Search

Abstract Background Growth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels. Case presentation We report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved. Conclusions GH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.

The hardenability of the 2050 Al–Li alloy ultra-thick plate was evaluated by end quenching and interrupted quench methods. Microstructural investigation at different thickness positions after quenching and aging were conducted using optical microscopy, scanning electron microscope, and transmission electron microscope. The factors affecting the hardenability were discussed in combination with cooling rate and composition examination using energy dispersive spectroscopy. The results indicated that the tensile strength of different thickness positions decreased as the distance from the quenching end increases. Coarse Cu-rich phase particles, formed at the grain and grain boundaries during the end quenching process, lead to solute depletion around the grain boundaries, causing a precipitate-free zone. This zone obstructs the formation of the T1 phase, thereby reducing strength. At identical distances from the quenching end, the tensile strength at the mid-thickness (T/2) location consistently exceeds that at the quarter-thickness (T/4) location. This is due to the original microstructural differences, where the T/2 position experiences a slower cooling rate, has a lower copper content, and shows an increase in the number but a decrease in the size of precipitated coarse Cu-rich phase particles from the supersaturated solution, with the solute consumption remaining relatively constant. Consequently, the tensile strength variation at equal distances from the quenching end is minimal.

Abstract Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function. This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide (LPS)-induced intestinal injury from the perspective of macrophage–intestinal epithelial cell interactions. Lactobacillus intervention improved the histopathological score; elevated ZO-1 and Occludin protein production; reduced CD16+ cell numbers; diminished IL-1β, IL-6, and TNF-α levels; decreased inducible nitric oxide synthase (iNOS) expression; increased CD163+ cell numbers; elevated IL-10 concentration; and increased arginase-1 (Arg1) expression in LPS-challenged piglets. Lactobacillus pretreatment also altered the colonic microbiota, thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets. Compared with those in the LPS group, sodium butyrate (SB) pretreatment decreased IL-1β, IL-6 and TNF-α secretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages. The SB-pretreated macrophages reduced the protein expression of TLR4, MyD88, and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells. Moreover, GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells. This study demonstrated that Lactobacillus improves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.

Abstract Toxoplasma gondii (T. gondii) is a protozoan parasite that infects approximately one-third of the global human population, often leading to chronic infection. While acute T. gondii infection can cause neural damage in the central nervous system and result in toxoplasmic encephalitis, the consequences of T. gondii chronic infection (TCI) are generally asymptomatic. However, emerging evidence suggests that TCI may be linked to behavioral changes or mental disorders in hosts. Astrocyte polarization, particularly the A1 subtype associated with neuronal apoptosis, has been identified in various neurodegenerative diseases. Nevertheless, the role of astrocyte polarization in TCI still needs to be better understood. This study aimed to establish a mouse model of chronic TCI and examine the transcription and expression levels of glial fibrillary acidic protein (GFAP), C3, C1q, IL-1α, and TNF-α in the brain tissues of the mice. Quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, and Western blotting were employed to assess these levels. Additionally, the expression level of the A1 astrocyte-specific marker C3 was evaluated using indirect fluorescent assay (IFA). In mice with TCI, the transcriptional and expression levels of the inflammatory factors C1q, IL-1α, and TNF-α followed an up-down-up pattern, although they remained elevated compared to the control group. These findings suggest a potential association between astrocyte polarization towards the A1 subtype and synchronized changes in these three inflammatory mediators. Furthermore, immunofluorescence assay (IFA) revealed a significant increase in the A1 astrocytes (GFAP+C3+) proportion in TCI mice. This study provides evidence that TCI can induce astrocyte polarization, a biological process that may be influenced by changes in the levels of three inflammatory factors: C1q, IL-1α, and TNF-α. Additionally, the release of neurotoxic substances by A1 astrocytes may be associated with the development of TCI.

Abstract Deuterium/Tritium (D/T) handling in defined proportions are pivotal to maintain steady-state operation for fusion reactors. However, the hydrogen isotope effect in metal-hydrogen systems always disturbs precise D/T ratio control. Here, we reveal the dominance of kinetic isotope effect during desorption. To reconcile the thermodynamic stability and isotope effect, we demonstrate a quantitative indicator of T gap and further a local coordination design strategy that comprises thermodynamic destabilization with vibration enhancement of interstitial isotopes for isotope engineering. Based on theoretical screening analysis, an optimized Ti-Pd co-doped Zr0.8Ti0.2Co0.8Pd0.2 alloy is designed and prepared. Compared to ZrCo alloy, the optimal alloy enables consistent isotope delivery together with a three-fold lower T gap, a five-fold lower energy barrier difference, a one-third lower isotopic composition deviation during desorption and an over two-fold higher cycling capacity. This work provides insights into the interaction between alloy and hydrogen isotopes, thus opening up feasible approaches to support high-performance fusion reactors.

Abstract Background Numerous studies have shown that Schistosoma japonicum infection correlates with an increased risk of liver hepatocellular carcinoma (LIHC). However, data regarding the role of this infection in LIHC oncogenesis are scarce. This study aimed to investigate the potential mechanisms of hepatocarcinogenesis associated with Schistosoma japonicum infection. Methods By examining chronic liver disease as a mediator, we identified the genes contributing to Schistosoma japonicum infection and LIHC. We selected 15 key differentially expressed genes (DEGs) using weighted gene co-expression network analysis (WGCNA) and random survival forest models. Consensus clustering revealed two subgroups with distinct prognoses. Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression identified six prognostic DEGs, forming an Schistosoma japonicum infection-associated signature for strong prognosis prediction. This signature, which is an independent LIHC risk factor, was significantly correlated with clinical variables. Four DEGs, including BMI1, were selected based on their protein expression levels in cancerous and normal tissues. We confirmed BMI1's role in LIHC using Schistosoma japonicum-infected mouse models and molecular experiments. Results We identified a series of DEGs that mediate schistosomiasis, the parasitic disease caused by Schistosoma japonicum infection, and hepatocarcinogenesis, and constructed a suitable prognostic model. We analyzed the mechanisms by which these DEGs regulate disease and present the differences in prognosis between the different genotypes. Finally, we verified our findings using molecular biology experiments. Conclusion Bioinformatics and molecular biology analyses confirmed a relationship between schistosomiasis and liver hepatocellular cancer. Furthermore, we validated the role of a potential oncoprotein factor that may be associated with infection and carcinogenesis. These findings enhance our understanding of Schistosoma japonicum infection's role in LIHC carcinogenesis.

In order to reveal the relationship between microstructure inhomogeneity and mechanical anisotropy, the Al–Cu–Li alloy 100 mm thick plate for aerospace was evaluated. The grain structure, crystallographic texture, phase structure and fractography of different thickness positions and directions were observed by optical microscopy (OM), X-ray diffraction (XRD), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The in-plane and through-thickness anisotropy were characterized by tensile properties, fracture toughness and hardness tests. The results demonstrate a greater in-plane anisotropy in yield strength at the same thickness position of the plate. The Brass texture component increases successively at T, T/4, and T/2 positions, while the Cu texture component exhibits minimal variation. The in-plane anisotropy mainly arises from the Brass texture. Through-thickness anisotropy in the same direction is primarily influenced by the diameter, number density, and volume fraction of the T1 strengthening phase. The average diameter and number density of the primary strengthening phase T1 within grains are highest at the T/2 position and lowest at the T position. The plate contains unrecrystallized, elongated pancake-like grains along the rolling direction. Fracture toughness tests conducted in the L-T and T-L directions predominantly reveal dimple-type transgranular shear fractures, while the S-L direction exhibits intergranular fracture as the primary characteristic. The crack divider delamination toughening mechanism is the main contributor to higher fracture toughness values in the L-T and T-L directions compared to those in the S-L direction. The results reveal the corresponding relationship between the microstructure inhomogeneity and the mechanical anisotropy of Al–Li alloy ultra-thick plates, and provide ideas for the adjustment of process parameters during processing deformation and the regulation of microstructure during heat treatment of large-scale Al–Li alloy thick plates, which has engineering application reference value.

BackgroundNeuropathic pain (NP) is a debilitating and refractory chronic pain with a higher prevalence especially in elderly patients. Cell senescence considered a key pathogenic factor in NP. The objective of this research is to discover genes associated with aging in peripheral blood of individuals with NP using bioinformatics techniques.MethodsTwo cohorts (GSE124272 and GSE150408) containing peripheral blood samples of NP were downloaded from the GEO database. By merging the two cohorts, differentially expressed aging-related genes (DE-ARGs) were obtained by intersection with aging-related genes. The potential biological mechanisms of DE-ARGs were further analyzed through GO and KEGG. Three machine learning methods, namely, LASSO, SVM-RFE, and Random Forest, were utilized to identify diagnostic biomarkers. A Nomogram model was developed to assess their diagnostic accuracy. The validation of biomarker expression and diagnostic effectiveness was conducted in three distinct pain cohorts. The CIBERSORT algorithm was employed to evaluate the immune cell composition in the peripheral blood of patients with NP and investigate its association with the expression of diagnostic biomarkers.ResultsThis study identified a total of 24 DE-ARGs, mainly enriched in “Chemokine signaling pathway,” “Inflammatory mediator regulation of TRP channels,” “HIF-1 signaling pathway” and “FOXO signaling pathway”. Three machine learning algorithms identified a total of four diagnostic biomarkers (CEBPA, CEACAM1, BTG3 and IL-1R1) with good diagnostic performance and the similar expression difference trend in different types of pain cohorts. The expression levels of CEACAM1 and IL-1R1 exhibit a positive correlation with the percentage of neutrophils.ConclusionUsing machine learning techniques, our research identified four diagnostic biomarkers related to aging in peripheral blood, providing innovative approaches for the diagnosis and treatment of NP.

Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas. Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018. Results: When considering tumor location, all 34 patients had intrasellar tumors, with 19 of them exhibiting suprasellar extensions. Of the 34 patients, 24 patients underwent resection under the microscope and the remaining 10 patients underwent transsphenoidal endoscopic surgery. Gross total tumor resection was achieved in 16 patients. Twelve patients underwent invaded sellar diaphragm resection, while the remaining 22 patients were not. Cerebrospinal fluid leaks occurred during surgery in 18 patients. Visual acuity improved in two patients. After an average follow-up of 31.1 months, 13 patients experienced tumor recurrence. The short term recurrence rate in the sellar diaphragm resection group was significantly lower compared to the non-resected group (P

An assessment of the freeze–thaw durability of pervious concrete was conducted using a rapid freezing method to investigate the durability of modified pervious concrete within a freeze–thaw environment. The optimal proportion of the modified material was determined by evaluating the mass-loss rate and the relative dynamic elastic modulus as indicators of freeze–thaw performance. Scanning electron microscopy (SEM) was employed to observe microcrack propagation and reaction products. A freeze–thaw damage model, based on the Weibull probability distribution, was formulated. Freeze–thaw damage analysis and life prediction assessment were carried out using curves such as freeze–thaw damage velocity curves, freeze–thaw damage acceleration curves, failure rate curves, and reliability life curves. The outcomes revealed that the inclusion of polyacrylonitrile (PAN) and silica ash had a favourable impact on improving the frost resistance of pervious concrete at later stages. The optimal proportions for PAN fibre and silica ash were determined as 0.6 % and 8 %, respectively. As the number of freeze–thaw cycles approached approximately 52.03 times, the freeze–thaw cycle velocity peaked. Subsequently, the freeze–thaw damage velocity was categorised into three stages based on the freeze–thaw damage acceleration curve. The degradation of pervious concrete due to freeze–thaw cycles followed a typical loss-type failure pattern. Notably, a 50 % increase in PAN fibre content resulted in a 62.92 % reduction in failure rate. Furthermore, a predictive analysis was conducted to estimate the lifespan of pervious concrete in a representative freeze–thaw region in China was performed.

ObjectiveRituximab (RTX) has been widely used for primary nephrotic syndrome (PNS) in children of frequent relapse or hormonal dependence. The authors applied RTX for childhood PNS in Ningxia for the first time and examined its efficacy.MethodsFrom January 1, 2020 to December 31, 2022, 7 PNS children received 3-year RTX dosing with parental consents after poor outcomes of glucocorticoids alone or glucocorticoids plus other immunosuppressants. There were 4 boys and 3 girls with an age range of (4.4-13.0) year. Urinary routine, urinary protein quantification and infection status were regularly monitored for evaluating the treatment effect, safety and expenses.ResultsAll of them were hormonal sensitive with a frequent recurrence. Two to 5 doses of RTX per child were offered over a follow-up period of (9-35) month. Urinary protein stayed long-term negative. There was only 1 relapsing case. Five cases discontinued glucocorticoids and immunosuppressants. No severe infection occurred. The average monthly expense per child after RTX dosing was significantly lower than that before dosing.ConclusionRTX is a safe, economic and effective treatment for PNS children. Early application of RTX may taper glucocorticoids and/or immunosuppressants and minimize adverse reactions.

This paper proposes a method for dynamically controlling the working slope configuration in seasonal stripping open-pit coal mines. Constructing a bench group working slope model calculates the cyclic advancement time of the stripping working slope. A mathematical optimization model is then established to minimize the transport work of the overburden, and a Sequential Quadratic Programming (SQP) algorithm is employed to solve it. The method is applied to the Shengli West No. 2 open-pit coal mine, and the results show that the number of benches in the bench group is 5. The working bench width is 89 m, and the working slope advancement meets the stripping and mining engineering continuity requirements while minimizing the transport work of the overburden. The maximum advancement speed of the working slope under this configuration is 320 m/year. The paper also analyzes the working slope’s maximum advancement speed variation with changes in the bench combination form and cyclic advancement distance.

Abstract Background Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. Objective To screen glioblastoma patients who may benefit from immunotherapy. Methods Eighty‐one patients receiving anti‐PD1/PD‐L1 treatment from a large‐scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI‐treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder‐relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. Results We defined two groups of ICI‐treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder‐relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN‐predicted responders had significantly better OS rates than nonresponders. Conclusion The 20‐gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI‐treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.

ObjectiveDouble pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure.MethodsTwo cases of DPA patients with Cushing’s disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission.ResultsAmong 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing’s syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (

Abstract Intracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.

Abstract Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.

Due to the discontinuity of the stripping project in seasonal stripping open-pit coal mines, the untimely advance distance of the working slope is huge. In order to reduce the advance stripping and save the stripping distance, research was carried out on dynamic control of the shape of the working slope and optimization of the limit advance speed of the working slope in seasonal stripped open-pit coal mines. This paper explains the shape and operation procedure of the working slope in seasonal stripped open-pit coal mines and analyzes factors that influence working slope shape and advance speed. Based on structural form of working slope and stripping operation mode of seasonally stripped open-pit coal mines, an engineering model for shape optimization of working slope is established. The relationship between circular advance distance of working slope with working bench width and exposed coal mode of stope is discussed. Bench group cycle advance engineering quantity and production capacity of layered equipment, advance time of the working slope cycle and calculation method for reliability of side slope transportation system are given. With optimization goal of minimizing transport work of stripping material and time-space continuity of stripping engineering as constraint condition, mathematical model for shape optimization of working slope in seasonally stripped open-pit coal mine is established. Sequential quadratic programming algorithm (SQP) is introduced to solve nonlinear programming. A method to realize dynamic control of shape of working slope of seasonally stripped open-pit coal mine by determining combination mode of stripping benches and working bench width and a method to optimize limit advance speed of stripped working slope are proposed. Taking Shengli West No.2 Open-pit Coal Mine as an engineering background, above-mentioned optimization control method is applied for research and calculation and solution are carried out by establishing form optimization model of stripping working slope and substituting actual parameters of West No.2 Open-pit Mine. Results show that when the number of benches in bench group is 5 and working bench width is 89 m, advance of working slope meets the requirements of space-time continuity in stripping engineering and transport work of stripped objects is smallest. In this shape, limit advance speed of the working slope is 320 m/a, and change of limit advance speed of the working slope is analyzed and determined when combination of benches and cyclic advance distance is changed.

Abstract Diabetic retinopathy (DR) is a serious and relatively under-recognized complication of diabetes. Müller glial cells extend throughout the retina and play vital roles in maintaining retinal homeostasis. Previous studies have demonstrated that TGR5, a member of the bile acid-activated GPCR family, could ameliorate DR. However, the role of TGR5 in regulating Müller cell function and the underlying mechanism remains to be ascertained. To address this, high glucose (HG)-treated human Müller cells and streptozotocin-treated Sprague-Dawley rats were used in the study. The IP3R1-GRP75-VDAC1 axis and mitochondrial function were assessed after TGR5 ablation or agonism. Cytosolic mitochondrial DNA (mtDNA)-mediated cGAS-STING activation was performed. The key markers of retinal vascular leakage, apoptosis, and inflammation were examined. We found that mitochondrial Ca2+ overload and mitochondrial dysfunction were alleviated by TGR5 agonist. Mechanically, TGR5 blocked the IP3R1-GRP75-VDAC1 axis mediated Ca2+ efflux from the endoplasmic reticulum into mitochondria under diabetic condition. Mitochondrial Ca2+ overload led to the opening of the mitochondrial permeability transition pore and the release of mitochondrial DNA (mtDNA) into the cytosol. Cytoplasmic mtDNA bound to cGAS and upregulated 2’3’ cyclic GMP-AMP. Consequently, STING-mediated inflammatory responses were activated. TGR5 agonist prevented retinal injury, whereas knockdown of TGR5 exacerbated retinal damage in DR rats, which was rescued by the STING inhibitor. Based on the above results, we propose that TGR5 might be a novel therapeutic target for the treatment of DR.

Aircraft ducts play an indispensable role in various systems of an aircraft. The regular inspection and maintenance of aircraft ducts are of great significance for preventing potential failures and ensuring the normal operation of the aircraft. Traditional manual inspection methods are costly and inefficient, especially under low-light conditions. To address these issues, we propose a new defect detection model called LESM-YOLO. In this study, we integrate a lighting enhancement module to improve the accuracy and recognition of the model under low-light conditions. Additionally, to reduce the model’s parameter count, we employ space-to-depth convolution, making the model more lightweight and suitable for deployment on edge detection devices. Furthermore, we introduce Mixed Local Channel Attention (MLCA), which balances complexity and accuracy by combining local channel and spatial attention mechanisms, enhancing the overall performance of the model and improving the accuracy and robustness of defect detection. Finally, we compare the proposed model with other existing models to validate the effectiveness of LESM-YOLO. The test results show that our proposed model achieves an mAP of 96.3%, a 5.4% improvement over the original model, while maintaining a detection speed of 138.7, meeting real-time monitoring requirements. The model proposed in this paper provides valuable technical support for the detection of dark defects in aircraft ducts.

Overlying river can accelerate the creep of the inner dump, so to master the creep characteristics of the overlying river can provide a theoretical basis for mine safety and discharge optimization. Taking the overlying river inner dump of Yuanbaoshan open-pit coal Mine in China as the research object, a design scheme is proposed to divide it into rolling zone and non-rolling zone. Based on the creep model obtained by in-situ deformation monitoring and laboratory rheological test, the creep evolution law and deformation of overlying channel after soil discharge, slope morphology and advancing position are simulated and analyzed. The results showed that the creep variable in the (non-) rolling zone had a nonlinear upward trend with time, and the initial upward trend was large. The maximum vertical and horizontal creep in the rolling area was located in the middle and upper part of the rolling line, while the maximum vertical and horizontal creep in the dump was located in the middle and upper part of the non-rolling area, respectively. The post-construction settlement and horizontal discharging increased with the increase of the discharge height, and the convergence creep of the top ten years after construction increased approximately linearly with the decrease of the distance from the shoulder of the inner dump. The rolled sand and gravel backfill belonged to the foundation of uniform settlement deformation in general, and the change of slope shape had little effect on the deformation of the slope top in the rolled area. The geoglage elongation in the dam area met the requirements. On the premise of ensuring the stability of the dump, the slope angle of the inner dump can be appropriately increased to increase the capacity of the inner dump. The research results can provide guidance for the construction of inner dump in open pit.

Recently, quantum biology and molecular quantum computation have attracted substantial attention. Quantum biology applies quantum mechanics to biological systems at the molecular scale. Molecular quantum computing explores the degrees of freedom of molecules that can be used to produce quantum coherence, such as charge, orbital, opto-spin (interplay between optical excitation and spin), vibration, and rotation, to process quantum information. Cognitive science focuses on understanding how learning processes are realized, particularly within the human brain. The most common topic among these three is the computational process, which can exploit different levels of representation, either classical or quantum. Here, we review progress in quantum biology, molecular quantum computing, and quantum theory in cognitive science. Based on our critical analysis and review, we highlight that molecular quantum computing could be an important bridging research area between quantum biology and a deeper understanding of neuronal cells in cognitive science. Thus, these three areas can be the core to understanding how the classical world emerges from the quantum world and human intelligence. To answer these questions, we may gain insight by studying the quantum processes that underlie biological systems, such as photosynthesis and enzyme catalysis. An unprecedented opportunity for molecular quantum computing is to perform functionalities similar to those of the human brain. In this manner, we could not only expand the boundaries for quantum computing but also gain a better understanding of cognitive processes.

Background: Toxoplasma gondii is an opportunistic parasitic protozoan that can cause highly fatal toxoplasmic encephalitis when the host immune system is compromised. However, the transition from chronic to acute infection remains poorly understood. In this study, we conducted a 180-day observation of tissue damage and inflammation in the brains of mice infected with T. gondii. Subsequently, we investigated the inflammatory factors that T. gondii infection may alter using two-sample Mendelian randomization (MR) analysis. Methods: We first established a mouse model of T. gondii infection. Subsequently, the mice were euthanized, the brain tissue collected, and immunohistochemistry and hematoxylin and eosin staining performed to observe tissue damage and inflammatory conditions at various time points. Our study also included a published large-scale genome-wide association study meta-analysis that encompassed the circulating concentrations of 41 cytokines. This dataset included 8293 individuals from three independent population cohorts in Finland. Genetic association data for T. gondii were sourced from the Integrative Epidemiology Unit and European Bioinformatics Institute datasets, which included 5010 and 559 individuals of European ancestry, respectively. To assess the causal relationship between T. gondii infection and inflammatory biomarkers, we applied a two-sample MR. Results: Inflammation and damage resulting from T. gondii infection varied among the distinct regions of the mouse brain. Based on the MR analysis results, three inflammatory biomarkers were chemically assigned to Chemokines and Others, including IP10 (interferon gamma inducible protein-10), MCP1 (monocyte chemoattractant protein-1), and TRAIL (TNF-related apoptosis-inducing ligand). Conclusion: Our study commenced with the assessment of tissue damage and progression of inflammation in distinct regions of the mouse brain after T. gondii infection. Subsequently, using MR analysis, we detected potential alterations in inflammatory factors associated with this infection. These findings offer valuable insights into the mechanisms underlying toxoplasmic encephalitis and suggest directions for the prevention and treatment of T. gondii infections.

Background Thyroid-associated orbitopathy (TAO) is a disease associated with autoimmune thyroid disorders and it can lead to proptosis, diplopia, and vision-threatening compressive optic neuropathy. To comprehensively understand the molecular mechanisms underlying orbital adipogenesis in TAO, we characterize the intrinsic molecular properties of orbital adipose/connective tissue from patients with TAO and control individuals. Methods RNA sequencing analysis (RNA-seq) was performed to measure the gene expression of orbital adipose/connective tissues of TAO patients. Differentially expressed genes (DEGs) were detected and analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The protein–protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified by the Cytoscape plug-in, cytoHubba. We validated several top DEGs through quantitative real-time polymerase chain reaction (qRT–PCR). Results We identified 183 DEGs in adipose tissue between TAO patients (n = 3) and control patients (n = 3) through RNA sequencing, including 114 upregulated genes and 69 downregulated genes. The PPI network of these DEGs had 202 nodes and 743 edges. PCR-based validation results of orbital adipose tissue showed multiple top-ranked genes in TAO patients (n = 4) are immune and inflammatory response genes compared with the control individual (n = 4). They include ceruloplasmin isoform x3 (CP), alkaline tissue-nonspecific isozyme isoform x1 (ALPL), and angiotensinogen (AGT), which were overrepresented by 2.27- to 6.40-fold. Meanwhile, protein mab-21-like 1 (MAB21L1), phosphoinositide 3-kinase gamma-subunit (PIK3C2G), and clavesin-2 (CLVS2) decreased by 2.6% to 32.8%. R-spondin 1 (RSPO1), which is related to oogonia differentiation and developmental angiogenesis, was significantly downregulated in the orbital muscle tissues of patients with TAO compared with the control groups (P = 0.024). Conclusions Our results suggest that there are genetic differences in orbital adipose-connective tissues derived from TAO patients. The upregulation of the inflammatory response in orbital fat of TAO may be consistent with the clinical phenotype like eyelid edema, exophthalmos, and excess tearing. Downregulation of MAB21L1, PIK3C2G, and CLVS2 in TAO tissue demonstrates dysregulation of differentiation, oxidative stress, and developmental pathways.

We performed an in-situ fatigue test by in-situ scanning electron microscope (SEM) to elucidate the deformation and failure behavior of equiatomic CoCrNi medium entropy alloy under cyclic loading. The SEM results indicate that the crack growth speed is slow at the initial stage, and the growth direction is perpendicular to the loading direction. As the cyclic loading continues, small cracks are generated in the material, which changes the direction of the main cracks and accelerates the growth of the main cracks. The deformation twins and elongated grains induced by cold rolling are frequently observed in samples before cyclic deformation. These grains are changed from nearly parallel elongated grains to irregular during cyclic deformation. However, deformation twins disappeared or became thinner after cyclic deformation. Molecular dynamics simulations are carried out to reveal the microstructure evolution mechanisms during cyclic deformation. The results show that the grain growth occurred after cyclic deformation in the model without deformation twins. However, the de-twinning, re-twinning and grain growth are observed in the models containing deformations twins. Molecular dynamic simulations also indicated that twin boundaries lead to higher strain energy density and significantly improve the material's fatigue resistance.

Prefabricated panel-assembled wall systems, comprising a confining frame and infill lightweight panels of autoclaved aerated concrete (AAC), are widely employed in framed structures. Different from studies on a main frame with infill walls, this study aimed to explore the seismic performance of partition walls, which were fabricated with AAC panel-assembled walls and located outside of the main frames. Two full-scale specimens, one with a door opening and the other without, were constructed and cyclic loading tests were executed to examine the failure modes, hysteresis characteristics, envelope curves, ductility, strength and stiffness degradation, as well as energy dissipation capacity of the AAC panel-assembled walls. Additionally, a restoring-force model for the panel-assembled walls was developed and a method for predicting the lateral load-bearing capacity of the AAC panel-assembled walls was proposed. The findings indicated that the panels enhanced the system’s lateral resistance, energy dissipation capacity, and deformation capability. The door frame increased the initial stiffness, peak lateral load and energy dissipation capacity of the AAC panel-assembled wall compared to the wall without a door frame. Compared to the specimen without a door frame, the peak lateral load of the specimen with a door frame increased by 19.7–30.1%. The deformation capacity of the panel-assembled walls aligned with the requirements for concrete framed structures.

Abstract Background Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus’s health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature. Methods An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities. Results Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4–10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001). Conclusion Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.

Abstract Slope stability is an important problem in the field of geotechnical engineering. In order to widen the application range of upper bound limit analysis in engineering practice, this paper analyzes layered distribution characteristics of slope soil and establishes horizontal layers slope failure mechanism which satisfies the separation of velocity, then proposes calculation method for external force power and internal energy dissipation power using discrete algorithm. On this basic, this paper prepares cycle flow of slope stability analysis by upper bound limit principle and strength reduction principle, and develops stability analysis system by computer programming technology. Taking typical mine excavation slope as engineering background and calculates stability coefficient corresponding to different slope angles and evaluate analysis results accuracy by combining with limit equilibrium method. The results show that the stability coefficient error rate of two methods is between 3 and 5%, which can satisfy requirements of engineering practice. Moreover, stability coefficient obtained by upper bound limit analysis is an upper limit solution, and calculation errors are easy to eliminate, so it has certain applicability in slope engineering practice.

IntroductionPediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified.MethodsWe conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor.Results232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery.ConclusionPediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.

Metastatic PitNETs are a rare life-threatening condition with poor prognosis and documentation. Due to the scarce literature and lack of precise treatment, we hope to better characterise PitNET using the next-generation whole exon sequencing (WES) and RNA sequencing. This case study outlines a 54 years-old man and a 52 years-old woman who were both diagnosed with PitNET and analysis of peripheral blood and tumours were performed by WES and RNA sequencing. Analysis showed that DICER1 mutations in precancerous lesions and LAG3 overexpression were significant in aiding the prognosis and diagnosis of PitNETs. The first case with overexpressed LAG3 and DICER1 mutation died 26 months later, and the second case with LAG3 overexpression achieved partial remission. This study revealed that heightened expression of LAG3 offered promising targets for ICI and mutations in DICER1 could provide markers for effective diagnosis and prognosis.

PurposeTo investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients.MethodsA retrospective, single-center study focused on 252 male acromegaly patients aged 18 years–60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed.ResultsForty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up.ConclusionThe invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

Abstract Purpose Diagnostic statements for pituitary adenomas (PAs) are complex and unstandardized. We aimed to determine the most commonly used elements contained in the statements and their combination patterns and variations in real-world clinical practice, with the ultimate goal of promoting standardized diagnostic recording and establishing an efficient element extraction process. Methods Patient medical records from 2012 to 2020 that included PA among the first three diagnoses were included. After manually labeling the elements in the diagnostic texts, we obtained element types and training sets, according to which an information extraction model was constructed based on the word segmentation model “Jieba” to extract information contained in the remaining diagnostic texts. Results A total of 576 different diagnostic statements from 4010 texts of 3770 medical records were enrolled in the analysis. The first ten diagnostic elements related to PA were histopathology, tumor location, endocrine status, tumor size, invasiveness, recurrence, diagnostic confirmation, Knosp grade, residual tumor, and refractoriness. The automated extraction model achieved F1-scores that reached 100% for all ten elements in the second round and 97.3–100.0% in the test set consisting of an additional 532 diagnostic texts. Tumor location, endocrine status, histopathology, and tumor size were the most commonly used elements, and diagnoses composed of the above elements were the most frequent. Endocrine status had the greatest expression variability, followed by Knosp grade. Among all the terms, the percentage of loss of tumor size was among the highest (21%). Among statements where the principal diagnoses were PAs, 18.6% did not have information on tumor size, while for those with other diagnoses, this percentage rose to 48% (P

Objectives To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with H. pylori infection. Methods A total of 971 H. pylori positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether H. pylori was eradicated. Results There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of H. pylori between dual therapy and quadruple therapy were 88.31% and 85.26% (p=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (p=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (p=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (p

This study proposes a novel multipoint transducer system by utilizing the single-mode-multimode-thin-cladding fiber (SMTC) structure. This structure leverages the disparity in mode field diameter between the multimode fiber (MMF) and thin-cladding fiber (TCF) to generate high-amplitude ultrasonic signals safely and efficiently. The fabricated transducer exhibits signal amplitudes 2–3-fold higher compared to conventional laser-ultrasonic transducers. Simulation analysis investigates the impact of the length of the MMF and the diameter of the TCF on coupling efficiency. The coupling efficiency of individual transducer units can be accurately controlled by adjusting the length of the MMF. A three-point energy-balanced laser-ultrasonic transducer system was achieved, with improved energy conversion efficiencies, and the optimal thickness of candle soot nanoparticles (CSNPs) is experimentally determined. Additionally, we carried out experiments to compare the performance of the proposed SMTC-based transducer system under different material conditions using two different photoacoustic materials: graphite–epoxy resin and candle soot nanoparticle–polydimethylsiloxane (CSNP–PDMS) composite. CSNPs, as a cost-effective and easy-to-prepare composite material, exhibit higher photoacoustic conversion efficiency compared to graphite–epoxy resin. The proposed system demonstrates the potential for applications in non-destructive testing techniques.

IntroductionIntracranial germ cell tumors (iGCTs), comprising of germinoma (GE) and non-germinomatous GCT (NGGCT), are a group of heterogenous brain tumors. Immunohistochemical markers, such as placental-like alkaline phosphatase (PLAP), are commonly used in diagnosis but show moderate sensitivity. Organic cation transporter 3/4 (OCT3/4) has been proposed as a novel biomarker for diagnosis and prognosis of iGCTs. This paper aimed to compare OCT3/4 with PLAP as potential immunohistochemical biomarkers in iGCTs diagnosis and clarify the relationship between OCT3/4 and prognosis of patients with iGCTs.MethodsMeta-analyses were performed to estimate pooled percentage point differences in positive rates between OCT3/4 and PLAP, their sensitivities, and correlation between OCT3/4 and prognosis in iGCTs.ResultsNine articles were included representing of 241 patients. A fixed-effects model meta-analysis revealed that OCT3/4s positive rate was 8.6% higher (95% CI, 0.7% lower to 17.9% higher) than that of PLAP. Using fixed-effects models, sensitivities of OCT3/4 as a potential immunohistochemical biomarker in CNS GE and NGGCT were 85% (95% CI, 79% to 89%) and 56% (95% CI, 39% to 71%), respectively. In comparison, PLAP had lower sensitivities in both GE (73%; 95% CI, 64% to 91%) and NGGCT (43%; 95% CI, 27% to 61%). Moreover, OCT3/4 was significantly negatively correlated with 5-year progression free survival in patients with CNS GE (HR = 2.56, 95 % CI 1.47 to 4.44; p = 0.0008). Sensitivity analyses showed similar results.DiscussionThis study provides the first comprehensive assessment of the efficacies of OCT3/4 and PLAP in iGCTs detection and prognosis prediction, indicating OCT3/4 seems to be a more sensitive and reliable immunohistochemical marker in iGCT diagnosis.

Abstract Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) signalling on the macrophage activation and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE2 expression was high in the laser-induced CNV lesions. Macrophage recruitment and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP1R)/protein kinase C (PKC) signalling was involved in M2 macrophage activation and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE2/EP1R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD. Graphical Abstract Video abstract

Abstract Background Fungi associated with insects represent one potentially rich source for the discovery of novel metabolites. However, a comprehensive understanding of the fungal communities of Apis mellifera ligustica remains elusive. Results Here, we investigated the phylogenetic diversity and community composition of honeybee-associated fungi using combination of culture-dependent and culture-independent approaches. A total of forty-five fungi were isolated and purified from the Apis mellifera ligustica, royal jelly, and honeycomb, which belonged to four classes and eleven different genera. Furthermore, 28 bacterial 16S rRNA gene sequences were obtained by PCR from the fungal metagenome. High-throughput sequencing analyses revealed that the fungal communities were more diverse, a total of 62 fungal genera were detected in the honeybee gut by culture-independent method, whereas only 4 genera were isolated by culture-dependent method. Similarly, 247 fungal genera were detected in the honeycomb, whereas only 4 genera were isolated. In addition, we assessed the antibacterial and antioxidant activities of fungal isolates. Most fungal crude extracts obtained from the cultivation supernatant exhibited antioxidant activities. Only two fungal crude extracts displayed moderate activity against Escherichia coli and Staphylococcus aureus. Chemical analysis of Chaetomium subaffine MFFC22 led to the discovery of three known compounds, including cochliodinol (1), emodin (2), chrysophanol (3). Among them, cochliodinol (1) showed intense DPPH radical scavenging activity with the 50% inhibitory concentration (IC50) of 3.06 μg/mL, which was comparable to that of the positive ascorbic acid (IC50 = 2.25 μg/mL). Compound 2 displayed weak inhibitory activities against Micrococcus tetragenus and S. aureus. Conclusions This research provided a fundamental clue for the complex interactions among honeybees, fungi, bacterial symbionts, and the effects on the honeybee. Furthermore, the diversity of honeybee-associated fungi had great potential in finding the resource of new species and antioxidants.

Abstract Background Cushing’s disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. Case presentation A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. Conclusions We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

BackgroundGrowth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported.ObjectivesThis study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center.MethodsWe retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital’s information system.ResultsBased on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P

Diagnosing and treating secondary psychiatric symptoms with accuracy can be challenging in clinical settings. In this case study, we report on a female patient with Cushing’s disease who was misdiagnosed with anxiety disorder during her first psychiatric visit. Following initial ineffective psychiatric intervention, unexplained hypokalemia, and hypothyroidism, the patient visited the endocrinology clinic and was diagnosed with Cushing’s disease. During the medical and surgical procedures that followed, high doses of psychotropic medication were continued to treat persisting anxiety. After discharge, the patient developed autonomic dysfunction and impaired consciousness. Upon readmission, serotonin syndrome due to inappropriate psychiatric medication was diagnosed. The management of secondary psychiatric syndromes must be adapted to changes in the patient’s primary condition, which necessitates interdisciplinary collaboration in general hospital settings.

AIM: To explore the functions of Chordin-like 2, which is encoded by CHRDL2, in the process of retinal pigmented epithelium (RPE) differentiation and damage repair. METHODS: The fetal RPE cells (fRPE) was obtained from aborted fetus which obeyed medical ethics. Real-time quantitative polymerase chain reaction was used to measure expression quantity of CHRDL2 and other functional genes expression. Knocking down and overexpression was used to analyze the functions about Chordin-like 2. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of bone morphogenetic proteins 4 (BMP4). Flow cytometry was used to analyze cell cycle. Cell morphology was observed by phase contrast microscope (PCM). RESULTS: In normal RPE cells, CHRDL2 was firstly upregulated and followed a downregulation but eventually, it was expressed higher than the cells which undergone epithelial-mesenchymal transition (EMT). After knocking down CHRDL2, the secretion of BMP4 was decreased, RPE-related genes (OTX2, MITF, RPE65) were downregulated while EMT-related genes (SNAI1, VIM) were upregulated. However, the expression of these related genes after overexpression of CHRDL2 had contrary results. Chordin-like 2 also regulated the cell cycle by regulating BMP pathway. When CHRDL2 was knocked down, more fRPE cells stayed in S phase of cell cycle, while adding BMP4 reduced the proportion of the cells in S phase. However, overexpression of CHRDL2 increased more BMP4 secretion, this effect decreased the number of cells in S phase, but exogenous BMP inhibitor also could change this effect. At last, in the process of RPE cells differentiation, adding BMP4 at early stage could intervene normal RPE differentiation. Compared with BMP4, inhibiting BMP pathway had no significant negative effect at early stage, but suppressed differentiation at late stage. CONCLUSION: BMP pathway can be activated in a correct temporal order, otherwise, the cells have incorrect differentiation orientation. And Chordin-like 2 plays a role in dynamic regulation of BMP pathway and it also regulates the differentiation of RPE cells. Therefore, this research enlightens a new direction to inhibit EMT and promote cell redifferentiation after injury.

Subwavelength grating metamaterial (SGM) waveguide is typically treated as a homogeneous medium without considering intra-waveguide reflection. However, this approximation is not always valid, especially in resonators. In this paper, we show that the reflection-induced mutual coupling between the clock-wise and counter-clock-wise resonant modes in a subwavelength grating metamaterial waveguide ring resonator (SGMRR) breaks the degeneracy of the two modes, leading to the formation of Autler–Townes splitting. This phenomenon could be leveraged to improve the detection limit of SGMRR-based sensors.

ObjectiveCblC deficiency, the most common cobalamin metabolic abnormality, is caused by pathogenic variants in the MMACHC gene. The renal complications of this disease have been described only in a small number of cases. This study aimed to better delineate renal phenotype and genetic characteristics in Chinese children with cblC defect.MethodsChildren with cblC deficiency who manifested as kidney damage were enrolled. Clinical, renal pathological, and genetic data were reviewed in detail.ResultsSeven cases were enrolled. Ages at disease onset ranged from 9 months to 5 years. All patients presented with hematuria and proteinuria, and 2/7 cases presented with nephrotic syndrome. Renal dysfunction was observed in 4/7 cases. Renal biopsy was performed in 5/7 cases, and all of them had renal thrombotic microangiopathy. Macrocytic anemia was detected in all seven patients. Six out of seven cases had hypertension, and 2/7 cases presented with pulmonary hypertension. Two of them had a mild intellectual disability, and one suffered from epilepsy. Increased urine methylmalonic acid and plasma homocysteine were detected in seven cases, while two patients had normal levels of urine methylmalonic acid at the initial evaluation. After diagnosis, all seven cases were treated with hydroxocobalamin IM. Six cases were followed-up for 3–8 years. After treatments, anemia was the first to be recovered, followed by proteinuria. Renal function recovered after 1 year in two cases, whereas patient 2 progressed to stage 2 chronic kidney disease 13 years after onset. While a case presented with end-stage kidney disease because of late diagnosis, one case died 3 months after disease onset due to giving up treatment. Three MMACHC pathogenic variants c.80A > G (8/14), c.609G > A (4/14), and c.658_660delAAG (2/14) were detected in all seven children.ConclusionMMACHC variant c.80A > G may be associated with prominent renal complications in Chinese cblC patients. Macrocytic anemia and hyperhomocysteinemia are useful clues for patients with hematuria and proteinuria caused by cblC defect. The most frequent renal pathological manifestation is thrombotic microangiopathy. Early diagnosis and treatment resulted in improving renal and hematological signs.

ObjectiveExcessive growth hormone and insulin-like growth factor 1 contribute to cutaneous changes in acromegaly. We investigated the sub-macroscopic skin manifestation of acromegaly patients and explored its reversibility upon hormone reduction after pituitary adenoma surgery.DesignProspectively cohort study.MethodsWe enrolled 26 patients with acromegaly and 26 patients with non-functioning pituitary adenomas undergoing pituitary adenomectomy at Peking Union Medical College Hospital from July 2021 to March 2022. Skin presentations were evaluated by dermatoscopy and ultra-high-frequency ultrasound before and after surgery.ResultsSkin thickening, follicular plugs, perifollicular pigmentations, perifollicular orange haloes, red structureless areas, increased hair shafts, honeycomb-like pigmentations, widened dermatoglyphics, dilated appendage openings, excessive seborrhea, hyperhidrosis, enlarged pores, and acne-like lesions were commonly occurring in acromegaly patients, and their incidences were higher than the controls (P1 skin lesions were younger (P=0.028) and had higher baseline GH levels (P=0.021) than those with improvement of ≤1 skin lesion.ConclusionsDermatoscopy and ultra-high-frequency ultrasound provided augmented visual examination of the cutaneous changes in acromegaly. Some of the skin lesions could improve or reverse after pituitary surgery. Baseline GH levels, age, and endocrine remission were correlated with skin improvement at 3-month follow-up.

BackgroundEpidermoid cysts of cavernous sinus (CS) are rare congenital neoplasms of the central nervous system. In previous literature reports, the treatment for CS epidermoid cysts was mainly microsurgical resection, and the surgical methods included simple microsurgery and endoscope-assisted microsurgery. The present case report demonstrates the first case of complete resection of a CS epidermoid cyst by a simple endoscopic endonasal transcavernous (EET) approach.Case presentationA 54-year-old woman presented with chronic persistent headaches and occasional syncope. Brain MRI demonstrated a space-occupying lesion of the left CS, and digital substruction angiography (DSA) showed a small aneurysm at the beginning of the left ophthalmic artery. Thrombotic therapy of carotid–ophthalmic aneurysms was performed first, and the patient underwent resection of the CS lesion secondary. Considering the location of the lesion and the neuroendoscopy technology and experience of the doctor, we made bold innovations and used an EET approach to achieve complete resection of the lesion. The postoperative pathological results were consistent with the characteristics of epidermoid cyst. During the 1-year follow up, the patient showed no apparent signs of recurrence on head MRI.ConclusionEpidermoid cyst of cavernous sinus is a rare benign occupying lesion in cavernous sinus. Reviewing the previous literature, the main treatment is microneurosurgery, and neuroendoscopy is only used as an auxiliary equipment. We present the first case of complete endoscopic resection of CS epidermoid cyst by EET approach according to CARE guidelines, aiming to share the new surgical plan for CS epidermoid cyst and provide more surgical options for this disease for neurosurgery colleagues.

ObjectiveTo develop a prediction nomogram for the risk of lung-related diseases (LRD) in construction workers.MethodsSeven hundred and fifty-two construction workers were recruited. A self- designed questionnaire was performed to collected relevant information. Chest X-ray was taken to judge builders' lung health. The potential predictors subsets of the risk of LRD were screened by the least absolute shrinkage and selection operator regression and univariate analysis, and determined by using multivariate logistic regression analysis, then were used for developing a prediction nomogram for the risk of LRD. C-index, calibration curve, receiver operating characteristic curve, decision curve analysis (DCA) and clinical impact curve analysis (CICA) were used to evaluation the identification, calibration, predictive ability and clinical effectiveness of the nomogram.ResultsFive hundred and twenty-six construction workers were allocated to training group and 226 to validation group. The predictors included in the nomogram were symptoms, years of dust exposure, work in shifts and labor intensity. Our model showed good discrimination ability, with a bootstrap-corrected C index of 0.931 (95% CI = 0.906–0.956), and had well-fitted calibration curves. The area under the curve (AUC) of the nomogram were (95% CI = 0.906–0.956) and 0.945 (95% CI = 0.891–0.999) in the training and validation groups, respectively. The results of DCA and CICA indicated that the nomogram may have clinical usefulness.ConclusionWe established and validated a novel nomogram that can provide individual prediction of LRD for construction workers. This practical prediction model may help occupational physicians in decision making and design of occupational health examination.

Abstract Background The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. Case presentation A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. Conclusion Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.

This study firstly proposes and experimentally demonstrates a phase demodulation method with high sensitivity for interferometric fiber sensors (IFSs) on the basis of the fast Fourier transform of a wavenumber domain. The phase information of IFSs triggered by changes in environmental parameters is obtained by calculating the initial phase variation of a specific Fourier-transformed spatial frequency. Theoretically, phase sensitivity can be improved by n times when the optical path difference (OPD) of a spatial frequency peak is increased by a multiple (n times) of the OPD of other spatial frequency domain peaks. To verify the method experimentally, this study designed a large laterally offset spliced sensor formed by common single-mode fibers on the basis of mode interference. The sensing characteristics of temperature and strain in each set of two-beam interference are analyzed simultaneously by calculating the phase sensitivities of the frequency domain peaks. Furthermore, the highest reported temperature and strain sensitivities of 0.0795 rad/°C and −0.0088 rad/μϵ, respectively, with good repeatability are realized.