Accelerating the design of pili-enabled living materials using an integrative technological workflow.

Bacteria can be programmed to create engineered living materials (ELMs) with self-healing and evolvable functionalities. However, further development of ELMs is greatly hampered by the lack of engineerable nonpathogenic chassis and corresponding programmable endogenous biopolymers. Here, we describe a technological workflow for facilitating ELMs design by rationally integrating bioinformatics, structural biology and synthetic biology technologies. We first develop bioinformatics software, termed Bacteria Biopolymer Sniffer (BBSniffer), that allows fast mining of biopolymers and biopolymer-producing bacteria of interest. As a proof-of-principle study, using existing pathogenic pilus as input, we identify the covalently linked pili (CLP) biosynthetic gene cluster in the industrial workhorse Corynebacterium glutamicum. Genetic manipulation and structural characterization reveal the molecular mechanism of the CLP assembly, ultimately enabling a type of programmable pili for ELM design. Finally, engineering of the CLP-enabled living materials transforms cellulosic biomass into lycopene by coupling the extracellular and intracellular bioconversion ability.

The unique salt bridge network in GlacPETase: a key to its stability.

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.

ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6: a first-in-human study.

PURPOSE: The cluster of differentiation (CD70) is a potential biomarker of clear cell renal cell carcinoma (ccRCC). This study aims to develop CD70-targeted immuno-positron emission tomography/computed tomography (immunoPET/CT) imaging tracers and explore the diagnostic value in preclinical studies and the potential value in detecting metastases in ccRCC patients. METHODS: Four novel CD70-specific single-domain antibodies (sdAbs) were produced and labelled with 18F by the aluminium fluoride restrained complexing agent (AlF-RESCA) method to develop radiotracers. The visualisation properties of the tracers were evaluated in a subcutaneous ccRCC patient-derived xenograft (PDX) model. In a registered prospective clinical trial (NCT06148220), six patients with pathologically confirmed RCC were included and underwent immunoPET/CT examination exploiting one of the developed tracers (i.e., [18F]RCCB6). RESULTS: We engineered four sdAbs (His-tagged RCCB3 and RCCB6, His-tag-free RB3 and RB6) specifically targeting recombinant human CD70 without cross-reactivity to murine CD70. ImmunoPET/CT imaging with [18F]RCCB3 and [18F]RCCB6 demonstrated a high tumour-to-background ratio in a subcutaneous ccRCC PDX model, with the latter showing better diagnostic potential supported by higher tumour uptake and lower bone accumulation. In comparison, [18F]RB6, developed by sequence optimisation, has significantly lower kidney accumulation than that of [18F]RCCB6. In a pilot translational study, [18F]RCCB6 immunoPET/CT displayed ccRCC metastases in multiple patients and demonstrated improved imaging contrast and diagnostic value than 18F-FDG PET/CT in a patient with ccRCC. CONCLUSION: The work successfully developed a series of CD70-targeted immunoPET/CT imaging tracers. Of them, [18F]RCCB6 clearly and specifically identified inoculated ccRCCs in preclinical studies. Clinical translation of [18F]RCCB6 suggests potential for identifying recurrence and/or metastasis in ccRCC patients.

Deterministic Magnetization Switching via Tunable Noncollinear Spin Configurations in Canted Magnets.

Spin obit torque (SOT) driven magnetization switching has been used widely for encoding consumption-efficient memory and logic. However, symmetry breaking under a magnetic field is required to realize the deterministic switching in synthetic antiferromagnets with perpendicular magnetic anisotropy (PMA), which limits their potential applications. Herein, we report all electric-controlled magnetization switching in the antiferromagnetic Co/Ir/Co trilayers with vertical magnetic imbalance. Besides, the switching polarity could be reversed by optimizing the Ir thickness. By using the polarized neutron reflection (PNR) measurements, the canted noncollinear spin configuration was observed in Co/Ir/Co trilayers, which results from the competition of magnetic inhomogeneity. In addition, the asymmetric domain walls demonstrated by micromagnetic simulations result from introducing imbalance magnetism, leading to the deterministic magnetization switching in Co/Ir/Co trilayers. Our findings highlight a promising route to electric-controlled magnetism via tunable spin configuration, improve our understanding of physical mechanisms, and significantly promote industrial applications in spintronic devices.

Incidence and Influencing Factors of Anxiety and Depression in Individuals with Acute Ischemic Stroke: A Retrospective Study.

BACKGROUND: Acute ischemic stroke (AIS) is the most common type of stroke in clinical practice, and individuals with stroke are more prone to psychological disorders than healthy individuals. This study aims to explore the incidence of anxiety and depression and related influencing factors in individuals with AIS. METHODS: In brief, 680 individuals with AIS admitted to Chun'an County First People's Hospital from January 2021 to January 2023 were selected as the research subjects, and their clinical data were retrospectively analyzed. All patients were evaluated with the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) to observe the occurrence of anxiety and depression, and single-factor and multi-factor logistic regression were used to analyze the influencing factors of anxiety and depression. RESULTS: Among the 680 individuals with AIS, there were 63 cases of mild anxiety (9.26%), 25 cases of moderate anxiety (3.68%), and 8 cases of severe anxiety (1.18%), with a total of 96 cases (14.12%) with anxiety symptoms. Additionally, there were 74 cases of mild depression (10.88%), 28 cases of moderate depression (4.12%), and 10 cases of severe depression (1.47%), with a total of 112 cases with depression (16.47%). The results of univariate analysis showed that there was a weak correlation between age, body mass index, disease duration, marital status, and the development of anxiety and depression in individuals with AIS (p > 0.05). Educational level, underlying diseases, family income, and place of residence were found to influence the development of anxiety and depression in individuals with AIS (p < 0.05). The results of multivariate logistic regression analysis showed that educational level (no higher education), underlying diseases (with), family income (<50,000 yuan/year, the average exchange rate of RMB to USD was 6.7261), and place of residence (rural area) were influencing factors for the development of anxiety and depression in individuals with AIS (p < 0.05). CONCLUSION: Depression and anxiety are common psychological disorders in patients with AIS. The level of education (no higher education), underlying diseases (with), family income (<50,000 yuan/year), and place of residence (rural area) were risk factors that may lead to anxiety and depression in individuals with AIS. For those with risk factors for anxiety and depression, reasonable intervention should be continually provided to guide early disease prediction and treatment of anxiety and depression in individuals with AIS.

External Fields Assisted Highly Efficient Oxygen Evolution Reaction of Confined 1T-VSe2 Ferromagnetic Nanoparticles.

As a clean and effective approach, the introduction of external magnetic fields to improve the performance of catalysts has attracted extensive attention. Owing to its room-temperature ferromagnetism, chemical stability, and earth abundance, VSe2 is expected to be a promising and cost-effective ferromagnetic electrocatalyst for the accomplishment of high-efficient spin-related OER kinetics. In this work, a facile pulsed laser deposition (PLD) method combined with rapid thermal annealing (RTA) treatment is used to successfully confine monodispersed 1T-VSe2 nanoparticles in amorphous carbon matrix. As expected, with external magnetic fields of 800 mT stimulation, the confined 1T-VSe2 nanoparticles exhibit highly efficient oxygen evolution reaction (OER) catalytic activity with an overpotential of 228 mV for 10 mA cm-2 and remarkable durability without deactivation after >100 h OER operation. The experimental results together with theoretical calculations illustrate that magnetic fields can facilitate the surface charge transfer dynamics of 1T-VSe2 , and modify the adsorption-free energy of *OOH, thus finally improving the intrinsic activity of the catalysts. This work realizes the application of ferromagnetic VSe2 electrocatalyst in highly efficient spin-dependent OER kinetics, which is expected to promote the application of transition metal chalcogenides (TMCs) in external magnetic field-assisted electrocatalysis.

Overlapping peak separation algorithm for ion mobility spectra based on multistrategy JAYA.

RATIONALE: In the field of separation science, ion mobility spectrometry (IMS) plays an important role as an analytical tool. However, the lack of sufficient structural resolution is a common problem in qualitative and quantitative analysis using IMS. A method is needed to solve the problem of overlapping peaks caused by insufficient resolution. METHODS: The method uses multiple strategies to more effectively use population information to balance exploration and exploitation capabilities, prevent local optimization, accurately resolve overlapping peaks, quickly obtain optimal spectral peak model coefficients, and accurately identify compounds. RESULTS: Multistrategy JAYA algorithm's (MSJAYA) performance is compared with improved particle swarm optimization (IPSO), dynamic inertia weight particle swarm optimization (DIWPSO), and multiobjective dynamic teaching-learning-based optimization (MDTLBO). The analysis shows that MSJAYA's maximum separation error is within 0.6%, a level of accuracy not guaranteed by the other algorithms. In addition, the separation error fluctuates within a much smaller range, demonstrating MSJAYA's superior robustness. CONCLUSIONS: Compared with other overlapping peak separation algorithms, MSJAYA is more applicable because no special parameters are used. The method allows fast deconvolution analysis of strong overlapping peaks with multiple components, which greatly improves the resolution of IMS.

A three-dimensional measurement study of fracture displacement in Garden I femoral neck fracture: a retrospective study.

BACKGROUND: Garden I femoral neck fractures are nondisplaced femoral neck fractures. Nonoperative treatment and in situ fixation are the preferred treatments. However, the postoperative outcome is not satisfactory and the incidence of complications remains high, which raises doubts about the accuracy of the diagnosis of nondisplaced Garden I fractures. Recently, three-dimensional (3D) reconstruction has been reported as a mature technology for reconstructing the bone structure of patients. We further extended this technique in the measurement of the fracture spatial displacement to verify the accuracy of Garden I femoral neck fractures. METHODS: This was a retrospective study of patients with Garden I femoral neck fractures from January 2013 to December 2018 at our institution, who were included according to specified criteria. A bilateral proximal femur model of each patient was established based on computed tomography (CT) data. The displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head and the rotation of the femoral head were measured in the bilateral model. RESULTS: A total of 102 patients diagnosed with Garden I fractures were included in this study. The cohort included 32 men and 70 women, with an average age of 55.88 ± 15.32 years. In these patients, the average displacement of the deepest portion of the femoral head fovea was 16.43 ± 7.69 mm. The minimum and maximum displacement was 3.58 and 44.32 mm, respectively. The average displacement of the center of the femoral head was 10.39 ± 5.47 mm and ranged from 2.16 to 34.42 mm. The rotational angle was 23.81 ± 10.15 ° and ranged from 3.71 ° to 61.19 °. CONCLUSIONS: Garden I fractures have large spatial displacement and cannot be considered incomplete or nondisplaced fractures. Therefore, we suggest that anatomical reduction should be considered during treatment.

A Flower Pollination Optimization Algorithm Based on Cosine Cross-Generation Differential Evolution.

The flower pollination algorithm (FPA) is a novel heuristic optimization algorithm inspired by the pollination behavior of flowers in nature. However, the global and local search processes of the FPA are sensitive to the search direction and parameters. To solve this issue, an improved flower pollination algorithm based on cosine cross-generation differential evolution (FPA-CCDE) is proposed. The algorithm uses cross-generation differential evolution to guide the local search process, so that the optimal solution is achieved and sets cosine inertia weights to increase the search convergence speed. At the same time, the external archiving mechanism and the adaptive adjustment of parameters realize the dynamic update of scaling factor and crossover probability to enhance the population richness as well as reduce the number of local solutions. Then, it combines the cross-generation roulette wheel selection mechanism to reduce the probability of falling into the local optimal solution. In comparing to the FPA-CCDE with five state-of-the-art optimization algorithms in benchmark functions, we can observe the superiority of the FPA-CCDE in terms of stability and optimization features. Additionally, we further apply the FPA-CCDE to solve the robot path planning issue. The simulation results demonstrate that the proposed algorithm has low cost, high efficiency, and attack resistance in path planning, and it can be applied to a variety of intelligent scenarios.

Computer-aided design combined with 3D-printed osteotomy guide-assisted derotational distal femoral osteotomy for treating recurrent patellar dislocation with increased femoral anteversion angle: a retrospective study.

PURPOSE: Derotational distal femoral osteotomy (DDFO) has good clinical outcomes for the treatment of the recurrent patellar dislocation combined with increased femoral anteversion angle (FAA). Currently, there is no uniform surgical technique. The purpose of this study was to evaluate the safety and efficacy of computer-aided design (CAD) combined 3D-printed osteotomy guide-assisted DDFO for treating these patients. METHODS: In a retrospective study of 36 patients with recurrent patellar dislocation (RPD) from December 2017 to December 2020, all patients had increased FAA and underwent DDFO assisted by CAD combined with a 3D-printed osteotomy guide. Patients' radiological parameters were used to assess the correction of increased femoral torsion and preoperative and postoperative subjective scores were recorded to evaluate the knee function. Complications were recorded to determine the safety of the surgery. RESULT: A total of 36 knees were included in this study, with a mean follow-up time of 32.6 ± 8.1 months. The mean age of the patients was 24.9±4.4 years and all patients experienced patellar dislocation preoperatively with a mean of 5.7±3.2 times. The patients' femoral anteversion angle decreased from 35.03±3.05° preoperatively to 14.80±0.87°, and the TT-TG distance decreased from 20.03±1.27 mm preoperatively to 19.22±1.22 mm. The hip-knee-ankle (HKA) angle and Insall-Salvatti index were not significantly different postoperatively compared to preoperatively. The knee function scores and visual analogue scale at the last follow-up were significantly improved compared to the preoperative scores. No major complications such as redislocation, nonunion, fixation or graft failure, or infection were observed in any patients. CONCLUSION: Computer-aided design combined with 3D-printed osteotomy guide-assisted derotational distal femoral osteotomy could correct the increased anterior femoral torsion and demonstrate good results. There were no patients experienced re-dislocation during follow-up period and the overall complication rate is low.

Interactions between Benzo(a)pyrene exposure and genetic polymorphisms of AhR signaling pathway on missed abortion.

Benzo(a)pyrene (BaP) is an environmental pollutant widely exposed to human beings. While the relationship between BaP and missed abortion is few understood. To explore the association between missed abortion and BaP, genetic polymorphisms of AhR pathway, we recruited 112 cases women with missed abortion and 137 controls women with normal pregnancy from Shanxi, China. The BPDE-DNA adducts level in the case group was higher than that in the control group (P < 0.001). The subjects were categorized according to the tertiles of BPDE-DNA adduct concentrations: T1 (

Synergistic neuroprotective effect of saikosaponin A and albiflorin on corticosterone-induced apoptosis in PC12 cells via regulation of metabolic disorders and neuroinflammation.

BACKGROUND: Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanisms are still unknown. METHODS AND RESULTS: The corticosterone-induced PC12 cells apoptosis model was employed to assess the neuroprotective effects of SSA and AF, and the synergistic effect was analyzed using three mathematical models. Meanwhile, cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites than a single agent and possessed a stronger adjustment effect on metabolites. The TCA cycle was regulated by SSA and AF via improving mitochondrial function. The purine metabolism was regulated by SSA via inhibition xanthine oxidase activity and the glutamate metabolism was regulated by AF via inhibition glutaminase activity. Moreover, the oxidative stress induced by the purine metabolism was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression. CONCLUSIONS: This study for the first time demonstrated the synergistic neuroprotective effects of SSA and AF, and the synergistic mechanisms were involved in metabolic disorders regulation and neuroinflammation inhibition.

Coordination Switch Drives Selective C-S Bond Formation by the Non-Heme Sulfoxide Synthases.

The non-heme iron ergothioneine synthase (EgtB) is a sulfoxide synthase that catalyzes oxidative C-S bond formation in the synthesis of ergothioneine, which plays roles against oxidative stress in cells. Despite extensive experimental and computational studies of the catalytic mechanisms of EgtB, the root causes for the selective C-S bond formation remain elusive. Using quantum mechanics/molecular mechanics (QM/MM) calculations, we show herein that a coordination switch of the sulfoxide intermediate is involved in the catalysis of the non-heme iron EgtB. This coordination switch from the S to the O atom is driven by the S/π electrostatic interactions, which efficiently promotes the observed stereoselective C-S bond formation while bypassing cysteine dioxygenation. The present mechanism is in agreement with all available experimental data, including regioselectivity, stereoselectivity and KIE results. This match underscores the critical role of coordination switching in the catalysis of non-heme enzymes.

GhWRKY1-like, a WRKY transcription factor, mediates drought tolerance in Arabidopsis via modulating ABA biosynthesis.

BACKGROUND: Drought stress has great negative effects on the plant growth and development. The tolerance of plants to such abiotic stress is triggered by complicated and multilayered signaling pathways to restore cellular homeostasis and to promote survival. The WRKY family is one of the largest transcription factor families in higher plants, and has been well recognized for the roles in regulating plants tolerance to abiotic and biotic stress. However, little is known about how the WRKY genes regulate drought resistance in cotton. RESULTS: In this work, we identified the WRKY transcription factor GhWRKY1-like from upland cotton as a positive regulator of tolerance to drought that directly manipulates abscisic acid (ABA) biosynthesis. Overexpression of GhWRKY1-like in Arabidopsis constitutively activated ABA biosynthesis genes, signaling genes, responsive genes and drought related maker genes, and led to enhanced tolerance to drought. Further analysis has shown that GhWRKY1-like can interact with "W-box" cis-elements of the promoters of AtNCED2, AtNCED5, AtNCED6 and AtNCED9 which are essential enzymes for ABA biosynthesis, and promotes the expression of those target genes. CONCLUSIONS: In summary, our findings suggest that GhWRKY1-like may act as a positive regulator in Arabidopsis tolerance to drought via directly interacting with the promoters of AtNCED2, AtNCED5, AtNCED6 and AtNCED9 to promote ABA biosynthesis.

Correlations between Dual-Pathway White Matter Alterations and Language Impairment in Patients with Aphasia: A Systematic Review and Meta-analysis.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.

Cryptococcal Meningitis in a Patient with Sjogren's Syndrome: a Case Report.

BACKGROUND: Cryptococcal meningitis (CM) is a life-threatening infectious disease and causes high morbidity and mortality. No information about Cryptococcal meningitis in populations with Sjogren's syndrome (SS) was available. METHODS: This report details the first case of Cryptococcal meningitis in a 75-year-old female patient with 10-years history of Sjogren's syndrome. RESULTS: Detailed findings of C. neoformans from CSF examinations, including routine examination, India ink stain, immunological test, culturing, mass spectrum analysis and molecular biology identification were all delineated in this case, which facilitated understanding of detection methods in C. neoformans infection. The etiological exploration was initiated from a positive finding of yeast cells in routine examination of unstained CSF in the present case. Morphology description of C. neoformans in unstained CSF was depicted for the first time. CONCLUSIONS: Clinicians should consider the possible complication of Cryptococcal meningitis when patients with Sjogren's syndrome show neurological symptoms. Importance of screening yeast cells from unstained CSF for routine examination was emphasized, which may reduce errors in cell counting and trigger further etiological ex-ploration of C. neoformans infection in laboratory and clinical practice.

Comparison of Oncoplastic Breast-Conserving Therapy and Standard Breast-Conserving Therapy in Early-Stage Breast Cancer Patients.

BACKGROUND The aim of this study was to compare the efficacy and safety of oncoplastic breast-conserving therapy (OBCT) and SBCT (standard breast-conserving therapy) in breast cancer surgery. MATERIAL AND METHODS We enrolled 192 breast cancer patients who underwent breast-conserving surgery during January 2015 to April 2018. The surgery strategies of OBCT and SBCT were performed according to the patients' condition. For measurement of surgical cosmetic effects, the Harris scale, the modified objective scores, and the subjective evaluation were all used. The basic clinical characteristics, intraoperative indices, postoperative complications, metastasis, and recurrence during the 2-year follow-up were recorded. RESULTS The mean surgical time was remarkably longer and the resected volume was markedly larger in the OBCT group than in the SBCT group. The excellent and good ratios of Harris scale, the modified objective scores, and the ratio of very satisfied and satisfied patients by subjective scale were all significantly higher in the OBCT group than in the SBCT group. The occurrence rates of seroma and poor incision healing were remarkably lower in the OBCT group. No significant difference was found for metastasis and recurrence. CONCLUSIONS OBCT had better cosmetic effects, fewer complications, and no adverse effects on metastasis and recurrence.

Ethnic disparities in stillbirth risk in Yunnan, China: a prospective cohort study, 2010-2018.

BACKGROUND: Racial and ethnic disparities in stillbirth risk had been documented in most western countries, but it remains unknown in China. This study was to determine whether exist ethnic disparities in stillbirth risk in mainland China. METHODS: Pregnancy outcomes and ethnicity data were obtained from the National Free Preconception Health Examination Project (NEPHEP), a nationwide prospective population-based cohort study conducted in Yunnan China from 2010-2018. The Han majority and other four main minorities including Yi, Dai, Miao, Hani were investigated in the analysis. The stillbirth hazards were estimated by life-table analysis. The excess stillbirth risk (ESR) was computed for Chinese minorities using multivariable logistic regression. RESULTS: Compared with other four minorities, women in Han majority were more likely to more educated, less multiparous, and less occupied in agriculture. The pattern of stillbirth hazard of Dai women across different gestation intervals were found to be different from other ethnic groups, especially in 20-23 weeks with 3.2 times higher than Han women. The ESR of the Dai, Hani, Miao, and Yi were 45.05, 18.70, -4.17 and 12.28%, respectively. Adjusted for maternal age, education, birth order and other general risk factors, the ethnic disparity still persisted between Dai women and Han women. Adjusted for preterm birth further (gestation age <37 weeks) can reduce 16.91% ESR of Dai women and made the disparity insignificant. Maternal diseases and congenital anomalies explained little for ethnic disparities. CONCLUSIONS: We identified the ethnic disparity in stillbirth risk between Dai women and Han women. General risk factors including sociodemographic factors and maternal diseases explained little. Considerable ethnic disparities can be attributed to preterm birth.

WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target.

BACKGROUND: Overexpression of Wilms' tumor-1 (WT1) transcription factor facilitates proliferation in acute myeloid leukemia (AML). However, whether WT1 is enriched in the leukemia-initiating cells (LICs) and leukemia stem cells (LSCs) and facilitates the self-renewal of LSCs remains poorly understood. METHODS: MLL-AF9-induced murine leukemia model was used to evaluate the effect of knockdown of wt1 on the self-renewal ability of LSC. RNA sequencing was performed on WT1-overexpressing cells to select WT1 targets. Apoptosis and colony formation assays were used to assess the anti-leukemic potential of a deubiquitinase inhibitor WP1130. Furthermore, NOD/SCID-IL2Rγ (NSG) AML xenotransplantation and MLL-AF9-induced murine leukemia models were used to evaluate the anti-leukemogenic potential of WP1130 in vivo. RESULTS: We found that wt1 is highly expressed in LICs and LSCs and facilitates the maintenance of leukemia in a murine MLL-AF9-induced model of AML. WT1 enhanced the self-renewal of LSC by increasing the expression of BCL2L2, a member of B cell lymphoma 2 (BCL2) family, by direct binding to its promoter region. Loss of WT1 impaired self-renewal ability in LSC and delayed the progression of leukemia. WP1130 was found to modify the WT1-BCL2L2 axis, and WP1130-induced anti-leukemic activity was mediated by ubiquitin proteasome-mediated destruction of WT1 protein. WP1130 induced apoptosis and decreased colony formation abilities of leukemia cells and prolonged the overall survival in the THP1-based xenograft NSG mouse model. WP1130 also decreased the frequency of LSC and prolonged the overall survival in MLL-AF9-induced murine leukemia model. Mechanistically, WP1130 induced the degradation of WT1 by positively affecting the ubiquitination of WT1 protein. CONCLUSIONS: Our results indicate that WT1 is required for the development of AML. WP1130 exhibits anti-leukemic activity by inhibiting the WT1-BCL2L2 axis, which may represent a new acute myeloid leukemia therapy target.

Large Linear Negative Thermal Expansion in NiAs-type Magnetic Intermetallic Cr-Te-Se Compounds.

A large linear negative thermal expansion (NTE) and expanded NTE temperature range (ΔTNTE) were obtained in magnetoelastic CrTe1-xSex (0 ≤ x ≤ 0.15) compounds. For CrTe compound, its thermal expansion coefficient of volume (αV) was calculated to be -28.8 ppm K-1 with the temperature ranging from 280 to 340 K. Substituting Te with Se atoms, the NTE behavior and magnetic properties can be well manipulated. With increasing Se in CrTe1-xSex (0 ≤ x ≤ 0.15) compounds, the ΔTNTE increases from 60 K (280-340 K for x = 0), to 80 K (240-320 K for x = 0.05), to 95 K (200-295 K for x = 0.1), and finally to 100 K (170-270 K for x = 0.15). Furthermore, a linear NTE remains independent of temperature for samples with x ≤ 0.1. The relationship between tunable NTE and magnetic properties was analyzed in detail, indicating that the NTE in CrTe1-xSex compounds originates from the magnetovolume effect (MVE).