Screening of prognostic factors and survival analysis based on histological type for perimenopausal endometrial carcinoma treated with hysterectomy.

PURPOSE: This study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy. METHODS: The PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients. RESULTS: A total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p < 0.05). Regardless of regional lymph nodes status and SEER-stage for OS and CSS, the low-grade endometrioid carcinoma had the best prognosis outcome, followed by the mix cell adenocarcinoma and high-grade endometrioid carcinoma, while the carcinosarcoma and undifferentiated carcinoma had relatively poor prognosis outcome. And the survival patterns of different histological types of PIPEC were diverse and changed along with the time. CONCLUSION: We identified the possible prognostic factors of PIPEC patients treated with hysterectomy. And survival analysis based on the regional lymph nodes status and SEER-stage revealed the different histological types of PIPEC had diverse survival patterns, which will be helpful for guiding clinical practice.

Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.

Tribbles pseudokinase 3 (TRIB3) expression significantly increases during terminal erythropoiesis in vivo. However, we found that TRIB3 expression remained relatively low during human embryonic stem cell (hESC) erythropoiesis, particularly in the late stage, where it is typically active. TRIB3 was expressed in megakaryocyte-erythrocyte progenitor cells and its low expression was necessary for megakaryocyte differentiation. Thus, we proposed that the high expression during late stage of erythropoiesis could be the clue for promotion of maturation of hESC-derived erythroid cells. To our knowledge, the role of TRIB3 in the late stage of erythropoiesis remains ambiguous. To address this, we generated inducible TRIB3 overexpression hESCs, named TRIB3tet-on OE H9, based on a Tet-On system. Then, we analyzed hemoglobin expression, condensed chromosomes, organelle clearance, and enucleation with or without doxycycline treatment. TRIB3tet-on OE H9 cells generated erythrocytes with a high proportion of orthochromatic erythroblast in flow cytometry, enhanced hemoglobin and related protein expression in Western blot, decreased nuclear area size, promoted enucleation rate, decreased lysosome and mitochondria number, more colocalization of LC3 with LAMP1 (lysosome marker) and TOM20 (mitochondria marker) and up-regulated mitophagy-related protein expression after treatment with 2 µg/mL doxycycline. Our results showed that TRIB3 overexpression during terminal erythropoiesis may promote the maturation of erythroid cells. Therefore, our study delineates the role of TRIB3 in terminal erythropoiesis, and reveals TRIB3 as a key regulator of UPS and downstream mitophagy by ensuring appropriate mitochondrial clearance during the compaction of chromatin.

Microplastics distribution, ecological risk and outflows of rivers in the Bohai Rim region of China - A flux model considering small and medium-sized rivers.

Microplastics (MPs) pollution and its ecological risks have attracted increasing global attention. The Bohai Rim region (BRR), as the economic and population center of the entire northern China, still lacks a precise assessment of MPs pollution. Although current attention on MPs pollution mainly focuses on large rivers, small and medium-sized rivers are more numerous and more closely connected to human activities. In this study, measurement data of MPs from 11 estuaries in the BRR was collected to understand MPs distribution and ecological risk. The results indicate that the overall MPs pollution in these estuaries is still at a low level, with an average abundance of 1254.3 particles m-3. While the pollution load index (1.85) is relatively low, the potential ecological risk of PVC in some area (S8, EPVC = 1433.78, III) warrants further attention. Then we integrated data from 22 relevant rivers (covering all size rivers) in this region from the literature to fit a MPs flux model and assessed the MPs outflow from the four provinces and cities in the region. A strong correlation is achieved between modeled estimates and field measurements (r2 = 0.74), which can well estimate the river MPs outflows in northern China such as the Nanfei River. The MPs outflow from the four provinces (cities) is calculated to be 123.235 (range 44.415-242.314) T year-1, of which Shandong accounted for >80 % (104.066 T year-1). The small and medium-sized rivers accounted for 47 % (58.08 T year-1), whose contribution to MPs outflows should not be underestimated. This study can help us to accurately assess MPs pollution in different coastal areas in northern China, benefiting the formulation of precise control measures and policies for marine MPs pollution.

In vitro simulated digestion and fermentation behaviors of polysaccharides from Pleurotus cornucopiae and their impact on the gut microbiota.

This study investigated the physicochemical characteristics and fermentative behavior between original polysaccharides (PCPs) and polysaccharides extracted after microwave cooking (MPCPs) from Pleurotus cornucopiae during simulated digestion and fecal fermentation. The results revealed notable physicochemical differences between of PCPs and MPCPs. MPCPs exhibited a higher total carbohydrate content, with an increased proportion of glucose. Additionally, MPCPs showed a lower molecular weight (MW) and, a blue shift in Fourier transform infrared spectroscopy (FT-IR). Digestion has a minimal effect on the physicochemical and structural characteristics of PCPs and MPCPs. Within the first 6 h of fermentation, the gut microbiota showed significantly higher utilization of MPCPs. However, PCPs were consumed faster and surpassed MPCPs later. After 24 h, both PCPs and MPCPs were degraded and utilized by the gut microbiota, showing an increased abundance of Firmicutes and Bacteroidota. PCPs excelled in promoting beneficial gut microbiota, such as Phascolarctobacterium, Megamonas, and Bacteroides. Conversely, MPCPs demonstrated a stronger ability to inhibit the growth of harmful opportunistic pathogenic gut microbiota, such as Fusobacterium and Parasutterella. In addition, the content of acetic, propionic, and butyric acids increased significantly in both PCPs and MPCPs. These findings highlight the potential of Pleurotus cornucopiae polysaccharides as prebiotics for intestinal homeostasis.

Higher Platelet Count Mostly in Normal Range is Associated with First Episode of Peritonitis Risk in Incident Peritoneal Dialysis Patients.

BACKGROUND: Platelets play parts in infection and immune processes. However, the association between platelet count and the risk of peritoneal dialysis-associated peritonitis is unclear. METHODS: This was a retrospective, observational, single-center cohort study. A Cox regression analysis was used to evaluate the independent association of platelet count with the occurrence of first PD-associated peritonitis. Models were adjusted for gender, age, BMI, cardiovascular disease, diabetes mellitus, white blood cell count, neutrophil-lymphocyte ratio, hemoglobin level, albumin level, potassium level, and anti-platelet medication usage. RESULTS: A total of 2374 patients were enrolled in this study (59% men; mean age 47.40 ± 12.12). The average platelet count was 229.30±82.12 x 109/L. 467 (20%) patients suffered from PD-associated peritonitis at least once. In the multivariable model, the adjusted hazard ratios (HRs) for quartiles 2, 3 and 4 versus quartile 1 were 1.428 (95% CI 1.060-1.924, P=0.019), 1.663 (95% CI 1.240-2.229, P<0.001) and 1.843 (95% CI 1.363-2.492, P<0.001) with baseline data. A nonlinear relationship between platelet count and first PD-associated peritonitis was observed. Further, the association between platelet and first PD-associated peritonitis was significant in the patients with hypokalemia (P for interaction=0.040). CONCLUSION: In PD patients, elevated platelet counts were significantly associated with an increased risk of the first onset of PD-associated peritonitis.

Stable and antibacterial tannic acid-based covalent polymeric hydrogel for highly selective Pb2+ recovery from lead-acid battery industrial wastewater.

The resource of trace lead (Pb2+) from wastewater bearing intricate components is imperative for sustainable progression of the lead-acid battery industry. Herein, we fabricated a tannic acid-based covalent polymeric hydrogel (TA@PMAM) with antimicrobial properties and stability via facile Michael addition reaction. The incorporation of tannic acid (TA) through robust covalent bond leads to a stable porous 3D covalent polymer network with almost no loss of mechanical properties even after 20 compression cycles. Batch adsorption experiments of TA@PMAM revealed an extraordinary adsorption capacity of Pb2+(Qe =196.6 mg/g), achieving 87.2 % of Pb2+ adsorption within the first 5 min owing to porous structure, numerous adsorption sites and good hydrophilicity. Moreover, TA@PMAM demonstrated a strong affinity for Pb2+ in the presence of the interfere metal ions (Cu2+, Co2+, Mn2+etc.) due to the carbonyl and phenolic hydroxyl that can specifically pair with Pb2+. Stable adsorption properties of TA@PMAM were confirmed in fixed bed column adsorption experiment using lead-acid batteries wastewater, retaining 79.56 % of initial adsorption capacity even after 10 times' reuse. Besides, TA@PMAM possesses a broad spectrum of antimicrobial properties. This study sheds novel light on the design and fabrication of adsorbent, which holds great potential for commercialization in recovering lead from battery industrial wastewater.

PROTAC-mediated vimentin degradation promotes terminal erythroid differentiation of pluripotent stem cells.

BACKGROUND: Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), can undergo erythroid differentiation, offering a potentially invaluable resource for generating large quantities of erythroid cells. However, the majority of erythrocytes derived from hPSCs fail to enucleate compared with those derived from cord blood progenitors, with an unknown molecular basis for this difference. The expression of vimentin (VIM) is retained in erythroid cells differentiated from hPSCs but is absent in mature erythrocytes. Further exploration is required to ascertain whether VIM plays a critical role in enucleation and to elucidate the underlying mechanisms. METHODS: In this study, we established a hESC line with reversible vimentin degradation (dTAG-VIM-H9) using the proteolysis-targeting chimera (PROTAC) platform. Various time-course studies, including erythropoiesis from CD34+ human umbilical cord blood and three-dimensional (3D) organoid culture from hESCs, morphological analysis, quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry, karyotyping, cytospin, Benzidine-Giemsa staining, immunofluorescence assay, and high-speed cell imaging analysis, were conducted to examine and compare the characteristics of hESCs and those with vimentin degradation, as well as their differentiated erythroid cells. RESULTS: Vimentin expression diminished during normal erythropoiesis in CD34+ cord blood cells, whereas it persisted in erythroid cells differentiated from hESC. Depletion of vimentin using the degradation tag (dTAG) system promotes erythroid enucleation in dTAG-VIM-H9 cells. Nuclear polarization of erythroblasts is elevated by elimination of vimentin. CONCLUSIONS: VIM disappear during the normal maturation of erythroid cells, whereas they are retained in erythroid cells differentiated from hPSCs. We found that retention of vimentin during erythropoiesis impairs erythroid enucleation from hPSCs. Using the PROTAC platform, we validated that vimentin degradation by dTAG accelerates the enucleation rate in dTAG-VIM-H9 cells by enhancing nuclear polarization.

Liver Function-Related Indicators and Risk of Gallstone Diseases-A Multicenter Study and a Systematic Review and Meta-Analysis.

Purpose of the study: We aim to examine the association between liver function-related indicators and gallstone disease (GSD) risk. Study design: The subjects who participated in the China Multicenter Physical Examination Cohort (CMPEC) were enrolled. Relative odds ratios (ORs) with 95% CIs and standardized mean differences (SMDs) were applied to investigate the effect of liver function-related indicators and GSD risk. Moreover, a systematic review and meta-analysis were conducted until July 2021. Additionally, the results in the CMPEC and the systematic review and meta-analysis were combined by meta-analysis. Finally, the results were validated by a cohort study of the UK Biobank (UKB). Results and conclusions: Totally, 369,931 subjects in CMPEC were included in the study. A total of 28 publications were incorporated into the systematic review and meta-analysis. The pooled analysis suggested that aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), and low albumin (ALB) were positively associated with the risk of GSD. Meanwhile, GSD present to have higher AST, ALT, gamma-glutamyl transferase (GGT), total bilirubin (TBil), globulin (G), and ALP levels and relatively lower TP and ALB levels than the healthy participants. These results were consistent when stratified by the study design, geographic background, and study quality. Only the association between ALP and GSD risk was validated in the UKB cohort. This study suggests liver function indicators were associated with GSD risk. The results may provide the basis for exploring the etiology of GSD and may help clinicians identify high-risk subjects. Trial Registration: PROSPERO (CRD42020179076).

Impaired macroautophagy confers substantial risk for intellectual disability in children with autism spectrum disorders.

Autism spectrum disorder (ASD) represents a complex of neurological and developmental disabilities characterized by clinical and genetic heterogeneity. While the causes of ASD are still unknown, many ASD risk factors are found to converge on intracellular quality control mechanisms that are essential for cellular homeostasis, including the autophagy-lysosomal degradation pathway. Studies have reported impaired autophagy in ASD human brain and ASD-like synapse pathology and behaviors in mouse models of brain autophagy deficiency, highlighting an essential role for defective autophagy in ASD pathogenesis. To determine whether altered autophagy in the brain may also occur in peripheral cells that might provide useful biomarkers, we assessed activities of autophagy in lympoblasts from ASD and control subjects. We find that lymphoblast autophagy is compromised in a subset of ASD participants due to impaired autophagy induction. Similar changes in autophagy are detected in postmortem human brains from ASD individuals and in brain and peripheral blood mononuclear cells from syndromic ASD mouse models. Remarkably, we find a strong correlation between impaired autophagy and intellectual disability in ASD participants. By depleting the key autophagy gene Atg7 from different brain cells, we provide further evidence that autophagy deficiency causes cognitive impairment in mice. Together, our findings suggest autophagy dysfunction as a convergent mechanism that can be detected in peripheral blood cells from a subset of autistic individuals, and that lymphoblast autophagy may serve as a biomarker to stratify ASD patients for the development of targeted interventions.