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Shuang Cai,1,* Cai-Hong Shi,2,* Xiangrong Zhang,2 Xiaojiao Tang,2 Hao Suo,2 Li Yang,2 Yuqing Zhao2 1Department of Pharmacy, The First Affiliated Hospital of China Medical University, 2Shenyang Pharmaceutical University, Shenyang, People's Republic of China *These authors contributed equally to this work Abstract: The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3β;12β;20-triol (25-OCH3-PPD). Optimized SMEDDS formulations for 25-OCH3-PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH3-PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH3-PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route. Keywords: 25-methoxydammarane-3β;12β;20-triol (25-OCH3-PPD), 25-OH-PPD, self-microemulsifying drug delivery system, bioavailability, pharmacokinetics

Abstract The comprehensive study of the relationship between lymph node metastasis (LNM) and its associated factors in patients with concurrent papillary thyroid carcinoma (PTC) and Hashimoto’s thyroiditis (HT) remains insufficient. Building upon the initial investigation of factors associated with LNM in patients with concurrent PTC and HT, we further analyzed the complex relationships between different severity indicators of LNM and these associated factors. This study included patients confirmed PTC with HT who underwent total thyroidectomy at Xiangya Hospital, from January 2020 to December 2021. A total of 271 patients from 2020 were used as the training set, and 300 patients from 2021 as the validation set. Univariate analysis and regression modeling were used to identify key factors associated with LNM. Model reliability was assessed using the area under the receiver operating characteristic curve (AUC). Network analysis was employed to explore associations between LNM severity and its related factors. The regression model indicated that age, calcification, free triiodothyronine (FT3), and tumor maximum diameter (TMD) are independent factors for LNM. The severity model showed free thyroxine (FT4) and hemoglobin (Hb) are independent protective factors for the region and quantity of LNM, respectively, while TMD is an independent risk factor for both. Network analysis revealed TMD has a closer relationship with LNM severity compared to other associated factors. This study innovatively combined regression models and network analysis to investigate factors related to LNM in patients with PTC and HT, providing a theoretical basis for predicting preoperative LNM in future clinical practice.

Abstract We read with great interest the report on the new anti-obesity potential in mice models of reversible monoamine oxidase B inhibitors by Moonsun et al., as opposed to the lack of such effects observed with irreversible MAO-B inhibitors (iMAO-Bi). Our research aimed to explore the potential anti-obesity effects of iMAO-Bi in patients with Parkinson’s disease (PD). This retrospective study included 37 PD in-patients from 2018 to 2023. Patients who took iMAO-Bi were assigned to the iMAO-Bi group, and those who never took iMAO-Bi were assigned to the control. The major outcomes were changes in body weight and body mass index (BMI) during follow-up. A subgroup analysis was conducted to compare the anti-obesity effect between the short-term and long-term administrations of the iMAO-Bi group. The results showed a slight yet insignificant trend of bodyweight loss among the iMAO-Bi group of PD patients. Subgroup analysis showed that short-term treatment of iMAO-Bi (less than six months) led to reductions in BMI and body weight, while the long-term treatment of iMAO-Bi displayed a slight increase in BMI and body weight. The results suggested that short-term administration of iMAO-Bi may have potential weight-loss effects. Further studies with larger sample sizes are needed to evaluate the weight-loss effect of iMAO-Bi.

The characteristics of composite inclusions between atomic interfaces has been investigated by combining high-angle annular dark field (HAADF) with first-principles computations. The characteristics of the composite inclusions reveal a core of Ca2Al2O5, with CaS and TiN adhering to its surface. According to mismatch degree theory and SEM characterization, the nucleation rate increases with a decreasing degree of mismatch. Notably, the adhesion work of the Ca2Al2O5/CaS interface is greater than that of the Ca2Al2O5/TiN interface, demonstrating the stronger bond strength of the Ca2Al2O5/CaS interface. The prediction of the lowest interfacial energy shows that a stable interface can form between Ca2Al2O5 and MX. Hence, Ca2Al2O5 can be effectively utilized as a nucleation side for CaS (TiN). The present work provides valuable theoretical and technical information for knowledge-based design and prediction of composite inclusion regulation for structural steels, especially for marine engineering steels.

Abstract Type 2 diabetes (T2DM) patients are at high risk for non-alcoholic fatty liver disease (NAFLD). Studies show SVD3 and dietary inflammatory index (DII) are associated with NAFLD. It’s unknown if they interact in T2DM patients with NAFLD. We collected data from 110 hospitalized T2DM patients, measured physiological and biochemical indicators, conducted dietary surveys, and converted data into DII and NFS, FIB-4, and BARD indices. We used logistic regression, mediation effect analysis, and moderation effect analysis to explore the relationship between DII and SVD3 with NAFLD and liver fibrosis in T2DM patients. DII was not significant in either NAFLD incidence in T2DM patients or liver fibrosis in NAFLD patients. SVD3 was positively correlated with NAFLD incidence in T2DM patients, but this correlation became insignificant as DII increased towards pro-inflammation. SVD3 is positively correlated with NAFLD incidence in T2DM patients, but this correlation becomes less significant as DII increases towards pro-inflammation.

Abstract The stress disturbances induced by deep tunnel excavation are a key factor leading to the instability and failure of surrounding rock. To investigate the stress evolution in surrounding rock, this study utilizes a physical simulation system for deep caverns to replicate the actual excavation process of tunnels. The study quantitatively analyzes changes in the magnitude and orientation of surrounding rock stresses, and validates the experimental results through numerical analysis. The study revealed that: (1) In elasto-plastic tests, the trajectories of the principal stress axes at the vault and bottom are symmetrical about the XZ plane, whereas in elastic tests, they exhibit symmetry about the origin. (2) The experimental and numerical simulation results of the principal stress axis evolution at four key monitoring points (vault, shoulder, waist, and bottom) are consistent. Using FLAC3D, the regions between these points were further divided, identifying seven distinct regions of surrounding rock, each characterized primarily by one of the four representative patterns, with the shoulder region acting as a transitional zone. (3) Regardless of whether the surrounding rock is in an elastic or elasto-plastic state, the evolution of the principal stress magnitudes and their angles with the coordinate axes remained entirely consistent.

Abstract Background Non-tuberculous mycobacteria (NTM) are common opportunistic pathogens, and the most common infection site is lung. NTM are found commonly in the environment. Many patients have NTM lung colonization (NTM-Col). NTM lung disease (NTM-LD) have no specific sympotms, though it is hard to differentiate NTM-LD and NTM-Col under this circumstance. The aim of this study is to explore the differences between NTM-LD and NTM-Col for future clinical diagnosis and treatment. Methods We retrospectively enrolled patients who had a history of NTM isolated from respiratory specimens in Peking Union Medical College Hospital (PUMCH) from January 1st, 2013 to December 31st, 2022. Patients were classified into NTM-LD group and NTM-Col group. Demographic characteristics, clinical manifestations, laboratory tests and imaging findings of the two groups were compared. Comparative analysis was also performed in peripheral blood lymphocyte subsets among three groups. Results A total of 127 NTM-LD patients and 37 NTM-Col patients were enrolled. Proportion of patients with bronchiectasis was higher in NTM-LD group than in NTM-Col group (P = 0.026). Predominant NTM isolates were Mycobacterium avium complex (MAC). NTM-LD group had a higher proportion of Mycobacterium intracellulare (P = 0.004). CD4+ T cells counts was lower in NTM-LD group (P = 0.041) than in NTM-Col group. Imaging finding of bronchiectasis (P = 0.006) was higher in NTM-LD group than in NTM-Col group. Imaging findings of bronchiectasis (OR = 6.282, P = 0.016), and CD4+ T cell count (OR = 0.997, P = 0.012) were independent associated factors for differential diagnosis between NTM-LD and NTM-Col. Conclusion NTM isolates from both NTM-LD and NTM-Col patients were predominantly MAC, with a higher Mycobacterium intracellulare isolation rate in NTM-LD group. Imaging findings of bronchiectasis and lower peripheral blood CD4+ T cell count may be helpful to separate the diagnosis of NTM-LD from NTM-Col.

Abstract Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa_circ_0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5′ UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy.

Objective·To summarize the clinical features, imaging features, and diagnosis and treatment experience of primary mediastinal yolk sac tumor (YST).Methods·Data of 29 patients with primary mediastinal YST, who attended Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to May 2023, were collected and comprehensively analyzed, including imaging examination results, serum indicators, pathology reports and treatment methods.Results·There were 22 cases of pure YST and 7 cases of mixed YST comprising 28 males and 1 female. The mean age of onset was (24.5±5.9) years. The initial symptoms were chest tightness (34.5%), chest pain (27.8%), cough (34.5%), expectoration (34.5%) and no specific symptoms (24.1%). Chest computerized tomography (CT) enhancement showed that all the 29 lesions were located in the anterior mediastinum. The maximum diameter of the lesions ranged from 5.6 cm to 18.2 cm. The lesions were irregular in shape, uneven in density, partially cystic and solid in density. The enhancement scan showed the solid part was slightly and moderately enhanced, and the low-density area was not enhanced. Tumor boundary was not clear because tumors often compressed and invaded surrounding tissues. Among the 29 newly diagnosed patients, serum alpha-fetoprotein (AFP) was significantly increased in 28 cases (1 case was not tested). Patients received multidisciplinary comprehensive treatment, including chemotherapy (25/29), surgery (26/29), and radiotherapy (8/29). Seven patients directly received surgery after diagnosis. Nineteen patients received chemotherapy first and then surgery; 16 (84.2%) cases were evaluated as lesion shrinkage after chemotherapy. After surgery, 73.1% (19/26) patients had a significant decrease in serum AFP. After chemotherapy, 56.0% (14/25) patients had decreased serum AFP.Conclusion·Primary mediastinal YST usually occurs in middle-aged and young men, with certain clinical and radiographic features and elevated serum AFP, which requires multidisciplinary comprehensive treatment.

This study examines the impact of judicial protection of intellectual property rights on firms' independent innovation. Using a staggered difference-in-differences model with panel data from Chinese manufacturing listed businesses (2014–2021) and the successive establishment of intellectual property courts in Chinese prefectural-level cities as a quasi-natural experiment, we find that establishing intellectual property courts in China encourages businesses to accumulate more technology-based intangible assets. Mechanism analysis suggests that judicial intellectual property protection enhances enterprises' independent innovation capacity by establishing a conducive institutional framework. This stimulating effect is particularly significant for industry-leading companies with technological supremacy. Heterogeneity analysis reveals that judicial intellectual property protection increases the generation of patents and trade secrets, with a more pronounced effect on firms receiving higher government research and development subsidies and better tax incentives. This study offers valuable insights for policymakers to encourage corporate independent innovation.

Abstract The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance’s core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.

Abstract Infection after anterior cruciate ligament reconstruction (ACLR) is a rare and catastrophic postoperative complication. The aims of this study were to investigate the diagnostic, treatment and rehabilitation measures for postoperative infection following after ACLR. A retrospective study was conducted on 1500 patients who underwent ACLR between January 2011 and January 2022. Twenty patients who met the criteria for summarizing the incidence patterns and treatment experiences were selected for a complete investigation of their diagnostic, therapeutic, and rehabilitation processes, as well as outpatient follow-up results. Among the 20 patients who developed postoperative infections, Staphylococcus aureus was the main pathogen (80%). The clinical manifestations mainly included fever (80%) and knee joint pain (100%). Laboratory tests demonstrated that C-reactive protein (CRP) levels were greater than 50 mmol/L in fifteen patients (75%). All of the patients received intravenous antibiotic therapy. Five patients (25%) of tendon socket infection were treated with continuous negative pressure suction irrigation, whereas the other fifteen patients with intra-articular infection were treated with arthroscopic debridement and continuous flushing. The Lysholm score of the affected knee was compared before treatment and 6 months after treatment, and the difference was statistically significant (t = 20.78, P

Abstract ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies.

Global precipitation observations have been realized through the development of satellite remote-sensing technology. However, there is a lack of evaluation of remote-sensing precipitation products in complex tropical island terrains. This study used hourly rain gauge data to conduct a multi-scale systematic evaluation of common precipitation products, such as CMORPH, CHIRPS, GsMAP, GPM, MSWEP, ERA5-Land, and PERSIANN, over Hainan Island, providing an in-depth analysis of the precipitation detection capabilities of various products in this region. The main conclusions are: (1) In a multi-temporal scale evaluation, GPM and GsMAP outperformed the other products across all time scales. On a 3-hour scale, GPM and GsMAP showed the highest correlation coefficients (0.53 and 0.52, respectively). On a daily scale, except for PERSIANN, all products showed correlation coefficients above 0.56, with GPM and GsMAP showing the best performance (R = 0.73 and 0.74, respectively). (2) In comparing annual precipitation, Hainan Island's average-annual precipitation over the past 20 years showed a fluctuating trend, with a mean of 1,776.4 mm/a. The CMORPH annual average of 1,765.1 mm/a was the closest to the CHM-PRE dataset, with minimal error. ERA5-Land and MSWEP significantly overestimated (2,504.3 mm/a) and underestimated (1,662.2 mm/a) the average-annual precipitation, respectively. (3) Spatial distribution pattern analysis revealed that the observed multi-year annual precipitation in Hainan Island ranges from 996.9 to 2,368.9 mm, exhibiting an annular-distribution pattern with higher precipitation in the east than in the west and the southwestern mountainous areas than in the northeastern plains. The precipitation range of 1,337.9‒2,287.0 mm observed in GsMAP was the closest to the rain gauge data and particularly matched that of the high-value center in the southeast of the island. (4) In a precipitation trend analysis, CMORPH, ERA5-Land, GPM, MSWEP, CHIRPS, and PERSIANN showed an increasing trend in local areas of Hainan Island, while GsMAP showed a stronger increasing trend. (5) In an analysis of extreme precipitation events, GsMAP, CMORPH, and GPM reproduced the spatiotemporal evolution of extreme precipitation events on a daily scale in Hainan relatively well. GPM better reproduced the spatial and temporal evolution characteristics of typhoon precipitation events in Hainan Island. However, the accuracy of the precipitation estimation still requires improvement. The results of this study not only contribute to our understanding of precipitation products applicable to Hainan but also provide insights for improving satellite-based precipitation products in tropical island environments. These findings underscore the importance of regional validation and the potential of multi-product fusion approaches for enhancing precipitation estimates in complex terrains.

Purpose – Temperature is an important load for a ballastless track. However, little research has been conducted on the dynamic responses when a train travels on a ballastless track under the temperature gradient. The dynamic responses under different temperature gradients of the slab are theoretically investigated in this work. Design/methodology/approach – Considering the moving train, the temperature gradient of the slab, and the gravity of the slab track, a dynamic model for a high-speed train that runs along the CRTS III slab track on subgrade is developed by a nonlinear coupled way in Abaqus. Findings – The results are as follows: (1) The upward transmission of the periodic deformation of the slab causes periodic track irregularity. (2) Because of the geometric constraint of limiting structures, the maximum bending stresses of the slab occur near the end of the slab under positive temperature gradients, but in the middle of the slab under negative temperature gradients. (3) The periodic deformation of the slab can induce periodic changes in the interlayer stiffness and contact status, leading to a large vibration of the slab. Because of the vibration-reduction capacity of the fastener and the larger mass of the concrete base, the accelerations of both the slab and concrete base are far less than the acceleration of the rail. Originality/value – This study reveals the influence mechanism of temperature gradient-induced periodic deformation in the dynamic responses of the train-track system, and it also provides a guide for the safe service of CRTS III slab track.

Abstract Background Hemoptysis resulting from rupture of the pulmonary artery pseudoaneurysm (PAP) is massive and fatal, while factor contributing to the rupture of pseudoaneurysm remains elusive. This study aimed to elucidate the clinical and radiological features of PAP and identify the risk factors associated with rupture. Methods Patients who developed hemoptysis with PAP were collected from January 2019 to December 2022 retrospectively. Clinical data of the demographic characteristics, radiological findings, treatment strategies, and prognosis were collected. A comparative analysis was performed on the characteristics in the ruptured and non-ruptured cases. Results A total of 58 PAPs were identified in the 50 patients. The most common causes were infection (86%) and cancer (8%). The PAPs were located predominantly in the upper lobes of both lungs, and 57 (99.3%) were distributed in the segmental or subsegmental pulmonary arteries. The median diameter was 6.1(4.3–8.7) mm. A total of 29 PAPs were identified adjacent to pulmonary cavitations, with the median diameter of the cavity being 18.9 (12.4–34.8) mm. Rupture of pseudoaneurysm occurred in 21 cases (42%). Compared to unruptured group, the ruptured group had a significantly higher proportion of massive hemoptysis (57.1% vs. 6.9%, p

Abstract Although the relationship between hypertension and hyperuricemia is widely recognized, there is still a relative lack of research on prehypertensive individuals and the individual associations of systolic and diastolic blood pressure with the risk of hyperuricemia. From 2011 to 2016, we conducted a study on 53,323 individuals at Wuhu City Hospital in China. Based on initial blood pressure readings, participants were categorized into normal, prehypertension, or hypertension groups. We used Cox regression to analyze the associations with baseline factors. In subgroup analyses, systolic and diastolic pressures were treated as continuous variables, and their relationship with the risk of hyperuricemia was examined using restricted cubic spline analysis. The risk increased in the prehypertension and hypertension groups compared to the normal blood pressure group, with hazard ratios of 1.192 and 1.350, respectively. For each unit increase in blood pressure, the risk of hyperuricemia rose by 0.8% (systolic) and 0.9% (diastolic), especially when blood pressure levels exceeded 115/78 mmHg. Additionally, we observed that factors such as gender, alcohol consumption habits, obesity, and dyslipidemia might further influence this association. These findings emphasize the importance of early risk assessment and intervention in these patient populations in clinical practice.

Abstract Purpose Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown. Patients and methods We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC. Results In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes. Conclusion Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis.

Abstract Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022. Patients with NEC (Bell’s stage ≥ II) were assigned to the NEC group. Gestational age- and birth weight-matched non-NEC infants born during the same period at the same hospital were assigned to the control group. The risk factors associated with NEC were analyzed with univariate and logistic regression models. During the study period, 2,912 SGA infants were enrolled, 150 (5.15%) of whom developed NEC. In total, 143 patients and 143 controls were included in the NEC and control groups, respectively. Logistic regression analysis revealed that sepsis (OR 2.399, 95% CI 1.271–4.527, P = 0.007) and anemia (OR 2.214, 95% CI 1.166–4.204, P = 0.015) might increase the incidence of NEC in SGA infants and that prophylactic administration of probiotics (OR 0.492, 95% CI 0.303–0.799, P = 0.004) was a protective factor against NEC. Therefore, sepsis, anemia and a lack of probiotic use are independent risk factors for NEC in SGA infants.

Abstract Background Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. Methods In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. Results 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (β=-0.0121, P

Abstract Due to high computation complexity, traditional design methods for LLC converter usually consider limited kinds of performance, and the process for searching the optimal parameter scheme is discrete, which might cause the missing of real optimal solution. In order to solve these problems, a multi‐objectives optimization design method for the LLC converter is proposed in this paper. According to the numerical calculation method, a closed parameter space for resonant parameters is established under the constraints of operation mode, switching frequency, zero voltage switching (ZVS), and voltage stress of resonant capacitor. Besides, the root‐mean‐square (RMS) value of resonant current and secondary current, as well as the core loss of the transformer, are selected as the optimization objectives. Non‐dominated sorting genetic algorithm (NSGA‐II) is utilized to deal with these multi‐objective formulations. In order to reduce the computation complexity, a data‐driven method, called adaptive polynomial approximation (APA), is selected to obtain the explicit expressions of the parameter space and the optimization objectives. Then, by substituting this simplified surrogate model into the NSGA‐II algorithm, the optimal parameter scheme is obtained. The comprehensive comparison analysis is performed, and a 400 W/48 V experimental prototype was built to verify the theoretical analysis, which shows that the proposed method features the highest efficiency of 95%.

Abstract Objectives Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. Methods Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. Results High-sensitivity C-reactive protein (p

The harmful effects of most synthetic corrosion inhibitors on the environment are the motivation for the study of environmentally friendly extracts. The main components of silkworm sand extract (SSE) were studied by infrared spectroscopy (FTIR) and ultraviolet visible spectroscopy (UV-vis). The scale inhibition effect of SSE as scale inhibitor in calcium chloride solution was studied by means of electrical conductivity, static scale inhibition and scanning electron microscopy (SEM). Electrochemical impedance (EIS) and potentiodynamic polarization curve (PDP) were used to study its corrosion inhibition performance in simulated cooling water. The results showed that chlorophyll was the main component of SSE. When the concentration of SSE was more than 30 mg/L, the scale inhibition efficiency of calcium carbonate and calcium sulfate was both more than 90%. SSE could inhibit the supersaturation of calcium carbonate, prolong the nucleation time, and change the crystal shape of calcium scale. SSE had a good corrosion inhibition effect on Q235 steel in salt solution, and its corrosion inhibition mechanism was that SSE formed a protective film on the surface of Q235 steel. SSE could play a dual role of scale inhibition and corrosion inhibition, which was a potential new, environmentally safe corrosion and scale inhibitor for cooling water system.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Objective A novel compound based on near-infrared fluorescence (NIRF) probe was prepared to achieve dynamic monitoring of an inflammatory brain edema model in mice and real-time evaluation of therapeutic effects through in vivo imaging. Methods The NIRF probe IR-783 was chemically linked with clinical brain edema therapeutic drug furosemide (FSM) to obtain the new compound, IR-783-FSM. The ultraviolet fluorescence properties of the compound were evaluated using an ultraviolet spectrophotometer. The uptake of the compound by mouse macrophage cells RAW 264.7 was detected with in vitro cellular experiments. Its cytotoxicity was evaluated through CCK8 assays. A brain edema model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS), confirmed by HE staining and dry-wet weight methods for brain tissues. The mice in the brain edema model were divided into control group, IR-783, and IR-783-FSM treatment groups, receiving intraperitoneal injections of PBS, IR-783, and IR-783-FSM, respectively. Real-time in vivo fluorescence imaging was then performed. The mice in each group were euthanized after 10 hours. Ex vivo brain imaging and dry-wet weight measurements were performed to observe the NIRF imaging characteristics and therapeutic effects of IR-783-FSM on brain edema model. Results The newly synthesized compound, IR-783-FSM, retained the excellent near-infrared fluorescence characteristics of IR-783. It could target mouse macrophages with an IC50 of 48.82 µmol/L. A brain edema model could be successfully constructed with intraperitoneal injection of LPS, with significantly higher brain tissue water content compared to the control group (P

Abstract In traditional von Neumann computing architecture, the efficiency of the system is often hindered by the data transmission bottleneck between the processor and memory. A prevalent approach to mitigate this limitation is the use of non-volatile memory for in-memory computing, with spin–orbit torque (SOT) magnetic random-access memory (MRAM) being a leading area of research. In this study, we numerically demonstrate that a precise combination of damping-like and field-like spin–orbit torques can facilitate precessional magnetization switching. This mechanism enables the binary memristivity of magnetic tunnel junctions (MTJs) through the modulation of the amplitude and width of input current pulses. Building on this foundation, we have developed a scheme for a reconfigurable spintronic logic gate capable of directly implementing Boolean functions such as AND, OR, and XOR. This work is anticipated to leverage the sub-nanosecond dynamics of SOT-MRAM cells, potentially catalyzing further experimental developments in spintronic devices for in-memory computing.

Abstract Introduction The correlation between radiation exposure before pregnancy and abnormal birth weight has been previously proven. However, for large-for-gestational-age (LGA) babies in women exposed to radiation before becoming pregnant, there is no prediction model yet. Material and methods The data were collected from the National Free Preconception Health Examination Project in China. A sum of 455 neonates (42 SGA births and 423 non-LGA births) were included. A training set (n = 319) and a test set (n = 136) were created from the dataset at random. To develop prediction models for LGA neonates, conventional logistic regression (LR) method and six machine learning methods were used in this study. Recursive feature elimination approach was performed by choosing 10 features which made a big contribution to the prediction models. And the Shapley Additive Explanation model was applied to interpret the most important characteristics that affected forecast outputs. Results The random forest (RF) model had the highest average area under the receiver-operating-characteristic curve (AUC) for predicting LGA in the test set (0.843, 95% confidence interval [CI]: 0.714–0.974). Except for the logistic regression model (AUC: 0.603, 95%CI: 0.440–0.767), other models’ AUCs displayed well. Thereinto, the RF algorithm’s final prediction model using 10 characteristics achieved an average AUC of 0.821 (95% CI: 0.693–0.949). Conclusion The prediction model based on machine learning might be a promising tool for the prenatal prediction of LGA births in women with radiation exposure before pregnancy.

Abstract Background Terpenes are important components of plant aromas, and terpene synthases (TPSs) are the key enzymes driving terpene diversification. In this study, we characterized the volatile terpenes in five different Chrysanthemum nankingense tissues. In addition, genome-wide identification and expression analysis of TPS genes was conducted utilizing an improved chromosome-scale genome assembly and tissue-specific transcriptomes. The biochemical functions of three representative TPSs were also investigated. Results We identified tissue-specific volatile organic compound (VOC) and volatile terpene profiles. The improved Chrysanthemum nankingense genome assembly was high-quality, including a larger assembled size (3.26 Gb) and a better contig N50 length (3.18 Mb) compared to the old version. A total of 140 CnTPS genes were identified, with the majority representing the TPS-a and TPS-b subfamilies. The chromosomal distribution of these TPS genes was uneven, and 26 genes were included in biosynthetic gene clusters. Closely-related Chrysanthemum taxa were also found to contain diverse TPS genes, and the expression profiles of most CnTPSs were tissue-specific. The three investigated CnTPS enzymes exhibited versatile activities, suggesting multifunctionality. Conclusions We systematically characterized the structure and diversity of TPS genes across the Chrysanthemum nankingense genome, as well as the potential biochemical functions of representative genes. Our results provide a basis for future studies of terpene biosynthesis in chrysanthemums, as well as for the breeding of improved chrysanthemum varieties.

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes, its therapeutic potential is compromised by its short half-life and narrow therapeutic index. Current long-acting insulin analogs, such as insulin-polymer conjugates, are mainly used to improve pharmacokinetics by reducing renal clearance. However, these conjugates are synthesized without sacrificing the bioactivity of insulin, thus retaining the narrow therapeutic index of native insulin, and exceeding the efficacious dose still leads to hypoglycemia. Here, we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated clearance. By impairing the binding affinity to the receptor and the activation of the receptor, di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly, increases its maximum tolerated dose 10-fold. The target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high dose. This work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

Shallow landslides and debris flows triggered by heavy rainfall are widespread catastrophic geological disasters in mountainous areas. Landslides with complex terrain are often the material source of debris flows as a disaster chain. However, the failure mechanism and dynamic process of landslide triggered debris flow are still not clear. In July 2023, an obvious rockslide occurred during heavy rainfall in Changtan Town, Chongqing City, Southwest China, resulting in one death and seven houses collapsed. In this paper, back analysis in the dynamic process of the Yanghuachi (YHC) landslide triggered debris flow is carried out by the coupled particle flow model and elastic viscoplastic model. The reults indicate that the sliding body moves downward along the sliding surface, pushing the loose deposits at the lower part of the landslide to slip and then extending along the gully to the right bank of the Modao River. The overall movement duration of the landslide in the study area is approximately 180 s, with a maximum sliding velocity of about 22.08 m/s and a final deposition thickness of approximately 10.91 m. This study provides a methodology for analyzing the dynamic process of landslide triggered debris flows.

Antibody drugs targeting single inflammatory cytokines have revolutionized the treatment of immune-mediated inflammatory diseases. To investigate whether dual targeting interleukin-17 (IL-17) and IL-36 enhances anti-inflammatory activity, bispecific Ab HB0043 was generated by linking the single chain fragment variables (scFvs) from humanized anti-IL-36R antibody (HB0034) to the C-terminus of the heavy chain of anti-IL-17A IgG1 (HB0017) Fc using a flexible peptide linker. HB0043 largely maintained the binding affinities and biological activities of the two parent monoclonal antibodies (mAbs) in vitro. IL-17 and IL-36 cooperated to amplify the expression of pro-inflammatory and pro-fibrotic genes in normal human dermal fibroblasts (NHDF). However, HB0043 more effectively blocked IL-6 and IL-8 production in NHDF stimulated by IL-17A and IL-36 compared to two monoclonal antibodies. In a mouse model of Oxazolone (OXA)-induced atopic dermatitis and Imiquimod (IMQ)-induced skin inflammation, administration of both anti-IL17A mAb HB0017 and anti-mouse IL-36R surrogate antibody HB0034SA showed improved effectiveness in alleviating skin thickening and inflammation based on histological assessment. Further, in cynomolgus monkeys, HB0043 showed no enhanced target-related toxicity compared with the two parental mAbs in vivo and with a moderate increase in production of anti-drug antibodies. Together, dual blockade of IL-17A and IL-36R in the form of a bispecific antibody may have advantages in blocking the overlapping and non-overlapping functions of these two cytokines in skin inflammation that could not optimally be curtailed with single mAbs. In conclusion, as monotherapy may reach therapeutic celling for certain difficult-to-treat inflammatory and fibrotic diseases, dual targeting could potentially pave a way to combat these diseases.

Abstract Sortilin‐related receptor 1 (SorL1) deficiency is a genetic predisposition to familial Alzheimer’s disease (AD), but its pathology is poorly understood. In SorL1‐null rats, a disorder of the global endosome‐lysosome network (ELN) is found in hippocampal neurons. Deletion of amyloid precursor protein (APP) in SorL1‐null rats could not completely rescue the neuronal abnormalities in the ELN of the hippocampus and the impairment of spatial memory in SorL1‐null young rats. These in vivo observations indicated that APP is one of the cargoes of SorL1 in the regulation of the ELN, which affects hippocampal‐dependent memory. When SorL1 is depleted, the endolysosome takes up more of the lysosome flux and damages lysosomal digestion, leading to pathological lysosomal storage and disturbance of cholesterol and iron homeostasis in the hippocampus. These disturbances disrupt the original homeostasis of the material‐energy‐subcellular structure and reprogram energy metabolism based on fatty acids in the SorL1‐null hippocampus, instead of glucose. Although fatty acid oxidation increases ATP supply, it cannot reduce the levels of the harmful byproduct ROS during oxidative phosphorylation, as it does in glucose catabolism. Therefore, the SorL1‐null rats exhibit hippocampal degeneration, and their spatial memory is impaired. Our research sheds light on the pathology of SorL1 deficiency in AD.

Abstract BackgroundAllergic diseases are associated with an increased susceptibility to respiratory tract infections. Although allergen immunotherapy (AIT) alters the course of allergies, there is limited evidence from clinical practice demonstrating its ability to enhance the host defense against pathogens. ObjectiveThe aim of this study was to investigate the protective effect of AIT against viral infection in patients with allergic rhinitis (AR) and allergic asthma (AS) based on clinical evidence. MethodsA multicenter, questionnaire-based survey was conducted during a tremendous surge in COVID-19 cases between February 10, 2023, and March 15, 2023, in 81 centers across China recruiting healthy volunteers and patients with AR and AS to investigate the clinical outcomes of COVID-19 infection. ResultsOf 10,151 participants recruited in the survey, 3654 patients and 2192 healthy volunteers who tested positive for COVID-19 were included in this analysis after screening. Overall, no significant differences in COVID-19 outcomes were observed between patients and healthy volunteers. An additional 451 patients were excluded due to their use of biologics as the sole add-on treatment, leaving 3203 patients in the further analysis. Of them, 1752 were undergoing routine medication treatment (RMT; the RMT group), whereas 1057 and 394 were receiving AIT and a combination of AIT and omalizumab (OMA) as adjunct therapies to RMT, respectively (AIT+RMT and AIT+OMA+RMT groups). The AIT group showed milder COVID-19 symptoms, shorter recovery periods, and a lower likelihood of hospitalization or emergency department visits than the RMT group (all PPPP ConclusionsOur multicenter observational study provides valuable clinical evidence supporting the protective effect of AIT against COVID-19 infection in patients with AR and AS.

The promotion of electric vehicles brings notable environmental and economic advantages. Precisely estimating the state of health (SOH) of lithium-ion batteries is crucial for maintaining their efficiency and safety. This study introduces an SOH estimation approach for lithium-ion batteries that integrates multi-feature analysis with a convolutional neural network and kolmogorov-arnold network (CNN-KAN). Initially, we measure the charging time, current, and temperature during the constant voltage phase. These include charging duration, the integral of current over time, the chi-square value of current, and the integral of temperature over time, which are combined to create a comprehensive multi-feature set. The CNN’s robust feature extraction is employed to identify crucial features from raw data, while KAN adeptly models the complex nonlinear interactions between these features and SOH, enabling accurate SOH estimation for lithium batteries. Experiments were carried out at four different charging current rates. The findings indicate that despite significant nonlinear declines in the SOH of lithium batteries, this method consistently provides accurate SOH estimations. The root mean square error (RMSE) is below 1%, with an average coefficient of determination (R2) exceeding 98%. Compared to traditional methods, the proposed method demonstrates significant advantages in handling the nonlinear degradation trends in battery life prediction, enhancing the model’s generalization ability as well as its reliability in practical applications. It holds significant promise for future research in SOH estimation of lithium batteries.

Abstract Background This study assesses the prevalence of sexually transmitted infections (STIs) in first time visitors to the STIs clinic in Hangzhou, China, considering different genders, ages and symptoms. And also explores howthe COVID‐19 pandemic has affected on STIs. Methods From 2019 to 2023, 27,283 first time visitors were tested for nine distinct STIs, including Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV), syphilis, Herpes Simplex Virus type 2 (HSV‐2), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and vaginal Candida. Results Symptomatic male and female visitors showed overall STI‐positive rates of 39.27% and 59.20%, respectively(p 50 years, regardless of gender and symptoms. During the COVID‐19 pandemic, symptomatic visitors showed lower positive rates for HPV, HIV, syphilis, and HSV‐2, while Candida, UU, CT, NG, and multiple infections increased. Among asymptomatic visitors, HPV had the lowest positive rate, while NG and multiple infections increased during the pandemic. Conclusion STI prevalence is notably high, particularly in those aged ≤ 20 and >50 years. It emphasizes the need for enhanced health education, condom use, and vaccination. The COVID‐19 pandemic impacting STIs through varied factors, such as reduced sexual activity and clinical service interruption.

Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease that presents with the proliferation of extensive, dense fibrous tissue in the mediastinum. Hemoptysis is a common clinical manifestation of FM. Clinically, most patients exhibit mild to moderate hemoptysis. We report a case of FM complicated with life-threatening massive hemoptysis. The patient was successfully rescued through a combination of bronchoscopic balloon closure, bronchial artery embolization (BAE), and surgical interventions. Although FM is frequently benign, vascular involvement can progress to life-threatening massive hemoptysis and must be treated appropriately.

Large-scale ancient landslides are widely distributed in Southwest China, yet their reactivation mechanisms remain complex and poorly understood. On 25 July 2020, one such landslide in Liujing Village, Wulong District, Chongqing, China, experienced reactivation. This event exhibited variable movement characteristics across different areas and times, ultimately manifesting as a chain-type failure. Combining field investigations and drilling works, this study describes the fundamental characteristics of the Zhongbao landslide and the variation rules of the seepage field and the stability by numerical simulations. The failure mechanism is preliminarily revealed, and the failure influencing factors are discussed. The results show that, the landslide’s progression was influenced by the stratigraphic lithology and the morphology of the sliding surface, resulting in two distinct turns during its movement. By analyzing the landslide’s spatial morphology, direction of sliding, material composition, extent of the accumulation area, and dynamic behavior, we have categorized the Zhongbao landslide into five principal zones. The failure process can be segmented into four stages: initiation, shear-out, acceleration, and accumulation blockage. Heavy rainfall served as the primary trigger for the landslide, while the microtopography of the sliding surface significantly influenced the failure dynamics. The insights gained from this study offer valuable guidance for understanding the reactivation mechanisms of similar chained ancient landslides in the geologically analogous regions of Southwest China.

ABSTRACT: Free gossypol (FG), the primary antinutritional component in cottonseed meal, can adversely affect the growth and health of poultry. Although younger geese are particularly sensitive to FG, the precise effects of FG on geese remain elusive. This study aimed to investigate the effects of gossypol acetate (GA), a form of FG, on the growth, serum biochemical parameters, and intestinal health of goslings. Seventy-two healthy male goslings, aged 7-day-old with similar body weight (BW), were randomly divided into 3 groups: a control group and 2 GA-treated groups (GA25 and GA50), which were orally administered GA (25 and 50 mg/kg BW) daily for 14 d. The results showed that oral administration of GA significantly suppressed BW, altered serum parameters, and impaired intestinal health in a dose- and time-dependent manner. Specifically, GA adversely affected intestinal morphology, induced oxidative stress, and inflammation, diminished immune function, and increased intestinal permeability and apoptosis of intestinal cells, consequently impairing nutrient absorption and utilization of goslings. Overall, these data indicate that GA adversely affects the growth, serum parameters, and intestinal health of goslings, providing valuable information further to understand the toxic effects of gossypol on goslings.

Mathematical modeling of epidemic dynamics is crucial to understand its underlying mechanisms, quantify important parameters, and make predictions that facilitate more informed decision-making. There are three major types of models: mechanistic models including the SEIR-type paradigm, alternative data-driven (DD) approaches, and hybrid models that combine mechanistic models with DD approaches. In this paper, we summarize our work in the COVID-19 Scenario Modeling Hub (SMH) for more than 12 rounds since early 2021 for informed decision support. We emphasize the importance of deep learning techniques for epidemic modeling via a flexible DD framework that substantially complements the mechanistic paradigm to evaluate various future epidemic scenarios. We start with a traditional curve-fitting approach to model cumulative COVID-19 based on the underlying SEIR-type mechanisms. Hospitalizations and deaths are modeled as binomial processes of cases and hospitalization, respectively. We further formulate two types of deep learning models based on multivariate long short term memory (LSTM) to address the challenges of more traditional DD models. The first LSTM is structurally similar to the curve fitting approach and assumes that hospitalizations and deaths are binomial processes of cases. Instead of using a predefined exponential curve, LSTM relies on the underlying data to identify the most appropriate functions, and is capable of capturing both long-term and short-term epidemic behaviors. We then relax the assumption of dependent inputs among cases, hospitalizations, and death. Another type of LSTM that handles all input time series as parallel signals, the independent multivariate LSTM, is developed. Independent multivariate LSTM can incorporate a wide range of data sources beyond traditional case-based epidemiological surveillance. The DD framework unleashes its potential in big data era with previously neglected heterogeneous surveillance data sources, such as syndromic, environment, genomic, serologic, infoveillance, and mobility data. DD approaches, especially LSTM, complement and integrate with the mechanistic modeling paradigm, provide a feasible alternative approach to model today’s complex socio-epidemiological systems, and further leverage our ability to explore different scenarios for more informed decision-making during health emergencies.

BackgroundSilicosis is a diffuse fibrosis of the lungs caused by long-term inhalation of free silicon dioxide (SiO2). It has a complex pathogenesis and lacks effective treatment. Brusatol (Bru) has a variety of biological activities, and its role in silicosis fibrosis is unclear yet. ObjectiveTo investigate the effects of different concentrations of Bru on SiO2-induced silicosis fibrosis in mice. MethodsThirty male C57BL/6J mice were randomly divided into five groups: a control group, a silica group, and three Bru intervention groups with low, medium, and high doses (1, 2, and 4 mg·kg−1), with 6 mice in each group. Except the control group, the remaining groups were established as SiO2-induced silicosis mouse models by using a single tracheal infusion of 50 μL 60 mg·mL−1 SiO2 suspension. The control group was dosed with equal amount of saline. The Bru intervention groups were injected intraperitoneally with Bru for 5 consecutive days and then injected every other day. After 28 d of exposure, the mice were executed and lung tissues were collected. The lung coefficient of the mice was measured, and the pathological changes of the lung tissues were observed after hematoxylin-eosin (HE) and Masson staining. The levels of apoptotic protein Cleaved-caspase 3, fibrosis-related protein α-smooth muscle actin (α-SMA), type I collagen (Col-I), autophagy-associated protein Beclin1, microtubule-associated protein 1 light chain 3 (LC3), Sequestosome 1 (p62/SQSTM1), Kelch like ECH-associated protein-1 (Keap1), and nuclear factor erythroid 2 related factor 2 (Nrf2) were detected by Western blot. The mRNA levels of Caspase 3, α-SMA, and Col-I were measured by realtime fluorescence-based quantitative PCR. ResultsCompared with the control group, the lung coefficient of mice in the silica group was significantly increased (P < 0.01); the lung tissues of the silicosis mice showed damaged alveolar walls, along with infiltration of inflammatory cells, fibrous nodules, and collagen deposition; furthermore, the protein and mRNA levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly increased (P < 0.01); the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were increased, while that of Keap1 was decreased (P < 0.05). The interventions with low and medium doses of Bru reduced lung coefficient (P < 0.05) and protected against pathological damage and collagen deposition in the lung tissues of the silicosis mice; the protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly decreased in the low and medium dose groups (P < 0.05, P < 0.01), the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were also decreased (P < 0.05, P < 0.01), and the expression level of Keap1 was increased in the medium dose group (P < 0.05). However, compared with the silica group, the differences in lung coefficient, pathological damage, and protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I in the Bru high dose group were not statistically significant (P > 0.05). In addition, the high dose of Bru decreased Beclin1, LC3-II/I, and Nrf2 expression levels (P < 0.01), did not change p62 protein expression level (P > 0.05), while increased Keap1 protein level (P < 0.01). ConclusionLow and medium doses of Bru might regulate autophagy through the Keap1-Nrf2 pathway, ameliorate autophagic degradation impairment, reduce pulmonary coefficient, attenuate apoptosis, and delay the progression of fibrosis in SiO2-induced silicosis mice.

On February 6, 2023, the doublet earthquake including two main shocks with magnitudes MW7.8 and MW7.5, occurred near the western side of the East Anatolian Fault at the southeast boundary of the Anatolian Plateau in Turkey. Based on the WGM2012 Bouguer gravity anomaly data and the Etopo1 topography data, this study first introduced a joint inversion of admittance and coherence functions and used the Bayesian optimal parameter estimation method to obtain the effective elastic thickness Te and loading ratio F of the lithosphere for various tectonic units in the Anatolian Plateau. Secondly, we discussed the characteristics and influencing factors of the lithospheric mechanical strength and analyzed its relationship with seismic activity. The lithospheric mechanical strength of the Anatolian Plateau showed clear lateral heterogeneity and a ''weak-strong-weak'' spatial pattern from east to west, reflecting various tectonic processes. At last, the strong seismic activity was found where the lithospheric strength was low in the Anatolian Plate. We also incorporated GPS strain rate and other results to investigate the tectonic background and primary causes of the MW7.8 and MW7.5 doublet earthquakes in Turkey. The results have a good insight into urban safety design in the Turkish region, including post-disaster rehabilitation, earthquake hazard assessment, and loss reduction.

Manganese cobaltite (MnCo2O4) is a promising electrode material because of its attractive redox chemistry and excellent charge storage capability. Our previous work demonstrated that the octahedrally-coordinated Mn are prone to react with the hydroxyl ions in alkaline electrolyte upon electrochemical cycling and separates on the surface of spinel to reconstruct into δ-MnO2 nanosheets irreversibly, thus results in a change of the reaction mechanism with K+ ion intercalation. However, the low capacity has greatly limited its practical application. Herein, we found that the tetrahedrally-coordinated Co2+ ions were leached when MnCo2O4 was equilibrated in 1 mol L−1 HCl solution, leading to the formation of layered CoOOH on MnCo2O4 surface which is originated from the covalency competition induced selective breakage of the CoT–O bond in CoT–O–CoO and subsequent rearrangement of free CoO6 octahedra. The as-formed CoOOH is stable upon cycling in alkaline electrolyte, exhibits conversion reaction mechanism with facile proton diffusion and is free of massive structural evolution, thus enables utilization of the bulk electrode material and realizes enhanced specific capacity as well as facilitated charge transfer and ion diffusion. In general, our work not only offers a feasible approach to deliberate modification of MnCo2O4's surface structure, but also provides an in-depth understanding of its charge storage mechanism, which enables rational design of the spinel oxides with promising charge storage properties.

In modern warfare, the use of UAV swarm to deceive and interfere with the hostile networked radar has been widely used as an effective countermeasure. However, when facing a complex combat environment, the digital storage and forwarding equipment carried by the UAV swarm has forwarding delay error due to its limited accuracy. This delay error will lead to a deviation between the generated false target point and the preset false target point to reduce the effectiveness of deception significantly. To address this issue, in given prior knowledge of the location and RF radiation parameters of networked radar stations, this paper proposes a solution based on the concept of “homologous test” and the certain spatial resolution of networked radar. The boundary conditions for effective deception jamming by digital storage and forwarding technology to networked radar are analyzed, and the influence of forwarding delay error on deception jamming effect in typical networked radar systems is identified. Simulation results demonstrate that the analysis and deduction results can provide a reliable assessment of whether the actual jammer performance can effectively deceive and interfere with the networked radar.

Abstract Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota. Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity.

Abstract Background With the dramatic uplift of the Qinghai–Tibet Plateau (QTP) and the increase in altitude in the Pliocene, the environment became dry and cold, thermophilous plants that originally inhabited ancient subtropical forest essentially disappeared. However, Quercus sect. Heterobalanus (QSH) have gradually become dominant or constructive species distributed on harsh sites in the Hengduan Mountains range in southeastern QTP, Southwest China. Ecological stoichiometry reveals the survival strategies plants adopt to adapt to changing environment by quantifying the proportions and relationships of elements in plants. Simultaneously, as the most sensitive organs of plants to their environment, the structure of leaves reflects of the long-term adaptability of plants to their surrounding environments. Therefore, ecological adaptation mechanisms related to ecological stoichiometry and leaf anatomical structure of QSH were explored. In this study, stoichiometric characteristics were determined by measuring leaf carbon (C), nitrogen (N), and phosphorus (P) contents, and morphological adaptations were determined by examining leaf anatomical traits with microscopy. Results Different QSH life forms and species had different nutrient allocation strategies. Leaves of QSH plants had higher C and P and lower N contents and higher N and lower P utilization efficiencies. According to an N: P ratio threshold, the growth of QSH species was limited by N, except that of Q. aquifolioides and Q. longispica, which was limited by both N and P. Although stoichiometric homeostasis of C, N, and P and C: N, C: P, and N: P ratios differed slightly across life forms and species, the overall degree of homeostasis was strong, with strictly homeostatic, homeostatic, and weakly homeostatic regulation. In addition, QSH leaves had compound epidermis, thick cuticle, developed palisade tissue and spongy tissue. However, leaves were relatively thin overall, possibly due to leaf leathering and lignification, which is strategy to resist stress from UV radiation, drought, and frost. Furthermore, contents of C, N, and P and stoichiometric ratios were significantly correlated with leaf anatomical traits. Conclusions QSH adapt to the plateau environment by adjusting the content and utilization efficiencies of C, N, and P elements. Strong stoichiometric homeostasis of QSH was likely a strategy to mitigate nutrient limitation. The unique leaf structure of the compound epidermis, thick cuticle, well-developed palisade tissue and spongy tissue is another adaptive mechanism for QSH to survive in the plateau environment. The anatomical adaptations and nutrient utilization strategies of QSH may have coevolved during long-term succession over millions of years.

Abstract Ferroptosis has important value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P. We identified 6 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan–Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature showed utility in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further study showed that NRAV competitively binds to miR-375-3P and attenuates the inhibitory effect of miR-375-3P on SLC7A11, affecting the prognosis of patients with HCC. In conclusion, We developed a novel ferroptosis-related lncRNAs prognostic model with important predictive value for the prognosis of HCC. NRAV is important in ferroptosis induction through the miR-375-3P/SLC7A11 axis.

The National Comprehensive Cancer Network (NCCN), as the world's leading non-profit consortium in the field of oncology, continues to update clinical practice guidelines for multiple malignancies annually and has become a benchmark for clinical practice guidelines in oncology worldwide. Currently, the NCCN clinical practice guidelines for hepatocellular carcinoma have been updated to version 2.2023, as compared with version 1.2023 of its main updates for the content of the discussion section. The NCCN guidelines for hepatobiliary cancers have been reorganized to separate guidelines for biliary tract cancers and hepatocellular carcinoma since version 1.2023. The main updates focus on tumor screening, diagnosis, surgery, adjuvant therapy, locoregional therapy, systemic therapy, and so on. The molecular testing was added for the first time. Therefore, the updates of version 1.2023 were highlighted again in the new version 2.2023. This article interpreted the new guidelines and focused on the aspects of updates.

Abstract Assessing the effectiveness of vegetation restoration along the Yangtze River shoreline and exploring its relationship with land use changes are imperative for providing recommendations for sustainable management and environmental protection. However, the impact of vegetation restoration post-implementation of the Yangtze River Conservation Project remains uncertain. In this study, utilizing Sentinel-2 satellite imagery and Dynamic World land use data from pre- (2016) and post- (2022) Yangtze River Conservation Project periods, pixel-based binary models, transition matrices, and geographically weighted regression models were employed to analyze the status and evolution of vegetation coverage along the Yangtze River shoreline. The results indicated that there had been an increase in the area covered by high and high-medium vegetation levels. The proportion of vegetation cover shifting to better was 4201.87 km2 (35.68%). Hotspots of vegetation coverage improvement were predominantly located along the Yangtze River. Moreover, areas witnessing enhanced vegetation coverage experienced notable land use changes, notably the conversion of water to crops (126.93 km2, 22.79%), trees to crops (59.93 km2, 10.76%), and crops to built area (59.93 km2, 10.76%). Notably, the conversion between crops and built area emerged as a significant factor influencing vegetation coverage improvement, with average regression coefficients of 0.68 and 0.50, respectively. These outcomes underscore the significance of this study in guiding ecological environmental protection and sustainable management along the Yangtze River shoreline.

This paper examines how businesses in Taiwan’s servicescapes are adapting to the growing trend of mobile payments and innovation ecosystems. Through the analysis of four case studies, we uncover the strategies these firms employ to address the challenges posed by changing consumer payment habits. Our research reveals that these companies are establishing efficient mechanisms within their ecosystems, supported by well-structured organizational frameworks. By leveraging innovation ecosystems, they are reshaping financial services and promoting collaborative growth among participants through technology, platforms, resource sharing, and knowledge exchange. This collaborative approach is driving significant changes in the sector, helping these businesses navigate through various challenges while fostering innovation and growth. Additionally, the scarcity of comprehensive observations of the digital payment ecosystem highlights the necessity for further exploration of actor interactions, regulatory mechanisms, and ecosystem management strategies. Such research efforts are crucial for enhancing our understanding of the evolving landscape of digital payments and innovation ecosystems, facilitating informed decision-making and promoting sustainable development in this dynamic industry.