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Additional file 3: Fig. S1. The sample and mutation information of included FH-RCC cases. Fig. S2. Copy number variation of 19 primary-metastatic paired FHRCC cases. Fig. S3. Fish plot of each FH-RCC case. Fig. S4. CNV-based phylogenetic trees. Fig. S5. Transcriptomic features of metastatic and primary FH-RCC. Fig. S6. Exploration of TME features of metastatic lesions. Fig. S7. Methylation phenotype and heterogeneity between primary and metastatic lesions. Fig. S8. Differential methylated probes of immune related genes.

Data valuation -- quantifying the contribution of individual data sources to certain predictive behaviors of a model -- is of great importance to enhancing the transparency of machine learning and designing incentive systems for data sharing. Existing work has focused on evaluating data sources with the shared feature or sample space. How to valuate fragmented data sources of which each only contains partial features and samples remains an open question. We start by presenting a method to calculate the counterfactual of removing a fragment from the aggregated data matrix. Based on the counterfactual calculation, we further propose 2D-Shapley, a theoretical framework for fragmented data valuation that uniquely satisfies some appealing axioms in the fragmented data context. 2D-Shapley empowers a range of new use cases, such as selecting useful data fragments, providing interpretation for sample-wise data values, and fine-grained data issue diagnosis., Comment: ICML 2023

Additional file 2: Table S1. Independent genome-wide significant lead SNPs associated with pulmonary embolism (PE) in the discovery stage and replication stage. Table S2. The allele frequency of identified loci in 1000Genomes. Table S3. Replication of associations for the known loci in our cohort. Table S4. Association results for genes that were significant in FUMA gene-based analysis. Table S5. Polygenic risk score variants. Table S6. Polygenic risk score (PRS) quantile and odds ratio (OR).

Additional file 1: Fig. S1. Regional association plot at genome-wide association study (GWAS) genome-wide significant loci. Fig. S2. Principal component analysis (PCA) plot of Han Chinese PE cohort. Fig. S3. FUMA Manhattan plot and QQ plot of genome-wide association study (GWAS) meta-analysis. Fig. S4. The transfection efficiency of cellular experiments for FABP2. Fig. S5. Low-density lipoprotein cholesterol (LDL-C) levels of patients with different genotypes of rs1799883. Fig. S6. Forest plot for the association of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) with PE. Fig. S7. Ancestry-specific polygenic risk score (PRS) ROC plot. Fig. S8. Performance of different PRSVTE in the CURES testing set.

Additional file 1: Table S1. Baseline characteristics of patients with FH-deficient RCC.

Supplement 1

To develop an approach to reduce the type 2 diabetic osteoporosis, this study investigated the protective effects of the combination of linagliptin and metformin against osteoporosis. Micro-CT and dynamic biomechanical measurements were used to determine the bone microstructure in the type 2 diabetes mellitus (T2DM) rats. MC3T3-E1 cells were cultured in high glucose environments. In addition, we used qRT-PCR and Western blotting to assess osteogenic markers and p38 and extracellular signal-regulated kinase (ERK) protein expression. The combination of linagliptin and metformin treatment significantly restored bone micro-architecture and femoral mechanical properties in the T2DM rats. In contrast, bone markers including osteocalcin, NH2-terminal propeptide of type I procollagen, COOH-terminal telopeptide of type I collagen and tartrate-resistant acid phosphatase were significantly reduced by the combination of linagliptin and metformin treatment. We used high glucose treated MC3T3-E1 cells to mimic the condition of T2DM. Linagliptin combined with metformin treatment significantly inhibited the phosphorylation of p38 and ERK induced by high glucose treatment. In conclusion, the linagliptin combined with metformin treatment improved the rats’ bone mineral density, bone structure, and osteogenic markers. Both p38 and ERK phosphorylation were reduced in high glucose MC3T3-E1 cells. Our findings highlight the potential of linagliptin combined with metformin for the treatment of T2DM-related osteoporosis.

Supplement 1

Pulmonary thromboembolism(PTE)is the third most common cause of cardiovascular death. However, only about 20% to 30% of patients with high-risk PTE received systemic thrombolysis in real world, due to concerns about the risks such as major bleeding. Although systemic thrombolysis could decrease all-cause mortality of patients with intermediate-risk PTE, the risk of bleeding outweighs the benefits. Ultrasound-assisted catheter-directed thrombolysis (UA-CDT) could directly deliver thrombolytic drugs to the thrombus with lower doses needed. Meanwhile, ultrasound waves could also enhance thrombolysis. Therefore, UA-CDT is emerging as a new tool, with good efficacy and safety records, for the treatment of PTE. In the present review article, we introduce the mechanism, required device, common protocol, efficacy and safety of UA-CDT and discuss directions for future studies.

ObjectiveTo investigate the clinical effect of entecavir antiviral therapy in chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT) and mild liver histological abnormalities. MethodsA retrospective analysis was performed for 181 patients with hepatitis B virus (HBV) infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from January 2008 to January 2018, and according to the baseline ALT level, they were divided into study group (61 patients with PNALT at baseline), control group 1 ［62 patients with an ALT level of (1-2)×upper limit of normal (ULN)］, and control group 2 (58 patients with an ALT level of ＞2×ULN). Entecavir antiviral therapy was given for at least 1 year, and clinical outcome was compared between the three groups. The life-table method was used to calculate the cumulative progression rates and annual incidence rates of virologic response, HBeAg serological response, and virologic breakthrough. An analysis of variance was used for comparison of continuous data between groups, and the SNK method was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 181 patients enrolled in this study, there were 124 male patients (68.5%) and 80 patients with positive HBeAg (44.2%), with a mean follow-up time of 3.63 years. The three groups had a mean annual incidence rate of virologic response of 74.37%, 71.89%, and 74.21%, respectively (χ2=2.91, P=0.371) and an annual incidence rate of virologic breakthrough of 3.48%, 5.17%, and 2.73%, respectively (χ2=1.72, P=0.097). For the patients with positive HBeAg, the three groups had a mean annual clearance rate of 9.79%, 37.16%, and 38.24%, respectively (χ2=1.37, P=0.01) and a mean annual HBeAg seroconversion rate of 9.10%, 31.35%, and 36.74%, respectively (χ2=5.61, P=0.021); the study group had significantly lower mean annual clearance rate and seroconversion rate of HBeAg than the control groups 1 and 2 (all P＜0.05). ConclusionCHB patients with PNALT level can obtain satisfactory virologic response after entecavir antiviral therapy, while immunological response needs to be further improved.

Information on the effects of pollutants in sediments at an ecosystem level to validate current and proposed risk-assessment procedures is scarce. The most frequent criticism of these procedures is that responses of surrogate species in the laboratory are not representative of responses of natural populations. A tiered approach using both laboratory and microcosm exposures (96-h and 21-d laboratory bioassays and a 3-mo field microcosm) was conducted to compare the impacts of sediment-spiked cadmium on the mortality, development, and abundance of Chironomidae larvae. The 96-h and 21-d lethal concentrations of sediment-spiked Cd to 50% of the species Chironomus riparius were estimated to be 201.07 and 172.66 mg/kg, respectively. In the 21-d laboratory bioassay, the endpoints, including the development rate and emergence ratio, were compared, and the lowest-observed-effect concentration (LOEC) values were 325.8 and 10.7 mg/kg, respectively. The abundance, richness, and biomass of field-collected larvae were compared among the different treatments in the field microcosm, and it was found that the order of sensitivities using different endpoints was biomass (2.6/5.2 mg/kg of no-observed-effect concentration/LOEC) > diversity (10.7/21.2 mg/kg) > abundance (41.2/82.7 mg/kg). The toxicity values based on lethal/sublethal changes in the laboratory bioassays might not fully protect field organisms against damage from chemicals, such as Cd, unless an assessment factor of 5 is used. These findings highlight the need to conduct field validation of criteria/guidelines before they are introduced to protect organisms/ecosystems in the field and provide a preliminary template for future field validation of criteria elsewhere. Environ Toxicol Chem 2021;40:2450-2462. © 2021 SETAC.

Nitric oxide (NO), as a bioeffector to improve chemosensitivity by reversing multidrug resistance (MDR), is highly attractive for developing combinational delivery systems to deal with MDR tumors, while it is highly challenged by the stability and controlled release of NO during the pathway. Here we design and synthesize a cyclic nitrate trimethylene carbonate monomer (NTC), followed by ring-opening polymerization to prepare amphiphilic biodegradable polycarbonate-based copolymers as polymeric NO donors with tailored contents. The copolymer with desirable molecular weight is readily self-assembled to biodegradable micelles (NO-M) with a uniform size of 130 nm for highly stabilizing NO donors at the physiological conditions, while triggered NO release from micelles is performed at the intracellular reduction conditions. More importantly, NO-M shows superior inhibition of P-gP expression to enhance the chemosensitivity of multidrug-resistant MCF7 cells (MCF7/DOX

Additional file 1: Supplementary figures.

Additional file 2: Supplementary tables.

Additional file 1: Acknowledgments. Supplementary Table S1. characteristicsof renal insufficient patients undertaken adjusted and conventional dose ofLMWH. Supplementary Table S2. Outcomes of renalinsufficient non-high risk PE patients with adjusted and conventional dose ofLMWH. Supplementary Figure S1. Forest plot of odds ratios for death, PE related death, bleeding and majorbleeding by different renal function groups. Supplementary Figure S2. Kaplan-Meier curves of cumulative death rates [Panel A] and cumulative PErelated death rates [Panel B] by different renal function groups forin-hospital PE patients.

Supplemental material, sj-docx-1-tar-10.1177_17534666221138001 for Predictors of early response to balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension by Xin Li, Yi Zhang, Qi Jin, Qin Luo, Qing Zhao, Tao Yang, Qixian Zeng, Lu Yan, Anqi Duan, Zhihua Huang, Meixi Hu, Changming Xiong, Zhihui Zhao and Zhihong Liu in Therapeutic Advances in Respiratory Disease

Additional file 3: Table S1. The proteins selected by LC-MS/MS

Supplemental material, sj-doc-1-taj-10.1177_20406223221102803 for Prognostic implication of noninvasive right ventricle-to-pulmonary artery coupling in chronic thromboembolic pulmonary hypertension by Anqi Duan, Xin Li, Qi Jin, Yi Zhang, Zhihui Zhao, Qing Zhao, Lu Yan, Zhihua Huang, Meixi Hu, Jiaran Liu, Chenhong An, Xiuping Ma, Changming Xiong, Qin Luo and Zhihong Liu in Therapeutic Advances in Chronic Disease

Additional file 1. RHC and BPA procedure.

Feng Sun, Ke Wu, Zhixian Yao, Xingyu Mu, Zhong Zheng, Menghao Sun, Yong Wang, Zhihong Liu, Yiyong Zhu Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of ChinaCorrespondence: Yiyong Zhu; Ke WuDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People’s Republic of ChinaTel +86 15902190823; +86 15800567782Email zyy1017@hotmail.com; doctorwuke@sjtu.edu.cnBackground: Metastatic disease caused by prostate cancer (PCa) is the principal cause of PCa-related mortality. Long non-protein-coding RNAs may possess significant cellular functions. Plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA encoded by the human PVT1 gene, is an oncogene, which can regulate several tumor-related genes. In PCa, the function and mechanism of PVT1 are unclear. NOP2 is being pursued as a prognostic marker for cancer aggressiveness, which promotes mouse fibroblast growth and tumor formation. Essentially, nothing is known about the specific interactions between the PVT1 and NOP2.Methods: 190 pairs of PCa tissues and adjacent normal tissues were collected andRNA sequencing was used to identify the differential lncRNAs.Real-time quantitative real-time PCR (RT-qPCR) confirmed these results and gene regulatory relationship.Lentiviral vectors were used to alter PVT1 and genes to analyze their effects on PCa progression.Transwell migration and invasion assays were performed to test the metastasis ability. Biofunction ofPVT1 andNOP2 were confirmed in vitro and in vivo.Results: In this study, we reported that the long noncoding RNA-PVT1 was upregulated in PCa metastasis tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of PVT1 significantly downregulated tumor suppressor microRNAs (miRNAs), such as miR-15b-5p, miR-27a-3p, miR-143-3p, and miR-627-5p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. In vitro and in vivo, PVT1 promotes PCa metastasis via targeting miRNAs. Furthermore, the expression level of PVT1 was positively associated with the expression of NOP2, a cancer metastasis-related protein. We demonstrated that NOP2 promoted invasion and migration of PCa. For specific mechanism, correlation analysis showed that PVT1 promoted metastasis by up-regulating NOP2.Conclusion: Taken together, our results show that PVT1 acts as an inducer of PCa metastasis via targeting miRNAs, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.Keywords: lncRNA PVT1, miRNAs, NOP2, metastasis, prostate cancer

N-p-n InGaP/GaAs double heterojunction bipolar transistor has been successfully grown on a 200 mm Ge/Si wafer using metalorganic chemical vapor deposition with low defect density of 107 cm $^{-2}$ . Non-gold metals of Ni/Ge/Al and Ti/Al are used to form the ohmic contact for small pieces device fabrication. Both direct-current (dc) and high-frequency characteristics of the device were measured. The device with emitter area of $6\times8 \mu {\text {m}}^2$ shows a dc gain of 55 at a collector current of $I_{c}$ = 4 mA, with high collector-emitter breakdown voltage of ~17 V. The high-frequency response with cutoff frequency ( $f_{T}$ T) of 23 GHz and maximum available frequency ( $f_{\text {max}}$ T) of 10 GHz can be achieved. These results demonstrate that InGaP/GaAs double heterojunction bipolar transistor grown on low defect density Ge/Si wafer has the potential for realizing III-V CMOS integrated platform for high-frequency applications.

The vacuum vessel (VV) is an important container for thermal fusion of plasma with extremely high manufacture requirements for the high temperature released by the fusion sets. During the welding process of the vacuum vessel, the influence of the bottom support mode on welding distortion cannot be ignored. This paper focuses on a research on topology optimization for the vertical supports of 1/16 vacuum vessel sector through the finite element. The optimization results show that the distortion of the vacuum vessel is minimal when the vacuum vessel supports are in the vertical state. And the bottom support model is established based on the analysis results.

The water-cooled ceramic breeder (WCCB) blanket is a component of the China Fusion Engineering Test Reactor (CFETR). The Reduced Activation Ferrite/Martensite (RAFM) steels are the preferred structural materials for WCCB blanket. As a kind of RAFM steels, China low activation martensitic (CLAM) steel was welded by electron beam welding (EBW), and then quenched-tempered treatment was carried out. The results show that at the welding state, the welding seam was composed of large martensite and δ ferrite and the organization of the heat-affected zone (HAZ) was changed slightly with the different heat input. Moreover, the hardness of welded joints was higher than that of base material (BM), but the impact toughness was very low. After quenched-tempered treatment, the δ ferrite in the weld was eliminated, the residual stress of the test plate decreased as a whole, and the mechanical properties were improved significantly.

Objective: We aimed to determine whether beryllium toxicity was associated with mitochondria apoptosis pathway in SD rats. Methods: Thirty-two SD rats were given an intratracheal instillation dose ...

Pneumoconiosis is a serious occupational disease that often occurs to coal workers with no early diagnosis and effective treatment at present. Diffuse pulmonary fibrosis is the major pathological change of pneumoconiosis, and its mechanism is still unclear. Epigenetics is involved in the development of many diseases, and it is closely associated with fibrosis. In this study, we investigated whether DNA methylation contributes to the pathogenesis of pulmonary fibrosis in pneumoconiosis. By exposure to coal dust or silica dust, we established the models of coal worker's pneumoconiosis (CWP), which showed an increased expression of COL-I, COL-III. We further found that DNMT1, DNMT3a, DNMT3b, MBD2, MeCP2 protein expression changed. Pretreatment with DNMT inhibitor 5-aza-dC reduced expression of COL-I, COL-III, and reduced pulmonary fibrosis. In summary, our results showed that DNA methylation contributes to dust-induced pulmonary fibrosis and that it may serve as a theoretical basis for testing DNA methyltransferase inhibitors in the treatment of CWP.

Advanced lung cancer is becoming a chronic disease threatening human life and health. Cachexia has been recognized as the most common problem associated with advanced lung cancer. Lung cancer-induced cachexia seriously affects patients' quality of life. The present article summarizes the pathogenesis of advanced lung cancer-induced cachexia from three aspects: anorexia, cytokines, and energy and metabolic abnormalities. In addition, the present article proposes corresponding nursing measures based on cachexia pathogenesis to improve the quality of life and survival rate of cachectic patients with advanced lung cancer by combining continuously advancing treatment regimens and effective nursing. The present article also provides references for healthcare professionals when administering related treatments and nursing care.

The effects of Fe2O3 and Bi2O3 addition on the microstructures and the piezoelectric and dielectric properties of 0.49Pb(Ni1/3Nb2/3)O3-0.51Pb(Hf0.3Ti0.7)O3 ceramics were investigated in detail. Results showed that 0.49Pb(Ni1/3Nb2/3)O3-0.51Pb(Hf0.3Ti0.7)O3 ceramics with better performance were prepared at a sintering temperature as low as 1050 °C via the addition of Fe2O3 and Bi2O3. In the case of 2% Fe2O3 and 2% Bi2O3, the optimal properties, i.e. d33 = 865 pC/N, kp = 0.60, er = 6500 and tanδ = 2.5%, were achieved for the sample. The d33 revealed the greatest value among the ever reported piezoceramics sintered at the temperature below 1100 °C. The results suggest Fe2O3 and Bi2O3 addition to be an effective approach to lower the sintering temperature and simultaneously improve the performance of Pb(Ni, Nb)O3-Pb(Hf, Ti)O3 ceramics.

The therapeutic potential of nitric oxide (NO) has been highly attractive to tumor treatment, especially for surmounting the multidrug resistance (MDR) of cancer. However, the NO-involved therapy remains extremely challenging because of the difficulty to simultaneously control the NO release rate and real-time concentration. Herein, we construct NO-containing polymersomes with high amount of NO donors inherently grown on the polymer chains to keep the stability. These polymersomes can be simultaneously loaded with photosensitizer of IR780 iodide on the membrane layer and chemotherapeutic of DOX·HCl in the lumen. NO release can be triggered by the reduction conditions, and further accelerated by remote NIR irradiation due to the increased local temperature. The instantaneous NO release with high concentration significantly inhibits the P-gp expression and sensitize the chemotherapy, thus overcoming the tumor MDR and improving the anti-tumor activity. Meanwhile, DOX·HCl release is highly promoted at the intracellular conditions because of the cleavage of acid-labile cis-aconitic amide at endo/lysosomal pH, and the improved hydrophilicity of the membrane layer after NO release. The in vivo results show that the single intravenous injection of polymersome formulation companying with NIR irradiation exerts multi-modal therapies of chemotherapy, PTT/PDT, and NO-therapy on the MCF-7/R tumor models, showing superior and combinational treatment efficacy with the complete eradication of tumors and few side effects.

IgA nephropathy (IgAN) is common worldwide and has heterogeneous phenotypes. Predicting long-term outcomes is important for clinical decision-making. As right-censored patients become common during the long-term follow-up, either excluding these patients from the cohort or labeling them as control will bias the risk estimation. Thus, we constructed a survival model using EXtreme Gradient Boosting for survival (XSBoost-Surv), to accurately predict the prognosis of IgAN patients by taking the time-to-event information into the modeling procedure. Shapley Additive exPlanations (SHAP) was employed to interpret the individual predicted result and the non-linear relationships between the predictors and outcome. Experiments on real-world data showed our model achieved superior discrimination performance over other conventional survival methods. By providing insights into the exact changes in risk induced by certain characteristics of the patients, this explainable and accurate survival model can help improve the clinical understanding of renal progression and benefit the therapies for the IgAN patients.

Fangbin Song,1,2 Hui Du,1,2 Aimin Xiao,1,2 Chun Wang,1,2 Xia Huang,1,2 Peisha Yan,1,2 Zhihong Liu,1,2 Xinfeng Qu,3 Jerome L Belinson,4,5 Ruifang Wu1,2 1Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen, People’s Republic of China; 3Sanming Project of Medicine in Shenzhen, Peking University Shenzhen Hospital, Shenzen, People’s Republic of China; 4Preventive Oncology International, Inc., Cleveland Heights, OH, USA; 5Gynecologic Oncology Division, Women’s Health Institute, Cleveland Clinic, Cleveland, OH,USACorrespondence: Ruifang Wu; Hui DuDepartment of Obstetrics and Gynecology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, Guangdong 518036, People’s Republic of ChinaEmail wurfpush@126.com; duhui_107108@163.comPurpose: When used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16INK4a immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16INK4a immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening.Methods: A total of 1197 cytology slides were immuno-stained using automatic p16INK4a staining system (PathCIN®p16INK4a) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16INK4a. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16INK4a, LBC and HPV test results.Results: In combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P< 0.0001). For primary screening: p16 immuno-cytology was more specific than HPV testing and was similar in sensitivity. Also, p16 immuno-cytology compared favorably with routine LBC (≥ASC-US or ≥LSIL) in sensitivity and specificity. For secondary screening: after LBC screening, “Triaging ASC-US with p16” gave a higher specificity and a similar sensitivity as compared to the “Triaging ASC-US with hrHPV” algorithm. After HPV primary screening, p16 immuno-cytology was more specific than LBC (≥ASC-US); the calculated colposcopy referral rate was also decreased by using p16 immuno-cytology as triage. Triage of “HPV16/18 and p16” had higher specificity and similar sensitivity as compared to triage of “HPV16/18 and LBC ≥ASC-US”.Conclusion: For primary screening, p16INK4a immuno-cytology compares favorably to routine LBC and HPV testing. p16INK4a immunostaining could be an efficient triage to reduce the colposcopy referral rate after primary hrHPV screening or LBC screening. Therefore, p16INK4a immuno-cytology may be applicable as a favorable technology for cervical cancer screening.Keywords: cervical intraepithelial neoplasia, human papillomavirus, p16, immunochemical staining, cervical cancer screening

With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in heterogeneous genetic backgrounds (heteroplasmy), which makes it difficult to conclude about their pathogenicity and functional consequences. As an organism amenable to mitochondrial DNA manipulation, able to survive by fermentation to loss-of-function mtDNA mutations, and where heteroplasmy is unstable, Saccharomyces cerevisiae is an excellent model for investigating novel human mtDNA variants, in isolation and in a controlled genetic context. We herein report the identification of a novel variant in mitochondrial ATP6 gene, m.8909T&gt, C. It was found in combination with the well-known pathogenic m.3243A&gt, G mutation in mt-tRNALeu. We show that an equivalent of the m.8909T&gt, C mutation compromises yeast adenosine tri-phosphate (ATP) synthase assembly/stability and reduces the rate of mitochondrial ATP synthesis by 20&ndash, 30% compared to wild type yeast. Other previously reported ATP6 mutations with a well-established pathogenicity (like m.8993T&gt, C and m.9176T&gt, C) were shown to have similar effects on yeast ATP synthase. It can be inferred that alone the m.8909T&gt, C variant has the potential to compromise human health.

Pofut1 gene encodes a O-fucosyltransferase that adds fucose to the serine/threonine residue in the sequence of C(2)XXXX(S/T)C(3) of EGF-like domain in a protein. O-fucosylation has been shown to be required for some EGF-like domain-containing proteins to function, e.g., Notch1, and POFUT1 deficiency could affect cellular function and cause diseases. Pofut1 is ubiquitously expressed, but its essentiality for most cell types is not known. In the present study, we examined the consequence of Pofut1 gene abrogation in mouse podocytes using Cre-loxP system, and found that the conditional knockout mice were indistinguishable from wild-type controls in urinary protein level, glomerular morphology, podocyte foot process ultrastructure, podocyte marker expression and podocyte numbers. These results indicated that POFUT1 is not essential for podocyte structure, function and survival in mice. To understand why POFUT1 is dispensable for podocytes, we searched mouse podocyte essential gene candidates (as determined by single-cell RNA-seq) and found only two POFUT1 substrates, NOTCH2 and tPA. It has been shown that abrogation of these genes does not cause podocyte injury, explaining dispensability of POFUT1 for mouse podocytes and demonstrating a feasibility to predict POFUT1 essentiality for a given cell type. At present, most mouse cell types have been subject to single-cell RNA-seq, making essential gene prediction and thus POFUT1 requirement prediction possible for the cell types.

Background: Human hair loss and regeneration has stimulated interest in the natural hair cycle worldwide; however, such research is difficult because the periodicity of human or mouse hair is not visually obvious. Dermal papilla cells (DP cells) play an important role in the development of hair follicles, but knowledge of the differentiation and mechanisms of DP stem cells during transition through the hair follicle cycle are still limited, although some studies have reported that DP cells may have an intermediate cell state during differentiation, the classification and function of specific cell states are not clear. Results: Here, we used cashmere goats, that have obvious periodicity of hair follicles, as model animals and, based on unbiased single cell RNA sequencing, we identified and isolated DP cell data. Pseudotime ordering analysis was used to successfully construct a DP cell lineage differentiation trajectory and revealed the sequential activation of key genes, signaling pathways, and functions involved in cell fate decisions. At the same time, we analyzed the mechanisms of different cell fates and revealed the function of four different intermediate cells: Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are suggested to be DP progenitor cells. Conclusions: In development and apoptosis, inner bulge cells not only earlier than outer bulge cells, but occurred faster and was more thorough,this helps a deeper understanding of the role of bulge cells. Pseudogenes play another important role in function which promoted the competitive endogenous RNA (ceRNA) hybridization of pseudogenes.In different hair follicle cycles, DP cells will differentiate into different intermediate state cells and perform different functions, and the marker genes of the cells also changed. Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are DP progenitor cells, this conclusion provides an unprecedented deeper understanding of the function of DP cells.

Differential privacy is heavily used in privacy protection due to it provides strong protection against private data. The existing differential privacy scheme mainly implements the privacy protection of nodes or edges in the network by perturbing the data query results. Most of them cannot meet the privacy protection requirements of multiple types of information. In order to overcome these issues, a differential privacy security mechanism with average path length (APL) query is proposed in this paper, which realize the privacy protection of both network vertices and edge weights. Firstly, by describing APL, the reasons for choosing this attribute as the query function are analyzed. Secondly, global sensitivity of APL query under the need of node privacy protection and edge-weighted privacy protection is proved. Finally, the relationship between data availability and privacy control parameters in differential privacy is analyzed through experiments.

A ratiometric two-photon probe was designed to visualize HClO levels in tissues, revealing the generation of HClO in the wound-repairing process of mice for the first time., HClO plays crucial roles in a wide range of biological and pathological processes. Recent studies have revealed that the generation of HClO has close links with the wound healing process. It's thus meaningful to develop a reliable method for monitoring HClO in wounded tissues. Toward this purpose, we herein report a rationally designed quinolone-based ratiometric two-photon fluorescent probe, QClO, for HClO. The probe QClO rapidly displays a drop in blue emission and an increase of green emission in response to HClO due to the oxidation of oxathiolane. The fluorescence intensity ratio (green/blue) can serve as the ratiometric detection signal for HClO with high sensitivity. After confirming its excellent sensing performance in vitro, the probe was validated by detecting exogenous and endogenous HClO in living cells. The probe was capable of monitoring HClO in situ in the wounded tissues of mice by two-photon microscopy, which demonstrated the production profile of HClO during the wound-healing process. This work affords a simple and reliable tool for the detection and imaging of HClO, which promises to find more applications in HClO-related biological and pathological studies.

0.49Pb(Ni1/3Nb2/3)O3-0.51Pb(Hf0.3Ti0.7)O3 (PNN-PHT) piezoelectric ceramics added with LiF were prepared, and the effect of the LiF addition on their piezoelectric properties was investigated. Results showed that LiF promoted the formation of pure perovskite phase and the densification of the PNN-PHT ceramics. The better piezoelectric properties, i.e. d33 = 957 pC/N and er = 7113, were obtained for the 4 at% LiF added sample which was prepared at a sintering temperature as low as 1100 °C. The mechanism of the improved properties by LiF addition was discussed. Results suggest the PNN-PHT ceramic to be an excellent candidate for lead-based piezoelectric materials applied in large displacement actuator.

Water- cooled ceramic breeder (WCCB) blanket is one of the candidate blanket for China Fusion Engineering Test Reactor (CFETR) independently developed by China Institute of plasma physics. The first wall (FW) is a component of WCCB, which directly faces the plasma. FW contains flow channels and has complex shape structure, therefore, it is difficult to complete the full-scale manufacturing by one kind of welding process. Hence, in the development process, the components of FW are first connected by hot isostatic pressing (HIP), and then connected by electron beam welding (EBW), so as to form the full-scaled FW connection. In this paper, the EBW process of FW was studied. The results showed that when the electron beam current was 50 mA and the focus was on the surface, the welded joint with 20 mm penetration and good shape can be formed. After the one time welding and the twice welding (overlapping first welding) of the weld, the tensile test fracture occurred in the base metal. The impact energy of the one time welding was 13 MPa, 18 MPa, and 21 MPa, respectively, and the impact energy of the twice welding was 19 MPa, 20 MPa, and 51 MPa, respectively. The microstructure of the joint was composed of δ-ferrite and lath martensite. When the weld penetration was increased to 50 mm, the lower the focus is, the smaller the porosity at the bottom of the weld is. Similarly, when the lower focus was used, the porosity at the bottom of the weld disappeared basically; The EBW test on the scaled FW with W/Cu sheets showed that when the we took the test pieces with the W-Cu sheet spacing is 4 mm, the welded joint with good surface shape and no internal defects can be formed without scanning deflection electron beam welding, and ultrasonic testing showed that EBW does not affect on the HIP interface. This provides a favorable basis for the future test of equal ratio FW test piece and the welding of actual FW.

Due to their different structures and virtually unlimited raw material source, organic materials could triumph over many inorganic compounds as electrodes. However, most organic materials suffer the weaknesses of poor electron conducting and being soluble in electrolytes, which leads to low capacities and short lifetimes of batteries. In order to address these weaknesses, we present a readily scale-up-able process to polymerize N-heterotriangulene triketone, resulting in an essentially insoluble, two-dimensional conjugated polymer PHTA, showing a layered morphology with an interlayer spacing of 3.53 A. Benefiting from the polycyclic aromatic hydrocarbonic features, PHTA is insoluble in electrolytes and has high electrical conductivities (2.33 × 10−2 S cm−1). In LIBs, the PHTA electrode reveals a specific capacity of 380 mAh g−1 with an average attenuation rate of 0.026%. These results indicate PHTA to be a superior candidate and open a seminal future for N-heterotriangulene polymers for energy storage.

Computing the homography matrix using the known matching points is a key step in computer vision for image registration. In practice, the number, accuracy, and distribution of the known matching points can affect the uncertainty of the homography matrix. This study mainly focuses on the effect of matching point distribution on image registration. First, horizontal dilution of precision (HDOP) is derived to measure the influence of the distribution of known points on fixed point position accuracy on the image. The quantization function, which is the average of the center points’ HDOP* of the overlapping region, is then constructed to measure the uncertainty of matching distribution. Finally, the experiments in the field of image registration are performed to verify the proposed function. We test the consistency of the relationship between the proposed function and the average of symmetric transfer errors. Consequently, the proposed function is appropriate for measuring the uncertainty of matching point distribution on image registration.