EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation in non-small cell lung cancer.

The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) is a recognized resistance mechanism and a hindrance to therapies using epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The paucity of pretranslational/posttranslational clinical samples limits the deeper understanding of resistance mechanisms and the exploration of effective therapeutic strategies. Here, we developed preclinical neuroendocrine (NE) transformation models. Next, we identified a transcriptional reprogramming mechanism that drives resistance to erlotinib in NE transformation cell lines and cell-derived xenograft mice. We observed the enhanced expression of genes involved in the EHMT2 and WNT/ß-catenin pathways. In addition, we demonstrated that EHMT2 increases methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/ß-catenin pathway and TKI-mediated NE transformation. Notably, the similar expression alterations of EHMT2 and SFRP1 were observed in transformed SCLC samples obtained from clinical patients. Importantly, suppression of EHMT2 with selective inhibitors restored the sensitivity of NE transformation cell lines to erlotinib and delayed resistance in cell-derived xenograft mice. We identify a transcriptional reprogramming process in NE transformation and provide a potential therapeutic target for overcoming resistance to erlotinib.

Virtual-scanning light-field microscopy for robust snapshot high-resolution volumetric imaging.

High-speed three-dimensional (3D) intravital imaging in animals is useful for studying transient subcellular interactions and functions in health and disease. Light-field microscopy (LFM) provides a computational solution for snapshot 3D imaging with low phototoxicity but is restricted by low resolution and reconstruction artifacts induced by optical aberrations, motion and noise. Here, we propose virtual-scanning LFM (VsLFM), a physics-based deep learning framework to increase the resolution of LFM up to the diffraction limit within a snapshot. By constructing a 40 GB high-resolution scanning LFM dataset across different species, we exploit physical priors between phase-correlated angular views to address the frequency aliasing problem. This enables us to bypass hardware scanning and associated motion artifacts. Here, we show that VsLFM achieves ultrafast 3D imaging of diverse processes such as the beating heart in embryonic zebrafish, voltage activity in Drosophila brains and neutrophil migration in the mouse liver at up to 500 volumes per second.

Designing Advanced Electrolytes for High-Safety and Long-Lifetime Sodium-Ion Batteries via Anion-Cation Interaction Modulation.

Safety hazards caused by flammable electrolytes have been major obstacles to the practical application of sodium-ion batteries (SIBs). The adoption of nonflammable all-phosphate electrolytes can effectively improve the safety of SIBs; however, traditional low-concentration phosphate electrolytes are not compatible with carbon-based anodes. Herein, we report an anion-cation interaction modulation strategy to design low-concentration phosphate electrolytes with superior physicochemical properties. Tris(2,2,2-trifluoroethyl) phosphate (TFEP) is introduced as a cosolvent to regulate the ion-solvent-coordinated (ISC) structure through enhancing the anion-cation interactions, forming the stable anion-induced ISC (AI-ISC) structure, even at a low salt concentration (1.22 M). Through spectroscopy analyses and theoretical calculations, we reveal the underlying mechanism responsible for the stabilization of these electrolytes. Impressively, both the hard carbon (HC) anode and Na4Fe2.91(PO4)2(P2O7) (NFPP) cathode work well with the developed electrolytes. The designed phosphate electrolyte enables Ah-level HC//NFPP pouch cells with an average Coulombic efficiency (CE) of over 99.9% and a capacity retention of 84.5% after 2000 cycles. In addition, the pouch cells can operate in a wide temperature range (-20 to 60 °C) and successfully pass rigorous safety testing. This work provides new insight into the design of the electrochemically compatibility electrolyte for high-safety and long-lifetime SIBs.

KDM1A, a potent and selective target, for the treatment of DNMT3A-deficient non-small cell lung cancer.

BACKGROUND: DNMT3A is a crucial epigenetic regulation enzyme. However, due to its heterogeneous nature and frequent mutation in various cancers, the role of DNMT3A remains controversial. Here, we determine the role of DNMT3A in non-small cell lung cancer (NSCLC) to identify potential treatment strategies. METHODS: To investigate the role of loss-of-function mutations of DNMT3A in NSCLC, CRISPR/Cas9 was used to induce DNMT3A-inactivating mutations. Epigenetic inhibitor library was screened to find the synthetic lethal partner of DNMT3A. Both pharmacological inhibitors and gene manipulation were used to evaluate the synthetic lethal efficacy of DNMT3A/KDM1A in vitro and in vivo. Lastly, MS-PCR, ChIP-qPCR, dual luciferase reporter gene assay and clinical sample analysis were applied to elucidate the regulation mechanism of synthetic lethal interaction. RESULTS: We identified DNMT3A is a tumour suppressor gene in NSCLC and KDM1A as a synthetic lethal partner of DNMT3A deletion. Both chemical KDM1A inhibitors and gene manipulation can selectively reduce the viability of DNMT3A-KO cells through inducing cell apoptosis in vitro and in vivo. We clarified that the synthetic lethality is not only limited to the death mode, but also involved into tumour metastasis. Mechanistically, DNMT3A deficiency induces KDM1A upregulation through reducing the methylation status of the KDM1A promoter and analysis of clinical samples indicated that DNMT3A expression was negatively correlated with KDM1A level. CONCLUSION: Our results provide new insight into the role of DNMT3A in NSCLC and elucidate the mechanism of synthetic lethal interaction between KDM1A and DNMT3A, which might represent a promising approach for treating patients with DNMT3A-deficient tumours.

Crystal structure of the iron-sulfur cluster transfer protein ApbC from Escherichia coli.

Iron-sulfur (Fe-S) clusters are ubiquitous and are necessary to sustain basic life processes. The intracellular Fe-S clusters do not form spontaneously and many proteins are required for their biosynthesis and delivery. The bacterial P-loop NTPase family protein ApbC participates in Fe-S cluster assembly and transfers the cluster into apoproteins, with the Walker A motif and CxxC motif being essential for functionality of ApbC in Fe-S protein biogenesis. However, the structural basis underlying the ApbC activity and the motifs' role remains unclear. Here, we report the crystal structure of Escherichia coli ApbC at 2.8 Å resolution. The dimeric structure is in a W shape and the active site is located in the 2-fold center. The function of the motifs can be annotated by structural analyses. ApbC has an additional N-terminal domain that differs from other P-loop NTPases, possibly conferring its inherent specificity in vivo.

Bacillus subtilis partially inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II.

IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologics or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

Ultracompact polarization multiplexing meta-combiner for augmented reality display.

Augmented reality (AR) display, as a next-generation innovative technology, is revolutionizing the ways of perceiving and communicating by overlaying virtual images onto real-world scenes. However, the current AR devices are often bulky and cumbersome, posing challenges for long-term wearability. Metasurfaces have flexible capabilities of manipulating light waves at subwavelength scales, making them as ideal candidates for replacing traditional optical elements in AR display devices. In this work, we propose and fabricate what we believe is a novel reflective polarization multiplexing gradient metasurface based on propagation phase principle to replace the optical combiner element in traditional AR display devices. Our designed metasurface exhibits different polarization modulations for reflected and transmitted light, enabling efficient deflection of reflected light while minimizing the impact on transmitted light. This work reveals the significant potential of metasurfaces in next-generation optical display systems and provides a reliable theoretical foundation for future integrated waveguide schemes, driving the development of next-generation optical display products towards lightweight and comfortable.

ALKBH5 regulates paclitaxel resistance in NSCLC via inhibiting CEMIP-mediated EMT.

N6-methyladenosine (m6A) is the most prevalent mRNA modification, and it is verified to be closely correlated with cancer occurrence and progression. The m6A demethylase ALKBH5 (alkB homolog 5) is dysregulated in various cancers. However, the role and underlying mechanism of ALKBH5 in the pathogenesis and especially the chemo-resistance of non-small cell lung cancer (NSCLC) is poorly elucidated. The current study shows that ALKBH5 expression is reduced in paclitaxel (PTX) resistant NSCLC cells and down-regulation of ALKBH5 usually implies poor prognosis of NSCLC patients. Over-expression of ALKBH5 in PTX-resistant cells can suppress cell proliferation and enhance chemo-sensitivity, while knockdown of ALKBH5 exerts the opposite effect, which further supports the tumor suppressive role of ALKBH5. Over-expression of ALKBH5 can also reverse the epithelial-mesenchymal transition (EMT) process in PTX-resistant cancer cells. Mechanistically, data from RNA-seq, real-time PCR and western blotting indicate that CEMIP (cell migration inducing hyaluronidase 1), also known as KIAA1199, may be the downstream target of ALKBH5. Furthermore, ALKBH5 negatively regulates the CEMIP level by reducing the stability of CEMIP mRNA. Collectively, the current data demonstrate that the ALKBH5/CEMIP axis modulates the EMT process in NSCLC, which in turn regulates the chemo-sensitivity of cancer cells to PTX.

O-GlcNAc of STING mediates antiviral innate immunity.

BACKGROUND: O-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown. METHODS: Metabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1-/- C57BL/6 mice (KOCMP-72512-Sting1-B6NVA) were infected with HSV-1 and treated with O-GlcNAcylation inhibitor for validating the role of STING O-GlcNAcylation in antiviral response. RESULTS: STING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response. CONCLUSION: HSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity.

Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

Isolation and characterization of a cold-tolerant heterotrophic nitrification-aerobic denitrification bacterium and evaluation of its nitrogen-removal efficiency.

With a view toward addressing the poor efficiency with which nitrogen is removed from wastewater below 10 °C, in this study, we isolated a novel cold-tolerant heterotrophic nitrification-aerobic denitrification (HN-AD) bacterium from a wetland and characterized its nitrogen removal performance and nitrogen metabolic pathway. On the basis of 16S rRNA gene sequencing, this strain was identified as a species of Janthinobacterium, designated J1-1. At 8 °C, strain J1-1 showed excellent removal efficiencies of 89.18% and 68.18% for single-source NH4+-N and NO3--N, respectively, and removal efficiencies of 96.23% and 79.64% for NH4+-N and NO3--N, respectively, when supplied with mixed-source nitrogen. Whole-genome sequence analysis and successful amplification of the amoA, napA, and nirK functional genes related to nitrogen metabolism provided further evidence in support of the HN-AD capacity of strain J1-1. The deduced HN-AD metabolic pathway of the strain was NH4+-N→NH2OH→NO2--N→NO3--N→NO2--N→NO→N2O. In addition, assessments of NH4+-N removal under different conditions revealed the following conditions to be optimal for efficient removal: a temperature of 20 °C, pH of 7, shaking speed of 150 rpm, sodium succinate as a carbon source, and a C/N mass ratio of 16. Given its efficient nitrogen removal capacity at 8 °C, the J1-1 strain characterized in this study has considerable application potential in the treatment of low-temperature wastewater.

High-performance pyrite nano-catalyst driven photothermal/chemodynamic synergistic therapy for Osteosarcoma.

Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis, and dreadful mortality. Chemotherapy is a commonly used approach for OS treatment but is limited by the development of drug resistance and long-term adverse effects. To date, OS still lacks the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS2@CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS2@CP NPs showed superior Fenton reaction catalytic activity. FeS2@CP NPs-based CDT efficaciously eradicated the tumor cells by initiating dual-effect of killing of apoptosis and ferroptosis. Furthermore, the generated heat from FeS2@CP under near-infrared region II (NIR-II) laser irradiation could not only inhibit tumor's growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy showed excellent osteosarcoma treatment effects both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.

Phosphorylation of STAT3 at Tyr705 contributes to TFEB-mediated autophagy-lysosomal pathway dysfunction and leads to ischemic injury in rats.

We previously reported that permanent ischemia induces marked dysfunction of the autophagy-lysosomal pathway (ALP) in rats, which is possibly mediated by the transcription factor EB (TFEB). However, it is still unclear whether signal transducer and activator of transcription 3 (STAT3) is responsible for the TFEB-mediated dysfunction of ALP in ischemic stroke. In the present study, we used AAV-mediated genetic knockdown and pharmacological blockade of p-STAT3 to investigate the role of p-STAT3 in regulating TFEB-mediated ALP dysfunction in rats subjected to permanent middle cerebral occlusion (pMCAO). The results showed that the level of p-STAT3 (Tyr705) in the rat cortex increased at 24 h after pMCAO and subsequently led to lysosomal membrane permeabilization (LMP) and ALP dysfunction. These effects can be alleviated by inhibitors of p-STAT3 (Tyr705) or by STAT3 knockdown. Additionally, STAT3 knockdown significantly increased the nuclear translocation of TFEB and the transcription of TFEB-targeted genes. Notably, TFEB knockdown markedly reversed STAT3 knockdown-mediated improvement in ALP function after pMCAO. This is the first study to show that the contribution of p-STAT3 (Tyr705) to ALP dysfunction may be partly associated with its inhibitory effect on TFEB transcriptional activity, which further leads to ischemic injury in rats.

Analysis of factors influencing hospitalization cost of patients with distal radius fractures: an empirical study based on public traditional Chinese medicine hospitals in two cities, China.

BACKGROUND: Distal radius fractures (DRFs) have become a public health problem for all countries, bringing a heavier economic burden of disease globally, with China's disease economic burden being even more acute due to the trend of an aging population. This study aimed to explore the influencing factors of hospitalization cost of patients with DRFs in traditional Chinese medicine (TCMa) hospitals to provide a scientific basis for controlling hospitalization cost. METHODS: With 1306 cases of DRFs patients hospitalized in 15 public TCMa hospitals in two cities of Gansu Province in China from January 2017 to 2022 as the study object, the influencing factors of hospitalization cost were studied in depth gradually through univariate analysis, multiple linear regression, and path model. RESULTS: Hospitalization cost of patients with DRFs is mainly affected by the length of stay, surgery and operation, hospital levels, payment methods of medical insurance, use of TCMa preparations, complications and comorbidities, and clinical pathways. The length of stay is the most critical factor influencing the hospitalization cost, and the longer the length of stay, the higher the hospitalization cost. CONCLUSIONS: TCMa hospitals should actively take advantage of TCMb diagnostic modalities and therapeutic methods to ensure the efficacy of treatment and effectively reduce the length of stay at the same time, to lower hospitalization cost. It is also necessary to further deepen the reform of the medical insurance payment methods and strengthen the construction of the hierarchical diagnosis and treatment system, to make the patients receive reasonable reimbursement for medical expenses, thus effectively alleviating the economic burden of the disease in the patients with DRFs.

Agonistic analog of growth hormone-releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke.

Ischemic stroke can induce neurogenesis. However, most stroke-generated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone-releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 µg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation-reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice.

Research on the purification efficiency and mechanism for road runoff pollutants in pervious concrete with recycled aggregates.

The use of recycled aggregate (RA) in pervious concrete (PC) is a green approach that can effectively mitigate urban waterlogging, excessive RA, and runoff pollution, thereby enhancing the urban ecological environment. This article focuses on the long-term purification efficiency of runoff pollutants by PC at different porosities and RA dosages. Moreover, the purification mechanism of pollutants by recycled aggregate pervious concrete (RAPC) was revealed utilizing particle size analysis, microstructure, and elemental analysis. Finally, the recovery effects of different maintenance approaches on the purification capacity of RAPC were explored. The results indicate that an increase in the RA dosage reduced the effective porosity of PC, thereby decreasing the permeability of RAPC. In addition, PC with a lower porosity demonstrated a slightly greater purification effectiveness for pollutants. However, the utilization of RA significantly enhanced the purification capacity of PC for various pollutants, primarily by leveraging advantages in terms of pore structure, micromorphology, and surface chemical composition. Additionally, RAPC exhibited nearly 100 % retention effectiveness for particles larger than 68.95 µm but relatively lower purification efficiency for particles ranging from 1.541 to 17.11 µm. In particular, it displayed the poorest purification performance for particles with a diameter of 6.396 µm. The surface of RAPC's pore channels exhibited a loose state with high porosity and appeared rough and uneven with numerous pits and grooves. RAPC had a larger surface area and contained more components, such as SiO2, CaCO3, and Al2O3, than regular PC. Therefore, RAPC possessed a higher purification capacity. High-pressure flushing (HPF) and sodium citrate flushing (SCF) under different maintenance frequencies significantly contributed to the recovery of the purification efficiency of RAPC. However, overall, a lower maintenance frequency led to a less favorable recovery effect. Furthermore, SCF had a better recovery effect than HPF.

Comparative efficacy of energy-restricted dietary interventions in overweight and obese populations: A systematic review and network meta-analysis.

This meta-analysis compared the effectiveness of different energy-restricted diets on body composition, glucose metabolism, and lipid metabolism in overweight and obese populations. Five databases were searched to identify relevant studies in English from inception until July 20, 2023, for randomized controlled trials of at least 2 weeks duration assessing the effects of continuous energy-restricted diets compared with any intermittent energy-restricted diet in obesity adults. The risk of bias was assessed using the Cochrane Risk of Bias Tool version 2.0, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to assess the certainty of the evidence. A non-informative prior distribution Bayesian network meta-analysis was conducted. Thirty-eight studies (3039 participants) assessing four energy-restricted diets were included. Three RCTs were at high risk of bias with a very low to moderate certainty of evidence. Combined with pairwise comparisons and surface under the cumulative ranking curve, alternate-day fasting may be the best energy restriction regimen with the potential to have the most beneficial effects on various aspects of the obesity population. More rigorously designed and long-term follow-up studies are warranted.

Non-line-of-sight imaging at infrared wavelengths using a superconducting nanowire single-photon detector.

Non-line-of-sight (NLOS) imaging can visualize a remote object out of the direct line of sight and can potentially be used in endoscopy, unmanned vehicles, and robotic vision. In an NLOS imaging system, multiple diffusive reflections of light usually induce large optical attenuation, and therefore, a sensitive and efficient photodetector, or, their array, is required. Limited by the spectral sensitivity of the light sensors, up to now, most of the NLOS imaging experiments are performed in the visible bands, and a few at the near-infrared, 1550 nm. Here, to break this spectral limitation, we demonstrate a proof-of-principle NLOS imaging system using a fractal superconducting nanowire single-photon detector, which exhibits intrinsic single-photon sensitivity over an ultra-broad spectral range. We showcase NLOS imaging at 1560- and 1997-nm two wavelengths, both technologically important for specific applications. We develop a de-noising algorithm and combine it with the light-cone-transform algorithm to reconstruct the shape of the hidden objects with significantly enhanced signal-to-noise ratios. We believe that the joint advancement of the hardware and the algorithm presented in this paper could further expand the application spaces of the NLOS imaging systems.

Developing a visual model for predicting depression in patients with lung cancer.

AIMS AND OBJECTIVES: To investigate and analyse the prevalence of depression among patients with lung cancer, identify risk factors of depression, and develop a visual, non-invasive, and straightforward clinical prediction model that can be used to predict the risk probability of depression in patients with lung cancer quantitatively. BACKGROUND: Depression is one of the common concomitant symptoms of patients with lung cancer, which can increase the risk of suicide. However, the current assessment tools cannot combine multiple risk factors to predict the risk probability of depression in patients. DESIGN: A cross-sectional study. METHODS: The clinical data from 297 patients with lung cancer in China were collected and analysed in this cross-sectional study. The clinical prediction model was constructed according to the results of the Chi-square test and the logistic regression analysis, evaluated by discrimination, calibration, and decision curve analysis, and visualised by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: 130 patients with lung cancer had depressive symptoms with a prevalence of 43.77%. A visual prediction model was constructed based on age, disease duration, exercise, stigma, and resilience. This model showed good discrimination at an AUC of 0.842. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSIONS: The visual prediction model developed in this study has excellent performance, which can accurately predict the occurrence of depression in patients with lung cancer at an early stage and assist the medical staff in taking targeted preventative measures. RELEVANCE TO CLINICAL PRACTICE: The visual, non-invasive, and simple nomogram can help clinical medical staff to calculate the risk probability of depression among patients with lung cancer, formulate personalised preventive care measures for high-risk groups as soon as possible, and improve the quality of life of patients.

An ARF24-ZmArf2 module influences kernel size in different maize haplotypes.

Members of the ADP-ribosylation factor family, which are GTP-binding proteins, are involved in metabolite transport, cell division, and expansion. Although there has been a significant amount of research on small GTP-binding proteins, their roles and functions in regulating maize kernel size remain elusive. Here, we identified ZmArf2 as a maize ADP-ribosylation factor-like family member that is highly conserved during evolution. Maize zmarf2 mutants showed a characteristic smaller kernel size. Conversely, ZmArf2 overexpression increased maize kernel size. Furthermore, heterologous expression of ZmArf2 dramatically elevated Arabidopsis and yeast growth by promoting cell division. Using expression quantitative trait loci (eQTL) analysis, we determined that ZmArf2 expression levels in various lines were mainly associated with variation at the gene locus. The promoters of ZmArf2 genes could be divided into two types, pS and pL, that were significantly associated with both ZmArf2 expression levels and kernel size. In yeast-one-hybrid screening, maize Auxin Response Factor 24 (ARF24) is directly bound to the ZmArf2 promoter region and negatively regulated ZmArf2 expression. Notably, the pS and pL promoter types each contained an ARF24 binding element: an auxin response element (AuxRE) in pS and an auxin response region (AuxRR) in pL, respectively. ARF24 binding affinity to AuxRR was much higher compared with AuxRE. Overall, our results establish that the small G-protein ZmArf2 positively regulates maize kernel size and reveals the mechanism of its expression regulation.