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Abstract Background Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment.

Abstract Background Exploration of novel combination mode of pyrotinib and chemotherapy for heavily pretreated HER2-positive metastatic breast cancer (MBC) and how to balance survival benefits and compliance are still urgent problems in clinical practice. The current single-arm prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib in combination with metronomic oral etoposide in heavily pretreated HER2-positive MBC. Methods HER2-positive MBC patients previously treated with trastuzumab were enrolled to receive oral pyrotinib 400 mg per day and metronomic oral etoposide 50 mg per day d1-21 every 28 days, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and safety. Results 22 patients were enrolled with a median of 4 prior treatment regimens for MBC. During the follow-up of 20 evaluable patients, the median PFS was 9.0 months (95% CI, 7.6–10.4 months), and the median OS was 27.0 months (95%CI, 20.9–33.1 months). The ORR was 30% (6/20), the DCR was 80% (16/20), and the CBR was 65% (13/20). The most common grade 3 adverse events (AEs) included nausea (15%), vomiting (15%), diarrhea (5%), anemia (5%), and peripheral neuropathy (5%). No grade 4 or lethal AEs were observed. Conclusion The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity. Trial registration Registry number: NCT03923179. Registered April 18, 2019.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology. Despite the increasing global incidence and poor prognosis, the exact pathogenic mechanisms remain elusive. Currently, effective therapeutic targets and treatment methods for this disease are still lacking. This study tried to explore the pathogenic mechanisms of IPF. We found elevated expression of SULF1 in lung tissues of IPF patients compared to normal control lung tissues. SULF1 is an enzyme that modifies heparan sulfate chains of heparan sulfate proteoglycans, playing a critical role in biological regulation. However, the effect of SULF1 in pulmonary fibrosis remains incompletely understood. Our study aimed to investigate the impact and mechanisms of SULF1 in fibrosis. Methods We collected lung specimens from IPF patients for transcriptome sequencing. Validation of SULF1 expression in IPF patients was performed using Western blotting and RT-qPCR on lung tissues. ELISA experiments were employed to detect SULF1 concentrations in IPF patient plasma and TGF-β1 levels in cell culture supernatants. We used lentiviral delivery of SULF1 shRNA to knock down SULF1 in HFL1 cells, evaluating its effects on fibroblast secretion, activation, proliferation, migration, and invasion capabilities. Furthermore, we employed Co-Immunoprecipitation (Co-IP) to investigate the regulatory mechanisms involved. Results Through bioinformatic analysis of IPF transcriptomic sequencing data (HTIPF) and datasets GSE24206, and GSE53845, we identified SULF1 may potentially play a crucial role in IPF. Subsequently, we verified that SULF1 was upregulated in IPF and predominantly increased in fibroblasts. Furthermore, SULF1 expression was induced in HFL1 cells following exposure to TGF-β1. Knockdown of SULF1 suppressed fibroblast secretion, activation, proliferation, migration, and invasion under both TGF-β1-driven and non-TGF-β1-driven conditions. We found that SULF1 catalyzes the release of TGF-β1 bound to TGFβRIII, thereby activating the TGF-β1/SMAD pathway to promote fibrosis. Additionally, TGF-β1 induces SULF1 expression through the TGF-β1/SMAD pathway, suggesting a potential positive feedback loop between SULF1 and the TGF-β1/SMAD pathway. Conclusions Our findings reveal that SULF1 promotes fibrosis through the TGF-β1/SMAD pathway in pulmonary fibrosis. Targeting SULF1 may offer a promising therapeutic strategy against IPF.

In order to assessing the heterogeneity of Bacillus sp. isolates spoilage potential, six Bacillus sp. isolates isolated from spoiled low-temperature sausages were used to investigate the heterogeneity of their spoilage properties at 20 ℃ (room temperature) and 37 ℃ (optimum growth temperature). The growth curve, acid production capacity, gas production capacity, protease activity, lipase activity, and amylase activity of six strains of Bacillus sp. were measured in the experiment. The results revealed that Bacillus cereus (C) had the greatest capacity for producing acid and that after 48 hours at 37 ℃, the pH in the culture medium dropped by 0.71 relative to the blank control group. Following a 5-day culture at 37 ℃, Bacillus amyloliquefaciens (G) displayed the greatest protease and amylase activities, with a maximum protease activity of 7.17 U/mL and a decomposition circle area of starch agar of 16.53 cm2. Bacillus cereus (C) exhibited the least comprehensive spoiling ability, as evidenced by its protease activity of 2.63 U/mL and the decomposition circle area of starch agar of 7.55 cm2 after 5 days of culture at 37 ℃. Furthermore, it was discovered that the growth temperature significantly impacted the spoilage potential of the strains. In summary, there was great heterogeneity in the spoilage characteristics of Bacillus sp.. When examining its spoilage traits, it is important to consider this heterogeneity.

Abstract The relationship of weight change has extended to accelerated ageing, yet little is known about the association between weight change and anti-aging protein α-Klotho. This study included 10,972 subjects from the National Health and Nutrition Examination Survey 2007–2016. Participants were measured body weight and height at baseline and recalled weight at young adulthood and middle adulthood. α-Klotho concentrations were quantified. Generalized linear regression models were used to assess the association between weight change and α-Klotho. Across adulthood, maximal overweight, non-obese to obese, and stable obesity were consistently associated with lower serum Klotho levels. Compared with participants who remained at normal weight, from middle to late adulthood, participants experiencing maximal overweight, moving from the non-obese to obese, and maintaining obesity had 27.97 (95% CI: − 46.57 to − 9.36), 39.16 (95% CI: − 61.15 to − 17.18), and 34.55 (95% CI: − 55.73 to − 13.37) pg/ml lower α-Klotho, respectively; similarly, from young to late adulthood, those had 29.21 (95% CI: − 47.00 to − 11.42) , 34.14 (95% CI: − 52.88 to − 15.40), and 36.61 (95% CI: − 65.01 to − 8.21) lower, respectively. Interestingly, from middle to late adulthood, the absolute weight change values of 590 participants who changed from obese to non-obese were negatively associated with serum α-Klotho. Each 1 kg of weight loss during the process of changing from obese to non-obese brought about a relative increase in α-Klotho levels of 3.03 pg/ml. The findings suggest the potential role of weight management across adulthood for aging.

Abstract Domain walls affect significantly ferroelectric and magnetic properties of magnetoelectric multiferroics. The stereotype is that the ferroelectric polarization will reduce at the domain walls due to the incomplete shielding of depolarization field or the effects of gradient energy. By combining transmission electron microscopy and first-principles calculations, we demonstrate that the ferroelectric polarization of tail-to-tail 180° domain walls in ε-Fe2O3 is regulated by the bound charge density. A huge enhancement (43%) of ferroelectric polarization is observed in the type I domain wall with a low bound charge density, while the ferroelectric polarization is reduced to almost zero at the type II domain wall with a high bound charge density. The magnetic coupling across the type I and type II ferroelectric domain walls are antiferromagnetic and ferromagnetic, respectively. Revealing mechanisms for enhancing ferroelectric polarization and magnetic behaviors at ferroelectric domain walls may promote the fundamental research and potential applications of magnetoelectric multiferroics.

Abstract This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non‐dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24‐h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24‐h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone‐renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24‐h wSD of systolic BP (β = 0.383).The study also found significant correlations between the 24‐h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24‐h urinary microalbumin, underscoring the critical role of the 24‐h wSD of systolic BP (β = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Abstract Urban greening is becoming an important strategy in improving urban ecosystem services and sustainability. Identifying the response of vegetation to urbanization and urban landscape patterns can help in planning for urban greening. Urbanization may lead to both direct and indirect effects on vegetation, and the indirect effects of urbanization on vegetation growth (UIE-VG) have been paid much attention recently in large scale. In this study, we investigated the spatiotemporal evolution of UIE-VG and the effects of landscape patterns on UIE-VG using the boosted regression tree model and remotely sensed data. An increase in average UIE-VG from 4 to 56% was found during urbanization of Kunming, the case study area in southwest China. However, UIE-VG exhibited high variations due to landscape pattern changes at the local scale. Overall, area-related and aggregation-related landscape metrics had greater effects on UIE-VG than the other metrics. The increase and aggregation of built-up land enhanced UIE-VG by 3.1–81.3% while the increase and aggregation of unused land and waterbodies reduced UIE-VG by 0.7–20.6%. Moreover, we found that the large and aggregated vegetation areas may mitigate the negative UIE-VG in low urbanization areas. Our findings have important implications for integrating urban landscape planning into sustainable urban greening strategies.

Abstract Objective Epidemiological studies revealed an unestablished association between neuroticism and posttraumatic stress disorder (PTSD) and we conducted mendelian randomization (MR) analyses to examine whether neuroticism clusters of worry, depressed affect, and sensitivity to environmental stress and adversity (SESA) were involved in the development of PTSD. Method We obtained data on three neuroticism clusters, PTSD, and nine other psychiatric disorders from genome‐wide association studies summary statistics and employed univariable, multivariable, and mediation MR analyses to explore causal associations among them. Results Neuroticism clusters were linked with PTSD (depressed affect (odds ratio [OR]: 2.94 [95% confidence interval: 2.21–3.92]); SESA (2.69 [1.95–3.71]; worry (1.81 [1.37–2.99])). Neuroticism clusters were also associated with psychiatric disorders, with the depressed effect on panic disorder (PD) (2.60 [1.14–5.91]), SESA on anorexia nervosa (AN) (2.77 [1.95–3.94]) and schizophrenia (2.55 [1.99–3.25]), worry on major depressive disorder (MDD) (2.58 [2.19–3.05]). In multivariable MR, only the SESA‐PTSD association remained (2.60 [2.096, 3.107]) while worry‐PTSD and depressed affect‐PTSD associations attenuated to nonsignificance. Mediation MR analyses suggested that PD mediated 3.76% of the effect of depressed effect on PTSD and AN mediated 10.33% of the effect of SESA on PTSD. Conclusion Delving deeper into neuroticism clusters, we comprehensively understand the role of neuroticism in PTSD.

Background: Inetetamab is a novel antibody targeting human epidermal growth factor receptor 2 (HER2) developed in China. Due to its optimized antibody-dependent cell-mediated cytotoxicity effect compared with trastuzumab, it has shown good efficacy and safety in the treatment of HER2-positive advanced breast cancer (ABC). Objectives: This study aimed to investigate the efficacy and safety of inetetamab combination therapy in the treatment of HER2-positive ABC in real-world clinical practice. Design: Retrospective study. Methods: A total of 133 patients with HER2-positive ABC who were treated with inetetamab-based regimens between March 2020 and January 2024 were retrospectively included in this study. The main endpoint was median progression-free survival (mPFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: The study included 133 HER2-positive ABC patients, and the median age was 55 years. The mPFS was 8.0 (6.7–9.3) months. The ORR was 50.4%, while the DCR was 88.7%. The mPFS for patients receiving inetetamab-based therapy as first to second, third to fourth, and later lines of metastatic treatment were 14.0, 7.0, and 6.0 months, respectively. Patients treated with inetetamab plus pyrotinib plus chemotherapy, especially with capecitabine, had the best outcomes (mPFS = 14.0 months). Multivariate analysis revealed that prior HER2-TKI treatment was significantly associated with worse PFS (hazard ratios 2.829, 95% confidence interval 1.265–6.328, p = 0.011). Subgroup analysis indicated that patients without visceral metastases had significantly better PFS (14.0 months vs 8.0 months, p = 0.003). The overall incidence of any grade adverse events (AEs) was 100%, with most being grades 1–2. Severe complications included neutropenia (37.6%) and leukopenia (33.1%). Conclusions: Inetetamab-based combination therapy shows promising efficacy and good safety in patients with HER2-positive ABC. It is one of the late-line treatment options for Chinese patients with HER2-positive ABC.

Abstract Early assessment and accurate staging of liver fibrosis may be of great help for clinical diagnosis and treatment in patients with chronic hepatitis B (CHB). We aimed to identify serum markers and construct a machine learning (ML) model to reliably predict the stage of fibrosis in CHB patients. The clinical data of 618 CHB patients between February 2017 and September 2021 from Zhejiang Provincial People's Hospital were retrospectively analyzed, and these data as a training cohort to build the model. Six ML models were constructed based on logistic regression, support vector machine, Bayes, K-nearest neighbor, decision tree (DT) and random forest by using the maximum relevance minimum redundancy (mRMR) and gradient boosting decision tree (GBDT) dimensionality reduction selected features on the training cohort. Then, the resampling method was used to select the optimal ML model. In addition, a total of 571 patients from another hospital were used as an external validation cohort to verify the performance of the model. The DT model constructed based on five serological biomarkers included HBV-DNA, platelet, thrombin time, international normalized ratio and albumin, with the area under curve (AUC) values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the training cohort were 0.898, 0.891, 0.907 and 0.944, respectively. The AUC values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the external validation cohort were 0.906, 0.876, 0.931 and 0.933, respectively. The simulated risk classification based on the cutoff value showed that the classification performance of the DT model in distinguishing hepatic fibrosis stages can be accurately matched with pathological diagnosis results. ML model of five serum markers allows for accurate diagnosis of hepatic fibrosis stages, and beneficial for the clinical monitoring and treatment of CHB patients.

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

Abstract Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.

Pancreatic fat is associated with obesity and type 2 diabetes mellitus (T2DM); however, the relationship between different types of pancreatic fat and diabetes status remains unclear. Therefore, we aimed to determine the potential of different types of pancreatic fat accumulation as a risk factor for T2DM in overweight or obese patients. In total, 104 overweight or obese patients were recruited from January 2020 to December 2022. The patients were divided into three groups: normal glucose tolerance (NGT), impaired fasting glucose or glucose tolerance (IFG/IGT), and T2DM. mDixon magnetic resonance imaging (MRI) was used to detect pancreatic fat in all three groups of patients. The pancreatic head fat (PHF), body fat (PBF), and tail fat (PTF) in the IFG/IGT group were 21, 20, and 31% more than those in the NGT group, respectively. PHF, PBF, and PTF were positively associated with glucose metabolic dysfunction markers in the NGT group, and inter-lobular fat volume (IFV) was positively associated with these markers in the IFG/IGT group. The areas under the receiver operating characteristic curves for PHF, PBF, and PTF (used to evaluate their diagnostic potential for glucose metabolic dysfunction) were 0.73, 0.73, and 0.78, respectively, while those for total pancreatic volume (TPV), pancreatic parenchymal volume, IFV, and IFV/TPV were 0.67, 0.67, 0.66, and 0.66, respectively. These results indicate that intra-lobular pancreatic fat, including PHF, PTF, and PBF, may be a potential independent risk factor for the development of T2DM. Additionally, IFV exacerbates glucose metabolic dysfunction. Intra-lobular pancreatic fat indices were better than IFV for the diagnosis of glucose metabolic dysfunction.

Underground coal gasification is currently the highest-temperature (over 1200 ℃) unconventional development method for fossil energy. Underground gasification of coal in the medium-deep (refer to the depth of 800～1500 m in this paper) has obvious advantages in improving the gasification pressure and reducing the geological safety risks. Scientific prediction of safe width of gasification cavity is important to ensure stable gasification operation. Since the method of calculating the safe width of gasification cavity based on Controlled Retreat Injection Point (CRIP) process has not yet been established, targeted research is needed to ensure the smooth implementation of field tests. Once the top plate of the gasification cavity is “exposed” to high temperature behind the gasification cavity. The generation position of thermal stresses inside the rock and the influence law of differences in the thermal expansion coefficient of particles and matrix on the magnitude of thermal stresses were studied by numerical simulation under compressive stress constraints. the thermal damage mechanism of rock under high temperature was clarified combined with the scanning electron microscope results of rock after high temperature treatment. According to the characteristics of CRIP gasification process, a thin plate model of gasification cavity roof considering the influence of high temperature was established, and a method for calculating the safe width of the gasification cavity was proposed in combination with the theory of “key layer”. The study revealed that, rock thermal damage was caused by the interaction and synergy of rock physicochemical reactions and thermal stress, and the rock undergone irregular deformation at high temperatures. Microstructural changes of rock caused by the thermal damage were the fundamental cause of changes in rock mechanical and physical properties. The maximum tensile thermal stress in rock occurred at the grain interfaces or in grains with small coefficient of thermal expansion. The maximum tensile thermal stress increased rapidly with decreasing the thermal expansion coefficient of the grain when the ratio of the thermal expansion coefficient of the grain to that of the matrix is in the range of [0.01−1). The microcracks of mudstone was developed when heated to 200 ℃, the crack development was more obvious when heated to 400 ℃, which mainly along the edge of the particles rupture. The number of cracks was increased and the size was larger when heated to 600−800 ℃. The larger cracks and numerous pores were formed when heated to 1000 ℃. The crack connectivity increased significantly at 1200 °C, and the stomatal development was larger. Due to the effect of high temperature, the step constant for the thin plate model is no longer a constant, and specific values need to be determined based on the extent of thermal damage to the roof of gasification cavity and the location of the hard rock layer on the top plate. The safe width of gasification cavity was affected by temperature. In the study, the calculated safe widths of sandstone roof at 35 and 1000 °C were 34.3 m and 14.1 m, respectively, with a difference of 58.9%. while the safe widths at 35 and 1000 °C were 16.7 m and 15.9 m, respectively, with a 4.8% difference. Lastly, a method of determining the longitudinal target area of coal seam was proposed from the perspective of reducing the risk of roof collapse and improving gasification control. When the coal seam thickness exceeded half of the gasification cavity safe width, it was suggested to design the longitudinal target area of horizontal well at a location not more than half of the safe width of gasification cavity from the top of the coal.

Abstract Eucalyptus was one of the most cultivated hardwood species worldwide, with rapid growth, good wood properties and a wide range of adaptability. Eucalyptus stem undergoes primary growth (longitudinal growth) followed by secondary growth (radial growth), which produces biomass that is an important source of energy worldwide. In order to better understand the genetic regulation of secondary growth in Eucalyptus grandis, Transcriptome analyses in stem segments along a developmental gradient from the third internode to the eleventh internode of E. grandis that spanned primary to secondary growth were carried out. 5,149 genes that were differentially expressed during stem development were identified. Combining the trend analysis by the Mfuzz method and the module-trait correlation analysis by the Weighted Gene Co-expression Network Analysis method, a total of 70 differentially expressed genes (DEGs) selected from 868 DEGs with high connectivity were found to be closely correlated with secondary growth. Results revealed that the differential expression of these DEGs suggests that they may involve in the primary growth or secondary growth. AP1, YAB2 TFs and EXP genes are highly expressed in the IN3, whereas NAC, MYB TFs are likely to be important for secondary growth. These results will expand our understanding of the complex molecular and cellular events of secondary growth and provide a foundation for future studies on wood formation in Eucalyptus.

Abstract Western cities have been confronted with the challenges of 'urban shrinkage' as changes in economic and production models have caused population migrations. China, in its recent history, has experienced rapid and dynamic growth in its cities. However, as its economy is evolving, it too is being confronted with 'urban shrinkage' challenges. Populations have been shifting inside small and medium sized cities in response to problems created during this rapid growth period. Most heritage areas have suffered from depopulation, neglect and disinvestment. The historic Puhuiquan neighborhood in Yulin City is a classic example of the current Chinese version of 'urban shrinkage'. Yulin City, founded as a military city five centuries ago, has shifted its focus away from its historic purpose into a resource-based city. Yulin’s planning developed new areas, drawing population out of the historic Puhuiquan neighborhood. This area is the home to a unique urban cultural landscape where land and architecture have merged to create the development of various types of 'cave' houses. Suffering from the effects of 'urban shrinkage', this research explores the causes and potential solutions for the area employing both 'smart shrinkage' and 'urban renewal' strategies, informed by local resident participation, to develop a sustainable renewal strategy for this heritage area.

Objective To observe the expression of serum interleukin(IL)-17 and procalcitonin(PCT) in elderly patients with severe chronic obstructive pulmonary disease(COPD) accompanied by pulmonary infection,and to explore their predictive value for the prognosis of patients. Methods A total of 120 elderly patients with severe COPD complicated with pulmonary infection admitted to Beijing Rehabilitation Hospital Affiliated with Capital Medical University from March 2021 to May 2022 were selected as the study subjects.All patients were followed up for 6 months. Serum IL-17 and PCT levels were measured,general data were collected,and the above data were statistically analyzed. Results At the end of follow-up,80 patients survived with a survival rate of 66.67% and 40 patients died with a mortality rate of 33.33%.There was no significant difference in gender,age,combined underlying diseases,smoking history and other data between the death group and the survival group(P>0.05);the serum IL-17 and PCT levels in the death group were higher than those in the survival group,and the duration of COPD and pulmonary infection was longer than those in the survival group,and the differences were statistically significant(P0.90. Conclusion Serum IL-17 and PCT levels are associated with prognosis in elderly patients with severe COPD with pulmonary infection and may be risk factors for increased risk of death.

Abstract We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.

Abstract Background Several researches have demonstrated that patients with sarcoidosis accompanied with the abnormality in blood glucose and/or lipids, however, the causal relationship between them remains uncertain. To elucidate the potential association and causality of blood glucose and lipids with sarcoidosis, we conducted a propensity score matching (PSM)-based observational study combined with mendelian randomization (MR) analysis. Methods All subjects in this study were retrospectively collected from Tongji Hospital during 2010 and 2023. 1:1 PSM was employed to control the potential confounders as appropriate. Univariable and multivariable logistic regression analyses were performed to estimate the associations of sarcoidosis with fasting glucose, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), total cholesterol (TC), and total triglyceride (TG). The further subtype analysis was also conducted. Afterwards, a bidirectional MR analysis based on public data deeply explored the causality among the 5 candidate traits and sarcoidosis, for which the inverse-variance weighted (IVW) method was utilized as the main inferring approach. Results In the observational study, a total number of 756 subjects were enrolled, with 162 sarcoidosis patients and 594 non-sarcoidosis participants, while 160 pairs of subjects were matched after PSM. Multivariable logistic regression analysis indicated that HDLC (OR: 0.151; 95% CI: 0.056–0.408; P

Abstract A recent single-cell survey of the small-intestinal epithelium suggests that mucosal pentraxin 2 (Mptx2) is a new Paneth cell marker, but its function and involved mechanism in the Paneth cell are still unknown. Therefore, we create Mptx2 knockout (Mptx2 −/− ) mice to investigate its precise effects on intestinal homeostasis using models of lipopolysaccharide (LPS), methicillin-resistant Staphylococcus aureus (MRSA) peritoneal infection, and dextran sulfate sodium (DSS)–induced intestinal injury and inflammation. We here find that Mptx2 is selectively expressed in Paneth cells in the small intestines of mice. Mptx2 −/− mice have increased susceptibility to intestinal inflammation and injured. Mptx2 deficiency reduces Paneth cell count and expression of antimicrobial factors, leading to altered intestinal bacteria composition. Loss of Mptx2 aggravates MRSA infection–induced damage in the intestine while decreasing autophagy in Paneth cells. Mptx2 −/− mice are more vulnerable to LPS-induced intestinal possibly due to inhibition of the autophagy/endoplasmic reticulum (ER) stress pathway. Mptx2 −/− mice are susceptible to DSS-induced colitis that could be ameliorated by treatment with gentamicin or vancomycin antibiotics. In conclusion, Mptx2 is essential to maintain intestinal homeostasis potentially via regulation of autophagy in Paneth cells.

As mental health issues become increasingly prominent, we are now facing challenges such as the severe unequal distribution of medical resources and low diagnostic efficiency. This paper integrates finite state machines, retrieval algorithms, semantic-matching models, and medical-knowledge graphs to design an innovative intelligent auxiliary evaluation tool and a personalized medical-advice generation application, aiming to improve the efficiency of mental health assessments and the provision of personalized medical advice. The main contributions include the folowing: (1) Developing an auxiliary diagnostic tool that combines the Mini-International Neuropsychiatric Interview (M.I.N.I.) with finite state machines to systematically collect patient information for preliminary assessments; (2) Enhancing data processing by optimizing retrieval algorithms for efficient filtering and employing a fine-tuned RoBERTa model for deep semantic matching and analysis, ensuring accurate and personalized medical-advice generation; (3) Generating intelligent suggestions using NLP techniques; when semantic matching falls below a specific threshold, integrating medical-knowledge graphs to produce general medical advice. Experimental results show that this application achieves a semantic-matching degree of 0.9 and an accuracy of 0.87, significantly improving assessment accuracy and the ability to generate personalized medical advice. This optimizes the allocation of medical resources, enhances diagnostic efficiency, and provides a reference for advancing mental health care through artificial-intelligence technology.

The inactivated COVID-19 vaccine has demonstrated high efficacy in the general population through extensive clinical and real-world studies. However, its effectiveness in immunocompromised individuals, particularly those living with HIV (PLWH), remains limited. In this study, 20 PLWH and 15 HIV-seronegative individuals were recruited to evaluate the immunogenicity of an inactivated COVID-19 vaccine in PLWH through a prospective cohort study. The median age of the 20 PLWH and 15 HIV-seronegative individuals was 42 years and 31 years, respectively. Of the PLWH, nine had been on ART for over five years. The median anti-SARS-CoV-2 S-RBD IgG antibody level on d224 was higher than that on d42 (8188.7 ng/mL vs. 3200.9 ng/mL, P < 0.05). Following COVID-19 infection, the antibody level increased to 29,872.5 ng/mL on dre+90, 12.19 times higher than that on d300. Compared with HIV-seronegative individuals, the antibody level in PLWH was lower on d210 (183.3 ng/mL vs. 509.3 ng/mL, P < 0.01), while there was no difference after d224. The symptoms of COVID-19 infection in PLWH were comparable to those in HIV-seronegative individuals. In this study, the inactivated COVID-19 vaccine demonstrated good immunogenicity in PLWH. The protective benefit of booster vaccinations for PLWH cannot be ignored. Implementing a booster vaccination policy for PLWH is an effective approach to providing better protection against the COVID-19 pandemic.

To increase the carbon conversion of char in gasification, this paper aimed to reveal the gasification behaviours of char residues. Char residues with different ash contents in this work were prepared from Shenmu char and Tejing char. Those char residues were gasified by different CO2 gas mixtures at different temperatures. The gasification process of char residue was different from the end stage of the gasification process of the corresponding raw char: the gasification rate of the char residue increased at first and then decreased, whereas the gasification rate of the corresponding raw char kept decreasing during the end stage of gasification. The highest gasification rate was achieved at a lower conversion in the gasification of char residue than in the gasification of the corresponding raw char. Catalytic minerals, high temperature, and high CO2 partial pressure benefited the gasification of gasified char residues. The char residues that contained more catalytic minerals were more reactive in gasification and were less sensitive to changes in temperature and CO2 partial pressure. The Modified Random Pore Model (MRPM) and Random Pore Model (RPM) were used to predict the gasification kinetics of the chars, and the MRPM describes the gasification processes of gasified char residues well.

Sleep–wake (SW) cycle detection is a key step for extracting temporal sleep metrics from actigraphy. Various supervised learning algorithms have been developed, yet their generalizability from sensor to sensor or study to study is questionable. In this paper, we detail and validate an unsupervised algorithm—CircaCP—for detecting SW cycles from actigraphy. It first uses a robust cosinor model to estimate circadian rhythm, then searches for a single change point (CP) within each circadian cycle. Using CircaCP, we estimated sleep/wake onset times (S/WOTs) from 2125 individuals’ data in the MESA sleep study and compared the estimated S/WOTs against self-reported S/WOT event markers, using Bland–Altman analysis as well as variance component analysis. On average, SOTs estimated by CircaCP were 3.6 min behind those reported by event markers, and WOTs by CircaCP were less than 1 min behind those reported by markers. These differences accounted for less than 0.2% variability in S/WOTs, considering other sources of between-subject variations. Rooted in first principles of human circadian rhythms, our algorithm transferred seamlessly from children’s hip-worn ActiGraph data to ageing adults’ wrist-worn Actiwatch data. The generalizability of our algorithm suggests that it can be widely applied to actigraphy collected by other sensors and studies.

Abstract Menispermaceae species, as early‐diverging eudicots, can synthesize valuable benzylisoquinoline alkaloids (BIAs) like bisbenzylisoquinoline alkaloids (bisBIAs) and sinomenines with a wide range of structural diversity. However, the evolutionary mechanisms responsible for their chemo‐diversity are not well understood. Here, a chromosome‐level genome assembly of Menispermum dauricum is presented and demonstrated the occurrence of two whole genome duplication (WGD) events that are shared by Ranunculales and specific to Menispermum, providing a model for understanding chromosomal evolution in early‐diverging eudicots. The biosynthetic pathway for diverse BIAs in M. dauricum is reconstructed by analyzing the transcriptome and metabolome. Additionally, five catalytic enzymes – one norcoclaurine synthase (NCS) and four cytochrome P450 monooxygenases (CYP450s) – from M. dauricum are responsible for the formation of the skeleton, hydroxylated modification, and C‐O/C‐C phenol coupling of BIAs. Notably, a novel leaf‐specific MdCYP80G10 enzyme that catalyzes C2′‐C4a phenol coupling of (S)‐reticuline into sinoacutine, the enantiomer of morphinan compounds, with predictable stereospecificity is discovered. Moreover, it is found that Menispermum‐specific CYP80 gene expansion, as well as tissue‐specific expression, has driven BIA diversity in Menispermaceae as compared to other Ranunculales species. This study sheds light on WGD occurrences in early‐diverging eudicots and the evolution of diverse BIA biosynthesis.

Introduction: Non-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. Pure total flavonoids from Citrus (PTFC) is extracted from the dried peel of Citrus, showing a protective effect on intestinal mucosal barrier with unclear mechanisms. Methods: In the present study, we used diclofenac (7.5 mg kg−1, i.g.) to induce a rat model of NSAIDs-related intestinal lesions. PTFC (50, 75, 100 mg·kg−1 d−1, i.g.) was administered 9 days before the initial diclofenac administration, followed by co-administration on the last 5 days. Exosomes were identified by western blotting and transmission electron microscopy (TEM), and then co-cultured with IEC-6 cells. The expression of long non-coding RNA (lncRNA) H19, autophagy-related 5 (Atg5), ZO-1, Occludin, and Claudin-1 were detected by quantitative real-time PCR (qRT-PCR). The expression of light chain 3 (LC3)-I, LC3-II, ZO-1, Occludin and Claudin-1 proteins was tested by western blotting. The localization of both exosomes and autophagosomes was examined by immunofluorescent technique. Results: The treatment of PTFC attenuated intestinal mucosal mechanical barrier function disturbance in diclofenac-induced NSAIDs rats. IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest levels of protective autophagy, and severe intestinal barrier injuries. Cells co-cultured with the exosomes extracted from rats administrated PTFC exhibited an improvement of autophagy and intestinal mucosal mechanical barrier function. The prevention effect was proportional to the concentration of PTFC administered. Conclusion: PTFC ameliorated NSAIDs-induced intestinal mucosal injury by down-regulating exosomal lncRNA H19 and promoting autophagy.

Background: The major facilitator superfamily glucose transporters (GLUTs), encoded by solute carrier 2A (SLC2A) genes, mediate the transmembrane movement and uptake of glucose. To satisfy the improved energy demands, glycolysis flux is increased in cancers compared with healthy tissues. Multiple diseases, including cancer, have been associated with GLUTs. Nevertheless, not much research has been done on the functions of SLC2As in pan-cancer prognosis or their clinical treatment potential. Methods: The SLC2A family genes' level of expression and prognostic values were analyzed in relation to pan-cancer. We then examined the association among SLC2As expression and TME, Stemness score, clinical characteristics, immune subtypes, and drug sensitivity. We merged bioinformatics analysis techniques with up-to-date public databases. Additionally, SLC2As from the KOBAS database were subjected to enrichment analysis. Results: We discovered that SLC2As' gene expression differed significantly between normal tissues and many malignancies. A number of tumors from various databases demonstrate a relationship between prognosis and SLC2A family gene expression. For instance, SLC2A2 and SLC2A5 were associated with the overall survival (OS) of hepatocellular carcinoma. SLC2A1 was associated with the OS of lung adenocarcinoma and pancreatic adenocarcinoma. Moreover, the SLC2A family gene expression is significantly correlated with the pan-cancer stromal and immune scores, and the RNA and DNA stemness scores. Furthermore, we found that the majority of SLC2As had a strong correlation with the tumor stages in KIRC. The immunological subtypes and all members of the SLC2A gene family exhibited a substantial correlation. Moreover, pathways containing insulin resistance and adipocytokine signaling pathway may influence the progression of some cancers. Finally, there is a significant positive or negative connection between drug sensitivity and SLC2A1 expression. Conclusion: Our research highlights the significant promise of SLC2As as prognostic indicators and offers insightful approaches for upcoming exploration of SLC2As as putative therapeutic targets in malignancies.

ObjectiveOur recently published study discovers that exosomal microRNA (miR)-186-5p promotes vascular smooth muscle cell viability and invasion to facilitate atherosclerosis. This research aimed to explore the prognostic implication of serum exosomal miR-186-5p in acute myocardial infarction (AMI) patients receiving percutaneous coronary intervention (PCI).MethodsOne hundred and fifty AMI patients receiving PCI and 50 healthy controls (HCs) were screened. Serum exosomal miR-186-5p was detected by reverse transcriptase-quantitative polymerase chain reaction assay in AMI patients at admission and after PCI, as well as in HCs after enrollment. Major adverse cardiac events (MACE) were recorded during follow-up in AMI patients receiving PCI.ResultsSerum exosomal miR-186-5p was raised in AMI patients vs. HCs (P

Study region: China and the different climatic zones. Study focus: Vapor pressure deficit (VPD) and soil moisture (SM) are vital for the land-atmosphere hydrological cycle and vegetation growth. Understanding the spatiotemporal variations of VPD and SM is essential for exploring vegetation dynamics and ecosystem changes. However, our current understanding of the simultaneous variations of VPD and SM within specific regions remains limited. This study utilized Empirical Orthogonal Function (EOF) methods to analyze the spatiotemporal variability of VPD, surface SM (SMsurf), and root-zone SM (SMroot), respectively. We then investigated the synchronous and asynchronous variations of VPD and SM and examined their relationships with climatic factors. New hydrologic insights for the region: From 1980–2020, VPD exhibited a significant upward trend across China and in various climate zones, indicating an increase in atmospheric dryness. However, the trends of SMsurf and SMroot showed a slight upward trend across China but divergent patterns in different climate zones. In summary, approximately 43% of China experiences a significant simultaneous increase in both VPD and SM, mainly in semi-arid and arid regions. Conversely, about 4% of China shows contrasting changes in VPD and SM, primarily in humid tropical and subtropical regions. These findings enhance our understanding of VPD and SM patterns in various climates, emphasizing the significance of soil drought in humid and semi-humid regions.

Background Alcohol drinking among adolescents is associated with their health development. However, the prevalence of alcohol drinking among adolescents in Southwestern China remains largely unexplored. This study aimed to investigate the prevalence of alcohol drinking, with a particular focus on gender differences, among primary and middle school students in Zigong, a city in Southwestern China. Additionally, we examined the association between alcohol consumption and demographic and family factors.Methods A school-based cross-sectional survey was conducted in a city in Southwestern China, encompassing a total of 89 360 students from 132 different ordinary schools, including both primary and middle schools. Participants were recruited through cluster sampling. The Alcohol Use Disorders Identification Test Consumption was employed to assess alcohol consumption. Gender differences in the prevalence of alcohol drinkers across various schools and grades were analysed. Multivariable logistic regression analysis was used to investigate factors associated with hazardous drinking.Results Out of the 89 360 participants, 19.0% reported alcohol drinking, with 2.1% classified as hazardous drinkers. There was a higher prevalence of alcohol drinking among boys compared with girls, as well as hazardous drinking. There were significant gender disparities in alcohol drinking observed across various schools and grade levels. A notable divergence between boys and girls was observed starting from grade 10, with a rising prevalence of hazardous drinking among boys and a decline among girls. Additionally, older age, male gender and being left-behind children were identified as risk factors for hazardous drinking, while belonging to a nuclear family and having parents who do not drink were protective factors against hazardous drinking.Conclusions Alcohol consumption is prevalent among Chinese adolescents, with some even classified as hazardous drinkers. These findings may offer valuable insights for policymakers and caregivers, guiding them in formulating appropriate interventions and support strategies.

BackgroundThe overall prevalence of cigarette smokers in China is very high, and China’s total cigarette consumption makes up more than 40% of the world’s consumption. In view of the lack of smoking cessation services and social support in China and the effectiveness of mobile phone apps for quitting smoking in other countries, we carried out a smartphone app–based smoking cessation trial in China. ObjectiveThis study aimed to evaluate the efficacy of a cognitive behavioral therapy (CBT)–based smoking cessation smartphone app among smokers seeking treatment in China. MethodsWe conducted a randomized controlled, web-based pilot clinical trial in China between February 23 and June 27, 2021. Eligible participants were randomly assigned to the smoking cessation app intervention group or the control group in a ratio of 1:1. The intervention group received the CBT smoking cessation intervention using a smartphone app, and the control group received a “thank you” message. The intervention was 4 weeks long, and the patients were followed up for 4 weeks. The primary outcome was self-reported continuous smoking abstinence at week 4 after the quit date. The secondary outcomes included self-reported 7-day point prevalence of smoking abstinence; reduction of the number of cigarettes smoked per day at weeks 1, 2, 3, and 4; and program acceptability. ResultsA total of 973 people were recruited to quit smoking, of whom 262 completed basic information, 56 were excluded, and 206 were randomized and included in the final analysis. There were 189 (91.7%) men and 17 (8.3%) women, with an average age of 34.46 (SD 7.53) years and an average daily smoking rate of 15.93 (SD 7.10) cigarettes/day. We found 30 (29.7%) of the 101 participants in the intervention group and 7 (6.7%) of the 105 participants in the control group reported continuous smoking cessation after the quit date at week 4 (odds ratio 5.92, 95% CI 3.78-9.26; P

Cancer is a leading cause of death worldwide, and the development of new diagnostic and treatment methods is crucial. Manganese-based nanomaterials (MnNMs) have emerged as a focal point in the field of cancer diagnosis and treatment due to their multifunctional properties. These nanomaterials have been extensively explored as contrast agents for various imaging technologies such as magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and near-infrared fluorescence imaging (NIR-FL). The use of these nanomaterials has significantly enhanced the contrast for precise tumor detection and localization. Moreover, MnNMs have shown responsiveness to the tumor microenvironment (TME), enabling innovative approaches to cancer treatment. This review provides an overview of the latest developments of MnNMs and their potential applications in tumor diagnosis and therapy. Finally, potential challenges and prospects of MnNMs in clinical applications are discussed. We believe that this review would serve as a valuable resource for guiding further research on the application of manganese nanomaterials in cancer diagnosis and treatment, addressing the current limitations, and proposing future research directions.

It is common that the sewage is discharged into rivers through a municipal drainage network. The hydraulic properties of the confluence between a lateral drainage pipe and a rectangular open channel are investigated using numerical simulation. The simulation results show that the recirculation zone, the separation area, and the secondary flow are highly influenced by the tailgate height and flow rate ratios. Both the recirculation zone and the separation zone enlarge with the increasing flow rate ratios. The recirculation zone also enlarges with the tailgate height within a certain range. It is worth noting that as the tailgate height increases, two vortices rotating in opposite directions at the same level initially merge into a counter-clockwise rotating vortex, and then one vortex splits into three. Ultimately, one of them dissipates and there are two vortices left on a vertical line. The tailgate can reduce the vertical velocity gradient and the streamwise velocity to moderate the erosion of the channel bed caused by the pipe flow inlet. HIGHLIGHTS The hydraulic properties of the confluence between a lateral drainage pipe and a rectangular open channel are studied.; Effects of the tailgate height and flow rate ratios on the recirculation zone and the secondary flow are studied.; Influences of the tailgate on the erosion of the channel bed caused by the pipe flow inlet are studied.;

Abstract A large number of La-related proteins (LARPs), most of which share a La-motif and one or more adjacent RNA-recognition (RRM) domains, are known to play a function in diverse processes. Among the LAPRs, LARP4 and LARP5 have been mainly reported to act as positive translation factors. In Phytophthora sojae, only one protein with typical LARP protein features was identified, and it was named LARP4_5 due to the presence of an RRM_LARP4_5-like domain. The PsLARP4_5 gene was significantly upregulated in zoospores and during the infection stage. By comparing the biological characteristics of a wild-type strain with three PsLARP4_5 knockout transformants, it was found that PsLARP4_5 was involved in mycelial growth, sporangium and zoospore production, and pathogenicity of P. sojae. Further analysis of the transcriptome indicated that many differentially expressed genes could participate in several essential biological processes in the PsLARP4_5 transformant, including translation, as structural constituents of ribosomes or cytosolic large ribosomal subunits and others. Notably, 76 genes with a role in the ribosome pathway were downregulated in the PsLARP4_5 transformant, suggesting that PsLARP4_5 might affect translation. Overall, these findings indicate that PsLARP4_5 plays an essential role in the development and pathogenicity of P. sojae.

Oil-rich coal is a special coal resource with a tar yield ≥ 7% and a combination of coal, oil, and gas attributes. It is an important resource and development direction for the clean utilization of coal, and has important scientific value in alleviating the shortage of national oil and gas resources and promoting the breakthrough development of coal chemical industry. There are a large number of tar-rich coal resources in the eastern basin of Xinjiang Uygur Autonomous Region. In order to find out the occurrence and distribution of tar-rich coal, the coal accumulation and occurrence characteristics of tar-rich coal were studied by means of sedimentary environment analysis, proximate analysis of coal, ultimate analysis of coal, and Gray-King assay for coal. The geological block method was used to estimate the resources of tar-rich coal. The results show that the tar-rich coal seams in the Santanghu Basin are mainly distributed in the upper section of the Badaowan Formation (J1b2), the Sangonghe Formation (J1s) and the lower section of the Xishanyao Formation (J2x1), the tar yield is about 13.67%, which is high tar-rich coal. The tar-rich coal seams in the Turpan-Hami Basin are developed in the middle section of the Xishanyao Formation (J2x2), and the tar yield is about 7.6%, which are tar-bearing coal and tar-rich coal. The tar-rich coal in the area is generally characterized by ultra-low to medium-low water content, low to medium-low ash content, medium-high to high volatile content, high tar yield, rich in oil generating components such as vitrinite and lipitnite, low degree of coalification, and formed in the lacustrine-deltaic sedimentary environment. The potential of rich oil coal resources in the study area is large. The resources of tar-rich coal in the Santanghu Basin is estimated to be 67.083 billion tonnes above a depth of 2 000 m, and the resources of tar-rich coal in the Turpan-Hami Basin is estimated to be 41.755 billion tonnes above a depth of 2 000 m, and the average thickness of the coal seams is more than 9 m. In order to effectively utilize the development of oil rich coal resources, the technical assumption of Underground Coal Pyrolysis (UCP) is proposed. The UCP refers to the establishment of heat introduction and product production channels in underground coal seams through petroleum engineering technology. Through artificial heating, coal undergoes in-situ carbonization reactions. The pyrolysis products include tar, gas (CH4, H2, light hydrocarbon C2+, etc.), and water. The carbon element in coal is mainly left underground in the form of semicoke, and the generated carbon dioxide can be used to drive oil in the Santanghu and Turpan-Hami Basins. The remaining carbon dioxide can be buried in-situ using the semicoke layer. The UCP achieves a clean conversion of coal resources through “hydrogen extraction and carbon retention”, which is expected to become a technical direction for the low-carbon green development of tar-rich coal.

Abstract Objective Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. Methods This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. Results Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P

Ferroptosis and neuroinflammation contribute to the development of Alzheimer's disease (AD). Isoforsythiaside (IFY) is a phenylethanoid glycoside isolated from the dried fruit of Forsythia suspensa (Thunb.) Vahl that has been confirmed to improve the memory and cognitive abilities of APP/PS1 mice in our previous study. The purpose of this study was to explore the anti-ferroptosis and anti-neuroinflammatory properties of IFY-mediated neuroprotection. In APP/PS1 mice, erastin-damaged HT22 cells, and LPS-exposed BV2 cells, the neuroprotective effects against ferroptosis and neuroinflammation were investigated using immunohistochemistry, label-free proteomics, western blot, ELISA, MTT, fluorescence, and TEM. IFY alleviated the expression levels of NO, IL-6, and IL-1β in LPS-exposed BV2 cells and improved the morphology of mitochondria in erastin-damaged HT22 cells. Additionally, IFY upregulated the expression levels of GPX4, FTH, FTL, p-GSK-3β, Nrf2, and NQO1, and downregulated the expression of TFR1, DMT1, p-Fyn, GFAP, p-IKKα+β, p-IκBα, p-NF-κB, and pro-inflammatory factors in the brains of APP/PS1 mice and erastin-damaged HT22 cells. In conclusion, IFY inhibits ferroptosis and neuroinflammation in erastin-damaged HT22 cells and APP/PS1 mice, at least partially by regulating the activation of Nrf2 and NF-κB signaling. IFY may prevent ferroptosis and neuroinflammation in AD and provide a new treatment strategy for AD.

The bacterial communities in the rhizosphere soil of plants facilitate the cycling of nutrient elements in the rhizosphere and regulate soil fertility. By analyzing the microecological structure of rhizosphere soil surrounding wild celery, we can provide a basis for the bionic cultivation of wild celery. In this experiment, rhizosphere soil samples from various wild celery varieties in Jilin Province were used as test materials, and high-throughput sequencing was employed to analyze and compare the rhizosphere bacterial community structures of these samples. After screening and removing chimeric sequences, a total of 1,020,108 high-quality sequences were obtained. Species classification results revealed that these bacteria encompassed 60 phyla, 183 classes, 431 orders, 702 families, and 1619 genera. There were certain differences in the composition and structure of bacterial communities among different rhizosphere soil samples. According to the richness indices, the performance order among samples was Tonghua water celery > Linjiang large-leaf celery > Linjiang old mountain celery > Tonghua large-leaf celery > Jiangyuan large-leaf celery > Tonghua old mountain celery > Linjiang water celery > artificially cultivated wild large-leaf celery > Huadian large-leaf celery > Huadian small-leaf celery > Dongfeng water celery > Jiangyuan old mountain celery. Among all bacterial communities, Pseudomonadota (37.79–22.48%) had the highest relative abundance across different regions, followed by Acidobacteriota (17.97–13.51%). RDA analysis indicated that soil pH, available phosphorus, available potassium, and alkali-hydrolyzable nitrogen in the celery rhizosphere were the primary factors influencing changes in bacterial communities. Based on the experimental analysis, it was demonstrated that there were differences in rhizosphere soil bacterial community diversity and composition among Tonghua large-leaf celery, Linjiang large-leaf celery, Jiangyuan large-leaf celery, Huadian large-leaf celery, Tonghua old mountain celery, Linjiang old mountain celery, Jiangyuan old mountain celery, Tonghua water celery, Linjiang water celery, Dongfeng water celery, Huadian small-leaf celery, and artificially cultivated wild large-leaf celery in Jilin Province.

High-cholesterol diet (HCD) and fine particulate matter (PM2.5) are related to stroke. However, little is known about the combined effects of stroke, especially for females. This study investigated the brain injuries in Apolipoprotein E−/− (ApoE−/−) female mice exposed to HCD plus PM2.5 for 6 months. The protein levels of the genes related to stroke and the blood–brain barrier (BBB) in different groups of mice were measured. The molecular regulation mechanisms were explored. The results showed that HCD and PM2.5 co-exposure altered brain–body weight ratio, behavior, brain pathology, and inflammatory markers in mice relative to exposure to HCD or PM2.5 alone. Co-exposure significantly changed the expressions of HIF-1α and the key genes in its signaling pathway in the brains of mice compared to the single exposure. It suggests that the HIF-1α pathway exerts an important regulatory role in brain injury and behavioral abnormality in female mice after 6-month exposure to HCD plus PM2.5, which are potential mechanisms for HCD and PM2.5-triggering stroke in female individuals.

Abstract Background This study sought to compare the benefits and safety of agents including Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors as second-line treatments for these patients by conducting a comprehensive systematic review and network meta-analysis. Methods The Medline, Embase and Cochrane Library databases were searched for randomized trials comparing CDK4/6 inhibitors, PI3K/mTOR inhibitors, or HDAC inhibitors vs. placebo with the addition of exemestane or fulvestrant as second-line treatments in patients with HR + advanced breast cancer up to December 16, 2021. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), clinical benefit rate (CBR), and grade 3–4 adverse drug events (ADEs). The present study was conducted according to the Cochrane Collaboration and PRISMA statements. The overall effect was pooled using the random effects model. Results Seventeen studies with a total of 9,100 participants were included in the current study. Compared with placebo plus fulvestrant, PFS was significantly improved by CDK4/6 inhibitor plus fulvestrant, mTOR inhibitor plus fulvestrant, mTOR inhibitor plus exemestane, and PI3K inhibitor plus fulvestrant, but not HDAC inhibitor plus exemestane. While mTOR inhibitor plus exemestane was the best regimen (SUCRA value 89.5%), the mTOR inhibitor plus exemestane regimen induced more severe adverse events (SAEs) than the HDAC inhibitor plus exemestane regimen [OR, 95% CI: 2.40 (1.40–4.10)]. Conclusion mTOR inhibitor and CDK4/6 inhibitor-based regimens demonstrated superior clinical efficacy and comparable safety profiles as second-line treatment in patients with HR-positive, HER2-negative advanced breast cancer.

Abstract Background Depressive and anxiety symptoms affect about one-fourth of Chinese secondary school students. However, the prevalence and correlates of mental distress among secondary school students from Western China remain largely unexplored. This study aimed to examine the prevalence and associations of depressive and anxiety symptoms with demographic, family, school, life, and behavior factors in a large, representative sample of secondary school students in Zigong, a city in Western China. Methods Secondary school students were recruited using cluster sampling. The 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder Questionnaire, Multidimensional Peer-Victimization Scale, the Pittsburgh Sleep Quality Index, and Nine-Item Internet Gaming Disorder Scale-Short Form were used. Descriptive statistic was used to describe the sociodemographic characteristics of participants. The clustering effect was adjusted by the “survey” package of R to calculate weighted prevalence. Univariate and multivariate logistic regression were used to explore associated factors of depression and anxiety, respectively. Results A total of 63,205 participants were involved, in which the weighted prevalence of depression in all subjects was 23.0% (95% CI: 19.6- 27.0%), and the weighted prevalence of anxiety was 13.9% (95% CI: 11.2- 17.0%). Logistic regression results showed girls, being single-child, non-nuclear family, peer bullying, sleep disturbance, and internet gaming disorder symptoms were positively associated with depressive and anxiety symptoms. Conclusion Depressive and anxiety symptoms were prevalent among secondary school students in Western China. Our results can guide policy strategies for the assessment, prevention, and intervention of psychological status among Chinese secondary school students.

Background: This study was conducted to evaluate the efficacy and safety of docetaxel/S-1 (TS) compared with docetaxel/capecitabine (TX) as a first-line treatment for advanced breast cancer. Methods: Patients with advanced metastatic breast cancer were randomly divided into the TS group (n = 54) and the TX group (n = 57) for first-line chemotherapy from August 2015 to April 2019 (ClinicalTrials.org registration no. NCT02947061). Following the completion of combination therapy, patients without progression received S-1 or capecitabine maintenance treatment. The primary end point was progression-free survival (PFS). Results: Among 111 enrolled patients, the median PFS did not differ significantly between the TS group and the TX group (TS vs. TX, 9.0 vs. 7.4 months, P = 0.365, 95% confidence interval [CI]: 0.50–1.11, hazard ratio [HR]: 0.75). There was also no statistically significant difference in median overall survival (OS) between the two groups (TS vs. TX, 40.2 vs. 41.3 months, P = 0.976). In addition, visceral metastasis and metastasis sites, such as the liver or lung, did not lead to a significant effect on PFS and OS. The two regimens showed no significant difference in adverse events, except hand-foot syndrome, which predominated in the TX group (38.6% vs. 7.4%, P = 0.001), and diarrhea (24.1% vs. 3.6%, P = 0.003) and elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels (14.8% vs. 3.5%, P = 0.049), which were more frequent in the TS group. Conclusions: The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer. The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen, representing an effective alternative option to the TX regimen. Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.

ObjectivesSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer’s disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function.MethodsThis study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed.ResultsCross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged.ConclusionThis study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum.Clinical Trial Registrationhttp://www.chictr.org.cn, ChiCTR2000034533.

Background: Serine protease inhibitor E (SERPINE) family genes participate in the tumor growth, cancer cell survival and metastasis. However, the SERPINE family members role in the prognosis and their clinical therapeutic potentials in various human cancer types have not been elaborately explored.Methods: We preliminarily analyzed expression levels and prognostic values of SERPINE family genes, and investigated the correlation between SERPINEs expression and tumor microenvironment (TME), Stemness score, clinical characteristic, immune infiltration, tumor mutational burden (TMB), immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of SERPINEs from DAVID and KOBAS databases.Results: SERPINE1, SERPINE2, and SERPINE3 expression were upregulated in nine cancers, twelve cancers, and six cancers, respectively. The expression of SERPINE family genes was associated with the prognosis in several cancers from The Cancer Genome Atlas (TCGA). Furthermore, SERPINE family genes expression also had a significant relation to stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. SERPINE1 and SERPINE2 expression significantly increased in tumor advanced stage in colon adenocarcinoma (COAD). Results showed that SERPINE1 and SERPINE2 expression were negatively related with B cells and Monocytes, respectively. SERPINE2 expression had a significantly positive relation with B cells and Macrophages. In terms of TMB, SERPINE1, SERPINE2, and SERPINE3 were found to associated with TMB in seven cancers, fourteen cancers, and four cancers, respectively. Moreover, all SERPINE gene family members were significantly correlated with immune subtypes. SERPINE1 expression had a significantly positive or negative correlation with drug sensitivity.Conclusion: The study indicated the great potential of SERPINE family genes as biomarkers for prognosis and provided valuable strategies for further investigation of SERPINE family genes as potential targets in cancer.

Road crack detection is one of the important parts of road safety detection. Aiming at the problems such as weak segmentation effect of basic U-Net on pavement crack, insufficient precision of crack contour segmentation, difficult to identify narrow crack and low segmentation accuracy, this paper proposes an improved U-net network pavement crack segmentation method. VGG16 and Up_Conv (Upsampling Convolution) modules are introduced as backbone network and feature enhancement network respectively, and the more abstract features in the image are extracted by using the Block depth separable convolution blocks, and the multi-scale features are captured and enhanced by higher level semantic information to improve the recognition accuracy of narrow cracks in the road surface. The improved network embedded the Ca(Channel Attention) attention mechanism in U-net's jump connection to enhance the crack portion to suppress background noise. At the same time, DG_Conv(Depthwise GSConv Convolution) module and UnetUp(Unet Upsampling) module are added in the decoding part to extract richer features through more convolutional layers in the network, so that the model pays more attention to the detailed part of the crack, so the segmentation accuracy can be improved. In order to verify the model's ability to detect cracks in complex backgrounds, experiments were carried out on CFD and Deepcrack datasets. The experimental results show that compared with the traditional U-net network F1-score and mIoU have increased by 13.6% and 9.9% respectively. Superior to advanced models such as U-net, Segnet and Linknet in accuracy and generalization ability, the improved model provides a new method for asphalt pavement crack detection. The model is more conducive to practical application and ground deployment, and can be applied in road maintenance projects.

Microalgae are widely used in wastewater treatment because they can absorb nitrogen and phosphorus pollutions and reduce CO2 emissions. However, they are hard to collected due to tiny cell sizes. Flocculation of microalgae by fungi to form the algal-mycelial pellets (AMPs) is one of the efficient collecting methods from wastewater. With the large amount of saline wastewater being discharged, the flocculating effects and mechanisms of AMPs in high saline wastewater are still unknown. Flocculation experiments were performed by Aspergillus niger and Chlorella sp. to study the effects and mechanisms in 0 %-4% salinities. Results showed that the flocculating efficiency (FE) in the 0 %–2% salinities exceeded 95 % at 24 h, whereas the FE reached only 63 % ± 2 % in the 4 % salinity. The flocculating biomass were also decreased with the increasing salinity. Fungi pellets increased in volume and mass at high salinity, resulting in a more compact mycelium structure with less space for microalgae to attach, which was not conducive to flocculation. Furthermore, contents of proteins (PN) and polysaccharides (PS) in the tightly bound EPS (TB-EPS) of AMPs at 4 % salinity decreased by 44 % ± 8 % and 33 % ± 4 % respectively compared to those at 0 % salinity. The decrease in the content of PN and PS led to a weakening of hydrophobicity, a rise in electrostatic repulsion, and an increase in the energy barrier of AMPs, all of which impeded flocculation. This study will provide theoretical bases for the treatment and the recovery of microalgae in high saline wastewater.

The immunoregulatory role of mesenchymal stem cells (MSCs) in inflammation is heterogeneous and can exhibit anti-inflammatory or proinflammatory properties depending on the microenvironment. We herein observed that the activation of Toll-like receptor 3 (TLR3) by polyinosinic : polycytidylic acid (poly(I : C)) stimulation facilitated the transformation of adipose-derived stem cells (ADSCs) into an anti-inflammatory phenotype. The enhanced anti-inflammatory properties were assessed in a taurocholate-induced pancreatitis model. The results demonstrated that poly(I : C) pretreated ADSCs exhibited enhanced anti-inflammatory properties than untreated ADSCs in taurocholate-induced pancreatitis. Mechanistically, poly(I : C)-treated ADSCs showed increased production and secretion of interleukin-10 (IL-10), which demonstrates a potent ability to alleviate inflammatory signaling cascades in acinar cells. Simultaneously, the heightened anti-inflammatory effects of poly(I : C)-treated ADSCs in pancreatitis were associated with the regulation of macrophage classical/alternative transformation, thereby mitigating inflammatory factor-mediated damage to the pancreatic acinar cell. We propose that TLR3 activation by poly(I : C) is an effective strategy to enhance the anti-inflammatory properties of MSCs, which offers a valuable consideration for improving the therapeutic efficacy of MSCs in inflammatory diseases.

The implementation of long-term ecological restoration projects and policies over the past two decades has played a crucial role in advancing the achievement of Sustainable Development Goal 15. However, the resulting dynamics of new forests remain unclear. In this study, we initially examined the distribution and sources of new forests and subsequently investigated the gross primary productivity (GPP) variations within these forested regions. We discovered that new forests are mainly converted from previously cultivated land, which is primarily due to the Grain for Green Project. The new forests are mainly distributed in mid-low altitude areas and gentle slope regions, indicating that accessible areas are prone to damage but also easy to recover. Over approximately two decades of ecological restoration projects, the GPP of new forests has significantly increased trends and the growth rates of new forests vary significantly in different climatic zones. Moreover, the GPP and growth rates of new forests displayed spatial heterogeneity. Specifically, the GPP in the new forests was highest in the eastern region, followed by the central south region, while the northwest region had the lowest GPP. Meanwhile, the southwest region shows the highest GPP growth rate among new forests, while the northwest region has the slowest growth rate. Furthermore, the average GPP of new forests is lower than stable forests, but new forests in China grow faster (3.735 vs. 2.587), highlighting their substantial carbon potential. These findings indicate that it's crucial to account for variations in stand and forest change rates when modeling forest carbon sequestration potential.

Abstract Field-effect transistor (FET) is regarded as the most promising candidate for the next-generation biosensor, benefiting from the advantages of label-free, easy operation, low cost, easy integration, and direct detection of biomarkers in liquid environments. With the burgeoning advances in nanotechnology and biotechnology, researchers are trying to improve the sensitivity of FET biosensors and broaden their application scenarios from multiple strategies. In order to enable researchers to understand and apply FET biosensors deeply, focusing on the multidisciplinary technical details, the iteration and evolution of FET biosensors are reviewed from exploring the sensing mechanism in detecting biomolecules (research direction 1), the response signal type (research direction 2), the sensing performance optimization (research direction 3), and the integration strategy (research direction 4). Aiming at each research direction, forward perspectives and dialectical evaluations are summarized to enlighten rewarding investigations.