Prediction of in-hospital mortality in patients with exertional heatstroke: a 13-year retrospective study.

Hyperactivity of coagulation is common in exertional heatstroke (EHS). Disseminated intravascular coagulation (DIC) is the most severe form of coagulation dysfunction and associated with poor outcome. DIC, temperature and Glasgow coma scale score were identified as independent risk factors for in-hospital mortality by multivariate logistic regression analysis, and we developed a nomogram for predicting in-hospital mortality in a 13-year EHS patient cohort. The nomogram was assessed by calibration curves and bootstrap with 1,000 resamples. The receiver operating characteristic curve was constructed, and the area under the curve (AUC) was compared. Two hundred and ten patients were included. The in-hospital mortality was 9.0%, and the incidence of DIC was 17.6%. The AUC of the nomogram was 0.897 (95% CI 0.848-0.935, p < .0001) and was non-inferior to SOFA and APACHE II scores but superior to SIRS score, which were widely-used score systems of disease severity. The nomogram contributed to the adverse outcome prediction of EHS.

Corrigendum: Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitumor effect.

[This corrects the article DOI: 10.3389/fphar.2023.1219362.].

Combination of PARP inhibitor and CDK4/6 inhibitor modulates cGAS/STING-dependent therapy-induced senescence and provides "one-two punch" opportunity with anti-PD-L1 therapy in colorectal cancer.

Although PARP inhibitor (PARPi) has been proven to be a promising anticancer drug in cancer patients harboring BRCA1/2 mutation, it provides limited clinical benefit in colorectal cancer patients with a low prevalence of BRCA1/2 mutations. In our study, we found PARPi talazoparib significantly induced cellular senescence via inhibiting p53 ubiquitination and activating p21. Furthermore, CDK4/6i palbociclib amplified this therapy-induced senescence (TIS) in vitro and in vivo. Mechanistically, talazoparib and palbociclib combination induced senescence-associated secretory phenotype (SASP), and characterization of SASP components revealed type I interferon (IFN)-related mediators, which were amplified by cGAS/STING signaling. More importantly, RNA sequencing data indicated that combination therapy activated T cell signatures and combination treatment transformed the tumor microenvironment (TME) into a more antitumor state with increased CD8 T cells and natural killer (NK) cells and decreased macrophages and granulocytic myeloid-derived suppressor cells (G-MDSCs). Moreover, clearance of the TIS cells by αPD-L1 promoted survival in immunocompetent mouse colorectal cancer models. Collectively, we elucidated the synergistic antitumor and immunomodulatory mechanisms of the talazoparib-palbociclib combination. Further combination with PD-L1 antibody might be a promising "one-two punch" therapeutic strategy for colorectal cancer patients.

Anti-osteoporosis mechanism of resistance exercise in ovariectomized rats based on transcriptome analysis: a pilot study.

Postmenopausal osteoporosis is the main cause of fractures in women. Resistance exercise has a positive effect on bone mineral density in postmenopausal osteoporosis patients, but its mechanism is unclear. The purpose of this study was to explore the mechanism of resistance exercise in improving ovariectomized osteoporotic rats based on the transcriptome sequencing technique. Eighteen female Sprague-Dawley rats were randomly divided into the sham-operated group, the non-exercise group, and the resistance exercise group. The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy. Ten weeks after the operation, the resistance exercise group received 2 weeks of adaptive training, and 12 weeks of resistance exercise began in the 13th week. The rats were trained 5 days per week, in 4 sets of 3 repetitions per day. After the intervention, all rats were sacrificed, and the body weight, bone mineral density, trabecular bone microarchitecture, and bone biomechanics were examined. At the same time, RNA-seq and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes were performed on the left tibias, followed by Elisa and RT-qPCR verification. It had been found that resistance exercise can effectively counteract the weight gain of ovariectomized osteoporotic rats, and has a good effect on bone mineral density and trabecular bone microarchitecture. Enrichment analysis showed that regulation of gene expression and osteoclast differentiation is the most closely related biological process and signaling pathway shared by RE/Ovx and NE/Ovx groups. Our results revealed that resistance exercise can play a role in inhibiting osteoclast activation and preventing the enhancement of osteoclast bone resorption function in ovariectomized osteoporotic rats by inhibiting Fos/Fosb-regulated TRAP activation and relieving Calcr inhibition, which has important application value in preventing bone loss caused by estrogen deficiency.

Enhancement of hemostatic properties of Cyclotella cryptica frustule through genetic manipulation.

BACKGROUND: The silicified cell wall of diatoms, also known as frustule, shows huge potential as an outstanding bio-nanomaterial for hemostatic applications due to its high hemostatic efficiency, good biocompatibility, and ready availability. As the architectural features of the frustule determine its hemostatic performance, it is of great interest to develop an effective method to modify the frustule morphology into desired patterns to further improve hemostatic efficiency. RESULTS: In this study, the gene encoding Silicalemma Associated Protein 2 (a silicalemma-spanning protein) of Cyclotella cryptica (CcSAP2) was identified as a key gene in frustule morphogenesis. Thus, it was overexpressed and knocked down, respectively. The frustule of the overexpress lines showed no obvious alteration in morphology compared to the wild type (WT), while the size, specific surface area (BET), pore volume, and pore diameter of the knockdown strains changed greatly. Particularly, the knockdown frustules achieved a more pronounced coagulation effect and in vivo hemostatic performance than the WT strains. Such observations suggested that silicalemma proteins are ideal genetic encoding targets for manipulating frustule morphology associated hemostatic properties. Furthermore, the Mantel test was adopted to identify the key morphologies associated with C. cryptica bleeding control. Finally, based on our results and recent advances, the mechanism of frustule morphogenesis was discussed. CONCLUSION: This study explores a new strategy for enhancing the hemostatic efficiency of the frustule based on genetic morphology modification and may provide insights into a better understanding of the frustule morphogenesis mechanism.

MIZ1 acts downstream of PGM1 in regulating root hydrotropism.

The MIZ1 play an important role in root hydrotropism. However, the relationship between MIZ1-regulated hydrotropism and amyloplast-mediated gravitropism remain largely unclear. Here, we generated the miz1/pgm1 double mutants by crossing the non-hydrotropic miz1 mutant with the amyloplast-defective pgm1 mutant, which lacks gravitropic response. Our results showed that the miz1/pgm1 mutants exhibited a significant reduction in amyloplast and gravitropic bending, while maintaining a similar ahydrotropic phenotype as the miz1 single mutant. These findings suggest that MIZ1 plays a role in hydrotropism downstream of PGM1. Understanding the mechanisms of interaction between hydrotropism and gravitropism is crucial for comprehending the rooting patterns of plants in natural conditions. The counteracting relationship between root hydrotropism and gravitropism in the miz1 mutant should receive attention in this field, particularly considering the interference from gravitropism on Earth.

Promising valorization method of chitin biomass by producing 5-hydroxymethylfurfural using microwave hydrothermal treatment.

Chitin biomass is the second largest biomass resource on Earth but under-utilized. In this study, pretreated shrimp shells were converted into value-added platform chemical 5-hydroxymethylfurfural (HMF) using microwave hydrothermal treatment. Under the combined pretreatment of acid decalcification at room temperature and microwave-assisted alkali deacetylation, the HMF yield could reach 1.8 wt%. The key process parameters, including the holding temperature, holding time, and pH value, were evaluated and optimized. The highest HMF yield of 6.5 wt% was obtained at 202.6°C at a holding time of 5.8 min and a pH value of 1.5. This result demonstrates the potential of synchronously treating waste and recycling it, thereby offering a highly promising valorization strategy for chitin-biomass utilization.

Turbulence induced shear controllable synthesis of nano FePO4 irregularly-shaped particles in a counter impinging jet flow T-junction reactor assisted by ultrasound irradiation.

FePO4 (FP) particles with a mesoporous structure amalgamated by nanoscale primary crystals were controllably prepared using an ultrasound-intensified turbulence T-junction microreactor (UTISR). The use of this type of reaction system can effectively enhance the micro-mixing and remarkably improve the mass transfer and chemical reaction rates. Consequently, the synergistic effects of the impinging streams and ultrasonic irradiation on the formation of mesoporous structure of FP nanoparticles have been systematically investigated through experimental validation and CFD simulation. The results revealed that the FP particles with a mesoporous structure can be well synthesised by precisely controlling the operation parameters by applying ultrasound irradiation with the input power in the range of 0-900 W and the impinging stream volumetric flow rate in the range of 17.15-257.22 mL·min-1. The findings obtained from the experimental observation and CFD modelling has clearly indicated that there exists a strong correlation between the particle size, morphology, and the local turbulence shear. The application of ultrasonic irradiation can effectively intensify the local turbulence shear in the reactor even at low Reynolds number based on the impinging stream diameter (Re < 2000), leading to an effective reduction in the particle size (from 273.48 to 56.1 nm) and an increase in the specific surface area (from 21.97 to 114.97 m2·g-1) of FP samples. The FPirregularly-shaped particles prepared by UTISR exhibited a mesoporous structure with a particle size of 56.10 nm, a specific surface area of 114.97 m2·g-1and a total pore adsorption volume of 0.570 cm3·g-1 when the volumetric flow rate and ultrasound power are 85.74 mL·min-1and 600 W, respectively.

Association and prediction of subjective sleep quality and postoperative delirium during major non-cardiac surgery: a prospective observational study.

BACKGROUND: Postoperative delirium (POD) is an acute form of brain dysfunction that can result in serious adverse consequences. There has been a link between cognitive dysfunction and poor sleep. The present study aimed to determine the association and prediction of subjective sleep quality and postoperative delirium during major non-cardiac surgery. METHODS: One hundred and thirty-four patients, aged 60 years or older, were scheduled for elective laparotomy or orthopaedic procedures. The Pittsburgh Sleep Quality Index (PSQI) and sleep log were used to assess perioperative subjective sleep quality in participants. Nursing Delirium Screening Checklist (NU-DESC) was used for screening, and the Confusion Assessment Method (CAM) was used to diagnose POD during the first seven days following surgery. The association between subjective sleep quality and POD was assessed using a multivariate logistic regression model. Thereafter, the prediction performance of subjective sleep quality was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: All assessments were completed on 119 patients who had an average PSQI score of 7.0 ± 2.4 before surgery. 23 patients (19.3%) suffered from POD. The multivariate logistic regression analysis showed that the occurrence of POD was closely related to age, BMI, PSQI and operation time. After adjusting for related factors, there was a statistically significant association between PSQI and POD occurrence (OR = 1.422, 95%CI 1.079-1.873, per 1-point increase in PSQI). The ROC curve analysis showed that the optimal PSQI cutoff value was 8.0 for predicting POD, and the area under the ROC (AUROC) value of PSQI was 0.741 (95%CI 0.635 to 0.817). The AUROC of the model developed by the multivariate logistic regression analysis was 0.870 (95%CI 0.797 to 0.925). CONCLUSIONS: The study found that preoperative subjective sleep quality was strongly associated with POD during major non-cardiac surgery. Additionally, PSQI combined with age, BMI, and operation time improved POD prediction.

Remote sensing detection of seagrass distribution in a marine lagoon (Swan Lake), China.

Seagrass, a submerged flowering plant, is widely distributed in coastal shallow waters and plays a significant role in maintaining marine biodiversity and carbon cycles. However, the seagrass ecosystem is currently facing degradation, necessitating effective monitoring. Satellite remote sensing observations offer distinct advantages in spatial coverage and temporal frequency. In this study, we focused on a marine lagoon (Swan Lake), located in the Shandong Peninsula of China which is characterized by a large and typical seagrass population. We conducted an analysis of remote sensing reflectance of seagrass and other objectives using a comprehensive Landsat satellite dataset spanning from 2002 to 2022. Subsequently, we constructed Seagrass Index I (SSI-I) and Seagrass Index II (SSI-II), and used them to develop a stepwise model for seagrass detection from Landsat images. Validation was performed using in situ acoustic survey data and visual interpretation, revealing the good performance of our model with an overall accuracy exceeding 0.90 and a kappa coefficient around 0.80. The long-term analysis (2002-2022) of the seagrass distribution area in Swan Lake, generated from Landsat data using our model, indicated that the central area of Swan Lake sustains seagrass for the longest duration. Seagrass in Swan Lake exhibits a regular seasonal variation, including seeding in early spring, growth in spring-summer, maturation in the middle of summer, and shrinkage in autumn. Furthermore, we observed an overall decreasing trend in the seagrass area over the past 20 years, while occasional periods of seagrass restoration were also observed. These findings provide crucial information for seagrass protection, marine blue carbon studies, and related endeavors in Swan Lake. Moreover, our study offers a valuable alternative approach that can be implemented for seagrass monitoring using satellite observations in other coastal regions.

Risk Factors for Diabetic Retinopathy in Chinese Patients with Different Diabetes Duration: Association of C-Peptide and BUN/Cr Ratio with Type 2 Diabetic Retinopathy.

Background and Aim: Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores whether the effect of those factors is modified by diabetes mellitus (DM) duration. Methods: A total of 1058 DM patients with information about DR assessment were included. DR was measured by a complete ophthalmic examination and was classified as having one or more distinct microaneurysms in the eyes. Data from the lab and clinical factors were gathered. Multivariate logistic analysis was used to examine the risk factors, and the best-fitting model was selected by a backward stepwise based on A1C. Results: In the current study, 274 (25.9%) patients developed DR. In the entire subjects, baseline age, the level of C-peptide, and urinary creatinine were all presented as protective effects of DR, whose odds ratios (ORs) and 95% confidence intervals (CIs) were 0.79 (0.62, 0.99), 0.75 (0.61, 0.91), and 0.70 (0.52, 0.93), respectively. Conversely, systolic pressure (SBP), urinary albumin, and BUN/Cr ratio were the important risk factors for DR with ORs (95% CIs) 1.21 (1.01, 1.46), 1.55 (1.30, 1.84), and 1.33 (1.11, 1.59), respectively. In stratification analysis, females with higher SBP would be more likely to develop DR in the short-duration group, while C-peptide and urinary creatinine showed protective effects in the long-duration group. BUN/Cr ratio all presented as a risk factor, with ORs 1.38 (p = 0.041) and 1.33 (p = 0.014) in short- and long-duration groups, respectively. Conclusion: Although renal functions presented a significant association with DR in all DM patients, the risk factors of DR varied widely in different disease-duration subjects. Target strategies to prevent DR should be put forward individually, considering the patient's DM duration. Improving the BUN/Cr ratio may be beneficial to delaying DR.

A distribution-based selective optimization method for eliminating periodic defects in harmonic signals.

Due to environmental interference and defects in measured objects, measurement signals are frequently affected by unpredictable noise and periodic defects. Moreover, there is a lack of effective methods for accurately distinguishing defect components from measurement signals. In this study, a distribution-based selective optimisation method (SOM) is proposed to mitigate the effects of noise and defect components. The SOM can be seen as a binary- or multiple-class signal classifier based on an error distribution, which can simultaneously eliminate periodic defect components of measurement signals and proceed with signal-fitting regression. The effectiveness, accuracy, and feasibility of the SOM are verified in theoretical and realworld measurement settings. Based on theoretical simulations under various parameter conditions, some criteria for selecting operation variables among a selection of parameter conditions are explained in detail. The proposed method is capable of separating defect components from measurement signals while also achieving a satisfactory fitting curve for the measurement signals. The proposed SOM has broad application prospects in signal processing and defect detection for mechanical measurements, electronic filtering, instrumentation, part maintenance, and other fields.

OsMED16, a tail subunit of ediator complex, interacts with OsE2Fa to synergistically regulate rice leaf development and blast resistance.

Mediator, a universal eukaryotic coactivator, is a multiprotein complex to transduce information from the DNA-bound transcription factors to the RNA polymerase II transcriptional machinery. In this study, the biofunctions of a rice mediator subunit OsMED16 in leaf development and blast resistance were characterized. OsMED16 encodes a putative protein of 1170 amino acids, which is 393 bp shorted than the version in Rice Genome Annotation Project databases. Overexpression of OsMED16 plants exhibited wider leaves with larger and more numerous cells in lateral axis, and enhanced resistance to M. oryzae with hyperaccumulated salicylic acid. Further analysis revealed that OsMED16 interacts with OsE2Fa in nuclei, and the complex could directly regulate the transcriptional levels of several genes involved in cell cycle regulation and SA mediated blast resistance, such as OsCC52A1, OsCDKA1, OsCDKB2;2, OsICS1 and OsWRKY45. Altogether, this study proved that OsMED16 is a positive regulator of rice leaf development and blast resistance, and providing new insights into the crosstalk between cell cycle regulation and immunity.

Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients.

Background: Schizophrenia (SCZ) is a serious chronic mental disorder. Our previous case-control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study. Methods: Genotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR. Results: Based on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137. Conclusion: The plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.

Exposure to parabens and dysglycemia: Insights from a Chinese population.

BACKGROUND: Parabens, a widely exposed environmental endocrine disruptor, were reported to disturb glucose metabolism through various pathways in animal models, but epidemiologic studies are limited. Therefore, this study aimed to investigate the plasma parabens level in rural populations and their effects of single and mixed paraben exposure on T2DM based on the Henan Rural Cohort. METHODS: A total of 1713 participants (880 T2DM and 833 controls) from the Henan Rural Cohort Study were included in this case-control study. Generalized linear regression models were performed to assess the single and joint effects of parabens on T2DM and glucose metabolism indicators. In addition, the dose-response relationship of plasma parabens with T2DM and glucose metabolism indicators were explored by the restricted cubic splines. Bayesian kernel machine regression (BKMR) and quantile g-computation models were utilized to assess overall associations of paraben mixtures with T2DM and glucose metabolism indicators. RESULTS: Σparabens and methylparaben (MeP) exposure significantly increased the risk of T2DM (P < 0.01). However, ethylparaben (EtP) and butylparaben (BuP) were negatively related to T2DM (P < 0.01). Notably, non-linear relationships of EtP and BuP with T2DM were observed. When the level of EtP or BuP was above the inflection point observed in dose-response curve, the ORs and 95% CIs were 1.453 (1.252, 1.686) and 1.982 (1.444, 2.721), respectively. Moreover, the result of quantile g-computation also showed that exposure to high concentration of parabens mixture was positively related to the risk of T2DM. BKMR model indicated that parabens mixture was associated with glycometabolism following a U-shape and parabens mixture increased the risk of dysglycemia when all parabens concentrations were at or above their 55th percentile compared with the median. CONCLUSION: MeP or paraben mixture exposure levels showed a linear positive association with risk of T2DM. EtP and BuP were nonlinearly associated with glucose metabolism and moderate-high exposure contributed to T2DM.

Conducting Polymer-Hydrogel Interpenetrating Networks for Improving the Electrode-Neural Interface.

Implantable neural microelectrodes are recognized as a bridge for information exchange between inner organisms and outer devices. Combined with novel modulation technologies such as optogenetics, it offers a highly precise methodology for the dissection of brain functions. However, achieving chronically effective and stable microelectrodes to explore the electrophysiological characteristics of specific neurons in free-behaving animals continually poses great challenges. To resolve this, poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)/poly(vinyl alcohol) (PEDOT/PSS/PVA) interpenetrating conducting polymer networks (ICPN) are fabricated via a hydrogel scaffold precoating and electrochemical polymerization process to improve the performance of neural microelectrodes. The ICPN films exhibit robust interfacial adhesion, a significantly lower electrochemical impedance, superior mechanical properties, and improved electrochemical stability compared to the pure poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)(PEDOT/PSS) films, which may be attributed to the three-dimensional (3D) porous microstructure of the ICPN. Hippocampal neurons and rat pheochromocytoma cells (PC12 cells) adhesion on ICPN and neurite outgrowth are observed, indicating enhanced biocompatibility. Furthermore, alleviated tissue response at the electrode-neural tissue interface and improved recording signal quality are confirmed by histological and electrophysiological studies, respectively. Owing to these merits, optogenetic modulations and electrophysiological recordings are performed in vivo, and an anxiolytic effect of hippocampal glutamatergic neurons on behavior is shown. This study demonstrates the effectiveness and advantages of ICPN-modified neural implants for in vivo applications.

Functional Involvement of circRNAs in the Innate Immune Responses to Viral Infection.

Effective viral clearance requires fine-tuned immune responses to minimize undesirable inflammatory responses. Circular RNAs (circRNAs) are a class of non-coding RNAs that are abundant and highly stable, formed by backsplicing pre-mRNAs, and expressed ubiquitously in eukaryotic cells, emerging as critical regulators of a plethora of signaling pathways. Recent progress in high-throughput sequencing has enabled a better understanding of the physiological and pathophysiological functions of circRNAs, overcoming the obstacle of the sequence overlap between circRNAs and their linear cognate mRNAs. Some viruses also encode circRNAs implicated in viral replication or disease progression. There is increasing evidence that viral infections dysregulate circRNA expression and that the altered expression of circRNAs is critical in regulating viral infection and replication. circRNAs were shown to regulate gene expression via microRNA and protein sponging or via encoding small polypeptides. Recent studies have also highlighted the potential role of circRNAs as promising diagnostic and prognostic biomarkers, RNA vaccines and antiviral therapy candidates due to their higher stability and lower immunogenicity. This review presents an up-to-date summary of the mechanistic involvement of circRNAs in innate immunity against viral infections, the current understanding of their regulatory roles, and the suggested applications.

The "Hand as Foot" teaching method in the bony labyrinth.

Teachers have applied the "Hand as Foot" teaching method in anatomy teaching. It helps students understand and remember effectively, triggers students' interest in learning, and stimulates creativity. Guided by the teacher, my classmates and I also attempted to design some simple gestures to show the anatomical structures of the bony labyrinth to facilitate memorization. Here, as a medical student, I am glad to share my ideas with you.

Loss of SPRY2 contributes to cancer-associated fibroblasts activation and promotes breast cancer development.

The communication between tumor cells and tumor microenvironment plays a critical role in cancer development. Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment and take part in breast cancer formation and progression. Here, by comparing the gene expression patterns in CAFs and normal fibroblasts, we found SPRY2 expression was significantly decreased in CAFs and decreased SPRY2 expression was correlated with worse prognosis in breast cancer patients. SPRY2 knockdown in fibroblasts promoted tumor growth and distant metastasis of breast cancer in mice. Loss of stromal SPRY2 expression promoted CAF activation dependent on glycolytic metabolism. Mechanically, SPRY2 suppressed Y10 phosphorylation of LDHA and LDHA activity by interfering with the interaction between LDHA and SRC. Functionally, SPRY2 knockdown in fibroblasts enhanced the stemness of tumor cell dependent on glycolysis in fibroblasts. Collectively, this work identified SPRY2 as a negative regulator of CAF activation, and SPRY2 in CAFs may potentially be therapeutically targeted in breast cancer treatment.

Dispersion-Corrected DFT-D4 Study of the Adsorption of Halobenzenes and 1,3,5-Trihalobenzenes on the Cu(111) Surface─Effect of Sigma Hole Properties.

Halogen bonds, characterized by directionality, tunability, hydrophobicity, and variable sizes, are ideal noncovalent interactions to design and control the formation of self-assembled nanostructures. The specific self-assembly cases formed by the halogen-bonding interaction have been well studied by scanning tunneling microscopy (STM) experiments and density functional theory (DFT) calculations. However, there is a lack of systematic theoretical adsorption studies on halogenated molecules. In this work, the adsorption of halobenzenes and 1,3,5-trihalobenzenes on the Cu(111) surface was examined by dispersion-corrected DFT methods. The adsorption geometries, noncovalent molecule-surface interactions, electronic densities, and electrostatic potential maps were examined for their most stable adsorption sites using the DFT-D4 method. Our calculations revealed that the iodo compounds favor a different adsorption geometry from aryl chlorides and bromides. Down the halogen group (Cl to I), the adsorption energy increases and the distance between the halogen atom and Cu surface decreases, which indicates stronger molecule-surface interactions. This is supported by the changes in the density of states upon adsorption. Noncovalent interaction analysis was also employed to further understand the nature and relative strength of the molecule-surface interactions. Electrostatic potential maps revealed that the positive character of the halogen sigma hole becomes stronger upon adsorption. Thus, surface adsorption of the halogenated molecule will enhance the formation of intermolecular halogen bonds. The present theoretical findings are expected to contribute toward a more comprehensive understanding of halogen bonding on the Cu(111) surface.