Effect of nitrogen reduction combined with biochar application on soda saline soil and soybean growth in black soil areas.

The combination of biochar and nitrogen (N) fertilization in agricultural salt-affected soils is an effective strategy for amending the soil and promoting production. To investigate the effect of nitrogen reduction combined with biochar application on a soda saline soil and soybean growth in black soil areas, a pot experiment was set up with two biochar application levels, 0 (B0) and 4.5 t/hm2 (B1); two biochar application depths, 0-20 cm (H1) and 0-40 cm (H2); and two nitrogen application levels, conventional nitrogen application (N0) and nitrogen reduction of 15% (N1). The results showed that the application of biochar improved the saline soil status and significantly increased soybean yield under lower nitrogen application. Moreover, increasing the depth of biochar application enhanced the effectiveness of biochar in reducing saline soil barriers to crop growth, which promoted soybean growth. Increasing the depth of biochar application increased the K+ and Ca2+ contents, soil nitrogen content, N fertilizer agronomic efficiency, leaf total nitrogen, N use efficiency, AN, Tr, gs, SPAD, leaf water potential, water content and soybean yield and its components. However, the Na+ content, SAR, ESP, Na+/K+, Ci and water use efficiency decreased with increasing biochar depth. Among the treatments with low nitrogen input and biochar, B1H1N1 resulted in the greatest soil improvement in the 0-20 cm soil layer compared with B0N0; for example, K+ content increased by 61.87%, Na+ content decreased by 44.80%, SAR decreased by 46.68%, and nitrate nitrogen increased by 26.61%. However, in the 20-40 cm soil layer, B1H2N1 had the greatest effect on improving the soil physicochemical properties, K+ content increased by 62.54%, Na+ content decreased by 29.76%, SAR decreased by 32.85%, and nitrate nitrogen content increased by 30.77%. In addition, compared with B0N0, total leaf nitrogen increased in B1H2N1 by 25.07%, N use efficiency increased by 6.7%, N fertilizer agronomic efficiency increased by 32.79%, partial factor productivity of nitrogen increased by 28.37%, gs increased by 22.10%, leaf water potential increased by 27.33% and water content increased by 6.44%. In conclusion, B1H2N1 had the greatest effect on improving the condition of saline soil; it not only effectively regulated the distribution of salt in soda saline soil and provided a low-salt environment for crop growth but also activated deep soil resources. Therefore, among all treatments investigated in this study, B1H2N1 was considered most suitable for improving the condition of soda saline soil in black soil areas and enhancing the growth of soybean plants.

Enhancing older care services: a comprehensive internet + community home indicator system.

OBJECTIVE: Constructing a demand-oriented Internet + community home care service indicator system, starting from the actual needs of the elderly, and quantifying the demand into specific service contents that can be provided, so as to realize the effective supply of services. It aims to provide a theoretical basis for the government to formulate relevant aging policies and provide a reference basis for promoting the innovation and development of the Internet + elderly care model. METHODS: Based on existence needs, relationship needs and growth needs abbreviated as "Existence, Relatedness, Growth (ERG)" demand theory, through the discussion in the group meeting, form the expert consultation questionnaire of the demand-oriented Internet + community home care service indicator system, select experts in related fields to conduct two rounds of Delphi expert consultation, summarize the experts' opinions to determine the indicator system items, and use the Analytic Hierarchy Process (AHP) method to construct the judgment matrix to derive the weighting coefficients of the indicators, and establish the ultimate demand-oriented Internet + community home care service indicator system. RESULTS: The effective recovery rates for the two rounds of expert consoulation questionnaires were 100%, with expert authority coefficients of 0.852 and 0.868, respectively. The Kendall coefficients for the second round of expert views varied from 0.226 to 0.431, with coefficients of variation for all indexes less than 0.25.The finalized demand-oriented Internet + community home care service indicator system includes 3 first-level indicators, 10 s-level indicators, and 46 third-level indicators. The consistency ratios of indicator judgment matrices at all levels are less than 0.10, suggesting that the hierarchical analysis findings are consistent, implying that the weight coefficient distribution is appropriate. CONCLUSION: The demand-oriented Internet + community home care service Indicator System, which was created through expert consultation and AHP method, has reasonable content and is more dependable as an evaluation tool for reliably assessing demand for elderly servic.

Design, synthesis, and biological evaluation of novel iNOS inhibitors as potent neuroprotective agents for ischemic stroke.

Ischemic stroke (IS) is characterized by intricate pathophysiological mechanisms, where single-target treatments have often proven insufficient. Thus, multi-target therapeutic approaches are essential for effective IS management. In this study, we employed a molecular hybridization strategy, merging the structures of the iNOS inhibitor 1400W and the multi-target neuroprotective agent NBP, to develop a series of novel iNOS inhibitors BN-1 ∼ BN-4 with neuroprotective properties. Among these, BN-4 exhibited the most potent cell protective activity in OGD/R-induced SH-SY5Y and BV-2 cells. BN-4 not only reduced ROS levels induced by OGD/R in SH-SY5Y cells but also mitigated necrosis and apoptosis. By binding to iNOS in a manner similar to 1400W, BN-4 significantly inhibited iNOS activity. Furthermore, BN-4 demonstrated high stability, excellent blood-brain barrier permeability, and more than 100-fold increase in aqueous solubility compared to NBP. Additionally, BN-4 notably decreased infarct size and showed neuroprotective effects in tMCAO rats. These findings indicate that BN-4 holds promise as a novel candidate for treatment IS, offering enhanced therapeutic efficacy due to its superior pharmacokinetic and pharmacodynamic properties.

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.

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).

Ultra-smooth processing of lithium niobate for outstanding mid-infrared transmittance.

The fabrication of anti-reflection (AR) subwavelength structures (SWSs) of lithium niobate (LN) is a challenging but rewarding task in mid-infrared LN laser systems. However, there are still some issues with the high-quality processing and fabrication of bifacial AR SWSs. Herein, a novel, to the best of our knowledge, approach to the fabrication of SWSs was proposed, which includes femtosecond laser ablation followed by wet etching and thermal annealing. The fabricated structures exhibit high surface quality (Ra = 0.08 nm) and uniformity. According to the experimental and simulated results, the transmittance of the mid-infrared AR SWSs with a period of 1.8 µm could be improved from 78% to 87% in the 3.6-5 µm band. Furthermore, the double-sided construction enabled a transmittance of up to 90%. The results have great potential in the promotion of the development of mid-infrared laser systems and LN-based photonics.

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.

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.

Can Loneliness be Predicted? Development of a Risk Prediction Model for Loneliness among Elderly Chinese: A Study Based on CLHLS.

Background: Loneliness is prevalent among the elderly, worsened by global aging trends. It impacts mental and physiological health. Traditional scales for measuring loneliness may be biased due to cognitive decline and varying definitions. Machine learning advancements offer potential improvements in risk prediction models. Methods: Data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), involving over 16,000 participants aged ≥65 years, were used. The study examined the relationships between loneliness and factors such as cognitive function, functional limitations, living conditions, environmental influences, age-related health issues, and health behaviors. Using R 4.4.1, seven predictive models were developed: logistic regression, ridge regression, support vector machines, K-nearest neighbors, decision trees, random forests, and multi-layer perceptron. Models were evaluated based on ROC curves, accuracy, precision, recall, F1 scores, and AUC. Results: Loneliness prevalence among elderly Chinese was 23.4%. Analysis identified 16 predictive factors and evaluated seven models. Logistic regression was the most effective model for predicting loneliness risk due to its economic and operational advantages. Conclusion: The study found a 23.4% prevalence of loneliness among elderly individuals in China. SHAP values indicated that higher MMSE scores correlate with lower loneliness levels. Logistic regression was the superior model for predicting loneliness risk in this population.

CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver.

Dysfunction of the ribosome manifests during cellular senescence and contributes to tissue aging, functional decline, and development of aging-related disorders in ways that have remained enigmatic. Here, we conducted a comprehensive CRISPR-based loss-of-function (LOF) screen of ribosome-associated genes (RAGs) in human mesenchymal progenitor cells (hMPCs). Through this approach, we identified ribosomal protein L22 (RPL22) as the foremost RAG whose deficiency mitigates the effects of cellular senescence. Consequently, absence of RPL22 delays hMPCs from becoming senescent, while an excess of RPL22 accelerates the senescence process. Mechanistically, we found in senescent hMPCs, RPL22 accumulates within the nucleolus. This accumulation triggers a cascade of events, including heterochromatin decompaction with concomitant degradation of key heterochromatin proteins, specifically heterochromatin protein 1γ (HP1γ) and heterochromatin protein KRAB-associated protein 1 (KAP1). Subsequently, RPL22-dependent breakdown of heterochromatin stimulates the transcription of ribosomal RNAs (rRNAs), triggering cellular senescence. In summary, our findings unveil a novel role for nucleolar RPL22 as a destabilizer of heterochromatin and a driver of cellular senescence, shedding new light on the intricate mechanisms underlying the aging process.

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.

Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation.

Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of The nuclear factor-kappaB (NF-κB) signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB-mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.

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.

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.

Impact of non-selective beta blockers on further decompensation and death in decompensated cirrhosis: Benefit and risk stratification by MELD score.

BACKGROUND: Non-selective beta blockers (NSBBs) can reduce the risk of decompensation, but their impact on further decompensation has been rarely investigated. AIMS: The aim is to evaluate the impact of NSBBs on further decompensation and death in decompensated cirrhosis stratified by the severity of liver disease. METHODS: Overall, 332 decompensated cirrhotic patients were retrospectively included, of whom 149 used NSBBs. Kaplan-Meier and Nelson-Aalen cumulative risk curves as well as Cox regression and competing risk analyses were used to estimate the associations of NSBBs with further decompensation and death, if appropriate. Hazard ratio (HR) and sub-distribution HR (sHR) were calculated. Subgroup analyses were performed based on the model for end-stage liver disease (MELD) score at admission. RESULTS: In the overall analysis, the use of NSBBs was not significantly associated with further decompensation in multivariate competing risk analysis (sHR = 1.09, p = 0.580). In the subgroup analysis of patients with a MELD score of ≤9, the use of NSBBs was significantly associated with decreased risk of further decompensation in multivariate competing risk analysis (sHR = 0.57, p = 0.021). In the subgroup analysis of patients with a MELD score of >9, the use of NSBBs was associated with increased risk of further decompensation in multivariate competing risk analysis (sHR = 1.45, p = 0.044). Regardless of overall and subgroup analyses, the use of NSBBs was not significantly associated with death in multivariate Cox regression analyses. CONCLUSION: NSBBs may be beneficial for the prevention of further decompensation in cirrhotic patients with a MELD score of ≤9, but deleterious in those with a MELD score of >9.

Effectiveness of acupuncture plus music therapy for post-stroke depression: Systematic review and meta-analysis.

BACKGROUND: Post-stroke depression (PSD) is a prevalent complication of stroke that adversely affects patient outcomes. The etiology of PSD is complex, and no universally effective treatment exists. Acupuncture, with its historical use, combined with music therapy, presents a novel approach for PSD treatment. This study aims to systematically evaluate the clinical efficacy of combining acupuncture with music therapy for PSD through a meta-analysis. METHODS: We systematically searched both Chinese and English literature in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and the Chinese Science and Technology Periodical Database (VIP Database) for randomized controlled trials evaluating acupuncture combined with music therapy for PSD. Two independent evaluators conducted quality assessments and data extraction. Statistical analyses were performed using RevMan 5.4 and Stata 18.0 software. RESULTS: This article contains 11 studies, involving a total of 698 patients. The results of the meta-analysis showed that, compared with the control group, the test group showed significant improvement on multiple outcome measures: HAMD score [mean difference (MD) = -3.18, 95% confidence interval (CI) (-3.61, -2.76), P < .00001], Self-Rating Depression Scale score [MD = -5.12, 95% CI (-6.61, -3.63), P < .00001], Pittsburgh sleep quality index score [MD = -2.40, 95% CI (-2.96, -1.84), P < .00001], BI score [MD = 14.16, 95% CI (4.37, 23.94), P = .005] were all significantly lower, significantly higher effectiveness [risk ratio = 1.21, 95% CI (1.11, 1.33), P < .0001]. These differences were also statistically significant. CONCLUSION: The use of acupuncture combined with music therapy is effective in reducing depression in PSD patients.

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.

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.

Fabrication and high-power testing of an X-band high-power phase shifter for the very compact inverse Compton scattering gamma-ray source.

This paper proposed an X-band phase shifter for the very compact inverse Compton scattering gamma-ray source program at Tsinghua University and conducted its structure design, numerical simulation, fabrication, cold test, and high-power testing. This phase shifter is composed of a polarizer, circular waveguide, and a piston with a choke structure. The simulation results show that the reflection coefficient of the phase shifter is under -40 dB and the insertion coefficient exceeds -0.06 dB at the operating frequency of 11.424 GHz. The phase variation is 20°/mm, and a linear phase change from 0° to 360° can be achieved with a piston displacement of 18 mm. The manufactured phase shifter has exhibited good performance in the cold test by using the vector network analyzer. After 16 h conditioning in the Tsinghua X-band high-power test stand, the phase shifter reached a peak power of 72 MW at 230 ns pulse width and a peak power of 82 MW at 130 ns pulse width. After processing signals from the high-speed oscilloscope, it was found that the transmission phase variations were in good agreement with the simulation results.