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This paper investigates the market effects of a reference price policy (the RP policy, hereafter) for resale housing of selected residential projects in Shenzhen, China. The RP policy sets ONE reference price per square meter for each regulated residential project, and requires housing listing prices as well as banks’ valuation in mortgage lending to be below the reference price, but it does not limit transaction prices. Using housing listing, transaction, and rental data, we have two findings. First, the policy lowers the probability of transaction in the regulated projects, which prolongs home sellers’ time on the market; the deeper the reference price is below the would-be listing price of a residential project, the more substantial the probability of transaction is reduced. But we do not find evidence that it significantly reduces housing transaction prices. Second, the RP policy induces more homes in regulated projects to be leased out and reduces housing rents. We explain the two findings as the outcome of home buyers’ and sellers’ reference-dependent and regret-avoidant behaviors. Additionally, we discuss the spillover of the policy effects from regulated to unregulated projects, as well as the possible confounding effect of the RP policy’ role as finance constraint for buyers.

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent whose incorporation into nucleic acid plays an essential role in its therapeutic efficacy. 5-FU induces severe reproductive toxicity, which has been shown to be reversible. However, the underlying mechanisms have not been fully elucidated. Since single-strand-selective monofunctional uracil-DNA glycosylase 1 (Smug1) is a key enzyme in the excision of 5-FU, we investigated its potential role in the reversible reproductive toxicity of 5-FU by integrating knockdown, overexpression and LC‒MS/MS approaches. 5-FU treatment increased Smug1 and Dkc1 expression but blocked rRNA maturation in preimplantation embryos. Smug1 knockdown inhibited Dkc1 expression and impaired rRNA maturation, leading to reduced preimplantation embryo development. In contrast, Smug1 overexpression alleviated the inhibitory effects of 5-FU on rRNA and oocyte maturation and partially rescued 5-FU-induced developmental defects in preimplantation embryos. LC‒MS/MS analysis further revealed that overexpression of Smug1 reduced the levels of RNA incorporated 5-FUrd, the metabolite of 5-FU, indicating that Smug1 potentially alleviates reproductive toxicity by excising 5-FU from RNA. Our findings revealed the active involvement of Smug1 in counteracting 5-FU-induced reproductive toxicity and provide valuable references for the development of new strategies to reduce the adverse effects of 5-FU.

The innate immune system serves as the primary barrier against viral invasion, utilizing pattern recognition receptors (PRRs) to orchestrate a rapid defense. Among these, the nucleotide-binding domain and leucine-rich repeat (NLR) containing proteins function as central signaling scaffolds, assembling into multiprotein complexes known as inflammasomes. These complexes drive the maturation of pro-inflammatory cytokines IL-1β and IL-18, and initiate gasdermin D (GSDMD)-mediated pyroptosis, a lytic cell death pathway that eliminates intracellular replication niches. This comprehensive review synthesizes the diversified landscape of inflammasome activation during viral infections, extending beyond the canonical NLRP3 inflammasome to include specialized sensors such as NLRP6, NLRP9, NLRP1, NLRP12, and NLRC4. We critically evaluate the evolutionary “arms race” between host defenses and viral pathogens, detailing the sophisticated immune evasion strategies employed by viruses—ranging from the expression of decoy proteins and direct proteolytic cleavage of immune sensors to the manipulation of post-translational modifications (PTMs). Furthermore, we discuss the dual nature of inflammasome activation, which balances protective viral clearance against pathological hyperinflammation, and provide an exhaustive analysis of novel therapeutic strategies, including direct NLR inhibitors and downstream cytokine blockers, currently navigating clinical transition.

Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines—tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate ‘LTP miRNAs’. Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. Here, the authors demonstrate that miR-26a and miR-384-5p affect the maintenance, but not induction, of LTP as well as spine enlargement by regulating the expression of RSK3.

Chimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.

Aged skeletal muscle satellite cells (MuSCs) exhibit impaired autophagy-related activity, reduced proliferative capacity, and compromised myogenic differentiation, which collectively contribute to defective muscle regeneration during aging. However, whether hypoxia-driven modulation of autophagy-related activity can improve aged MuSC function and the underlying molecular mechanisms remain incompletely understood. In this study, aged MuSCs were divided into three groups: normoxia, hypoxia, and hypoxia combined with an autophagy inhibitor. Aged MuSCs exhibited a decreased LC3B-II/LC3B-I ratio and Beclin-1 expression, together with elevated p62 levels, indicating altered autophagy-related activity. Hypoxic culture was associated with enhanced autophagy-related activity in aged MuSCs, accompanied by HIF-1α stabilization, BNIP3 upregulation, and reduced p62 accumulation. Functionally, hypoxia significantly promoted the proliferation and myogenic differentiation of aged MuSCs. Pharmacological inhibition of autophagy using 3-methyladenine, as well as BNIP3 suppression, markedly attenuated these hypoxia-induced functional improvements. Collectively, these findings suggest that hypoxia is associated with improved proliferative and myogenic capacities of aged MuSCs, potentially involving autophagy-related activity regulated by the HIF-1α/BNIP3 pathway. This study provides insight into the relationship between hypoxic signaling and autophagy in aged MuSCs and may inform future strategies aimed at improving muscle regeneration during aging.

Hypertension is a major modifiable risk factor for chronic kidney disease (CKD), accelerating renal injury by promoting arterial stiffness. Estimated pulse wave velocity (ePWV), an indicator of arterial stiffness, is associated with CKD progression, but its relationship with urinary albumin‐to‐creatinine ratio (UACR) in non‐diabetic hypertensive patients remains unclear. This retrospective study included 509 non‐diabetic adults with essential hypertension. Participants were classified as having early renal impairment (UACR ≥30 mg/g, n = 167) or not (UACR <30 mg/g, n = 342). ePWV was calculated from age and mean blood pressure (MBP). The impairment group showed significantly higher ePWV (P < 0.001). Restricted cubic splines revealed a positive linear correlation between ePWV and UACR (P for nonlinear = 0.938). Multivariable logistic regression identified that ePWV was an independent risk factor for early renal impairment. Each 1 m/s increase in ePWV was associated with a 43.9% elevated risk of early renal impairment (OR = 1.439, 95% CI: 1.176–1.761), with the highest ePWV quartile (>9.70 m/s) showing an OR of 4.894 (95% CI: 2.019–11.86). ROC analysis showed that ePWV had the highest AUC at 0.710, higher than age (0.585) and MBP (0.693), and it provided greater incremental value for identifying early renal impairment than age and MBP when incorporated into the base model. Subgroup analyses by sex, age, BMI, and eGFR consistently supported these associations. In conclusion, ePWV is an independent risk marker for early renal impairment in non‐diabetic hypertensive patients, supporting its potential use in early risk stratification.

Parents influence the physical activity (PA) of the childhood cancer survivors (CCS). This mixed-methods study, aiming to obtain an understanding of Chinese parents’ perceptions of PA in CCS and how the cancer experience changes their views, which may affect these children’s PA engagement. A mixed methods study was conducted at two hospitals in Hangzhou. A qualitative investigation using the thematic descriptive phenomenological approach analyzed data concerning the parents of 9-18-year-old childhood cancer survivors who had completed hospitalized treatment for at least three months. A cross-sectional investigation examined the association between parents’ attitudes and children’s PA levels using unconditioned binary logistic regression analysis. The qualitative investigation included 35 parents (74.3% female). More than half of the parents understood the benefits of regular PA. Most parents supported children’s participation in low-intensity PA, but opposed high-intensity activities. Many parents changed their parenting style after cancer diagnosis, which might affect the development and persistence of children’s PA. In the cross-sectional investigation, CCS were more likely to engage in low-level moderate-to-vigorous physical activity (MVPA) or less MVPA when receiving less paternal support (adjusted OR = 0.92, 95%CI:0.88–0.96) and maternal support (adjusted OR = 0.91, 95%CI:0.87–0.95). Insufficient paternal MVPA engagement (adjusted OR = 3.83, 95%CI: 2.57–5.70) and maternal MVPA engagement (adjusted OR = 5.65, 95%CI: 3.74–8.54) were associated with lower MVPA engagement in CCS. This study identified the understanding of parents of childhood cancer survivors concerning PA engagement and related life changes brought about by cancer experiences from the parental perspectives. These changes affect parental attitude towards children’s participation in PA, and parental attitude and behavior affect children’s participation in PA. Based on the above findings, some tentative practical implications for physical activity participation among childhood cancer survivors are drawn: (1) childhood cancer survivors should be encouraged to participate in more MVPA and consult a rehabilitation physician if necessary; (2) parents and children engage in exercise together is an important way to promote the levels of physical activity among childhood cancer survivors; (3) Chinese parents have insufficient awareness of the benefits of childhood cancer survivors participation in physical activity. We should strengthen health education for parents, promote parents to support childhood cancer survivors participate in physical activity.

Diabetes mellitus severely impairs skeletal muscle regeneration after injury, limiting satellite cell activation and angiogenesis and disrupting barrier integrity while increasing fibrosis. Hypobaric hypoxia has been proposed to improve the regenerative microenvironment through hypoxia-responsive signaling, but its temporal effects and the coordination between vascular and myogenic programs in diabetic muscle remain unclear. To clarify these processes, adult male mice were divided into five groups: diabetes mellitus control (DM), cardiotoxin-injured (CTX) diabetes assessed on days 7 and 14 (CTX7, CTX14), and hypobaric-hypoxia-treated diabetic injury assessed on days 7 and 14 (H+CTX7, H+CTX14). Animals in the hypoxia groups were exposed to a hypobaric hypoxia chamber for 8 h per day for 14 days. Fibrosis, angiogenic and myogenic markers, and endothelial junctional genes were examined using histology, immunofluorescence, immunoblotting, and qRT-PCR (Quantitative Real-Time PCR). Hypobaric hypoxia on day 7 enhanced HIF-1α (hypoxia-inducible factor 1 alpha), VEGF (vascular endothelial growth factor), eNOS (endothelial nitric oxide synthas), Kdr (kinase insert domain receptor, VEGFR-2), and Angpt2 (angiopoietin-2) expression, accompanied by simultaneous endothelial sprouting and early myogenic stimulation compared to CTX7. Improvements were observed in Angpt1 (angiopoietin-1), Cdh5 (cadherin-5, VE-cadherin), Emcn (endomucin), the Angpt1/Angpt2 ratio, and CD31 density. Myogenin and MyHC (myosin heavy chain) were induced with a reduction in eMyHC (embryonic myosin heavy chain) in accordance with stabilization of endothelium and maturation of fibers, which occurred by day 14. A decrease in fibrosis and an increase in the myofiber cross-sectional area occurred. These findings suggest that hypobaric hypoxia modulates HIF-1α signaling, which in turn induces the VEGF-Kdr-eNOS pathway and the angiopoietin–Tie2–VE-cadherin pathway. Together, these pathways coordinate vascular remodeling and myogenic regeneration, ultimately improving the structural and functional recovery of diabetic muscle.

Background Metabolic disorders represented by insulin resistance (IR) are at risk of chronic kidney disease (CKD). Estimated glucose disposal rate (eGDR) reflects IR. The relationship between eGDR and CKD was unclear. This study aimed at discussing the association between eGDR and the prevalence of CKD in general population and the mortality of CKD patients, and compare it with other IR indicators. Methods The data from the National Health and Nutrition Examination Survey (NHANES) were used to conduct a cross-sectional study with linked mortality follow-up. The association between eGDR and CKD prevalence was determined using logistic regression, restricted cubic spline (RCS) analysis and stratified analysis. Receiver-operating characteristic (ROC) curves, weighted quantile sum (WQS) model, random forest and extreme gradient boost (XGBoost) machine learning models were performed to explore the importance of IR indicators components and CKD risk factors. The association between eGDR and mortality was analyzed by sub-distribution hazard model in CKD patients. Results Among 29,621 participants finally included, the median eGDR was 8.64 mg/kg/min and the CKD prevalence was 12.47%. Logistic regression and stratified analysis showed eGDR was associated with CKD prevalence independently, especially in people aged 40–60 years, with overweight or impaired glucose tolerance. RCS curve indicated the association between decreased eGDR and increased CKD risk was a U-shaped curve. ROC analysis showed eGDR assessed the CKD prevalence better. WQS model implied blood glucose control level was the main influencing factor in IR components. In machine learning models, the weights of age, eGDR, uric acid and heart failure were high. During 71 months follow-up, the all-cause mortality was 23.33% and cardiovascular disease (CVD) mortality was 8.9%. Sub-distribution hazard model showed eGDR independently predicted all-cause mortality rather CVD mortality in CKD patients after adjusting for confounding factors. Conclusions eGDR was a better indicator to assess CKD risk in general population and could predict all-cause mortality rather CVD mortality in CKD patients.