Overexpression of OsNAR2.1 by OsNAR2.1 promoter increases drought resistance by increasing the expression of OsPLDα1 in rice.

BACKGROUND: pOsNAR2.1:OsNAR2.1 expression could significantly increase nitrogen uptake efficiency and grain yield of rice. RESULT: This study reported the effects of overexpression of OsNAR2.1 by OsNAR2.1 promoter on physiological and agronomic traits associated with drought tolerance. In comparison to the wild-type (WT), the pOsNAR2.1:OsNAR2.1 transgenic lines exhibited a significant improvement in survival rate when subjected to drought stress and then irrigation. Under limited water supply conditions, compared with WT, the photosynthesis and water use efficiency (WUE) of transgenic lines were increased by 39.2% and 28.8%, respectively. Finally, the transgenic lines had 25.5% and 66.4% higher grain yield than the WT under full watering and limited water supply conditions, respectively. Compared with the WT, the agronomic nitrogen use efficiency (NUE) of transgenic lines increased by 25.5% and 66.4% under full watering and limited water supply conditions, and the N recovery efficiency of transgenic lines increased by 29.3% and 50.2%, respectively. The interaction between OsNAR2.1 protein and OsPLDα1 protein was verified by yeast hybrids. After drought treatment, PLDα activity on the plasma membrane of the transgenic line increased 85.0% compared with WT. CONCLUSION: These results indicated that pOsNAR2.1:OsNAR2.1 expression could improve the drought resistance of rice by increasing nitrogen uptake and regulating the expression of OsPLDα1.

[Establishment and analysis of an early prognosis model of patients with acute kidney injury in intensive care unit].

OBJECTIVE: To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance. METHODS: A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation II (APACHE II) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI. RESULTS: A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHE II score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day "n", with y = 1.246 2x1.164 9 and an R2 of 0.860 1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day "n", with y = -0.260 6x2+3.010 7x-1.612 and an R2 of 0.998 9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 µmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. CONCLUSIONS: The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.

Changes in muscle strength and risk of cardiovascular disease among middle-aged and older adults in China: Evidence from a prospective cohort study.

BACKGROUND: Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear. METHODS: The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference. RESULTS: A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories. CONCLUSIONS: The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Rolling circle amplification assisted CRISPR/Cas12a dual-cleavage photoelectrochemical biosensor for highly sensitive detection of miRNA-21.

BACKGROUND: MicroRNA-21 has been determined to be the only microRNA overexpressed in 11 types of solid tumors, making it an excellent candidate as a biomarker for disease diagnosis and therapy. Photoelectrochemical (PEC) biosensors have been widely used for quantification of microRNA-21. However, most PEC biosensing processes still suffer from some problems, such as the difficulty of avoiding the influence of interferents in complex matrices and the false-positive signals. There is a pressing need for establishing a sensitive and stable PEC method to detect microRNA-21. RESULTS: Herein, a nicking endonuclease-mediated rolling circle amplification (RCA)-assisted CRISPR/Cas12a PEC biosensor was fabricated for ultrasensitive detection of microRNA-21. The p-p type heterojunction PbS QDs/Co3O4 polyhedra were prepared as the quencher, thus the initial PEC signal attained the "off" state. Furthermore, the target was specifically identified and amplified by the RCA process. Then, its product single-stranded DNA S1 activated the cis- and trans-cleavage abilities of CRISPR/Cas12a, leading to almost all of the PbS QDs/Co3O4 polyhedra to leave the electrode surface, the p-n semiconductor quenching effect to be disrupted, and the signal achieving the "super-on" state. This pattern of PEC signal changed from "off" to "on" eliminated the interference of false-positive signals. The proposed PEC biosensor presented a satisfactory linear relationship ranging from 1 fM to 10 nM with a detection limit of 0.76 fM (3 Sb/N). SIGNIFICANCE AND NOVELTY: With innovatively synthesized PbS QDs/Co3O4 polyhedra as the effective quencher for PEC signal, the CRISPR/Cas12a dual-cleavage PEC biosensor possessed excellent selectivity, stability and repeatability. Furthermore, the detection of various miRNAs can be realized by changing the relevant base sequences in the constructed PEC biosensor. It also provides a powerful strategy for early clinical diagnosis and biomedical research.

Strand displacement amplification triggered 3D DNA roller assisted CRISPR/Cas12a electrochemiluminescence cascaded signal amplification for sensitive detection of Ec-16S rDNA.

BACKGROUND: Escherichia coli can cause gastrointestinal infection, urinary tract infection and other infectious diseases. Accurate detection of Escherichia coli 16S rDNA (Ec-16S rDNA) in clinical practice is of great significance for the identification and treatment of related diseases. At present, there are various types of sensors that can achieve accurate detection of Ec-16S rDNA. Electrochemiluminescence (ECL) has attracted considerable attention from researchers, which causes excellent performance in bioanalysis. Based on the previous research, it is significance to develop a novel, sensitive and efficient ECL biosensor. RESULTS: In this work, an ECL biosensor for the detection of Ec-16S rDNA was constructed by integrating CRISPR/Cas12a technology with the cascade signal amplification strategy consisting of strand displacement amplification (SDA) and dual-particle three-dimensional (3D) DNA rollers. The amplification products of SDA triggered the operation of the DNA rollers, and the products generated by the DNA rollers activated CRISPR/Cas12a to cleave the signal probe, thereby realizing the change of the ECL signal. The cascade amplification strategy realized the exponential amplification of the target signal and greatly improved the sensitivity. Manganese dioxide nanoflowers (MnO2 NFs) as a co-reaction promoter effectively enhanced the ECL intensity of tin disulfide quantum dots (SnS2 QDs). A new ternary ECL system (SnS2 QDs/S2O82-/MnO2 NFs) was prepared, which made the change of ECL intensity of biosensor more significant. The proposed biosensor had a response range of 100 aM-10 nM and a detection limit of 27.29 aM (S/N = 3). SIGNIFICANCE AND NOVELTY: Herein, the cascade signal amplification strategy formed by SDA and dual-particle 3D DNA rollers enabled the ECL biosensor to have high sensitivity and low detection limit. At the same time, the cascade signal amplification strategy was integrated with CRISPR/Cas12a to enable the biosensor to efficiently detect the target. It can provide a new idea for the detection of Ec-16S rDNA in disease diagnosis and clinical analysis.

Refine localizations of functional variants affecting eggshell color of Lueyang black-boned chicken in the SLCO1B3.

Table eggs with color-uniformity shell are visually attractive for consumers. Lueyang black-boned chicken (LBC) lays colorful eggs, which is undesirable for sale of table eggs, but provides a segregating population for mapping functional variants affecting eggshell color. SLCO1B3 was identified as the causative gene for blue eggs in the Dongxiang and Araucana chickens. The aim of this study is to map functional variants associated with chicken eggshell color in the SLCO1B3. Eggshell color of LBC (n = 383) was measured using the L*a*b color space. SLCO1B3 was resequencing using a subset (n = 30) of 383 samples. Linkage disequilibrium among 139 SNP was analyzed. Association of 16 SNP in the SLCO1B3 and 8 in CPOX, ALAS1, and ABCG2 genes with L*a*b were tested by a polygenic model (LMM) and a polygenic/oligogenic mixed model (BSLMM). Chromatin state annotations were retrieved from the UCSC database. Effect of SLCO1B3 variants distributed in mapping and upstream 1.6-kb regions on promoter activities were analyzed using dual-luciferase reporter assay. One hundred and thirty-nine variants maintained low linkage disequilibrium with 80% of r2 less than 0.226. Fifteen SLCO1B3 variants were significantly associated with a*, of which 1B3_SNP108 was showed the strongest association and the largest effect on a*. In the BSLMM, 1B3_SNP108 alone appeared in the Markov chain Monte Carlo as major variants in 100% of posterior inclusion probability. None of variants in CPOX, ALAS1, and ABCG2 were significantly associated with color indexes except that 2 ALAS1 variants were associated with L*. 1B3_SNP108 distributes in the Intron4 where 6 active enhancers and 1 ATAC island were enriched. However, 1B3_SNP108-containing constructs showed negligible activities in the reporter assay. No significant differences of activities between haplotypes were found for five 5'-deleted promoter constructs. The data recognizes 1B3_SNP108 as a valuable marker for breeding of eggshell color. Functional variants are localized in the region adjacent to the 1B3_SNP108 due to low linkage disequilibrium in the LBC. Our findings extend the role of SLCO1B3 from a causative gene for blue eggs to a major regulator driving continuous variation of LBC eggshell color.

YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia†.

Genomic integrity is critical for sexual reproduction, ensuring correct transmission of parental genetic information to the descendant. To preserve genomic integrity, germ cells have evolved multiple DNA repair mechanisms, together termed as DNA damage response. The RNA N6-methyladenosine is the most abundant mRNA modification in eukaryotic cells, which plays important roles in DNA damage response, and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) is a well-acknowledged N6-methyladenosine reader protein regulating the mRNA decay and stress response. Despite this, the correlation between YTHDF2 and DNA damage response in germ cells, if any, remains enigmatic. Here, by employing a Ythdf2-conditional knockout mouse model as well as a Ythdf2-null GC-1 mouse spermatogonial cell line, we explored the role and the underlying mechanism for YTHDF2 in spermatogonial DNA damage response. We identified that, despite no evident testicular morphological abnormalities under the normal circumstance, conditional mutation of Ythdf2 in adult male mice sensitized germ cells, including spermatogonia, to etoposide-induced DNA damage. Consistently, Ythdf2-KO GC-1 cells displayed increased sensitivity and apoptosis in response to DNA damage, accompanied by the decreased SET domain bifurcated 1 (SETDB1, a histone methyltransferase) and H3K9me3 levels. The Setdb1 knockdown in GC-1 cells generated a similar phenotype, but its overexpression in Ythdf2-null GC-1 cells alleviated the sensitivity and apoptosis in response to DNA damage. Taken together, these results demonstrate that the N6-methyladenosine reader YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia, which provides novel insights into the mechanisms underlying spermatogonial genome integrity maintenance and therefore contributes to safe reproduction.

The Prognostic Significance of the TEAD4 in Hepatocellular Carcinoma.

Background: Abnormal expression of genes causes tumorigenesis, tumor progression, and poor prognosis in hepatocellular carcinoma (HCC). Therefore, the aims of this study were to explore the transcription enhancer domain factor 4 (TEAD4) in patients with liver cancer and its relationship with prognosis. Methods: HTSeq-FPKM data and corresponding clinical data of HCC patients were obtained from The Cancer Genome Atlas (TCGA). Difference in TEAD4 expression between normal and tumor and the correlation with clinical characteristics were analyzed by the chi-squared test based on UALCAN. HepG2 cell lines were used to study the effect of TEAD4 on HCC cell lines. The expression and clinical significance of TEAD4 in HCC were detected in clinical cases. Results: The transcription and post-transcription levels of TEAD4 were higher in HCC tumors than normal illustrated different expressed transcription of TEAD4 in gender, nodal metastasis status, tumor grades, and individual cancer stages. The high TEAD4 expression was significantly associated with tumor grades. The high expression of TEAD4 was significantly correlated to shorter 2-5 years overall survival. Inhibition of TEAD4 expression in HepG2 cells resulted in significantly decreased cell proliferation and invasion. Conclusion: TEAD4 was identified as an independent prognostic factor, and inhibition of TEAD4 expression in HepG2 cells resulted in significantly decreased cell proliferation and invasion.

OsGSTU17, a Tau Class Glutathione S-Transferase Gene, Positively Regulates Drought Stress Tolerance in Oryza sativa.

As a great threat to the normal growth of rice, drought not only restricts the growth of rice, but also affects its yield. Glutathione S-transferases (GSTs) have antioxidant and detoxification functions. In rice, GSTs can not only effectively cope with biological stress, but also play a defense role against abiotic stress. In this study, we selected OsGSTU17, a member gene that was induced by drought, to explore the role of GSTs and analyze their physiological mechanisms that are involved in rice drought tolerance. With the CRISPR/Cas9 knockout system techniques, we obtained two independent mutant lines of osgstu17. After 14 days of drought stress treatment, and then re-supply of the water for 10 days, the survival rate of the osgstu17 mutant lines was significantly reduced compared to the wild-type (WT). Similarly, with the 10% (w/v) PEG6000 hydroponics experiment at the seedling stage, we also found that compared with the WT, the shoot and root biomass of osgstu17 mutant lines decreased significantly. In addition, both the content of the MDA and H2O2, which are toxic to plants, increased in the osgtu17 mutant lines. On the other hand, chlorophyll and proline decreased by about 20%. The activity of catalase and superoxide dismutase, which react with peroxides, also decreased by about 20%. Under drought conditions, compared with the WT, the expressions of the drought stress-related genes OsNAC10, OsDREB2A, OsAP37, OsP5CS1, OsRAB16C, OsPOX1, OsCATA, and OsCATB in the osgtu17 mutant lines were significantly decreased. Finally, we concluded that knocking out OsGSTU17 significantly reduced the drought tolerance of rice; OsGSTU17 could be used as a candidate gene for rice drought-tolerant cultivation. However, the molecular mechanism of OsGSTU17 involved in rice drought resistance needs to be further studied.

Effect of diabetes mellitus on young female patients with acute coronary syndrome.

BACKGROUND: Diabetes mellitus (DM) is one of the most important risk factors of acute coronary syndrome (ACS). There have been many studies on the relationship between DM and ACS. However, the effect of DM on young females with ACS is still unclear. OBJECTIVE: To explore the effect of DM on coronary arteries lesions in young females with ACS. METHODS: 1278 young females (age ≤ 44 years) undergoing coronary angiography were divided into DM group (n = 197) and control group (n = 1081) according to whether they had diabetes. Based on whether the patient has ACS, each group was further divided into DM-ACS subgroup and Non-DM-ACS subgroup to compare the characteristics and severity of coronary artery lesions and follow-up outcomes. RESULTS: The prevalence of diabetes was 15.41% (197/1278). Overweight (58.88%) and depression or anxiety (11.17%) in the DM group was significantly higher than those (32.22% and 6.20%) in the control group (P < 0.05). The prevalence of ACS (85.28%) in the DM group was significantly higher than that (25.35%) in the control group (P < 0.05). The proportion of type A lesions in the DM-ACS subgroup was lesser than that in the Non-DM-ACS subgroup (P < 0.05). The type C lesions in the DM-ACS subgroup were significantly higher than that in the Non-DM-ACS subgroup (P < 0.01). The number of stents implantation in the DM-ACS subgroup was no significant difference compared with the Non-DM-subgroup (P > 0.05). The length of stent implantation in the DM-ACS subgroup was significantly longer than that in the Non-DM-ACS subgroup (P < 0.05). The rate of MACE was not statistically significant between the two subgroups (P > 0.05), but the rate of all-cause death (2.98%) in the DM-ACS subgroup was significantly higher than that (0.36%) in the Non-DM-ACS subgroup (P < 0.05). CONCLUSIONS: DM is an important risk factor in young females with ACS. Young women with diabetes are prone to coronary heart disease. The coronary artery lesions in DM patients were more severe than those in Non-DM patients, despite the protective effect of estrogen on the cardiovascular system. Therefore, young women with DM should be treated to prevent ACS and future events activelyandpurposefully.

Spider Silk Protein Forms Amyloid-Like Nanofibrils through a Non-Nucleation-Dependent Polymerization Mechanism.

Amyloid fibrils-nanoscale fibrillar aggregates with high levels of order-are pathogenic in some today incurable human diseases; however, there are also many physiologically functioning amyloids in nature. The process of amyloid formation is typically nucleation-elongation-dependent, as exemplified by the pathogenic amyloid-ß peptide (Aß) that is associated with Alzheimer's disease. Spider silk, one of the toughest biomaterials, shares characteristics with amyloid. In this study, it is shown that forming amyloid-like nanofibrils is an inherent property preserved by various spider silk proteins (spidroins). Both spidroins and Aß capped by spidroin N- and C-terminal domains, can assemble into macroscopic spider silk-like fibers that consist of straight nanofibrils parallel to the fiber axis as observed in native spider silk. While Aß forms amyloid nanofibrils through a nucleation-dependent pathway and exhibits strong cytotoxicity and seeding effects, spidroins spontaneously and rapidly form amyloid-like nanofibrils via a non-nucleation-dependent polymerization pathway that involves lateral packing of fibrils. Spidroin nanofibrils share amyloid-like properties but lack strong cytotoxicity and the ability to self-seed or cross-seed human amyloidogenic peptides. These results suggest that spidroins´ unique primary structures have evolved to allow functional properties of amyloid, and at the same time direct their fibrillization pathways to avoid formation of cytotoxic intermediates.

Systematic assessment of hexavalent chromium-induced damage to male fertility and the preventive role of melatonin: a longitudinal study from the translational point of view.

Chromium (Cr) and its compounds are closely associated with individuals' lives and extensively used in industry. Excessive exposure to hexavalent chromium (Cr(VI)) induces oxidative damage of various organs including the testes, posing a serious threat to male reproductive fitness. As an endogenous antioxidant, melatonin holds potent antioxidative and anti-inflammatory properties, becoming a potential candidate for treatment of a variety of diseases, including reproductive disorders. Here, by using a mouse model, we systematically assessed Cr(VI)-induced damage to male fertility as well as the preventive role of melatonin. We analyzed the histology and pathology of the testis and epididymis, the density, viability, and malformation of caudal epididymal sperm, the proliferative activity and apoptosis of various spermatogenic subtypes and Sertoli cells, as well as the fertility of mice at five timepoints within one cycle of spermatogenesis (Days 0, 14, 21, 28, and 35) post 14 days of Cr(VI) and/or melatonin intraperitoneal injection. We identified that the testicular damage caused by Cr(VI) persisted to Day 21 after administration and then started to be alleviated, with clear alleviation on Day 35. Pretreatment with melatonin evidently reduced Cr(VI)-induced testicular damage and accelerated spermatogenic restoration, generating an almost normal phenotype on Day 35. Melatonin pretreatment also retained the sperm quality at all time points investigated. Moreover, melatonin to some extent preserved the fertility of Cr(VI)-treated mice without apparent side effects. The findings shed light on the future clinical application of melatonin as a therapeutic agent for environmental heavy metal toxicant-induced male subfertility or infertility.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

Regulation of Fatty Acid Metabolism and Inhibition of Colorectal Cancer Progression by Erchen Decoction.

Erchen decoction (ECD) is a traditional Chinese prescription widely used in the treatment of various diseases such as obesity, fatty liver, diabetes, and hypertension. In this study, we investigated the effect of ECD on fatty acid metabolism in a colorectal cancer (CRC) mouse model fed a high-fat (HF) diet. The HF-CRC mouse model was established by azoxymethane (AOM)/dextran sulphate sodium (DSS) combined with a high-fat diet. Mice were then gavaged with ECD. Change in the body weight was recorded every two weeks for 26 weeks. Changes in blood glucose (GLU), total cholesterol (TC), total triglycerides (TG), and C-reactive protein (CRP) were measured. Colorectal tissues were collected to observe changes in colorectal length and tumorigenesis. Hematoxylin-eosin (HE) staining and immunohistochemical staining were performed to observe changes in intestinal structure and inflammatory markers. Fatty acids and the expression of related genes in colorectal tissues were also studied. ECD gavage inhibited HF-induced weight gain. CRC induction and HF diet intake resulted in increased GLU, TC, TG, and CRP, where ECD gavage reduced these elevated indicators. ECD gavage also increased colorectal length and inhibited tumorigenesis. HE staining revealed that ECD gavage suppressed inflammatory infiltration of colorectal tissues. ECD gavage suppressed the fatty acid metabolism abnormalities caused by HF-CRC in colorectal tissues. Consistently, ECD gavage lowered ACSL4, ACSL1, CPT1A, and FASN levels in colorectal tissues. Conclusions. ECD inhibited HF-CRC progression through the regulation of fatty acid metabolism.

Potential predictive value of CT radiomics features for treatment response in patients with COVID-19.

INTRODUCTION: This study aims to explore the predictive value of CT radiomics and clinical characteristics for treatment response in COVID-19 patients. METHODS: Data were collected from clinical/auxiliary examinations and follow-ups of COVID-19 patients. Whole lung radiomics feature extraction was performed at baseline chest CT. Radiomics, clinical, and combined features (nomogram) were evaluated for predicting treatment response. RESULTS: Among 36 COVID-19 patients, mild, common, severe, and critical disease symptoms were found in 1, 21, 13, and 1 of them, respectively. Twenty-five (1 mild, 18 common, and 6 severe) patients showed a good response to treatment and 11 poor/fair responses. The clinical classification (p = 0.025) and serum creatinine (p = 0.010) on admission and small area emphasis (p = 0.036) from radiomics analysis significantly differed between the two groups. Predictive models were constructed based on the radiomics, clinical features, and nomogram showing an area under the curve of 0.651, 0.836, and 0.869, respectively. The nomogram achieved good calibration. CONCLUSION: This new, non-invasive, and low-cost prediction model that combines the radiomics and clinical features is useful for identifying COVID-19 patients who may not respond well to treatment.

YTHDF2 controls hexavalent chromium-induced mitophagy through modulating Hif1α and Bnip3 decay via the m6A/mRNA pathway in spermatogonial stem cells/progenitors.

Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and SSC homeostasis is essential for lifelong male fertility. Currently, environmental pollution remains one of the factors affecting human reproductive health. Chromium is a prevalent metal element, and excessive exposure to hexavalent chromium (Cr (VI)) can cause male reproductive disorders. Nevertheless, the toxic effects of Cr (VI) on SSCs and the underlying mechanisms remain incompletely understood. Here, we showed that Cr (VI) exposure triggered mitophagy in mouse SSCs/progenitors in a time-dependent manner. Concurrently, Cr (VI) treatment caused reactive oxygen species (ROS) accumulation and activated the HIF1α-mediated BNIP3 expression to trigger mitophagy. In addition, Cr (VI) exposure significantly decreased the level of m6A modification. Further, we identified that YTHDF2 regulated the stability of Bnip3 and Hif1α mRNAs in an m6A-dependent manner, which was involved in Cr (VI)-induced mitophagy. Collectively, our study not only expands the mechanisms for Cr (VI)-caused male reproductive toxicity, but also provides pharmacological targets for prevention and treatment of Cr (VI)-induced male fertility impairment.

Clinical and vascular lesion characteristics of the patients with takayasu arteritis manifested firstly as acute myocardial infarction at onset.

Objective: To explore clinical and vascular lesion characteristics of the patients with Takayasu arteritis (TA) manifested firstly as acute myocardial infarction (AMI) at onset and to improve the diagnostic rate of TA. Methods: The clinical and angiographic data of six patients with TA manifested firstly as AMI at onset were retrospectively analyzed. Results: Of six patients (16-25 years old), 83.33% (five cases) was female, three patients had a history of hypertension and three patients did not have any medical history. One patient had intermittent effort chest tightness. On admission patients all presented with chest pain, dyspnea, hypotension, cardiogenic shock, abnormal electrocardiogram, and elevated cardiac troponin I. The vessel involvement was left coronary main trunk 83.33%, left anterior descending artery 33.33% and left circumflex branch 16.67%, right coronary artery 66.67%, subclavian artery 83.33%, and renal artery 50%. Five patients received the emergency PCI. One patient died of heart failure. During follow-up 3 patients received again PCI treatment. Conclusion: Clinical and vascular lesion characteristics of those patients were no discomfort before admission, and the suddenly typical manifestation of AMI. Severe stenosis or occlusion occurred in main coronary artery ostia and peripheral large artery. For the TA patients with hemodynamic instability the effectiveness of emergency PCI is positive.

Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) patients with depression have a higher risk of complications and mortality than T2DM without depression. However, the exact neuropathophysiological mechanism remains unclear. Consequently, the current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in T2DM patients with and without depression. METHODS: The demographic data, clinical variables, neuropsychological tests, and functional and anatomical magnetic resonance imaging of depressed T2DM (n = 47) of non-depressed T2DM (n = 59) and healthy controls (n = 41) were collected and evaluated. The correlation analysis, stepwise multiple linear regression, and receiver operating characteristic curve were performed for further analysis. RESULTS: Abnormal neural activities in the bilateral posterior cingulate cortex (PCC) and hippocampus were observed in depressed and non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore, the cortical amplitude of low-frequency fluctuation (ALFF) in PCC, subcortical DC in the putamen of depressed T2DM, and hippocampus of non-depressed T2DM was correlated with cognitive scores. In contrast, the cortical fractional ALFF in PCC of non-depressed T2DM was correlated with depression scores. CONCLUSIONS: The abnormalities of spontaneous cortical activity in PCC and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2DM. Notably, the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2DM, which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2DM. This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2DM with and without depression.

Dietary folic acid addition reduces abdominal fat deposition mediated by alterations in gut microbiota and SCFA production in broilers.

Intensive selective breeding for high growth rate and body weight cause excess abdominal fat in broilers. Gut microbiota and folic acid were reported to regulate lipid metabolism. A total of 210 one-day-old broilers were divided into the control (folic acid at 1.3 mg/kg) and folic acid groups (folic acid at 13 mg/kg) to illustrate the effects of folic acid on growth performance, abdominal fat deposition, and gut microbiota, and the experiment lasted 28 d. Results revealed that dietary folic acid addition decreased abdominal fat percentage (P < 0.05) and down-regulated genes expression related to cell proliferation and differentiation in abdominal fat including IGF1, EGF, C/EBPα, PPARγ, PLIN1, FABP4 and PCNA (P < 0.05). Folic acid addition decreased caecal Firmicutes-to-Bacteroidetes ratio (P < 0.01) and increased the proportions of Alistipes, Oscillospira, Ruminococcus, Clostridium, Dehalobacterium and Parabacteroides (P < 0.05). Caecal acetic acid, and propionic acid contents were found to be higher under folic acid treatment (P < 0.05), which were negatively related to genes expression associated with adipocyte proliferation and differentiation (P < 0.05). Ruminococcus was positively correlated with caecal acetic acid content, and the same phenomenon was detected between propionic acid and Oscillospira and Ruminococcus (P < 0.05). Acetic acid and Oscillospira were identified to be negatively associated with abdominal fat percentage (P < 0.05). In conclusion, our data demonstrated that dietary supplementation of folic acid reduced fat deposition in broilers by inhibiting abdominal adipocyte proliferation and differentiation, which might be mediated by changes in gut microbiota and short chain fatty acid production.