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Metal nanoclusters have served as an emerging class of programmable nanomaterials with customized structures. However, it remains highly challenging to achieve the single-atom regulation of metal nanoclusters without altering their structural frameworks. Here, we achieve the single-point defects manipulation based upon a cluster pair of Au 21 and Au 22 by meticulously complementing the surface defects of the former nanocluster with an additional single-Au complex. The two nanoclusters exhibited identical geometric structures, but their pronounced quantum-confinement effects resulted in different electronic properties, evident in their distinct optical absorption and emission characteristics. Temperature-dependent steady-state photoluminescence spectra and femtosecond transient absorption spectra showed that the manipulation of a single-point defect in Au 22 inhibited non-radiative decay pathways, reduced electron loss at higher energy levels, and accelerated intersystem crossing, which ultimately enhanced its emission intensity. Overall, the Au 21 and Au 22 cluster system in this study provides a cluster platform with controllable surface single-point defects, enabling the regulation of the photophysical dynamics at the atomic level. The properties of atomically precise nanoclusters depend on their structural composition, but controlling them is challenging. Here, the authors demonstrate the manipulation of single-point defects, converting Au 21 into Au 22 and thereby regulating the photophysical dynamics.

Genome-wide association studies (GWAS) have identified many genetic loci associated with complex traits and diseases in the past 20 years. Multiple heritable covariates may be added into GWAS regression models to estimate direct effects of genetic variants on a focal trait, or to improve the power by accounting for environmental effects and other sources of trait variations. When one or more covariates are causally affected by both genetic variants and hidden confounders, adjusting for them in GWAS will produce biased estimation of SNP effects, known as collider bias. Several approaches have been developed to correct collider bias through estimating the bias by Mendelian randomization (MR). However, these methods work for only one covariate, some of which utilize MR methods with relatively strong assumptions, both of which may not hold in practice. In this paper, we extend the bias-correction approaches in two aspects: first we derive an analytical expression for the collider bias in the presence of multiple covariates, then we propose estimating the bias using a robust multivariable MR (MVMR) method based on constrained maximum likelihood (called MVMR-cML), allowing the presence of invalid instrumental variables (IVs) and correlated pleiotropy. We also established the estimation consistency and asymptotic normality of the new bias-corrected estimator. We conducted simulations to show that all methods mitigated collider bias under various scenarios. In real data analyses, we applied the methods to two GWAS examples, the first a GWAS of waist-hip ratio with adjustment for only one covariate, body-mass index (BMI), and the second a GWAS of BMI adjusting metabolomic principle components as multiple covariates, illustrating the effectiveness of bias correction.

Triggering economic growth is a requirement to promote human welfare and realize sustainable development in many developing countries. However, place-based policies’ impact on economic growth is debatable, and its underlying mechanism is unknown. China’s Old Revolutionary Development Program (ORDP) is a large-scale and novel type of place-based policy targeted at undeveloped regions in China. We evaluate the effect of ORDP on economic growth by employing a time-varying difference-in-differences model and further explore the potential mechanisms and heterogeneity effects. VIIRS/DNB nightlight data is used to measure economic growth. We find that ORDP can significantly promote economic growth by 4.0% and the result is still robust after several tests. Mechanism analysis shows that ORDP can improve economic growth through government intervention, industrial structure optimization, and information infrastructure construction. Heterogeneity analysis indicates that the ORDP performs better on economic growth in central Chinese cities and high-economy cities. At the same time, our paper provides three practical suggestions for stimulating economic growth in ORDP, which can be enlightening for other developing countries.

This study investigates the mechanical properties, moisture stability, and environmental safety of microbial-induced carbonate precipitation (MICP)-treated phosphogypsum (PG)-based mixtures (MPGT) for road base utilization. Optimal cementation solution concentrations and bacterial-to-cementation solution ratios were determined via unconfined compressive strength (UCS), California bearing ratio (CBR), and splitting tensile strength tests. Durability was compared with untreated mixtures, and enhancement mechanisms were analyzed using XRD, SEM, and FTIR. Additionally, toxicity leaching tests evaluated environmental safety. Results indicated optimal parameters of 2.0 mol/L cementation solution and a 2:1 bacterial/cementation solution ratio for maximum mechanical strength. Under these conditions, MPGT durability significantly improved compared to untreated mixtures. Mechanism analysis revealed that MICP-generated calcium carbonate coats PG particles and fills voids, enhancing strength and durability. Furthermore, F− and PO43− leaching concentrations were significantly reduced. In summary, MICP improves the mechanical performance, durability, and environmental safety of PG-based mixtures, promoting PG recycling in road engineering.

Tomatoes are widely cultivated worldwide and contribute substantially to vegetable production. However, the root-knot nematode (RKN) disease caused by Meloidogyne incognita poses a serious threat to tomato cultivation. The most economical and effective way to control this disease is to deploy resistant cultivars. While the disease resistance provided by the original Mi-1 gene is gradually weakening, highlighting the need to identify new resistance genes for tomato breeding. In this study, RNA sequencing (RNA-seq) was performed on root samples from the resistant tomato cultivar 'Jinpeng M6' and the susceptible cultivar ‘Jinpeng No.1’, with sampling conducted at Stage 1 and 2 for ‘Jinpeng M6’ and Stage 1-6 for ‘Jinpeng No.1’ based on characterized M. incognita infection dynamics. Comparative transcriptome analysis identified differentially expressed genes (DEGs), and qRT PCR validated the expression patterns of 12 selected DEGs. A total of 9,673 DEGs were identified, with Stage 2 representing a critical period for distinguishing the infection-responsive patterns between the two cultivars. KEGG enrichment analysis revealed a dominant “Plant-pathogen interaction” pathway in resistant cultivar, while the susceptible cultivar showed enriched “Plant hormone signal transduction” and “Circadian rhythm - plant” pathways. qRT PCR confirmed DEG expression consistency with RNA-seq, and the shared phenylpropanoid biosynthesis pathway in both cultivars showed significant DEG expression divergence at Stage 2. The results indicate that the phenylpropanoid biosynthesis pathway exhibits cultivar-specific responses to nematode infection and potential roles in tomato resistance. This study provides a theoretical foundation forelucidating the molecular mechanism of tomato resistance to M. incognita , and a scientific basis for screening RKN-resistant tomato germplasm resources.

Growth differentiation Factor 9 ( GDF9 ) has been confirmed to be closely related to the reproductive capacity of sheep. This study systematically investigated the genetic variation of the GDF9 gene across 75 global sheep breeds ( n  = 2,409) and explored its association with gestation days in Australian White sheep (AUW, n  = 120). Through whole-genome sequencing and SNP analysis, 49 SNPs (26 located in introns, 22 in exons, and 1 in the 3′ UTR region) and 20 InDel loci were identified within GDF9 gene. Haplotype analysis revealed six major haplotypes strongly correlated with geographical population distribution. Association studies in Australian White sheep demonstrated a significant difference between three SNPs loci (g.42115010T > C, g.42115254T > C, and g.42114509T > C) and gestation days: primiparous ewes with the CC genotype at g.42,115,010 exhibited the shortest gestation days (146.42 ± 2.57 days, P  = 0.030), while fourth-parity ewes with the AG genotype at g.42,114,509 showed an abnormally prolonged gestation (155.00 ± 12.81 days, P  = 0.030). Key missense mutations (e.g., E241K, R87H) were predicted to alter protein 3D structure, suggesting functional impacts on reproductive regulation. Despite limited sample sizes in certain parity groups, suggests that GDF9 may serve a potential genetic marker for optimizing reproductive efficiency, offering molecular strategies to shorten primiparous gestation and uncovering its evolutionary role in sheep domestication.

Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by Mycolicibacterium cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered mycolicibacterial strains has been effectively enhanced by sterol core metabolic modification. In recent years, research on the non-core metabolic pathway of steroids (NCMS) in mycolicibacterial strains has made significant progress. This review discusses the molecular mechanisms and metabolic modifications of NCMS for accelerating sterol uptake, regulating coenzyme I balance, promoting propionyl-CoA metabolism, reducing reactive oxygen species, and regulating energy metabolism. In addition, the recent applications of biotechnology in steroid intermediate production are summarized and compared, and the future development trend of NCMS research is discussed. This review provides powerful theoretical support for metabolic regulation in the biotransformation of phytosterols.

The oxygen evolution reaction involves complex interplay among electrolyte, solid catalyst, and gas-phase and liquid-phase reactants and products. Monitoring catalysis interfaces between catalyst and electrolyte can provide valuable insights into catalytic ability. But it is a challenging task due to the additive solid supports in traditional measurement. Here we design a nanodevice platform and combine on-chip electrochemical impedance spectroscopy measurement, temporary I-V measurement of an individual nanosheet, and molecular dynamic calculations to provide a direct way for nanoscale catalytic diagnosis. By removing O 2 in electrolyte, a dramatic decrease in Tafel slope of over 20% and early onset potential of 1.344 V vs. reversible hydrogen electrode are achieved. Our studies reveal that O 2 reduces hydroxyl ion density at catalyst interface, resulting in poor kinetics and negative catalytic performance. The obtained in-depth understanding could provide valuable clues for catalysis system design. Our method could also be useful to analyze other catalytic processes. Electrocatalysis offers important opportunities for clean fuel production, but uncovering the chemistry at the electrode surface remains a challenge. Here, the authors exploit a single-nanosheet electrode to perform in-situ measurements of water oxidation electrocatalysis and reveal a crucial interaction with oxygen.

Spasmolytic polypeptide-expressing metaplasia (SPEM) is an injury-induced gastric epithelial reprogramming state with limited therapeutic options. Although mitochondrial dysfunction has been implicated in epithelial stress responses, its contribution to SPEM development remains incompletely understood. Traditional herbal decoctions have shown potential in alleviating gastric epithelial injury, yet their underlying mechanisms remain largely unclear. This study aimed to investigate whether refined Jianpi Huayu Jiedu Decoction attenuates tamoxifen (TAM)-induced SPEM, with a focus on LCN2-associated mitochondrial dysfunction. TAM-induced SPEM models were established in mice and gastric epithelial cells. Histological, molecular, and mitochondrial analyses were performed to evaluate SPEM features and epithelial stress responses. UPLC-MS/MS-based chemical profiling, network pharmacology, transcriptomic analysis, and LCN2 knockdown experiments were integrated to explore the underlying regulatory mechanisms. Refined Jianpi Huayu Jiedu Decoction significantly alleviated TAM-induced gastric mucosal injury and suppressed the expression of SPEM-associated markers in vivo and in vitro. JHJD treatment improved mitochondrial function, reduced oxidative stress, and normalized mitochondrial dynamics, accompanied by downregulation of LCN2 expression. Chemical profiling identified multiple bioactive components of JHJD, and integrative analyses combining transcriptomics, network pharmacology, and molecular docking suggested that these components are associated with LCN2-related epithelial stress and mitochondrial regulatory networks. Functional validation further demonstrated that LCN2 knockdown partially recapitulated the protective effects of JHJD on mitochondrial homeostasis and epithelial reprogramming. These findings indicate that refined Jianpi Huayu Jiedu Decoction attenuates TAM-induced SPEM in association with restoration of mitochondrial homeostasis and suppression of LCN2-related stress signaling, providing mechanistic insight into early gastric epithelial reprogramming.

We aimed to investigate the potential pro-oncogenic properties of GREM1 by Pan-cancer multi-omics analysis. Accumulating evidence has highlighted that GREM1 (Gremlin 1), serves as an inhibitor of BMP (Bone Morphogenetic Protein) family, involve in bone related diseases, carcinogenesis, cell stemness, and cell differentiation. However, the effect and underlying mechanism of GREM1 on the cancer biology remain largely elusive. The mRNA expression of GREM1 were extracted from GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) database. Analysis of OS (Overall Survival), PFI (Progression Free Interval), DSS (Disease-Specific Survival), and ROC (Receiver Operating Characteristic) were performed to predicted prognostic value of GREM1 in various cancers. The TIMER (Tumor Immune Estimation Resource) online tool was used to investigate the relationship between GREM1 transcriptional level and infiltration of immune cells. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis and GO (Gene Ontology) analysis were used to investigate the GREM1 related molecular events, and then constructed a PPI (Protein-Protein Interaction) network via the STRING (Search Tool for the Retrieval of Interaction Genes/Proteins) online tool. Western blot was performed to investigate the indicated protein expression. In the present study, our results showed that GREM1 tended to be upregulated in various cancers, which would correlate with the poor prognosis. Mechanistically, our results showed that GREM1 involve in regulating the ECM-receptor interaction pathway, upregulation of MMP activity, angiogenesis, and immune cell infiltration. In vitro studies, our results further showed that BMP agonist significantly decreased the protein level of GREM1 in GES-1 cells and BGC cells, which accompanied by inhibiting migration and proliferation in GES-1 cells and BGC cells. BMP inhibitor significantly promoted GREM1 expression and migration in BGC cells, but not GES-1 cells. GREM1 might serve as a potential and promising prognostic biomarker for drug development and cancer treatment.