Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

High-Performance Self-Powered Photoelectrochemical Ultraviolet Photodetectors Based on an In2O3 Nanocube Film.

Ultraviolet photodetectors (UV PDs) have attracted significant attention due to their wide range of applications, such as underwater communication, biological analysis, and early fire warning systems. Indium oxide (In2O3) is a candidate for developing high-performance photoelectrochemical (PEC)-type UV PDs owing to its high UV absorption and good stability. However, the self-powered photoresponse of the previously reported In2O3-based PEC UV PDs is unsatisfactory. In this work, high-performance self-powered PEC UV PDs were constructed by using an In2O3 nanocube film (NCF) as a photoanode. In2O3 NCF photoanodes were synthesized on FTO by using hydrothermal methods with a calcining process. The influence of the electrolyte concentration, bias potential, and irradiation light on the photoresponse properties was systematically studied. In2O3 NCF PEC UV PDs exhibit outstanding self-powered photoresponses to 365 nm UV light with a high responsivity of 44.43 mA/W and fast response speed (20/30 ms) under zero bias potential, these results are superior to those of previously reported In2O3-based PEC UV PDs. The improved self-powered photoresponse is attributed to the higher photogenerated carrier separation efficiency and faster charge transport of the in-situ grown In2O3 NCF. In addition, these PDs exhibit excellent multicycle stability, maintaining the photocurrent at 98.69% of the initial value after 700 optical switching cycles. Therefore, our results prove the great promise of In2O3 in self-powered PEC UV PDs.

Descriptive study of causes of death and COVID-19-associated morbidities from the New York City electronic death record: first wave of the pandemic March-July 2020.

OBJECTIVE: Assessing excess deaths from benchmarks across causes of death during the first wave of the COVID-19 pandemic and identifying morbidities most frequently mentioned alongside COVID-19 deaths in the death record. METHODS: Descriptive study of death records between 11 March 2020 and 27 July 2020, from the New York City Bureau of Vital Statistics. Mortality counts and percentages were compared with the average for the same calendar period of the previous 2 years. Distributions of morbidities from among forty categories of conditions were generated citywide and by sex, race/ethnicity and four age groups. Causes of death were assumed to follow Poisson processes for Z-score construction. RESULTS: Within the study period, 46 563 all-cause deaths were reported; 132.9% higher than the average for the same period of the previous 2 years (19 989). Of those 46 563 records, 19 789 (42.5%) report COVID-19 as underlying cause of death. COVID-19 was the most prevalent cause across all demographics, with respiratory conditions (prominently pneumonia), hypertension and diabetes frequently mentioned morbidities. Black non-Hispanics had greater proportions of mentions of pneumonia, hypertension, and diabetes. Hispanics had the largest proportion of COVID-19 deaths (52.9%). Non-COVID-19 excess deaths relative to the previous 2-year averages were widely reported. CONCLUSION: Mortality directly due to COVID-19 was accompanied by significant increases across most other causes from their reference averages, potentially suggesting a sizable COVID-19 death undercount. Indirect effects due to COVID-19 may partially account for some increases, but findings are hardly dispositive. Unavailability of vaccines for the time period precludes any impact over excess deaths. Respiratory and cardiometabolic-related conditions were most frequently reported among COVID-19 deaths across demographic characteristics.

Protective effects of sugarcane polyphenol against UV-B-induced photoaging in Balb/c mouse skin: Antioxidant, anti-inflammatory, and anti-glycosylation Effects.

Although the benefits of sugarcane polyphenol (SP) are well documented, its function in preventing photoaging has not yet been investigated. This study aimed to investigate the protective effects of SP in preventing ultraviolet (UV)-B-induced skin photoaging in Balb/c mice, as well as the underlying mechanism. Chlorogenic acid was determined to be the primary component of SP by using high-performance liquid chromatography-mass spectrometry. SP and chlorogenic acid were orally administrated to mice for 56 days, and UV-B radiation exposure was administered 14 days after SP and chlorogenic acid administration and lasted 42 days to cause photoaging. SP and chlorogenic acid administrations significantly alleviated the UV-B-induced mouse skin photoaging, as indicated by the decrease in epidermal thickness, increase in the collagen (COL) volume fraction, and elevation in type 1 and type 3 COL contents. Notably, both SP and chlorogenic acid effectively reversed the overexpression of matrix metalloproteinase induced by UV-B exposure in the mouse skin. Furthermore, SP and chlorogenic acid reduced the expression of receptor for advanced glycosylation end products in the mice; amplified the activities of antioxidant enzymes superoxide dismutase and catalase; reduced malondialdehyde levels; and decreased inflammatory cytokines interleukin 1ß, interleukin 6, and tumor necrosis factor α levels. SP could be a prospective dietary supplement for anti-photoaging applications due to its antioxidant, anti-inflammatory, and anti-glycosylation attributes, and chlorogenic acid might play a major role in these effects. PRACTICAL APPLICATION: This study can provide a scientific basis for the practical application of sugarcane polyphenols. We expect that sugarcane polyphenols can be used in food and beverage products to provide flavor while combating skin aging.

Global profiling of protein S-palmitoylation in the second-generation merozoites of Eimeria tenella.

The intracellular protozoan Eimeria tenella is responsible for avian coccidiosis which is characterized by host intestinal damage. During developmental cycle, E. tenella undergoes versatile transitional stages such as oocyst, sporozoites, merozoites, and gametocytes. These developmental transitions involve changes in cell shape and cell size requiring cytoskeletal remodeling and changes in membrane proteins, which may require transcriptional and translational regulations as well as post-translational modification of proteins. Palmitoylation is a post-translational modification (PTM) of protein that orchestrates protein targeting, folding, stability, regulated enzymatic activity and even epigenetic regulation of gene expression. Previous research revealed that protein palmitoylation play essential role in Toxoplasma gondii, Trypanosoma cruzi, Trichomonas vaginalis, and several Plasmodium parasites. Until now, there is little information on the enzymes related to palmitoylation and role of protein acylation or palmitoylation in E. tenella. Therefore, palmitome of the second-generation merozoite of E. tenella was investigated. We identified a total of 2569 palmitoyl-sites that were assigned to 2145 palmitoyl-peptides belonging to 1561 protein-groups that participated in biological processes including parasite morphology, motility and host cell invasion. In addition, RNA biosynthesis, protein biosynthesis, folding, proteasome-ubiquitin degradation, and enzymes involved in PTMs, carbohydrate metabolism, glycan biosynthesis, and mitochondrial respiratory chain as well as vesicle trafficking were identified. The study allowed us to decipher the broad influence of palmitoylation in E. tenella biology, and its potential roles in the pathobiology of E. tenella infection. Raw data are publicly available at iProX with the dataset identifier PXD045061.

Altered volume of the amygdala subregions in patients with chronic low back pain.

Background: Neuroimaging studies have suggested a pivotal role for the amygdala involvement in chronic low back pain (CLBP). However, the relationship between the amygdala subregions and CLBP has not yet been delineated. This study aimed to analyze whether the amygdala subregions were linked to the development of CLBP. Methods: A total of 45 patients with CLBP and 45 healthy controls (HCs) were included in this study. All subjects were asked to complete a three-dimensional T1-weighted magnetic resonance imaging (3D-T1 MRI) scan. FreeSurfer 7.3.2 was applied to preprocess the structural MRI images and segment the amygdala into nine subregions. Afterwards, comparisons were made between the two groups in terms of the volumes of the amygdala subregions. Correlation analysis is utilized to examine the relationship between the amygdala subregion and the scale scores, as well as the pain duration in patients with CLBP. Additionally, logistic regression was used to explore the risk of the amygdala and its subregions for CLBP. Results: In comparison to HCs, patients with CLBP exhibited a significant enlargement of the left central nucleus (Ce) and left cortical nucleus (Co). Furthermore, the increased volume of the left Ce was associated with a higher risk of CLBP. Conclusion: Our study suggests that the left Ce and left Co may be involved in the pathophysiological processes of CLBP. Moreover, the volume of the left Ce may be a biomarker for detecting the risk of CLBP.

Rydberg atom electric field sensing for metrology, communication and hybrid quantum systems.

Rydberg atoms-based electric field sensing has developed rapidly over the past decade. A variety of theoretical proposals and experiment configurations are suggested and realized to improve the measurement metrics, such as intensity sensitivity, bandwidth, phase, and accuracy. The Stark effect and electromagnetically induced transparency (EIT) or electromagnetically induced absorption (EIA) are fundamental physics principles behind the stage. Furthermore, various techniques such as amplitude- or frequency-modulation, optical homodyne read-out, microwave superheterodyne and frequency conversion based on multi-wave mixing in atoms are utilized to push the metrics into higher levels. In this review, different technologies and the corresponding metrics they had achieved were presented, hoping to inspire more possibilities in the improvement of metrics of Rydberg atom-based electric field sensing and broadness of application scenarios.

Overexpression of a Fragaria vesca NAM, ATAF, and CUC (NAC) Transcription Factor Gene (FvNAC29) Increases Salt and Cold Tolerance in Arabidopsis thaliana.

The NAC (NAM, ATAF1/2, CUC2) family of transcription factors (TFs) is a vital transcription factor family of plants. It controls multiple parts of plant development, tissue formation, and abiotic stress response. We cloned the FvNAC29 gene from Fragaria vesca (a diploid strawberry) for this research. There is a conserved NAM structural domain in the FvNAC29 protein. The highest homology between FvNAC29 and PaNAC1 was found by phylogenetic tree analysis. Subcellular localization revealed that FvNAC29 is localized onto the nucleus. Compared to other tissues, the expression level of FvNAC29 was higher in young leaves and roots. In addition, Arabidopsis plants overexpressing FvNAC29 had higher cold and high-salinity tolerance than the wild type (WT) and unloaded line with empty vector (UL). The proline and chlorophyll contents of transgenic Arabidopsis plants, along with the activities of the antioxidant enzymes like catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) under 200 mM NaCl treatment or -8 °C treatment, were higher than those activities of the control. Meanwhile, malondialdehyde (MDA) and the reactive oxygen species (ROS) content were higher in the WT and UL lines. FvNAC29 improves transgenic plant resistance to cold and salt stress by regulating the expression levels of AtRD29a, AtCCA1, AtP5CS1, and AtSnRK2.4. It also improves the potential to tolerate cold stress by positively regulating the expression levels of AtCBF1, AtCBF4, AtCOR15a, and AtCOR47. These findings suggest that FvNAC29 may be related to the processes and the molecular mechanisms of F. vesca response to high-salinity stress and LT stress, providing a comprehensive understanding of the NAC TFs.

MaC2H2-IDD regulates fruit softening and involved in softening disorder induced by cold stress in banana.

Chilling stress causes banana fruit softening disorder and severely impairs fruit quality. Various factors, such as transcription factors, regulate fruit softening. Herein, we identified a novel regulator, MaC2H2-IDD, whose expression is closely associated with fruit ripening and softening disorder. MaC2H2-IDD is a transcriptional activator located in the nucleus. The transient and ectopic overexpression of MaC2H2-IDD promoted "Fenjiao" banana and tomato fruit ripening. However, transient silencing of MaC2H2-IDD repressed "Fenjiao" banana fruit ripening. MaC2H2-IDD modulates fruit softening by activating the promoter activity of starch (MaBAM3, MaBAM6, MaBAM8, MaAMY3, and MaISA2) and cell wall (MaEXP-A2, MaEXP-A8, MaSUR14-like, and MaGLU22-like) degradation genes. DLR, Y1H, EMSA, and ChIP-qPCR assays validated the expression regulation. MaC2H2-IDD interacts with MaEBF1, enhancing the regulation of MaC2H2-IDD to MaAMY3, MaEXP-A2, and MaGLU22-like. Overexpressing/silencing MaC2H2-IDD in banana and tomato fruit altered the transcript levels of the cell wall and starch (CWS) degradation genes. Several differentially expressed genes (DEGs) were authenticated between the overexpression and control fruit. The DEGs mainly enriched biosynthesis of secondary metabolism, amino sugar and nucleotide sugar metabolism, fructose and mannose metabolism, starch and sucrose metabolism, and plant hormones signal transduction. Overexpressing MaC2H2-IDD also upregulated protein levels of MaEBF1. MaEBF1 does not ubiquitinate or degrade MaC2H2-IDD. These data indicate that MaC2H2-IDD is a new regulator of CWS degradation in "Fenjiao" banana and cooperates with MaEBF1 to modulate fruit softening, which also involves the cold softening disorder.

Ultrasensitive SERS quantitative detection of antioxidants via diazo derivatization reaction and deep learning for signal fluctuation mitigation.

Synthetic antioxidants serve as essential protectors against oxidation and deterioration of edible oils, however, prudent evaluation is necessary regarding potential health risks associated with excessive intake. The direct adsorption of antioxidants onto conventional surface-enhanced Raman scattering (SERS) substrates is challenging due to the presence of phenolic hydroxyl groups in their molecular structures, resulting in weak Raman scattering signals and rendering direct SERS detection difficult. In this study, a diazo derivatization reaction was employed to enhance SERS signals by converting antioxidant molecules into azo derivatives, enabling the amplification of the weak Raman scattering signals through the strong vibrational modes induced by the N = N double bond. The resulting diazo derivatives were characterized using UV-visible absorption and infrared spectroscopy, confirming the occurrence of diazo derivatization of the antioxidants. The proposed method successfully achieved the rapid detection of three commonly used synthetic antioxidants, namely butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), and propyl gallate (PG) on interfacial self-assembled gold nanoparticles. Furthermore, rapid predictions of BHA, PG, and TBHQ within the concentration range of 1 × 10-6 to 2 × 10-3 mol/L were achieved by integrating a convolutional neural network model. The predictive range of this model surpassed the traditional quantitative method of manually selecting characteristic peaks, with linear coefficients (R2) of 0.9992, 0.9997, and 0.9997, respectively. The recovery of antioxidants in real soybean oil samples ranged from 73.0 % to 126.4 %. Based on diazo derivatization, the proposed SERS method eliminates the need for complex substrates and enables the analysis and determination of synthetic antioxidants in edible oils within 20 min, providing a convenient analytical approach for quality control in the food industry.

Evaluation and optimization of outdoor wind environment in block based on space syntax and CFD simulation.

The wind environment quality at the height of pedestrians can significantly affect the thermal comfort and physical and mental health of pedestrians, promote the diffusion of air pollutants and inhibit the formation of urban heat island effect, and has been paid more and more attention in the field of urban and rural planning. This paper takes Jianlan Road commercial pedestrian Street as an example to maximize the thermal comfort of pedestrians. Based on CFD numerical simulation technology and space syntax theory, the pedestrian wind environment of the accessible space of the block is selected for quantitative research. Through numerical simulation, the influence of block spatial form on the wind environment at pedestrian height under the initial condition of uniform air flow is analyzed, and some suggestions are put forward for the optimization of block spatial form. Finally, the block optimization scheme is verified and simulated. The visualization results show that the wind environment quality of the optimized high-accessibility space is significantly improved, the proportion of comfort zone is increased from 58.2% to 86%, and the static wind rate is reduced from 41.8% to 14%. The wind environment optimization effect is obvious.

Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel.

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation. Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel. Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine. Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

The Function of SD1 on Shoot Length and its Pyramiding Effect on Shoot Length and Plant Height in Rice (Oryza sativa L.).

Strong seedling vigor is imperative to achieve stable seedling establishment and enhance the competitiveness against weeds in rice direct seeding. Shoot length (SL) is one of the important traits associated with seedling vigor in rice, but few genes for SL have been cloned so far. In the previous study, we identified two tightly linked and stably expressed QTLs for SL, qSL-1f and qSL-1d by genome-wide association study, and cloned the causal gene (LOC_Os01g68500) underlying qSL-1f. In the present study, we identify LOC_Os01g66100 (i.e. the semidwarf gene SD1), a well-known gene controlling plant height (PH) at the adult-plant stage, as the causal gene underlying qSL-1d through gene-based haplotype analysis and knockout transgenic verification. By measuring the phenotypes (SL and PH) of various haplotypes of the two genes and their knockout lines, we found SD1 and LOC_ Os01g68500 controlled both SL and PH, and worked in the same direction, which provided the directly genetic evidence for a positive correlation between SL and PH combined with the analysis of SL and PH in the diverse natural population. Moreover, the knockout transgenic experiments suggested that SD1 had a greater effect on PH compared with LOC_ Os01g68500, but no significant difference in the effect on SL. Further investigation of the pyramiding effects of SD1 and LOC_Os01g68500 based on their haplotype combinations suggested that SD1 may play a dominant role in controlling SL and PH when the two genes coexist. In this study, the effect of SD1 on SL at the seedling stage is validated. In total, two causal genes, SD1 and LOC_ Os01g68500, for SL are cloned in our studies, which controlled both SL and PH, and the suitable haplotypes of SD1 and LOC_ Os01g68500 are beneficial to achieve the desired SL and PH in different rice breeding objectives. These results provide a new clue to develop rice varieties for direct seeding and provide new genetic resources for molecular breeding of rice with suitable PH and strong seedling vigor.

Correlation between plasma PSGL-1 and FIGO stage, tumor metastasis, and survival in epithelial ovarian cancer.

Plasma circulating P-selectin glycoprotein ligand-1 (PSGL-1) levels and its clinical correlation in patients with epithelial ovarian cancer (EOC) are unknown. The study determined plasma PSGL-1 levels in EOC patients and investigated its relationship with clinicopathological factors and prognosis. Plasma PSGL-1 levels were measured using ELISA in 69 patients with EOC, 34 patients with benign ovarian cystadenoma, and 36 healthy controls. Subsequently, the relationship between PSGL-1 levels and clinicopathological characteristics of patients, as well as the prognosis of EOC patients, was examined. Additionally, the specificity and sensitivity of plasma PSGL-1 were assessed through ROC curve analysis. Plasma PSGL-1 was upregulated in EOC patients compared with healthy subjects and/or patients with benign ovarian cystadenoma (p < 0.01). Elevated levels of PSGL-1 in the plasma were positively associated with advanced FIGO stage (p < 0.001), tumor size (p = 0.001), tumor metastasis (p = 0.036), and tumor recurrence (p = 0.013), while was negatively correlated with residual tumor size (p < 0.001). Kaplan-Meier survival analysis showed that high plasma PSGL-1 levels were associated with progression-free survival (p = 0.0345). In univariate and multivariate Cox regression analyses, PSGL-1 (HR = 1.456, p = 0.009) was an independent prognostic marker. Plasma PSGL-1 levels distinguished EOC patients and healthy individuals (AUC = 0.905), patients at late and early FIGO stages (AUC = 0.886), and metastatic and non-metastatic EOC (AUC = 0.722). The expression of plasma PSGL-1 is significantly increased in patients with EOC, serving as a reliable biomarker to differentiate between healthy individuals and those with EOC. Furthermore, PSGL-1 in patients is correlated with prognostic indicators, such as advanced FIGO stage, tumor lymph node metastasis, and progression-free survival.

DNA Image Cytometry for Screening the Carcinogenetic Risk of Oral Potential Malignant Disorders.

Background: Oral Submucosal Fibrosis (OSF) and Oral Leukoplakia (OLK) are well-known oral potentially malignant disorders, and cases of Oral Submucosal Fibrosis concomitant Oral Leukoplakia (OSF+OLK) are now being reported clinically. DNA image cytometry is an objective and non-invasive method for monitoring the risk of precancerous lesions in the oral cavity. Methods: A total of 111 patients with clinically characterized oral mucosal lesions underwent simultaneous and independent histopathological and DNA imaging cytometry assessments. Clinical data were also collected for each patient. Results: The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.003) for OLK. The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.035) for OSF+OLK. The differences of DNA content abnormality in age, sex, dietary habit, smoking, and alcohol intake were not observed in OLK and OSF+OLK. The study indicates an association between DNA content abnormality and pathological examination in OSF+OLK ( χ2 test, P = 0.007). OLK showed higher sensitivity and specificity than OSF, while the sensitivity and specificity of OSF+OLK are higher than OLK only and OSF only. Conclusion: DNA image cytometry can be utilized as an adjunctive device for the initial detection of oral potentially malignant disorders that require further clinical management.

Suppression of the METTL3-m6A-integrin ß1 axis by extracellular acidification impairs T cell infiltration and antitumor activity.

The acidic metabolic byproducts within the tumor microenvironment (TME) hinder T cell effector functions. However, their effects on T cell infiltration remain largely unexplored. Leveraging the comprehensive The Cancer Genome Atlas dataset, we pinpoint 16 genes that correlate with extracellular acidification and establish a metric known as the "tumor acidity (TuAci) score" for individual patients. We consistently observe a negative association between the TuAci score and T lymphocyte score (T score) across various human cancer types. Mechanistically, extracellular acidification significantly impedes T cell motility by suppressing podosome formation. This phenomenon can be attributed to the reduced expression of methyltransferase-like 3 (METTL3) and the modification of RNA N6-methyladenosine (m6A), resulting in a subsequent decrease in the expression of integrin ß1 (ITGB1). Importantly, enforced ITGB1 expression leads to enhanced T cell infiltration and improved antitumor activity. Our study suggests that modulating METTL3 activity or boosting ITGB1 expression could augment T cell infiltration within the acidic TME, thereby improving the efficacy of cell therapy.

HNRNPC promotes estrogen receptor-positive breast cancer cell cycle by stabilizing WDR77 mRNA in an m6A-dependent manner.

Breast cancer has become the most commonly diagnosed cancer. Heterogeneous nuclear ribonucleoprotein C (HNRNPC), a reader of N6-methyladenosine (m6A), has been observed to be upregulated in various types of cancer. Nevertheless, the role of HNRNPC in breast cancer and whether it is regulated by m6A modification deserve further investigation. The expression of HNRNPC in breast cancer was examined by quantitative real-time polymerase chain reaction and western blot analysis. RNA immunoprecipitation was performed to validate the binding relationships between HNRNPC and WD repeat domain 77 (WDR77). The effects of HNRNPC and m6A regulators on WDR77 were investigated by actinomycin D assay. The experiments in vivo were conducted in xenograft models. In this research, we found that HNRNPC was highly expressed in breast cancer, and played a crucial role in cell growth, especially in the luminal subtype. HNRNPC could combine and stabilize WDR77 mRNA. WDR77 successively drove the G1/S phase transition in the cell cycle and promoted cell proliferation. Notably, this regulation axis was closely tied to the m6A modification status of WDR77 mRNA. Overall, a critical regulatory mechanism was identified, as well as promising targets for potential treatment strategies for luminal breast cancer.

Overexpression of a 'Beta' MYB Factor Gene, VhMYB15, Increases Salinity and Drought Tolerance in Arabidopsis thaliana.

'Beta' is a hybrid of Vitis riparia L. and V. labrusca and has a strong ability to adapt to adverse growth environments and is mainly cultivated and used as a resistant rootstock. At present, the most extensively studied MYB TFs are R2R3-type, which have been found to be involved in plant growth, development, and stress response processes. In the present research, VhMYB15, a key transcription factor for abiotic stress tolerance, was screened by bioinformatics in 'Beta' rootstock, and its function under salinity and drought stresses was investigated. VhMYB15 was highly expressed in roots and mature leave under salinity and drought stresses. Observing the phenotype and calculating the survival rate of plants, it was found that VhMYB15-overexpressing plants exhibited relatively less yellowing and wilting of leaves and a higher survival rate under salinity and drought stresses. Consistent with the above results, through the determination of stress-related physiological indicators and the expression analysis of stress-related genes (AtSOS2, AtSOS3, AtSOS1, AtNHX1, AtSnRK2.6, AtNCED3, AtP5CS1, and AtCAT1), it was found that transgenic Arabidopsis showed better stress tolerance and stronger adaptability under salinity and drought stresses. Based on the above data, it was preliminarily indicated that VhMYB15 may be a key factor in salinity and drought regulation networks, enhancing the adaptability of 'Beta' to adverse environments.

[Inhibitory Effect of Metformin and Arsenic Trioxide on KG1a Cell Proliferation].

OBJECTIVE: To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism. METHODS: CCK-8 method was used to detect the killing effect of metformin, arsenic trioxide and combined application on KG1a cells. Annexin V-FITC/PI Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1a cells. Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein. RESULTS: Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1a cells and induce apoptosis of KG1a cells, and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P <0.05). The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P <0.05). CONCLUSION: Metformin can synergize with arsenic trioxide to kill KG1a cells, and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Basic-helix-loop-helix family member e41 suppresses osteoclastogenesis and abnormal bone resorption disease via NFATc1.

Overactivation of osteoclasts due to altered osteoclastogenesis causes multiple bone metabolic diseases. However, how osteoclast differentiation is tightly regulated and involved in multiple pathophysiological states remains mystery. In this study, we noticed that the downregulation of BHLHE41 (basic-helix-loop-helix family member e41) was tightly associated with osteoclast differentiation and osteoporosis. Functionally, the upregulation or downregulation of BHLHE41 suppressed or promoted osteoclast differentiation, respectively, in vitro. A mechanism study indicated that the direct binding of BHLHE41 to the promoter region of NFATc1 that led to its downregulation. Notably, the inhibition of NFATc1 abrogated the enhanced osteoclast differentiation in BHLHE41-knockdown bone marrow macrophages (BMMs). Additionally, upregulation of BHLHE41 impeded bone destruction in OVX mice with osteoporosis. Therefore, our research reveals the mechanism by which BHLHE41 regulates osteoclast differentiation and bone resorption via NFATc1, and targeting BHLHE41 is a potential strategy for the treatment of osteoporosis.