Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

BACKGROUND AND AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation oriented composite endpoint (BOCE). RESULTS: Among 1,170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality (5.4% vs. 1.3%; adjusted hazard ratio [HR] 3.20, 95% confidence interval [CI]: 1.16-8.80). The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.

DeDoc2 Identifies and Characterizes the Hierarchy and Dynamics of Chromatin TAD-Like Domains in the Single Cells.

Topologically associating domains (TADs) are functional chromatin units with hierarchical structure. However, the existence, prevalence, and dynamics of such hierarchy in single cells remain unexplored. Here, a new generation TAD-like domain (TLD) detection algorithm, named deDoc2, to decode the hierarchy of TLDs in single cells, is reported. With dynamic programming, deDoc2 seeks genome partitions with global minimal structure entropy for both whole and local contact matrix. Notably, deDoc2 outperforms state-of-the-art tools and is one of only two tools able to identify the hierarchy of TLDs in single cells. By applying deDoc2, it is showed that the hierarchy of TLDs in single cells is highly dynamic during cell cycle, as well as among human brain cortex cells, and that it is associated with cellular identity and functions. Thus, the results demonstrate the abundance of information potentially encoded by TLD hierarchy for functional regulation. The deDoc2 can be freely accessed at https://github.com/zengguangjie/deDoc2.

Comprehensive Analysis of Purine-Metabolism-Related Gene Signature for Predicting Ovarian Cancer Prognosis, Immune Landscape, and Potential Treatment Options.

Purine metabolism is an important branch of metabolic reprogramming and has received increasing attention in cancer research. Ovarian cancer is an extremely dangerous gynecologic malignancy for which there are no adequate tools to predict prognostic risk. Here, we identified a prognostic signature consisting of nine genes related to purine metabolism, including ACSM1, CACNA1C, EPHA4, TPM3, PDIA4, JUNB, EXOSC4, TRPM2, and CXCL9. The risk groups defined by the signature are able to distinguish the prognostic risk and the immune landscape of patients. In particular, the risk scores offer promising personalized drug options. By combining risk scores with clinical characteristics, we have created a more detailed composite nomogram that allows for a more complete and individualized prediction of prognosis. In addition, we demonstrated metabolic differences between platinum-resistant and platinum-sensitive ovarian cancer cells. In summary, we have performed the first comprehensive analysis of genes related to purine metabolism in ovarian cancer patients and created a feasible prognostic signature that will aid in risk prediction and support personalized medicine.

Efficacy and Safety Evaluation of Bilateral Pedicle Approach Combined with Positional Reduction for the Treatment of Osteoporotic Thoracolumbar Burst Fractures.

Background: Osteoporotic thoracolumbar burst fractures (OTLBF) pose challenges for vertebroplasty due to the risk of cement leakage and spinal injury resulting from the fracture of the posterior vertebra and spinal canal occupancy. It limits the application of vertebroplasty in these patients. Objective: This study investigates the efficacy and safety of a bilateral pedicle approach combined with postural reduction for treating OTLBF using vertebroplasty. Material and Methods: Thirteen patients (aged ≥ 65 years) with thoracolumbar fractures without neurological deficits underwent vertebroplasty. The fractures affected the anterior and middle columns of the vertebrae, with mild compression of the canal. Clinical symptoms, procedure effects, patient mobility, and pain were assessed before the procedure and between 1 day and 3 months post-procedure. Kyphosis correction, wedge angle, and height restoration were also measured. Results: Immediate improvements in pain and mobility were observed in all patients following vertebroplasty, with sustained improvements over 6 months. Significant improvements were observed between 1 day and 6 months post-procedure, with at least a 4-level reduction in pain after 6 months. No comorbidities were observed. Kyphosis correction, wedge angle, and height restoration were improved. In one patient, postoperative computed tomography revealed polymethylmethacrylate leakage into the disc space and paravertebral space through the endplate fracture site, while no intraspinal leakage was found in other patients. Conclusions: Although vertebroplasty is generally considered contraindicated in OTLBF patients with posterior body involvement, this study demonstrates successful and safe treatment without causing neurological deficits. Percutaneous vertebroplasty combined with body reduction may serve as an alternative method for treating OTLBF, effectively preventing major surgical complications. Furthermore, it offers superior kyphosis correction, vertebral body reduction, pain reduction, early mobilization, and pain relief for patients.

Diabetes mellitus with mild or moderate kidney dysfunction is associated with poor prognosis in patients with coronary artery disease: A large-scale cohort study.

AIM: Both kidney dysfunction and diabetes mellitus (DM) predict long-term poor prognosis in patients with coronary artery disease (CAD). We aimed to evaluate the clinical outcomes according to the combined status of DM and different stages of kidney dysfunction in CAD patients. METHODS: From January 2013 to December 2013, 9293 eligible patients hospitalized for percutaneous coronary intervention (PCI) at Fuwai hospital were followed up for major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause mortality, myocardial infarction and stroke. Baseline kidney function was considered as stage I: normal or high kidney function; stage II: mild dysfunction and stage III: moderate dysfunction according to estimated glomerular filtration rate (eGFR). Upon baseline kidney function, diabetic and non-diabetic patients were divided into six groups. RESULTS: During a median follow-up of 2.4 years, 326 (3.5%) MACCEs occurred. Compared to patients in the stage I/non-DM group, patients in the stage II/DM and stage III/DM groups had significantly increased MACCE risk [adjusted hazard ratio (aHR), 1.53; 95% confidence interval (CI), 1.09-2.15; P = 0.014; aHR, 3.00; 95%CI, 1.74-5.18; P < 0.002, respectively]. Additionally, there were J-shaped associations of eGFR with MACCE risk regardless of glycemic metabolism status after adjusted for confounders. Furthermore, moderate kidney dysfunction conferred an increased MACCE risk in diabetic patients with uncontrolled glycemia (aHR, 2.93; 95%CI, 1.48-5.78; P = 0.002). CONCLUSIONS: DM with mild or moderate kidney dysfunction is associated with poor prognosis in CAD patients. Categorical classification of patients with DM and kidney dysfunction could provide prognostic information for risk stratification of CAD patients.

Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8+ T cells in the tumor microenvironment.

Metabolic alterations in the microenvironment significantly modulate tumor immunosensitivity, but the underlying mechanisms remain obscure. Here, we report that tumors depleted of fumarate hydratase (FH) exhibit inhibition of functional CD8+ T cell activation, expansion, and efficacy, with enhanced malignant proliferative capacity. Mechanistically, FH depletion in tumor cells accumulates fumarate in the tumor interstitial fluid, and increased fumarate can directly succinate ZAP70 at C96 and C102 and abrogate its activity in infiltrating CD8+ T cells, resulting in suppressed CD8+ T cell activation and anti-tumor immune responses in vitro and in vivo. Additionally, fumarate depletion by increasing FH expression strongly enhances the anti-tumor efficacy of anti-CD19 CAR T cells. Thus, these findings demonstrate a role for fumarate in controlling TCR signaling and suggest that fumarate accumulation in the tumor microenvironment (TME) is a metabolic barrier to CD8+ T cell anti-tumor function. And potentially, fumarate depletion could be an important strategy for tumor immunotherapy.

Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer.

Background: Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death in men. Androgen deprivation therapy (ADT) has become the first-line therapy for inhibiting PCa progression; however, nearly all patients receiving ADT eventually progress to castrate-resistant prostate cancer. Therefore, this study aimed to identify hub genes related to bicalutamide resistance in PCa and provide new insights into endocrine therapy resistance. Methods: The data were obtained from public databases. Weighted correlation network analysis was used to identify the gene modules related to bicalutamide resistance, and the relationship between the samples and disease-free survival was analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, and hub genes were identified. The LASSO algorithm was used to develop a bicalutamide resistance prognostic model in patients with PCa, which was then verified. Finally, we analyzed the tumor mutational heterogeneity and immune microenvironment in both groups. Results: Two drug resistance gene modules were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that both modules are involved in RNA splicing. The protein-protein interaction network identified 10 hub genes in the brown module LUC7L3, SNRNP70, PRPF3, LUC7L, CLASRP, CLK1, CLK2, U2AF1L4, NXF1, and THOC1) and 13 in the yellow module (PNN, PPWD1, SRRM2, DHX35, DMTF1, SALL4, MTA1, HDAC7, PHC1, ACIN1, HNRNPH1, DDX17, and HDAC6). The prognostic model composed of RNF207, REC8, DFNB59, HOXA2, EPOR, PILRB, LSMEM1, TCIRG1, ABTB1, ZNF276, ZNF540, and DPY19L2 could effectively predict patient prognosis. Genomic analysis revealed that the high- and low-risk groups had different mutation maps. Immune infiltration analysis showed a statistically significant difference in immune infiltration between the high- and low-risk groups, and that the high-risk group may benefit from immunotherapy. Conclusion: In this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.

Evaluation of large-scale highly polymorphic microhaplotypes in complex DNA mixtures analysis using RMNE method.

DNA mixture interpretation is one of the most challenging problems in forensics. Complex DNA mixtures are more difficult to analyze when there are more than two contributors or related contributors. Microhaplotypes (MHs) are polymorphic genetic markers recently discovered and employed in DNA mixture analysis. However, the evidentiary interpretation of the MH genotyping data needs more debate. The Random Man Not Excluded (RMNE) method analyzes DNA mixtures without using allelic peak height data or the number of contributors (NoC) assumptions. This study aimed to assess how well RMNE interpreted mixed MH genotyping data. We classified the MH loci from the 1000 Genomes Project database into groups based on their Ae values. Then we performed simulations of DNA mixtures with 2-10 unrelated contributors and DNA mixtures with a pair of sibling contributors. For each simulated DNA mixture, incorrectly included ratios were estimated for three types of non-contributors: random men, parents of contributors, and siblings of contributors. Meanwhile, RMNE probability was calculated for contributors and three types of non-contributors, allowing loci mismatch. The results showed that the MH number, the MH Ae values, and the NoC affected the RMNE probability of the mixture and the incorrectly included ratio of non-contributors. When there were more MHs, MHs with higher Ae values, and a mixture with less NoC, the RMNE probability, and the incorrectly included ratio decreased. The existence of kinship in mixtures complicated the mixture interpretation. Contributors' relatives as non-contributors and related contributors in the mixture increased the demands on the genetic markers to identify the contributors correctly. When 500 highly polymorphic MHs with Ae values higher than 5 were used, the four individual types could be distinguished according to the RMNE probabilities. This study reveals the promising potential of MH as a genetic marker for mixed DNA interpretation and the broadening of RMNE as a parameter indicating the relationship of a specific individual with a DNA mixture in the DNA database search.

Value of diffusion-weighted imaging in diagnosis and therapy response assessment of hepatic fungal infection in patients with acute leukemia.

OBJECTIVE: To investigate the role of diffusion-weighted imaging (DWI) for diagnosis and posttreatment assessment of hepatic fungal infection in patients with acute leukemia. METHODS: Patients with acute leukemia and highly suspected hepatic fungal infection were collected in the study. All the patients underwent MRI examination, including initial and follow-up DWI. The apparent diffusion coefficient (ADC) values of the lesions and the normal liver parenchyma were compared using Student's t-test. The ADC values of the hepatic fungal lesions of pretreatment and posttreatment were compared using paired t-test. RESULTS: A total of 13 patients with hepatic fungal infections have enrolled this study. Hepatic lesions were rounded or oval shaped, measured from 0.3 to 3 cm in diameter. The lesions showed significantly hyperintense signal on DWI and markedly hypointense signal on the ADC map, reflecting a marked restricted diffusion. The mean ADC values of the lesions were significantly lower than those of normal liver parenchyma (1.08 ± 0.34 × 10-3 vs. 1.98 ± 0.12 × 10-3 mm2 /s, p < 0.001). After treatment, the mean ADC values of the lesions were significantly increased when comparing with those of pretreatment (1.39 ± 0.29 × 10-3 vs. 1.06 ± 0.10 × 10-3 mm2 /s, p = .016). CONCLUSION: DWI can provide diffusion information of hepatic fungal infection in patients with acute leukemia, which could be taken as a valuable tool for diagnosis and therapy response assessment of these patients.

Plasmon-Assisted Trapping of Single Molecules in Nanogap.

The manipulation of single molecules has attracted extensive attention because of their promising applications in chemical, biological, medical, and materials sciences. Optical trapping of single molecules at room temperature, a critical approach to manipulating the single molecule, still faces great challenges due to the Brownian motions of molecules, weak optical gradient forces of laser, and limited characterization approaches. Here, we put forward localized surface plasmon (LSP)-assisted trapping of single molecules by utilizing scanning tunneling microscope break junction (STM-BJ) techniques, which could provide adjustable plasmonic nanogap and characterize the formation of molecular junction due to plasmonic trapping. We find that the plasmon-assisted trapping of single molecules in the nanogap, revealed by the conductance measurement, strongly depends on the molecular length and the experimental environments, i.e., plasmon could obviously promote the trapping of longer alkane-based molecules but is almost incapable of acting on shorter molecules in solutions. In contrast, the plasmon-assisted trapping of molecules can be ignored when the molecules are self-assembled (SAM) on a substrate independent of the molecular length.

WRINKLED1 Positively Regulates Oil Biosynthesis in Carya cathayensis.

Hickory (Carya cathayensis Sarg.) is a kind of important woody oil tree species, and its nut has high nutritional value. Previous gene coexpression analysis showed that WRINKLED1 (WRI1) may be a core regulator during embryo oil accumulation in hickory. However, its specific regulatory mechanism on hickory oil biosynthesis has not been investigated. Herein, two hickory orthologs of WRI1 (CcWRI1A and CcWRI1B) containing two AP2 domains with AW-box binding sites and three intrinsically disordered regions (IDRs) but lacking the PEST motif in the C-terminus were characterized. They are nucleus-located and have self-activated ability. The expression of these two genes was tissue-specific and relatively high in the developing embryo. Notably, CcWRI1A and CcWRI1B can restore the low oil content, shrinkage phenotype, composition of fatty acid, and expression of oil biosynthesis pathway genes of Arabidopsis wri1-1 mutant seeds. Additionally, CcWRI1A/B were shown to modulate the expression of some fatty acid biosynthesis genes in the transient expression system of nonseed tissues. Transcriptional activation analysis further indicated that CcWRI1s directly activated the expression of SUCROSE SYNTHASE2 (SUS2), PYRUVATE KINASE ß SUBUNIT 1 (PKP-ß1), and BIOTIN CARBOXYL CARRIER PROTEIN2 (BCCP2) involved in oil biosynthesis. These results suggest that CcWRI1s can promote oil synthesis by upregulating some late glycolysis- and fatty acid biosynthesis-related genes. This work reveals the positive function of CcWRI1s in oil accumulation and provides a potential target for improving plant oil by bioengineering technology.

Different responses of Chlorella vulgaris to silver nanoparticles and silver ions under modulation of nitric oxide.

Silver nanoparticles (Ag-NPs) are widely used in daily life because of their antibacterial properties. A fraction of Ag-NPs are released into the ecosystem during their production and utilization. The toxicity of Ag-NPs has been reported. However, it is still disputed whether the toxicity is mainly due to the released silver ions (Ag+). In addition, few studies have reported the response of algae to metal nanoparticles under modulation of nitric oxide (NO). In this study, Chlorella vulgaris (C. vulgaris) was used as a model organism to study the toxic effects of Ag-NPs and Ag+ released from Ag-NPs on algae under the modulation of NO. The results showed that the biomass inhibition rate of Ag-NPs (44.84%) to C. vulgaris was higher than that of Ag+ (7.84%). Compared with Ag+, Ag-NPs induced more severe damage to photosynthetic pigments, photosynthetic system II (PSII) performance, and lipid peroxidation. More serious damage to cell permeability led to higher internalization of Ag under Ag-NPs stress. Application of exogenous NO reduced the inhibition ratio of photosynthetic pigments and chlorophyll autofluorescence. Further, NO reduced the MDA levels by scavenging reactive oxygen species induced by Ag-NPs. NO modulated the secretion of extracellular polymers and hampered the internalization of Ag. All these results showed that NO alleviates the toxicity of Ag-NPs to C. vulgaris. However, NO did not improve the toxic effects of Ag+. Our results provide new insights into the toxicity mechanism of Ag-NPs to algae modulated by the signal molecule NO.

High absolute neutrophil count with type 2 diabetes is associated with adverse outcome in patients with coronary artery disease: A large-scale cohort study.

Background: Inflammatory processes crucially modulate the development, progression, and outcomes of coronary artery disease (CAD). Since hyperglycemia could alter inflammatory responses, this study aimed to investigate the effect of ANC, a novel and rapidly available inflammatory biomarker, on the prognosis of patients undergoing PCI with or without type 2 diabetes (T2D). Methods: A total of 7,826 patients with CAD hospitalized for PCI at Fuwai Hospital were consecutively recruited. According to the median ANC value, patients were stratified as having high ANC (ANC-H) or low ANC (ANC-L) and were further classified into four groups by T2D. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause mortality, myocardial infarction, stroke, and target vessel revascularization. Results: During a median follow-up of 2.4 years, 509 (6.5%) MACCEs were documented. Diabetic patients with increased ANC were at significantly higher risk of MACCEs (aHR, 1.55; 95% CI, 1.21-1.99; P = 0.001) compared to those in the ANC-L/non-T2D group (P for interaction between T2D and ANC categories = 0.044). Meanwhile, multivariable regression analysis demonstrated the highest MACCE risk in diabetic patients with a higher level of ANC than others (P for trend <0.001). Conclusion: This study suggests that stratification of patients with elevated ANC and T2D could provide prognostic information for CAD patients undergoing PCI.

4-Methylumbelliferone-Functionalized Polyphosphazene and Its Assembly into Biocompatible Fluorinated Nanocoatings with Selective Antiproliferative Activity.

Advanced multifunctional biomaterials are increasingly relying on clinically dictated patterns of selectivity against various biological targets. Integration of these frequently conflicting features into a single material surface may be best achieved by combining various complementary methodologies. Herein, a drug with a broad spectrum of activity, i.e., 4-methylumbelliferone (4-MU), is synthetically multimerized into water-soluble anionic macromolecules with the polyphosphazene backbone. The polymer structure, composition, and solution behavior are studied by 1H and 31P NMR spectroscopy, size-exclusion chromatography, dynamic light scattering, and UV and fluorescence spectrophotometry. To take advantage of the clinically proven hemocompatibility of fluorophosphazene surfaces, the drug-bearing macromolecule was then nanoassembled onto the surface of selected substrates in an aqueous solution with fluorinated polyphosphazene of the opposite charge using the layer-by-layer (LbL) technique. Nanostructured 4-MU-functionalized fluoro-coatings exhibited a strong antiproliferative effect on vascular smooth muscle cells (VSMCs) and fibroblasts with no cytotoxicity against endothelial cells. This selectivity pattern potentially provides the opportunity for highly desirable fast tissue healing while preventing the overgrowth of VSMCs and fibrosis. Taken together with the established in vitro hemocompatibility and anticoagulant activity, 4-MU-functionalized fluoro-coatings demonstrate potential for applications as restenosis-resistant coronary stents and artificial joints.

[Effectiveness of temporal island flap pedicled with perforating branch of zygomatic orbital artery to repair the defects after periocular malignant tumor resection].

Objective: To summarize the effectiveness of the temporal island flap pedicled with the perforating branch of zygomatic orbital artery for repairing defects after periocular malignant tumor resection. Methods: Between January 2015 and December 2020, 15 patients with periocular malignant tumors were treated. There were 5 males and 10 females with an average age of 62 years (range, 40-75 years). There were 12 cases of basal cell carcinoma and 3 cases of squamous carcinoma. The disease duration ranged from 5 months to 10 years (median, 2 years). The size of tumors ranged from 1.0 cm×0.8 cm to 2.5 cm×1.5 cm, without tarsal plate invasion. After extensive resection of the tumors, the left defects in size of 2.0 cm×1.5 cm to 3.5 cm×2.0 cm were repaired with the temporal island flap pedicled with the perforating branch of zygomatic orbital artery via subcutaneous tunnel. The size of the flaps ranged from 3.0 cm×1.5 cm to 5.0 cm×2.0 cm. The donor sites were separated subcutaneously and sutured directly. Results: All flaps survived after operation and the wounds healed by first intention. The incisions at donor sites healed by first intention. All patients were followed up 6-24 months (median, 11 months). The flaps were not obviously bloated, the texture and color were basically the same as the surrounding normal skin, and the scars at recipient sites were not obviously. There was no complication such as ptosis, ectropion, or incomplete closure of the eyelids and recurrence of tumor during follow-up. Conclusion: The temporal island flap pedicled with the perforating branch of zygomatic orbital artery can repair the defects after periorbital malignant tumors resection and has the advantages of reliable blood supply, flexible design, and good morphology and function.

Changing iodine status and the incidence of thyroid disease in mainland China: A prospective 20-year follow-up study.

BACKGROUND: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow up. METHODS: The original prospective cohort study, started in 1999 (n=3,761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared to Zhangwu, which iodine status changed from more than adequate to adequate iodine (from 214µg/L to 167.2µg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UIC), serum thyroid hormone concentration, and thyroid antibodies were measured. RESULTS: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88µg/L to 141.9µg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody (TPOAb), positive thyroglobulin antibody (TgAb), and goiter decreased significantly (p<0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared to the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p<0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634µg/L to 266.7µg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter (p<0.05 for all), were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p<0.001) was seen. CONCLUSIONS: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders.

RNF20 is required for male fertility through regulation of H2B ubiquitination in the Sertoli cells.

BACKGROUND: Spermatogenesis depends on the supporting of the Sertoli cells and their communications with germ cells. However, the regulation of crosstalk between the Sertoli cells and germ cells remains unclear. RESULTS: In this report, we used conditional knockout technology to generate the Sertoli cells-specific knockout of Rnf20 in mice. The Amh-Rnf20-/- male mice were infertile owing to spermatogenic failure that mimic the Sertoli cell-only syndrome (SCOS) in humans. Knockout of Rnf20 resulted in the H2BK120ub loss in the Sertoli cells and impaired the transcription elongation of the Cldn11, a gene encoding a component of tight junction. Notably, RNF20 deficiency disrupted the cell adhesion, caused disorganization of the seminiferous tubules, and led to the apoptotic cell death of both spermatogonia and spermatocytes in the seminiferous tubules. CONCLUSIONS: This study describes a Rnf20 knockout mouse model that recapitulates the Sertoli cell-only syndrome in humans and demonstrates that RNF20 is required for male fertility through regulation of H2B ubiquitination in the Sertoli cells.

Integrated emergy and economic evaluation of the dominant organic rice production systems in Jiangsu province, China.

Changing from conventional to organic farming might have fewer negative environmental impacts because of the avoidance of synthetic fertilizer and chemical pesticides. In this study, the economic viability and environmental and sustainability performance of the four dominant organic (rice-green manure rotation (RG), rice-duck co-culture (RD), rice-crayfish co-culture (RCF) and rice monoculture (RM)) and one conventional (rice monoculture (CRM)) rice production modes were evaluated in Jiangsu Province, China. Compared with the CRM mode, organic rice production increased economic benefits density and improved the economic benefit of crop land and irrigation water use. With the lowest total emergy input and the highest rice yield, the CRM mode showed the highest ecological efficiency in converting resources to total available energy content and nutrition density unit among the five rice production modes. However, the RCM mode showed higher environmental pressure and lower sustainability than the four organic modes due to the larger proportion of nonrenewable emergy input. The RM mode was the most uneconomic organic rice production mode with the highest cost input and the lowest product output but had relatively higher sustainability due to the higher proportion of renewable resources to total emergy inputs. Compared with the RM mode, the value-to-cost ratio, economic benefit density and benefit-cost ratio were increased in the RG, RD and RCF modes. Although the RD and RCF modes had higher efficiency in converting resources to total nutrition density units and monetary value, they imposed higher environmental pressure with a lower renewable fraction and emergy sustainability index than those in the RM mode. The RG mode had higher emergy utilization efficiency and the highest renewable fraction and emergy sustainability index among the four organic rice production modes. Considering the ecological and economic effects, the RG mode was conducive to improving the economic viability and sustainability of organic rice production.

Guided vs. conventional anti-platelet therapy for patients with acute coronary syndrome: A meta-analysis of randomized controlled trials.

Background: Whether guided antiplatelet therapy in patients with acute coronary syndrome (ACS) is effective in improving net clinical benefits compared with conventional antiplatelet therapy remains controversial. Therefore, we assessed the safety and efficacy of guided antiplatelet therapy in patients with ACS and undergoing percutaneous coronary intervention. Method: We searched PubMed, EMBASE, and Cochrane Library databases to select the relevant randomized controlled trials comparing the guided and conventional antiplatelet therapy in patients with ACS. The primary and safety outcomes are major adverse cardiovascular events (MACE) and major bleeding, respectively. The efficacy outcomes included myocardial infarction, stent thrombosis, all-cause death, and cardiovascular death. We selected the relative risk (RR) and 95% confidence intervals (CIs) as effect size and calculated it using the Review Manager software. In addition, we evaluated the final results by trial sequential analysis (registered by PROSPERO, CRD 42020210912). Results: We selected seven randomized controlled trials and included 8,451 patients in this meta-analysis. Guided antiplatelet therapy can significantly reduce the risk of MACE (RR 0.64, 95% CI 0.54-0.76, P < 0.00001), myocardial infarction (RR 0.62, 95% CI 0.49-0.79, P = 0.0001), all-cause death (RR 0.61, 95% CI 0.44-0.85, P = 0.003), and cardiovascular death (RR 0.66, 0.49-0.90, P = 0.009). In addition, there is no significant difference between the two groups in stent thrombosis (RR 0.67, 95% CI 0.44-1.03, P = 0.07) and major bleeding (RR 0.86, 95% CI 0.65-1.13, P = 0.27). The subgroup analysis showed that the guided group based on genotype tests could bring benefits in MACE and myocardial infarction. Conclusions: The guided antiplatelet therapy is not only associated with a comparable risk of bleeding but also with a lower risk of MACE, myocardial infarction, all-cause death, cardiovascular death, and stent thrombosis than the conventional strategy in patients with ACS.