Association between ABO blood groups and hematological myeloid neoplasms in adolescents and adults.

Background: Prior research suggests a potential link between ABO blood types and susceptibility to various malignancies. The correlation between ABO blood types and hematological myeloid neoplasms, however, remains inadequately explored. Objective: This study investigates the association between ABO blood groups and the incidence of hematological myeloid neoplasms in adolescents and adults. Methods: In this retrospective clinical study, 1,022 adolescent and adult cases of myeloid neoplasms diagnosed at our institution were initially considered. After excluding conditions potentially linked to ABO blood types from prior studies, 792 eligible cases were analyzed. These cases were categorized based on disease subtypes and compared with a control group for blood type distribution. Results: Our findings reveal a significantly higher prevalence of blood type A in patients with myeloid neoplasms compared to the control group, except for chronic myelocytic leukemia and myeloproliferative neoplasms. Conversely, the prevalence of blood type AB in myeloid neoplasms was notably lower than in the control group. Conclusion: The study suggests a potential association between ABO blood types and the risk of developing hematological myeloid neoplasms in adolescents and adults. Further research is warranted to elucidate the underlying mechanisms of this relationship.

Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial.

PURPOSE: This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival. MATERIALS AND METHODS: The patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022. RESULTS: Between April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%). CONCLUSION: For patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.

ARR1 and ARR12 modulate arsenite toxicity responses in Arabidopsis roots by transcriptionally controlling the actions of NIP1;1 and NIP6;1.

Cytokinin is central to coordinating plant adaptation to environmental stresses. Here, we first demonstrated the involvement of cytokinin in Arabidopsis responses to arsenite [As(III)] stress. As(III) treatment reduced cytokinin contents, while cytokinin treatment repressed further primary root growth in Arabidopsis plants under As(III) stress. Subsequently, we revealed that the cytokinin signaling members ARR1 and ARR12, the type-B ARABIDOPSIS RESPONSE REGULATORs, participate in cytokinin signaling-mediated As(III) responses in plants as negative regulators. A comprehensive transcriptome analysis of the arr1 and arr12 single and arr1,12 double mutants was then performed to decipher the cytokinin signaling-mediated mechanisms underlying plant As(III) stress adaptation. Results revealed important roles for ARR1 and ARR12 in ion transport, nutrient responses, and secondary metabolite accumulation. Furthermore, using hierarchical clustering and regulatory network analyses, we identified two NODULIN 26-LIKE INTRINSIC PROTEIN (NIP)-encoding genes, NIP1;1 and NIP6;1, potentially involved in ARR1/12-mediated As(III) uptake and transport in Arabidopsis. By analyzing various combinations of arr and nip mutants, including high-order triple and quadruple mutants, we demonstrated that ARR1 and ARR12 redundantly function as negative regulators of As(III) tolerance by acting upstream of NIP1;1 and NIP6;1 to modulate their function in arsenic accumulation. ChIP-qPCR, EMSA, and transient dual-LUC reporter assays revealed that ARR1 and ARR12 transcriptionally activate the expression of NIP1;1 and NIP6;1 by directly binding to their promoters and upregulating their expression, leading to increased arsenic accumulation under As(III) stress. These findings collectively provide insights into cytokinin signaling-mediated plant adaptation to excessive As(III), contributing to the development of crops with low arsenic accumulation.

Predictive Modeling with Temporal Graphical Representation on Electronic Health Records.

Deep learning-based predictive models, leveraging Electronic Health Records (EHR), are receiving increasing attention in healthcare. An effective representation of a patient's EHR should hierarchically encompass both the temporal relationships between historical visits and medical events, and the inherent structural information within these elements. Existing patient representation methods can be roughly categorized into sequential representation and graphical representation. The sequential representation methods focus only on the temporal relationships among longitudinal visits. On the other hand, the graphical representation approaches, while adept at extracting the graph-structured relationships between various medical events, fall short in effectively integrate temporal information. To capture both types of information, we model a patient's EHR as a novel temporal heterogeneous graph. This graph includes historical visits nodes and medical events nodes. It propagates structured information from medical event nodes to visit nodes and utilizes time-aware visit nodes to capture changes in the patient's health status. Furthermore, we introduce a novel temporal graph transformer (TRANS) that integrates temporal edge features, global positional encoding, and local structural encoding into heterogeneous graph convolution, capturing both temporal and structural information. We validate the effectiveness of TRANS through extensive experiments on three real-world datasets. The results show that our proposed approach achieves state-of-the-art performance.

CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and Cystic Fibrosis mice.

Extravasation of CCR2-positive monocytes into tissue and to the site of injury is a fundamental immunological response to infections. Nevertheless, exuberant recruitment and/or activity of these monocytes and monocyte-derived macrophages can propagate tissue damage, especially in chronic inflammatory disease conditions. We have previously shown that inhibiting the recruitment of CCR2-positive monocytes ameliorates lung tissue damage caused by chronic neutrophilic inflammation in cystic fibrosis (CF) mouse models. A potential concern with targeting monocyte recruitment for therapeutic benefit in CF, however, is whether they are essential for eradicating infections such as Pseudomonas aeruginosa (PA), a pathogen that commonly colonizes and damages the lungs of patients with CF. In this study, we investigated the role of CCR2-positive monocytes in the immune response to acute pulmonary PA infection. Our data show that the altered host immune response caused by the lack of monocyte recruitment to the lungs does not impact PA lung colonization, clearance, and the severity of the infection. These results also hold up in a CF mouse background, which have a hyper-inflammatory immune response, yet exhibit reduced bactericidal activity. Thus, we lay the groundwork for future studies to investigate the use of CCR2 inhibitors as a potential therapy to ameliorate lung tissue damage in CF. This could be given alone or as an adjunct therapy with CFTR modulators that significantly improve clinical outcomes for eligible patients, but do not completely resolve the persistent infection and inflammation that drive lung tissue damage.

Impact of exacerbation history on future risk and treatment outcomes in chronic obstructive pulmonary disease patients: A prospective cohort study based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) A and B classifications.

Background: In this study, we aimed to explore the impact of exacerbation history on future exacerbation and mortality with different inhaled drugs in chronic obstructive pulmonary disease (COPD) patients based on a Global Initiative Chronic Obstructive Lung Disease (GOLD) A and B classifications. Methods: This observational study was based on the cohort study Real World Research of Diagnosis and Treatment of COPD (RealDTC). We collected data from COPD patients in China from 1 July 2017 to 31 December 2022. Patients were followed up until December 2023 or death. Further, we separated GOLD A and B patients into GOLD A0 and B0, who had no exacerbation during the previous year, and GOLD A1 and B1, who had only one exacerbation during the previous year. Study outcomes included moderate-to-severe exacerbation, hospitalisation, frequent exacerbation in the first year and all-cause mortality during total follow-up. Results: Of the 8318 eligible patients, GOLD E group of patients suffered from a greater risk of exacerbation in the first year and death than patients in the GOLD A and B groups. GOLD A1 group had a higher risk of moderate-to-severe exacerbation (hazard ratio (HR) = 2.087; 95% confidence interval (CI) = 1.419-3.068), hospitalisation (HR = 1.704; 95% CI = 1.010-2.705) and frequent exacerbation (HR = 1.983; 95% CI = 1.046-3.709) compared to GOLD A0. GOLD B1 group had a risk of moderate-to-severe exacerbation (HR = 1.321; 95% CI = 1.105-1.679) and mortality (HR = 1.362; 95% CI = 1.026-1.963) that exceeded the risk in GOLD B0 group. The treatment outcome of different inhaled drugs had no statistical differences in GOLD A0 group. In GOLD A1 group, only inhaled corticosteroids (ICS), in addition to long-acting ß-2 agonist (LABA) and long-acting muscarinic antagonist (LAMA), reduced the risk of moderate-to-severe exacerbation in the first year compared to only LAMA. As for the GOLD B0 group, LABA and LAMA decreased the odds of moderate-to-severe exacerbation, hospitalisation, frequent exacerbation and mortality compared to only LAMA. ICS, LABA, and LAMA in GOLD B0 also down-regulated the risk of frequent exacerbation, compared to only LAMA. In addition, GOLD B1 patients treated with LABA and LAMA or ICS, LABA, and LAMA had a lower risk of moderate-to-severe exacerbation and hospitalisation. Meanwhile, ICS, LABA, and LAMA also reduced the risk of frequent exacerbation and mortality, compared to only LAMA in the multivariate Cox analysis. Conclusions: Compared to the GOLD A or B group without exacerbation history, GOLD A patients with exacerbation history had a higher risk of future exacerbation, and GOLD B patients with exacerbation history had a higher risk of future exacerbation and mortality and benefited more from triple inhaler therapy.

Potent Inhibition and Rapid Photoactivation of Endogenous Bruton's Tyrosine Kinase Activity in Native Cells via Opto-Covalent Modulators.

Naturally, kinases exert their activities in a highly regulated fashion. A number of ingenious approaches have been developed to artificially control kinase activity by external stimuli, such as the incorporation of unnatural amino acids or the fusion of additional protein domains; however, methods that directly modulate endogenous kinases in native cells are lacking. Herein, we present a facile and potent method that takes advantage of recent developments in targeted covalent inhibitors and rapid light-mediated uncaging chemistry. Using an important drug target, Bruton's tyrosine kinase (BTK), as an example, these opto-covalent modulators successfully blocked the activity of endogenous BTK in native cells after simple incubation and washout steps. However, upon a few minutes of light irradiation, BTK activity was cleanly restored, and could be blocked again by conventional inhibitors. Promisingly, this photoactivation strategy easily worked in human peripheral blood mononuclear cells (hPBMCs).

Associations between plasma metals and hemoglobin in female college students with dysmenorrhea.

Background: Hemoglobin (HGB) was the most important factors which could cause dysmenorrhea in women. Metals exposure and hemoglobin level in dysmenorrhea female was unclear. We aimed to explore the associations of multi-metal exposure and HGB level in female college students with dysmenorrhea. Methods: 253 female students who had dysmenorrhea was included in our study. The Last Absolute Shrinkage and Selection Operator (LASSO) regression, generalized linear model (GLM), and Bayesian Kernel Machine Regression (BKMR) models were used to explore the associations of multi-metal exposure and HGB levels in female college students with dysmenorrhea. Results: GLM results showed that plasma Fe, Ni and Rb was positively associated with HGB and plasma Co was negatively associated with HGB. In menarche age ≤13 years old group, plasma Co and Rb only was negatively and positively associated with HGB level, respectively, and plasma Ni had positive association with HGB level in menarche age >13 years old group. BKMR results showed the reverse U-shaped relationship between the five metals mixture (Co, Fe, Ni, Cu and Rb) and HGB levels in overall and menarche age ≤13 years old group. However, there were positive association between the five metals mixture and HGB levels in menarche age >13 years old group. Conclusion: Our present study revealed that metals (Fe, Ni, Co, Rb, Cu) mixture exposure could effect HGB levels in female college students with dysmenorrhea. And the relationships were different during different menarche age in female college students.

Characterization of Trap States in AlGaN/GaN MIS-High-Electron-Mobility Transistors under Semi-on-State Stress.

Devices under semi-on-state stress often suffer from more severe current collapse than when they are in the off-state, which causes an increase in dynamic on-resistance. Therefore, characterization of the trap states is necessary. In this study, temperature-dependent transient recovery current analysis determined a trap energy level of 0.08 eV under semi-on-state stress, implying that interface traps are responsible for current collapse. Multi-frequency capacitance-voltage (C-V) testing was performed on the MIS diode, calculating that interface trap density is in the range of 1.37×1013 to 6.07×1012cm-2eV-1 from EC-ET=0.29 eV to 0.45 eV.

The bifunctional transcription factor NAC32 modulates nickel toxicity responses through repression of root-nickel compartmentalization and activation of auxin biosynthesis.

Nickel (Ni) is an important micronutrient, but excess Ni is toxic to many plant species. Currently, relatively little is known about the genetic basis of the plant responses to Ni toxicity. Here, we demonstrate that NAC32 transcription factor functions as a core genetic hub to regulate the Ni toxicity responses in Arabidopsis. NAC32 negatively regulates root-Ni concentration through the IREG2 (IRON REGULATED2) encoding a transporter. NAC32 also induces local auxin biosynthesis in the root-apex transition zone by upregulating YUCCA 7 (YUC7)/8/9 expression, which results in a local enhancement of auxin signaling in root tips, especially under Ni toxicity, thereby impaired primary root growth. By analyses of various combinations of nac32 and ireg2 mutants, as well as nac32 and yuc7/8/9 triple mutants, including high-order quadruple mutant, we demonstrated that NAC32 negatively regulates Ni stress tolerance by acting upstream of IREG2 and YUC7/8/9 to modulate their function in Ni toxicity responses. ChIPqPCR, EMSA (electrophoretic mobility shift assay) and transient dual-LUC reporter assays showed that NAC32 transcriptionally represses IREG2 expression but activates YUC7/8/9 expression by directly binding to their promoters. Our work demonstrates that NAC32 coordinates Ni compartmentation and developmental plasticity in roots, providing a conceptual framework for understanding Ni toxicity responses in plants.

Patient-derived organoids in precision cancer medicine.

Organoids are three-dimensional (3D) cultures, normally derived from stem cells, that replicate the complex structure and function of human tissues. They offer a physiologically relevant model to address important questions in cancer research. The generation of patient-derived organoids (PDOs) from various human cancers allows for deeper insights into tumor heterogeneity and spatial organization. Additionally, interrogating non-tumor stromal cells increases the relevance in studying the tumor microenvironment, thereby enhancing the relevance of PDOs in personalized medicine. PDOs mark a significant advancement in cancer research and patient care, signifying a shift toward more innovative and patient-centric approaches. This review covers aspects of PDO cultures to address the modeling of the tumor microenvironment, including extracellular matrices, air-liquid interface and microfluidic cultures, and organ-on-chip. Specifically, the role of PDOs as preclinical models in gene editing, molecular profiling, drug testing, and biomarker discovery and their potential for guiding personalized treatment in clinical practice are discussed.

Clinical and Prognostic Characteristics of Acute BAD-Related Stroke: A Multicenter MRI-Based Prospective Study.

BACKGROUND: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Targeting ALDOA to modulate tumorigenesis and energy metabolism in retinoblastoma.

This study aims to elucidate the pivotal role of aldolase A (ALDOA) in retinoblastoma (RB) and evaluate the potential of the ALDOA inhibitor itaconate in impeding RB progression. Utilizing single-cell RNA sequencing, ALDOA consistently exhibits overexpression across diverse cell types, particularly in cone precursor cells, retinoma-like cells, and retinoblastoma-like cells. This heightened expression is validated in RB tissues and cell lines. ALDOA knockdown significantly diminishes RB cell viability, impedes colony formation, and induces notable metabolic alterations. RNA-seq analysis identifies SUSD2, ARHGAP27, and CLK2 as downstream genes associated with ALDOA. The application of itaconate demonstrates efficacy in inhibiting RB cell proliferation, validated through in vitro and in vivo models. This study emphasizes ALDOA as a promising target for innovative RB therapies, with potential implications for altering tumor energy metabolism.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Recurrent ventricular arrhythmias and heart failure induced by osimertinib- a case report.

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib. Case summary: A 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655 ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17 ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490 ms and LVEF of 42% after a 6-month follow up. Conclusion: Regular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.

Examining the audiovisual therapy effects on hospital groups of varying linear canopy landscapes and those with hydrodynamic forces.

Recent research has highlighted the beneficial effects of urban green spaces on physical and mental health. This study focused on the hospital population and innovatively subdivided the population into four groups: doctors, caregivers, patients and nurses. A total of 96 volunteers participated in this virtual reality experiment to assess the restoration of a linear canopy landscape and a landscape with different levels of hydrodynamics through interactive audiovisual immersion. We utilized pre-research method, brainwave monitoring technique, psychological scales, observation and interviews in this experiment. The research identified five key findings. First, both linear canopy landscapes and those with low to medium hydrodynamic forces significantly enhance physiological and psychological restoration for all groups, with the most substantial physiological benefits observed in doctors and patients, and the greatest psychological relief noted in caregivers. Second, landscapes with medium hydrodynamic forces yield higher restorative effects than those with low forces in hospital settings. Third, green landscapes with medium and low-density canopies prove more conducive to patient recovery compared to those with high-density canopies. Fourth, the inclusion of bird songs does not markedly affect physiological restoration across the hospital groups. Finally, landscapes that incorporate elements of water dynamics, open skies, and lightly foliated canopies draw significant interest from all groups involved. This study advocates for the integration of natural blue and green elements into hospital environments as complementary therapeutic interventions, aiming to alleviate stress and promote health recovery among hospital communities.

Evidence summary of prevention strategies for catheter-related infections among cancer patients with home parenteral nutrition.

Objective: To provide a comprehensive summary of evidence on prevention strategies for catheter-related infections among cancer patients with home parenteral nutrition. Methods: A systematic literature search was conducted for identifying prevention strategies for catheter-related infections among cancer patients with home parenteral nutrition, including clinical decisions, guidelines, best practices, expert consensus, evidence summaries, and systematic reviews. The search period includes publications from January 2000 to April 2024. Results: Seven articles were included in the review, comprising four guidelines, one expert consensus, and two systematic reviews. This resulted in the identification of five evidence themes and 33 best evidence statements, addressing safety and monitoring, team and education training, hand hygiene and aseptic techniques, catheter and exit site selection, and catheter care and protection. Conclusions: This evidence summary identifies the prevention of catheter-related infections in home parenteral nutrition, and offers valuable resources for clinical application and guidance for preventing infections among cancer patients receiving home parenteral nutrition.

Tightening policy and housing price bubbles: Examining an episode in the Chinese housing market.

Housing markets are often characterized by price bubbles, and governments have instituted policies to stabilize them. Under this circumstance, this study addresses the following questions. (1) Does policy tightening change expectations in housing prices, revealing a regime change? (2) If so, what determines the housing market's reaction to policy tightening? To answer these questions, we examine the effects of policy tightening that occurred in 2016 on the Chinese housing market where a price boom persisted in the post-2000 period. Using a log-periodic power law model and employing a modified multi-population genetic algorithm for parameter estimation, we find that tightening policy in China did not cause a market crash; instead, shifting the Chinese housing market from faster-than-exponential growth to a soft landing. We attribute this regime shift to low sensitivity in the Chinese housing market to global perturbations. Our findings suggest that government policies can help stabilize housing prices and improve market conditions when implemented expediently. Moreover, policymakers should consider preparedness for the possibility of an economic crisis and other social needs (e.g., housing affordability) for overall social welfare when managing housing price bubbles.

Metabolic variation and oxidative stress responses of clams (Ruditapes philippinarum) perturbed by ofloxacin exposure.

Ofloxacin (OFL), one of the most widely used fluoroquinolone antibiotics, has been frequently detected in marine environments. Nonetheless, researchers are yet to focus on the effects of OFL on the benthos. In the present study, marine clams (Ruditapes philippinarum) were exposed to OFL (0.5, 50, and 500 µg/L) for 14 d, followed by a 7 d depuration period. The accumulation of OFL, antioxidative defense responses, neurotoxicity, burrowing behavior, and metabolomic changes in clams were evaluated. The results indicated that OFL could accumulate in clams, albeit with a low bioaccumulation capacity. The intermediate (50 µg/L) and high (500 µg/L) levels of OFL induced significant antioxidative responses in the gills and digestive glands of clams, mainly manifesting as the inhibition of catalase activities and the induction of superoxide dismutase and glutathione S-transferase activities, which ultimately elevated the content of malondialdehyde, causing oxidative damage. Furthermore, the significant induction of acetylcholinesterase activities was observed, coinciding with a significant increase in burrowing rates of clams. The high level of OFL affected glycerophospholipid, arachidonic acid, steroid hormone biosynthesis, unsaturated fatty acids biosynthesis, and glycolysis/glycogenesis metabolism. In conclusion, this study has contributed to the understanding of the physiological and biochemical effects and molecular toxicity mechanisms of OFL to marine bivalves.

Nano-alumina induced developmental and neurobehavioral toxicity in the early life stage of zebrafish, associated with mTOR.

The study aims to investigate the effects of nano-alumina (AlNPs) on the early development and neurobehavior of zebrafish and the role of mTOR in this process. After embryos and grown-up larvae exposed to AlNPs from 0 to 200 µg/mL, we examined the development, neurobehavior, AlNPs content, and mTOR pathway genes. Moreover, embryos were randomly administered with control, negative control, mTOR knockdown, AlNPs, and mTOR knockdown + AlNPs, then examined for development, neurobehavior, oxidative stress, neurotransmitters, and development genes. As AlNPs increased, swimming speed and distance initially increased and then decreased; thigmotaxis and panic-avoidance reflex substantially decreased in the high-dose AlNPs group; aluminum and nanoparticles considerably accumulated in the 100 µg/mL AlNPs group; AlNPs at high dose decreased mTOR gene and protein levels, stimulating autophagy via increasing ULK1 and ULK2. mTOR knockdown exacerbated the harm to normal development rate, eye and body length, and neurobehavior induced by AlNPs through raising ROS, SOD, and ACH levels but decreasing AchE activity and development genes. Therefore, AlNPs suppress neurobehavior through downregulating mTOR, and mTOR knockdown further aggravates their early development and neurobehavior loss, suggesting mTOR could be a potential target for the toxicity of AlNPs.