiari landslide, and the InSAR technology should also be used for early identification, monitoring and early warning of landslide hazards. This study provides an important basis for the prevention and control of reservoir bank landslide in Lenggu Hydropower Station, and has a certain reference significance for the study of the same type of landslide. This study provides an important basis for the prevention and control of reservoir bank landslide in Lenggu Hydropower Station, and has a certain reference significance for the study of the same type of landslide.

Abstract Objective To explore the analgesic effects of different concentrations of ropivacaine in transversalis fascia plane (TFP) block during laparotomy. Methods Ninety patients who underwent laparotomy admitted to our hospital from March 2019 to March 2020 were selected as the study subjects and were divided equally into a low concentration group, a medium concentration group, and a high concentration group according to the randomized grouping method. The low concentration group adopted 0.4% ropivacaine 40 ml, the medium concentration group was given 0.5% ropivacaine 40 ml, and the high concentration group was given 0.6% ropivacaine 40 ml. The hemodynamic indexes and the incidence of adverse reactions in the two groups were compared. The Numerical Rating Scale (NRS) was used to assess the postoperative pain in the three groups, the Bruggrmann comfort scale (BCS) was used to assess the comfort level in the three groups, and the Mini-mental State Examination (MMSE) was used to evaluate the postoperative cognitive function of the three groups of patients. Results The mean artery pressure (MAP) and heart rate (HR) levels at T1 and T2 were significantly lower in the medium concentration group than in the other two groups (P

Abstract Objective To evaluate the relationship of postoperative cervical axial pain with different vertebral distraction methods used during ACDF procedures in cervical spondylosis patients. Methods Ninety-four single-level cervical spondylotic myelopathy patients with significantly loss of intervertebral disc height who underwent ACDF surgery in our institute between January 2018 and January 2020 were enrolled. Cervical spine lateral radiographs were taken preoperatively, 3 days, 1-month, 2-month and 6-month after the surgery. The intervertebral disc height (IDH), interfacet distance (IFD), JOA (Japanese Orthopaedic Association) score, NDI (Neck Disability Index) score, nVAS (Neck Visual Analogue Scale) score and aVAS (Arm Visual Analogue Scale) score were measured. The correlation of clinical parameters and intervertebral disc height was evaluated. Then the correlation of clinical outcomes and different distraction method was evaluated. The patients were randomly divided into two groups, one uses Casper pin distractor system alone for distraction (Caspar alone group) and the other uses spreader assisted distraction method (Casper + spreader group). In biomechanical study, four cervical spine cadavers were selected for facet pressure measurements under different vertebral distraction methods, and the facet joint pressure was measured using force sensors. Results Satisfactory cervical fusion and neurological recovery were achieved in all patients. No significant correlation of IDH, IFD, JOA, NDI or aVAS with nVAS score was found. No significant difference between the change in disc height and clinical outcomes was found. However, by comparing the clinical parameters of patients in different vertebral distraction groups, we found significant changes in the early nVAS and NDI scores (P = 0.11, P = 0.48) of the Casper + spreader group (3 days postoperation), and was associated with a better nVAS score at 2 months postoperation (P

The widely use of covered conductor increases the reliability of distribution network. However, a new problem of partial discharge caused by covered conductor at the position of tower head is generated at the same time. This kind of partial discharge will damage the insulation layer or accelerate the deterioration of insulation, which may cause the single-phase grounding fault and affect the power supply reliability. At present, there is few systematic studies on the characteristics of this partial discharge. This paper mainly analyzes the electric field distribution near the covered conductor around tower head, builds the partial discharge experiment platform, and obtains the pulse current characteristics of partial discharge under different working conditions. The results show that the maximum electric field intensity is located at the interface between covered conductor, binding wire and air. The main causes of partial discharge are the wet and dirty of the surface of porcelain insulator and conductor insulation. The minor cause is the breakage of covered conductor insulation. Under different conditions, the initial partial discharge pulse current wave front time is 8ns ~ 45ns, the tail time is 30ns ~ 150ns. The discharge time interval can be as low as $30~\mu \text{s}$ . In addition, it is found that there are two types of partial discharge through spectral analysis. One occurs when the covered conductor insulation is damaged under binding wire; the other is the covered conductor insulation is intact.