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Peptides with suitable aggregation behavior and electrical properties are potential siRNA delivery vectors. However, identifying suitable peptides with ideal delivery and safety features is difficult owing to the variations in amino acid sequences. Here, a holistic program based on computer modeling and single‐cell RNA sequencing (scRNA‐seq) is used to identify ideal siRNA delivery peptides. Stage one of this program consists of a sequential screening process for candidates with ideal assembly and delivery ability; stage two is a cell subtype‐level analysis program that screens for high in vivo tissue safety. The leading candidate peptide selected from a library containing 12 amino acids showed strong lung‐targeted siRNA delivery capacity after hydrophobic modification. Systemic administration of these compounds caused the least damage to liver and lung tissues and has little impact on macrophage and neutrophil numbers. By loading STAT3 siRNA, strong anticancer effects are achieved in multiple models, including patient‐derived xenografts (PDX). This screening procedure may facilitate the development of peptide‐based RNA interference (RNAi) therapeutics. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Primary stage IV breast cancer is associated with a poor prognosis. At present, the value of local surgical treatment for patients with stage IV breast cancer remains uncertain; therefore, treatment principles remain controversial. Because of the high heterogeneity of these patients, it is often difficult to evaluate their prognoses. As a result, this study aimed to establish a prognostic nomogram to evaluate the prognosis of patients with breast cancer experiencing primary bone metastasis.The clinical characteristics and follow‐up data of patients with primary breast cancer and bone metastasis from 2010 to 2018 were collected from the Surveillance, Epidemiology, and End Results database and from 2013 to 2021 at the Peking Union Medical College Hospital. Patients were divided into training and validation groups. Multivariate Cox regression analysis was used to identify the independent prognostic variables for predicting cancer‐specific survival (CSS). On the basis of these independent risk factors, a nomogram was developed and used calibration curves to evaluate its accuracy. Patients were divided into three risk groups according to their scores and surgery‐related survival curves plotted using the log‐rank test.Overall, 6372 patients were included, with 6319 from the Surveillance, Epidemiology, and End Results database and 53 from the Peking Union Medical College Hospital Breast Surgery Department. Multivariate analysis showed that age, race, marital status, grade, tumor stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and burden of other metastatic lesions were all associated with CSS. Based on these results, a nomogram that predicted the 1‐, 3‐, and 5‐year CSS rates in patients with primary breast cancer and bone metastasis (concordance index > 0.69) was developed. After dividing patients into low‐risk, high‐risk, or super‐high‐risk groups based on nomogram scoring criteria, survival analysis revealed that patients in the low‐ and high‐risk groups had significant survival benefits from primary focal surgery.Independent risk factors for primary breast cancer in patients with bone metastasis were analyzed and a nomogram established to predict CSS. The prognostic tool derived in this study can assist clinicians in predicting the survival and surgical benefits of these patients through scoring, thereby providing further guidance for treatment strategies. [ABSTRACT FROM AUTHOR]

The injectable progestin depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in sub-Saharan Africa although mouse models indicate it weakens genital epithelial integrity and barrier function and increases susceptibility to genital infection. The intravaginal ring NuvaRing® is another contraceptive option that like DMPA suppresses hypothalamic pituitary ovarian (HPO) axis function with local release of progestin (etonogestrel) and estrogen (ethinyl estradiol). As we previously reported that treating mice with DMPA and estrogen averts the loss of genital epithelial integrity and barrier function induced by DMPA alone, in the current investigation we compared genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and genital epithelial permeability in rhesus macaques (RM) treated with DMPA or a NuvaRing®re-sized for RM (N-IVR). While these studies demonstrated comparable inhibition of the HPO axis with DMPA or N-IVR, DMPA induced significantly lower genital DSG1 levels and greater tissue permeability to intravaginally administered low molecular mass molecules. By identifying greater compromise of genital epithelial integrity and barrier function in RM administered DMPA vs. N-IVR, our results add to the growing body of evidence that indicate DMPA weakens a fundamental mechanism of anti-pathogen host defense in the female genital tract. [ABSTRACT FROM AUTHOR]

In situ vaccination is a desirable strategy for cancer immunotherapy due to its convenience and capacity to target tumor antigens. Here, an in situ nanovaccine based on a cationic peptide with cholesterol‐modified, DP7‐C, for cancer immunotherapy is rationally designed, and developed a cancer nanovaccine that is easy to preparate. The nanovaccine includes cocktail small interfering RNAs (siRNAs) and immunologic adjuvant CpG ODNs, has synergistic effect in the cancer treatment. This nanovaccine can induce tumor cell death, promote antigen presentation and relieve immune suppression in the tumor microenvironment (TME). Moreover, this nanovaccine is administered to CT26 (hot) and B16F10 (cold) tumor model mice, in which it targeted the primary tumors and induced systemic antitumor immunity to inhibit metastasis. It is validated that the nanovaccine can convert cold tumors into hot tumors. Furthermore, the nanovaccine increased the immune response to anti‐PD‐1 therapy by modulating the TME in both CT26‐ and B16F10‐tumor‐bearing mice. The siRNA cocktail/CpG ODN/self‐assembling peptide nanovaccine is a simple and universal tool that can effectively generate specific tumor cell antigens and can be combined with immuno‐oncology agents to enhance antitumor immune activity. The versatile methodology provides an alternative approach for developing cancer nanovaccines. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the unknown genetic causes of teratozoospermia, and determine the pathogenicity of candidate variants. Methods: A primary infertile patient and his family members were recruited in the West China Second University Hospital of Sichuan University. Whole-exome sequencing was performed to identify causative genes in a man with teratozoospermia. Immunofluorescence staining and western blotting were applied to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with teratozoospermia. Results: We performed whole-exome sequencing (WES) and detected a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 on a primary infertile male patient. Intriguingly, we identified abnormal sperm morphology in this patient, with recurrent respiratory infections and chronic cough. Furthermore, we confirmed that this mutation resulted in negative effects on DNAJB13 expression in the spermatozoa of the affected individual, causing ultrastructural defects in his sperm. Remarkably, our staining revealed that DNAJB13 was expressed in the cytoplasm of primary germ cells and in the flagella of spermatids during spermiogenesis in humans and mice. Finally, we are the first group to report a favorable prognosis using ICSI for a patient carrying this DNAJB13 mutation. Conclusion: Our study revealed a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 involved in teratozoospermia phenotype. Our study greatly expands the spectrum of limited DNAJB13 mutations, and is expected to provide a better understanding of genetic counseling diagnoses and subsequent treatment of male infertility. [ABSTRACT FROM AUTHOR]

Supramolecular peptide hydrogel has shown promising potential in vaccine development largely because of its ability to function both as antigen depot and immune adjuvant. Nap‐GdFdFdY, a tetrapeptide hydrogel that has been previously reported to exhibit adjuvant effect, is inadvertently found to contain conserved peptide sequence for insulin, proinsulin, and glutamic acid decarboxylase, 3 major autoantigens for the autoimmune type 1 diabetes (T1D). At present, despite being managed clinically with insulin replacement therapy, T1D remains a major health threat with rapidly increasing incidences, especially in children and young adults, and antigen‐specific immune tolerance induction has been proposed as a feasible approach to prevent or delay T1D progression at an early stage. Here, it is reported that innoculation of Nap‐GdFdFdY leads to complete protection of nonobese diabetic (NOD) mice from T1D development till the age of 36 weeks. Better maintenance of pancreatic islet morphology with minimal immune cell infiltration is also observed from mice exposed to Nap‐GdFdFdY. This beneficial impact is mainly due to its facilitative role on enhancing peripheral T regulatory cell (Treg) population, shown as increased splenic Treg percentage, and function, demonstrated by maintenance of circulating TGF‐β1 level. Serum cytokine microarray data further implicate a "buffering" role of Nap‐GdFdFdY on systemic inflammatory tone in NOD mice. Thus, with its versatility, applicability, and excellent potency, Nap‐GdFdFdY is posited as a novel therapeutic intervention for T1D. [ABSTRACT FROM AUTHOR]

Supramolecular peptide hydrogel has shown promising potential in vaccine development largely because of its ability to function both as antigen depot and immune adjuvant. Nap‐GdFdFdY, a tetrapeptide hydrogel that has been previously reported to exhibit adjuvant effect, is inadvertently found to contain conserved peptide sequence for insulin, proinsulin, and glutamic acid decarboxylase, 3 major autoantigens for the autoimmune type 1 diabetes (T1D). At present, despite being managed clinically with insulin replacement therapy, T1D remains a major health threat with rapidly increasing incidences, especially in children and young adults, and antigen‐specific immune tolerance induction has been proposed as a feasible approach to prevent or delay T1D progression at an early stage. Here, it is reported that innoculation of Nap‐GdFdFdY leads to complete protection of nonobese diabetic (NOD) mice from T1D development till the age of 36 weeks. Better maintenance of pancreatic islet morphology with minimal immune cell infiltration is also observed from mice exposed to Nap‐GdFdFdY. This beneficial impact is mainly due to its facilitative role on enhancing peripheral T regulatory cell (Treg) population, shown as increased splenic Treg percentage, and function, demonstrated by maintenance of circulating TGF‐β1 level. Serum cytokine microarray data further implicate a "buffering" role of Nap‐GdFdFdY on systemic inflammatory tone in NOD mice. Thus, with its versatility, applicability, and excellent potency, Nap‐GdFdFdY is posited as a novel therapeutic intervention for T1D. [ABSTRACT FROM AUTHOR]

Cancer metastasis is a complex process influenced by various factors, including epithelial-mesenchymal transition (EMT), tumor cell proliferation, tumor microenvironment, and cellular metabolic status, which remains a significant challenge in clinical oncology, accounting for a majority of cancer-related deaths. TEAD4, a key mediator of the Hippo signaling pathway, has been implicated in regulating these factors that are all critical in the metastatic cascade. TEAD4 drives tumor metastasis and chemoresistance, and its upregulation is associated with poor prognosis in many types of cancers, making it an attractive target for therapeutic intervention. TEAD4 promotes EMT by interacting with coactivators and activating the transcription of genes involved in mesenchymal cell characteristics and extracellular matrix remodeling. Additionally, TEAD4 enhances the stemness of cancer stem cells (CSCs) by regulating the expression of genes associated with CSC maintenance. TEAD4 contributes to metastasis by modulating the secretion of paracrine factors and promoting heterotypic cellular communication. In this paper, we highlight the central role of TEAD4 in cancer metastasis and chemoresistance and its impact on various aspects of tumor biology. Understanding the mechanistic basis of TEAD4-mediated processes can facilitate the development of targeted therapies and combination approaches to combat cancer metastasis and improve treatment outcomes. • TEAD4 drives metastasis via regulating EMT, TME and metabolism. • TEAD4 induces chemoresistance by upregulating drug efflux and anti-apoptotic proteins. • Targeting TEAD4 represents a promising cancer therapy. [ABSTRACT FROM AUTHOR]

This pot experiment aimed to investigate the influence of rice straw biochar (BC 0, 1, and 3%, w/w) and organic manure (OM 0, 1, and 2%, w/w) addition on the growth, nutrient and cadmium (Cd) uptake of forage soybean in 10 mg Cd kg−1 contaminated soils. Compared with non-biochar treatments, biochar decreased shoot biomass, height and nitrogen (N) contents. Organic manure markedly increased the shoot biomass, shoot phosphorus (P), potassium (K), calcium (Ca) and magnesium (Mg) concentration, and root N, P, Ca contents without biochar addition treatments, while in the case of 3% biochar, there were no significant effects on N, K, Ca, and Mg contents of shoot and root among organic manure treatments. In comparison with other treatments, the minimum Cd content of shoots and roots both occurred in the treatment of BC3%+OM2%, while shoot Cd content reached the maximum value in OM2% treatment. Thus, these results suggested that organic manure addition can elevate forage soybean yield and nutrient content, while biochar had no positive effects. High biochar (3%) addition in combination with highest dose of organic manure (2%) can decline the Cd content of soybean and contribute to the agricultural product safety. [ABSTRACT FROM AUTHOR]

Purpose: Empty follicle syndrome (EFS) refers to the inability to obtain mature oocytes after appropriate ovarian stimulation during the process of in vitro fertilization (IVF). However, the specific cause and mechanism of action underlying EFS remain to be further explored. Herein we aimed to investigate the clinical and genetic characteristics of EFS. Methods: After data were collected in an infertile family, we performed whole-exome sequencing (WES) on the patient and confirmed the pathogenic mutations through Sanger sequencing. Western immunoblotting, immunofluorescence staining, and minigene assay were further used to investigate the negative effects of these mutations. Results: Absence of oocytes was observed over 2 cycles of IVF in the patient, and we evaluated the novel compound heterozygous mutations c.2T>A (p. M1K) and c.1112+1G>T of the zona pellucida glycoprotein 1 gene (ZP1, MIM# 195000) by WES. For the family under study, EFS was classified as an autosomal recessive inheritance pattern. The results of western blotting and immunofluorescence staining analyses confirmed that the missense mutation of c.2T>A [p. M1K] resulted in almost missing protein production. Additionally, using a minigene assay, we demonstrated the deleterious effect on the ZP1 gene of the splice site mutation c.1112+1G>T, which caused truncation of ZP1 protein. Conclusions: The compound heterozygous mutations of ZP1 gene identified in this study by genetic and functional experiments constituted a novel genetic cause of EFS, and further study will expand its use in the clinical and molecular diagnoses of EFS. [ABSTRACT FROM AUTHOR]

Background: Brachydactyly (BD) is a rare autosomal dominant inherited disease characterized by shortness of the fingers and/or toes, which has been classified into the subtypes A–E. However, the exact cause and mechanism of BD remain to be illuminated. Here, we aim to reveal the clinical and genetic characteristics of a subtype of BD, brachydactyly‐anonychia. Methods: In this study, a large Chinese family with three members affected by brachydactyly‐anonychia was investigated. Both whole‐exome sequencing and microarray‐based comparative genomic hybridization (CGH) were performed on this family and the results of copy number variation (CNV) were verified by quantitative real‐time PCR (qPCR). Results: All the affected individuals showed short fingers and toes as well as missing nails; and the absence of middle phalanges in figure II‐V of the upper and lower extremities was observed by X‐ray examination. A duplication involving in the region of 17q24.3 was detected by CGH. The results of qPCR also represented this duplication in 17q24.3 in all the patients. Conclusion: In summary, our findings suggest that 17q24.3 duplication is the genetic cause of brachydactyly‐anonychia in this family, which support the prior report that brachydactyly‐anonychia is associated with 17q24.3 duplication, and further indicates the pathogenic correlation between BD and CNVs. [ABSTRACT FROM AUTHOR]

The purpose of the study was to examine biochar amendment, phosphorus (P) fertilizer and arbuscular mycorrhizal fungi (AMF) on the yield, nutrient and cadmium (Cd) absorption of Lolium multiflorum in acidic soil. It was shown that mycorrhizal inoculation had no positive influence on the plant shoot biomass and the contents of nitrogen (N), P, potassium (K), calcium (Ca) and magnesium (Mg) in plants at all biochar and P level treatments. Irrespective of mycorrhizal inoculation and P level, biochar amendments markedly elevated the soil available P and K uptake in plant tissues. In contrast, biochar significantly decreased the translocation factor of plants, soil exchangeable Cd, and acid and neutral phosphatase activities, regardless of the mycorrhizal inoculation and P fertilizer. Without P fertilization, biochar amendments significantly promoted shoot P content, while biochar amendments significantly reduced shoot P content when P fertilizer was applied. Without biochar application, P fertilizer application significantly promoted the biomass and N uptake of shoots in both AMF inoculation treatments, while P fertilizer increased these only in the presence of biochar and mycorrhizal inoculation. The increased N content induced by the biochar amendment elevated the shoot N:P ratio and alleviated the N deficiency with P fertilizer input. Thus, we concluded that the addition of biochar and P fertilizer showed more positive effects on the promotion of growth and nutrient uptake of L. multiflorum than AMF grown in acidic Cd-contaminated soils. Image 1 • AMF had no positive influence on shoot biomass and nutrient uptakes. • Biochar markedly elevated soil P level and plant K uptake. • Biochar decreased translocation factor. • Biochar increased shoot N:P ratio with P fertilization. • Biochar and P fertilizer had more positive effects on ryegrass than AMF. [ABSTRACT FROM AUTHOR]

Tetrahexahedral particles (~10 to ~500 nanometers) composed of platinum (Pt), palladium, rhodium, nickel, and cobalt, as well as a library of bimetallic compositions, were synthesized on silicon wafers and on catalytic supports by a ligand-free, solid-state reaction that used trace elements [antimony (Sb), bismuth (Bi), lead, or tellurium] to stabilize high-index facets. Both simulation and experiment confirmed that this method stabilized the {210} planes. A study of the PtSb system showed that the tetrahexahedron shape resulted from the evaporative removal of Sb from the initial alloy—a shape-regulating process fundamentally different from solution-phase, ligand-dependent processes. The current density at a fixed potential for the electro-oxidation of formic acid with a commercial Pt/carbon catalyst increased by a factor of 20 after transformation with Bi into tetrahexahedral particles. [ABSTRACT FROM AUTHOR]

Abstract The synergistic effects of arbuscular mycorrhizal fungi (AMF) inoculation and biochar application on plant growth and heavy metal uptake remain unclear. A pot experiment was carried out to investigate the influence of AMF inoculation, biochar and cadmium (Cd) addition on the growth, nutrient and cadmium uptake of Medicago sativa , as well as soil biological and chemical characteristics. In comparison to the non-Cd pollution treatment, Cd addition significantly decreased mycorrhizal colonization, biomass, and N, P, Ca and Mg contents of shoots and roots in the absence of biochar. Biochar amendment did not increase mycorrhizal colonization at either Cd levels. Regardless of the biochar amendment, AMF inoculation significantly promoted contents of N and P in plant shoots grown in the Cd-contaminated soils. Nevertheless, in the presence of Cd pollution, biochar dramatically elevated the biomass and N, P, K and Ca contents of plant tissues in both AMF inoculation treatments. Biochar addition significantly reduced soil DTPA-extracted Cd. The treatments with AMF inoculation and biochar amendment showed the lowest shoot Cd concentrations and contents, highest plant tissue N and P contents in the Cd addition group. These results suggested that combined use of AMF inoculation and biochar amendment had significant synergistic effects not only on nutrient uptake but also on the reduction in cadmium uptake of alfalfa grown in Cd-polluted soil. Graphical abstract Unlabelled Image Highlights • AMF only promoted N and P uptake of plant shoots. • Biochar facilitated N, P, K and Ca contents of plants grown in Cd-contaminated soils. • Biochar was more effective at increasing plant nutrient uptake. • Both AMF and biochar could decrease plant Cd concentration. [ABSTRACT FROM AUTHOR]

Nanomaterials that form as heterostructures have applications in catalysis, plasmonics, and electronics. Multielement nanoparticles can now be synthesized through a variety of routes, but how thermodynamic phases form in such structures and how specific interfaces between them can be designed and synthesized are still poorly understood. We explored how palladium-tin alloys form mixed-composition phases with metals with known but complex miscibilities. Nanoparticles with up to seven elements were synthesized, and many form triphase heterostructures consisting of either three-interface or two-interface architectures. Density functional theory calculations and experimental work were used to determine the balance between the surface and interfacial energies of the observed phases. From these observations, design rules have been established for making polyelemental systems with specific heterostructures, including tetraphase nanoparticles with as many as six junctions. [ABSTRACT FROM AUTHOR]

• Erlotinib combined with mAbs achieved a significant PFS benefit compared to erlotinib alone. • The PFS benefit was not influenced by the difference in treatment effect across the subgroups. • The combination treatment did not lead to better overall survival. • Erlotinib combined with mAbs could be linked to more severe adverse events. Immuno-combination therapy is emerging as an effective treatment for advanced non-small cell lung carcinoma (NSCLC). However, compared to monotherapy, such as monoclonal antibodies or kinase inhibitors, whether combination therapy can enhance antitumor efficacy or alleviate side effects remains unclear. A systematic literature search was undertaken using the PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases to identify eligible studies concentrating on treatment with erlotinib or erlotinib plus monoclonal antibodies in NSCLC patients published between January 2017 and June 2022. The primary outcomes included progression-free survival (PFS), overall survival (OS), response rate (RR) and treatment-related adverse events (AEs). Seven independent randomized, controlled clinical trials including 1513 patients were obtained for the final analysis. Erlotinib plus monoclonal antibodies was significantly associated with the improvement of PFS (hazards ratio [HR], 0.60; 95% CI 0.53–0.69; z = 7.59, P < 0.01) and with moderate performance regarding OS (HR, 0.81; 95% CI 0.58–1.13; z = 1.23, P = 0.22) and RR (odds ratio [OR], 1.25; 95% CI 0.98–1.59; z = 1.80, P = 0.07), irrespective of EGFR mutation status. In the safety evaluation, erlotinib plus monoclonal antibodies had a markedly higher occurrence of adverse events (AEs) of Clavien grade 3 or higher (OR, 3.32; 95% CI 2.66–4.15; z = 10.64, P < 0.01). Compared with erlotinib alone, combination therapy (erlotinib plus monoclonal antibodies) was associated with significantly improved PFS in NSCLC therapy, accompanied by increased treatment-related AEs. Registration : Our systematic review protocol was registered in the PROSPERO international register of systematic reviews (CRD42022347667). [ABSTRACT FROM AUTHOR]

The FY-4B satellite is one of the second generation of China's geosynchronous meteorological satellites aiming at numerical weather forecasts. The space environment monitoring package (SEMP) onboard the FY-4B is a comprehensive instrument package for plasma, high-energy particle, and energetic neutral particle measurements. The low-energy particle analyzer (LEPA) is one of the instruments of the SEMP and consists of two top hat electrostatic analyzers designed for plasma detection. The electron and ion sensors are back-to-back assembled and are integrated to a shared electronic box. It measures the three-dimensional velocity distribution of low-energy electrons and ions on the geosynchronous orbit. In this paper, we present the ground calibration and in-flight performance of the instrument. With the electrostatic deflectors and the cylindrically symmetric structure, the instrument provides high-cadence measurements of electron and ion velocity distributions with a wide field of view (FOV) of 180° by 100°, an angular resolution of 16.7° × 20°, and a broad energy range for both the electrons and ions from tens of eV to above 30 keV, with a 1 s time resolution. The geometric factors of the electron and ion analyzers are 1.1 × 10−3 cm2·sr·eV/eV and 1.4 × 10−3 cm2·sr·eV/eV, respectively, which fulfills the requirements of the low-energy plasma measurement. The LEPA monitored typical space environment disturbance such as geomagnetic storms and successfully recorded the responses of plasma energy fluxes. Satellite surface charging events were measured, with the highest potentials of −2000 V in the shadow period and −500 V in the nonshadow period. [ABSTRACT FROM AUTHOR]

Anti-drug antibody formation occurs with most biological agents across disease states, but the mechanism by which they are formed is unknown. The formation of anti-drug antibodies to adalimumab (AAA) may decrease its therapeutic effects in some patients. HLA alleles have been reported to be associated with autoantibody formation against interferons and other TNF inhibitors, but not adalimumab. We analyzed samples from 634 subjects with either rheumatoid arthritis (RA) or hidradenitis suppurativa (HS): 37 subjects (17 RA and 20 HS) developed AAA (AAA+) during adalimumab treatment and 597 subjects (348 RA, 249 HS) did not develop AAA (AAA-) during the clinical trials. Using next-generation sequencing-based HLA typing, we identified three protective HLA alleles (HLA-DQB1*05, HLA-DRB1*01,and HLA-DRB1*07) that were less prevalent in AAA+ than AAA–subjects (ORs: 0.4, 0.25 and 0.28, respectively; and P values: 0.012, 0.012 and 0.018, respectively) and two risk HLA alleles (HLA-DRB1*03 and HLA-DRB1*011) that were more abundant in AAA+ than AAA–subjects (ORs: 2.52, and 2.64, respectively; and P values: 0.006 and 0.019). Similar to the finding of Billiet et al. who found that carriage of the HLA-DRB1*03 allele was more prevalent in those with anti-infliximab antibodies (OR = 3.6, p = 0.002, 95% CI: [1.5,8.6]).), we found HLA-DRB1*03 allele was also more prevalent in anti-adalimumab positive (OR = 2.52, p = 0.006, 95% CI: [1.37,4.63]). The results suggest that specific HLA alleles may play a key role in developing AAAs in RA and HS patients treated with adalimumab. [ABSTRACT FROM AUTHOR]

This study aimed to explore whether nitrogen availability could influence mycorrhizal function and their associations with host plants in Cd-contaminated acidic soils or not. A greenhouse pot experiment was conducted to assess the effects of mycorrhizal inoculation (non-mycorrhizal inoculation (NM), Glomus aggregatum (Ga), G. tortuosum (Gt) and G. versiforme (Gv)) and inorganic N amendment on the growth, nutrient and Cd uptake of Medicago sativa grown in Cd-contaminated acidic soils (10 mg Cd kg −1 soil). AMF inoculations significantly increased the shoot and total biomass and decreased the shoot Cd concentration in comparison to plants uninoculated. N addition increased markedly concentration and content of N and decreased those of P in plants at all inoculation treatments. Shoot K, Na and Mg concentration in plants inoculated with Ga and Gv were decreased by N addition, whereas shoot K, Na, Ca and Mg concentration in plants inoculated with Gt were not negatively affected. It was observed that N addition only increased mycorrhizal colonization, shoot biomass, shoot K, Ca and Mg content of plants inoculated with Gt. Irrespective of N addition, plants with Gt inoculation got the maximum shoot and root P concentration and content, as well as P/Cd concentration molar ratio among all inoculation treatment. Neither AMF nor N fertilizer contributed to the decrease of soil exchangeable Cd and increase of soil pH. These results suggested that N fertilizer only elevated plant performance of alfalfa with Gt inoculation grown in acidic soil, by diluting Cd concentration and alleviating of nutrient deficiency, especially P. [ABSTRACT FROM AUTHOR]

This paper analyzes sharpness mismatch between stereoscopic views. Sharpness mismatch is a special binocular mismatch and can occur through e.g. focus mismatch between stereoscopic cameras, errors in post-processing or asymmetric coding for low-bandwidth transmission, where one view is subsampled or transmitted at a much lower rate. Although blurred edges in one view can be suppressed by the corresponding sharper edges in the other view according to the binocular suppression phenomenon, sharpness mismatch can still be perceived and cause eye strain for viewers. Subjective studies were carried out with a test video dataset, in which the stereoscopic views are asymmetrically blurred by Gaussian low-pass filters since defocus-based effects of lens aberrations can be modeled as Gaussian blur. Also, an efficient novel automatic no-reference approach to measure the probability of sharpness mismatch is presented in this paper. The sharpness mismatch score is estimated by measuring width deviations of edge pairs in each “edge-significant” depth plane based on depth edges in both views. The probability of sharpness mismatch (PSM) is then calculated considering the perceptibility of edge width deviations considering absolute depth at which the edges occur. This PSM metric is evaluated using the test video dataset and blurriness dataset of LIVE 3D Phase II database. The experimental results show that the proposed metric outperforms the state-of-the-art stereo 3D quality metrics on analyzing sharpness mismatch between stereoscopic views. [ABSTRACT FROM AUTHOR]

In recent decades, the surge in China's CO 2 emissions has caused serious environmental problem. According to the CO 2 reduction commitment in 12th Five-Year Plan, this paper classifies total CO 2 emissions in accordance with industry and analyses CO 2 emissions changing trend of residential consumption and the three major industries which include the primary, secondary and tertiary industry. Cointegration and Granger causality test are proposed to select different influencing factors of three major industries and residential consumption CO 2 emissions respectively as well as check the influencing factors with different leading lengths. Least squares support vector machine (LSSVM) is applied to predict different types of carbon dioxide emissions. Case studies reveal that classification and prediction of CO 2 emissions can highly improve forecast accuracy. The effectiveness of LSSVM has been proved by the final simulation which shows that the proposed method outperforms logistic model, back propagation artificial neural network (BPNN) and GM (1, 1) model in the CO 2 emissions forecasting. [ABSTRACT FROM AUTHOR]

Reducing the dependence on fossil-fuel-based resources is becoming significant due to the detrimental effects on environment and global energy-dependent. Thus, increased attention has been paid to wind power, a type of clean and renewable energy. However, owing to the stochastic nature of wind speed, it is essential to build a wind speed forecasting model with high-precision for wind power utilization. Therefore, this paper proposes a hybrid model which combines fast ensemble empirical model decomposition (FEEMD) with regularized extreme learning machine (RELM). The original wind speed series are first decomposed into a limited number of intrinsic mode functions (IMFs) and one residual series. Then RELM is built to forecast the sub-series. Partial auto correlation function (PACF) is applied to analyze the intrinsic relationships between the historical speeds so as to select the inputs of RELM. To verify the developed models, short-term wind speed data in July 2010 and monthly data from January 2000 to May 2010 in Hong songwa wind farm, Chengde city are used for model construction and testing. Two additional forecasting cases in Hebei province are also applied to prove the model’s validity. The simulation test results show that the built model is effective, efficient and practicable. [ABSTRACT FROM AUTHOR]

Temperature data from SABER/TIMED and Empirical Orthogonal Function (EOF) analysis are taken to examine possible modulations of the temperature migrating diurnal tide (DW1) by latitudinal gradients of zonal mean zonal wind ( $$\overline \zeta $$). The result shows that $$\overline \zeta $$ increases with altitudes and displays clearly seasonal and interannual variability. In the upper mesosphere and lower thermosphere (MLT), at the latitudes between 20°N and 20°S, when $$\overline \zeta $$ strengthens (weakens) at equinoxes (solstices) the DW1 amplitude increases (decreases) simultaneously. Stronger maximum in March-April equinox occurs in both $$\overline \zeta $$ and the DW1 amplitude. Besides, a quasi-biennial oscillation of DW1 is also found to be synchronous with $$\overline \zeta $$. The resembling spatial-temporal features suggest that $$\overline \zeta $$ in the upper tropic MLT probably plays an important role in modulating semiannual, annual, and quasi-biennial oscillations in DW1 at the same latitude and altitude. In addition, $$\overline \zeta $$ in the mesosphere possibly affects the propagation of DW1 and produces SAO of DW1 in the lower thermosphere. Thus, SAO of DW1 in the upper MLT may be a combined effect of $$\overline \zeta $$ both in the mesosphere and in the upper MLT, which models studies should determine in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor (CAR)-T cell therapy has been highly successful in treating hematological malignancies like leukemia and lymphoma, leading to advancements in immunotherapy. The approval of anti-CD19 CAR-T cells by the FDA in 2017 has paved the way for CAR-T therapies to be extended to various cancers, autoimmune disorders, viral infections, and fibrosis. However, the therapy faces challenges, including severe side effects like cytokine release syndrome and graft-versus-host disease. Additionally, CAR-T therapy has limited efficacy against solid tumors and antigen escape, poor persistence, and difficulties in industrialization. Overall, this review provides a comprehensive understanding of the challenges and opportunities associated with CAR-T cell therapy, highlighting the need for further advancements in CAR-T cell construction and production. By facilitating future research and development, CAR-T therapy has the potential to become a powerful tool in the fight against cancer and other diseases. Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target multiple antigens and overcome individual limitations. Despite these advancements, some shortcomings prevent the widespread use of CAR-T therapy, including life-threatening toxicities, T-cell exhaustion, and inadequate infiltration for solid tumors. Researchers have made considerable efforts to address these issues by developing new strategies for improving CAR-T cell function and reducing toxicities. This review provides an overview of the path of CAR-T cell development and highlights some of the prominent advances in its structure and manufacturing process, which include the strategies to improve antigen recognition, enhance T-cell activation and persistence, and overcome immune escape. Finally, the review briefly covers other immune cells for cancer therapy and ends with the discussion on the broad prospects of CAR-T in the treatment of various diseases, not just hematological tumors, and the challenges that need to be addressed for the widespread clinical application of CAR-T cell therapies. [ABSTRACT FROM AUTHOR]

Ten years of SABER/TIMED temperature data are used to analyze the global structure and seasonal variations of the migrating 6-h tide from the stratosphere to the lower thermosphere. The amplitudes of the migrating 6-h tide increase with altitudes. In the stratosphere, the migrating 6-h tide peaks around 35°N/S. The climatologically annual mean of the migrating 6-h tide clearly shows the manifestation of the (4, 6) Hough mode between 70 and 90 km that peaks at the equator and near 35°N/S. Above 90 km, the 6-h tide shows more than one Hough mode with the (4, 6) mode being the dominant one. The migrating 6-h tide is stronger in the southern hemisphere. Annual, semiannual, 4-, and 3-month oscillations are the four dominant seasonal variations of the tidal amplitude. In the stratosphere and stratopause, the spring enhancement of the 6-h tide at middle latitudes is the most conspicuous feature. From the mesosphere to the lower thermosphere, the tidal amplitude at low latitudes is gradually in the scale of that at middle latitudes and exhibits different temporal variations at different altitudes and latitudes. Both ozone heating in the stratosphere and the background atmosphere probably affect the generation and the seasonal variations of the migrating 6-h tide. In addition, the non-linear interaction between different tidal harmonics is another possible mechanism. [ABSTRACT FROM AUTHOR]

Power load forecasting is a key element for power system management and planning. However, it has been proven to be a hard task due to various unstable factors. This paper presents a forecasting methodology based on this particular type of neural network. The scope of this study presents a solution for short-term load forecasting based on a three-stage model which starts with pattern recognition via self-organizing map (SOM), a clustering of the previous partition by K-means algorithm, and finally demand forecasting for each cluster with back propagation neural network (BPNN) improved by additional momentum and variable learning rate methods. The effectiveness of SOM-K-BPNN model has been verified by the final simulation which shows that the proposed model outperforms the BPNN model with default parameters and Grey System GM (1, 1); therefore, empirical results show that the proposed SOM-K-BPNN model is feasible and can fulfil the short-term load forecasting requirements of China. [ABSTRACT FROM AUTHOR]

Murine infection models are needed to develop therapeutics and vaccines to combat the Plasmodium parasites causing malaria. Herein, we describe an easy to perform flow cytometry-based methodology for detecting green fluorescent protein-expressing Plasmodium berghei in the peripheral red blood cells (RBC) of mice. This methodology uses one-step staining and simplified gating strategies to streamline the process of Plasmodium quantification and can detect parasitemia at an earlier time point after infection compared to traditional light microscopy-based techniques. • Flow cytometry-based methodology detects Plasmodium parasitemia in mice at earlier time points than microscopy. • Method is quickly performed and does not require antibody staining. • Methodology amenable to high-throughput screening of antimalarial vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

Background: Multiple morphological abnormalities of the sperm flagella (MMAF), which is characterized as asthenoteratospermia involving absent, short, bent, coiled, and/or irregular‐caliber flagella, is a rare recessive inherited disorder associated with male infertility. To date, genetic causes of MMAF cases are not fully explored. Methods: Whole‐exome sequencing was conducted to identify pathogenic variants in a patient with MMAF. The functional effect of the identified mutations was investigated by immunofluorescence staining and western blotting. Intracytoplasmic sperm injection was used to assist fertilization for the patient with MMAF. Results: We identified novel biallelic mutations, a splicing variant NC_000004.12:g.146937593C>T (c.254+1G>A), and a nonsense mutation NM_001300761.4:c.1185C>G (NP_001287690.1:p.Tyr395*), in TTC29 from an infertile patient. In addition to the typical MMAF phenotype, the patient also presented aberrant morphology of sperm heads. Further functional experiments confirmed the absence of TTC29 expression in the spermatozoa. We also explored the specific expression pattern of TTC29 in human and mouse spermatogenesis. The outcome of intracytoplasmic sperm injection in the patient was unsuccessful, while additional female risk factors should not be excluded. Conclusions: Our study revealed the novel biallelic mutations in TTC29 in a MMAF patient, which findings expand the mutational spectrum of TTC29 and further contribute to the diagnosis, genetic counseling, and prognosis of male infertility. [ABSTRACT FROM AUTHOR]

Bacterial toxin-antitoxin (TA) systems (or "addiction modules") typically facilitate cell survival during intervals of stress by inducing a state of reversible growth arrest. However, upon prolonged stress, TA toxin action leads to cell death. TA systems have also been implicated in several clinically important phenomena: biofilm formation, bacterial persistence during antibiotic treatment, and bacterial pathogenesis. TA systems harbored by pathogens also serve as attractive antibiotic targets. To date, the mechanism of action of the majority of known TA toxins has not yet been elucidated. We determined the mode of action of the Doc toxin of the Phd-Doc TA system. Doc expression resulted in rapid cell growth arrest and marked inhibition of translation without significant perturbation of transcription or replication. However, Doc did not cleave mRNA as do other addiction-module toxins whose activities result in translation inhibition. Instead, Doc induction mimicked the effects of treatment with the aminoglycoside antibiotic hygromycin B (HygB): Both Doc and HygB interacted with 30S ribosomal subunits, stabilized polysomes, and resulted in a significant increase in mRNA half-life. HygB also competed with ribosome-bound Doc, whereas HygB-resistant mutants suppressed Doc toxicity, suggesting that the Doc-binding site includes that of HygB (i.e.. helix 44 region of 165 rRNA containing the A, P. and E sites). Overall, our results illuminate an intracellular target and mechanism of TA toxin action drawn from aminoglycoside antibiotics: Doc toxicity is the result of inhibition of translation elongation, possibly at the translocation step, through its interaction with the 305 ribosomal subunit. [ABSTRACT FROM AUTHOR]

• We identified two novel pathogenic mutations in FSIP2 on a MMAF patient. • The patient carrying FSIP2 mutations had poor ICSI prognosis. • Genetic analysis can play a crucial role in FSIP2 diagnosis and prognosis. Multiple morphological abnormalities of the sperm flagella (MMAF) is defined as deformities that cause sperm motility disorders, further resulting in male infertility. However, the reported genes related to sperm flagellar defects can only explain approximately 60% of human MMAF cases. Here, we report two novel compound heterozygous mutations, c.16246_16247insCCCAAATATCACC (p. T5416fs*7) and c.17323C > T (p.Q5774*), in the fibrous sheath-interacting protein 2 gene (FSIP2 ; OMIM: 615796) in an infertile patient by whole-exome sequencing (WES). Western blotting and immunofluorescence staining confirmed that the compound heterozygous mutations abrogated FSIP2 protein expression. Notably, our staining revealed that FSIP2 is expressed in the cytoplasm of primary germ cell and flagella of spermatids during the spermiogenesis. Moreover, intracytoplasmic sperm injection (ICSI) was carried out using sperm from this patient; however, pregnancy failed after embryo transfer through one cycle. Our findings may be helpful in establishing a genetic diagnosis for MMAF, as well as provide additional beneficial knowledge for genetic counseling and infertility treatment. [ABSTRACT FROM AUTHOR]

Carbon emissions from civil buildings refer to the carbon emissions generated during the operation of civil buildings. With the continuous development of the urban economy and the improvement of people's living standards, this part of carbon emission puts tremendous pressure on China to achieve the goal of carbon peaking and carbon neutral. In the context of rapid urbanization, studying the spatiotemporal characteristics and influencing factors of the carbon emissions from civil buildings have strong practical significance for China to achieve the "dual carbon" goal. Based on the emission data from 104 prefecture-level cities in China, we examine the spatiotemporal characteristics of the civil building carbon emissions from the perspectives of temporal evolution trend, spatial distribution and its dynamic evolution, spatial difference and its decomposition, and spatial autocorrelation characteristics. Finally, we reveal the influencing factors of the carbon emissions from civil buildings using static panel data models and spatial dynamic panel data models. The results of the study show that: (1) During the sample period, the carbon emissions from civil buildings have increased year by year. The civil building carbon emissions have become an important source of China's overall carbon emissions. Realizing energy saving and emission reduction in the operational stage of civil buildings is crucial to realizing China's "dual carbon" goal. (2) According to the estimated results, there is a significant inverted U-shaped non-linear relationship between urbanization and civil building carbon emissions. Most Chinese cities are located in the upward part of the inverted U-shaped curve at present. Thus, the traditional economic growth model characterized by high energy consumption and high emission during rapid urbanization should be abandoned to reduce the carbon emissions from civil buildings. (3) Technological progress and fixed asset investment can effectively reduce the carbon emissions from civil buildings. At the same time, the level of marketization and social consumption expenditure positively affect the carbon emissions from civil buildings. It is necessary to improve the relevant market mechanisms, policy subsidies, and other means to encourage the application of green energy-saving technologies in civil buildings. Also, it is needed to guide the urban residents' consumption structure and lifestyle in a low-carbon direction, to reduce the energy consumption and carbon emissions during the operation of civil buildings. [ABSTRACT FROM AUTHOR]

Glioma is recognized as the most infiltrative and lethal form of central nervous system tumors and is known for its limited response to standard therapeutic interventions, high recurrence rate, and unfavorable prognosis. Recent progress in gene and immunotherapy presents a renewed sense of optimism in the treatment of glioblastoma. However, the barriers to overcome include the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), as well as the suppressive immune microenvironment. Overcoming these barriers remains a significant challenge. Here, we developed a lipid nanoparticle platform incorporating a dual-functional peptide (cholesterol-DP7-ACP-T7-modified DOTAP or DAT-LNP) capable of targeting glioma across the BBB and BBTB for brain tumor immunotherapy. This system was designed to achieve two key functions. First, the system could effectively penetrate the BBB during accumulation within brain tissue following intravenous administration. Second, this system enhances the maturation of dendritic cells, the polarization of M1 macrophages, and the activation of cytotoxic CD8+ T cells. This multifaceted approach effectively mitigates the immunosuppressive tumor microenvironment of glioma and promotes robust antitumor immune responses. Overall, the intravenous administration of the delivery system designed in this study demonstrates significant therapeutic potential for glioma and holds promising applications in the field of cancer immunotherapy. [Display omitted] • The peptide DAT was designed based on the immunomodulatory transmembrane peptide DP7 and brain tumor targeting T7. • DAT modified siRNA delivery system can overcome the blood-brain barrier and blood-brain tumor barrier. • The DAP-LNP/siRNA delivery system is capable of reshaping the immunosuppressive tumor microenvironment to treat glioma. [ABSTRACT FROM AUTHOR]

In recent years, natural draft dry cooling systems with only one tower have been adopted in some 2 × 660 MW power-generating units owing to the advantage of lower construction costs. The operating cases of two power-generating units and one power-generating unit will both appear based on the power load requirement, which may lead to very different flow and heat transfer performances of this typical cooling system. Therefore, this research explores the local thermo-flow characteristics of air-cooled heat exchangers and sectors, and then analyzes the overall cooling performance of the above two operating cases under various wind conditions. Using the numerical modeling method, the results indicate that the flow and heat transfer performance of this cooling system decreases significantly in the case of one unit with half sectors dismissed. At wind speeds lower than 8 m/s, the difference in turbine back pressure between two units and one unit appears obviously higher than in other wind conditions, even reaching 4.37 kPa. Furthermore, the air-cooled heat exchanger in the lower layer always has better cooling capability than that in the upper layer, especially in conditions where there is an absence of wind and under low wind speeds. The operating case of one unit is not recommended for this dry cooling system because of the highly decreased energy efficiency. In conclusion, this research could provide theoretical support for the engineering operation of this typical natural draft dry cooling system in 2 × 660 MW power plants. [ABSTRACT FROM AUTHOR]

Background and Objectives: Elagolix is an orally active, gonadotropin-releasing hormone receptor antagonist approved for the management of endometriosis-associated pain and heavy menstrual bleeding associated with uterine fibroids. Elagolix population pharmacokinetics and factors affecting elagolix exposure in healthy women and women with endometriosis have been reported previously. The purpose of this study was to extend the population pharmacokinetics model with additional modifications to incorporate data from phase III studies of elagolix with hormonal add-back therapy in women with uterine fibroids. Methods: Data from 13 clinical studies (a total of 2168 women) consisting of six phase I studies in healthy premenopausal women, four phase III studies in premenopausal women with endometriosis, and three phase III studies in premenopausal women with uterine fibroids were analyzed using a non-linear mixed-effects modeling approach. Results: Elagolix population pharmacokinetics was best described by a two-compartment model with first-order absorption, lag time in absorption, and first-order elimination. Out of the covariates tested on elagolix apparent clearance, apparent volume of distribution, and/or relative bioavailability, only organic anion transporting polypeptide 1B1 genotype status and body weight had a statistically significant but no clinically meaningful effect on elagolix relative bioavailability and apparent volume of distribution, respectively. There were no clinically meaningful differences in elagolix population pharmacokinetics in healthy women or women with endometriosis or uterine fibroids. Conclusions: Elagolix population pharmacokinetics modeling did not reveal any patient-related factors or clinical parameters that would require dose adjustments for the approved dosage of 300 mg twice daily with estradiol 1 mg /norethindrone acetate 0.5 mg daily, in women with heavy menstrual bleeding associated with uterine fibroids. Clinical Trial Registration: ClinicalTrials.gov identifiers: NCT01620528 (EM-1), NCT01760954 (EM-1-Extend), NCT01931670 (EM-2), NCT02143713 (EM-2-Extend), NCT02654054 (UF-1), NCT02691494 (UF-2), NCT0295494 (UF-Extend). [ABSTRACT FROM AUTHOR]

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss‐of‐function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility. [ABSTRACT FROM AUTHOR]

The Multiband Ultraviolet Spectrum Imager (MUSI) is an optical remote sensing instrument scheduled to launch on the Fengyun‐4C meteorological satellite in 2024. MUSI is designed to measure the airglow emissions between ∼120 and 160 nm above the East Asia and Pacific region from a geostationary orbit to infer ionospheric parameters. Here we develop a lookup‐table algorithm for retrieving the peak electron density (nmF2) and the Total Electron Content (TEC) from nighttime observations of the OI 135.6 nm emission. The algorithm takes into account the north‐south asymmetry of the equatorial ionization anomaly and the atmospheric variations with solar activity and local time. Analysis of synthetic observations shows that the assumptions made in the algorithm only lead to ∼2%–4% uncertainties in the retrievals under the modeled ionospheric conditions. The algorithm is verified by retrieving nmF2 and TEC from the Global‐Scale Observations of the Limb and Disk (GOLD) mission and comparing with coincided radio measurements. The comparison indicates almost negligible systematic differences (typically less than ∼3%) between the GOLD and the ionosonde nmF2, which are within the error limit of the GOLD retrievals. The accuracy of the GOLD TEC retrievals is shown to be comparable to (or in some sense even better than) that of the measurements from the Global Navigation Satellite System. Several simplified yet robust retrieval methods are also developed, which can be readily implemented for both existing and upcoming missions. Our results promote far ultraviolet (FUV) remote sensing to be a key technology for accurate determination of the ionospheric state. Key Points: We develop a lookup‐table algorithm for ionosphere retrieval with the FUV spectral imager on the Fengyun‐4C geostationary satelliteAssumptions made in the algorithm lead to only ∼2%–4% uncertainties in the nmF2 and Total Electron Content (TEC) retrievals under the modeled ionospheric conditionsThe algorithm is verified by retrieving nmF2 and TEC from the Global‐Scale Observations of the Limb and Disk observations and comparing with external radio measurements [ABSTRACT FROM AUTHOR]

Scanning probe block copolymer lithography (SPBCL), in combination with density-functional theory (DFT), has been used to design and synthesize hydrogen evolution catalysts. DFT was used to calculate the hydrogen adsorption energy on a series of single-element, bimetallic, and trimetallic (Au, Pt, Ni, and Cu) substrates to provide leads that could be synthesized in the form of alloy or phase-separated particles via SPBCL. PtAuCu (18 nm, ~1:1:1 stoichiometry) has been identified as a homogeneous alloy phase that behaves as an effective hydrogen evolution catalyst in acidic aqueous media, even when it is made in bulk form via solution phase methods. Significantly, the bulk-prepared PtAuCu/C nanocatalyst discovered via this process exhibits an activity seven times higher than that of the state-of-the-art commercial Pt/C catalyst (based upon Pt content). The advantage of using SPBCL in the discovery process is that one can uniformly make particles, each consisting of a uniform phase combination (e.g., all alloy or all phase-segregated species) at a fixed elemental ratio, an important consideration when working with polyelemental species where multiple phases may exist. [ABSTRACT FROM AUTHOR]

Background: Ultrasound is more widely used than mammography for early diagnosis of breast cancer in China as most Chinese women have small and dense mammary glands. This study compared the diagnostic performance of ultrasound and mammography for breast cancer among Chinese women with suspected breast lesions. Methods: From November 2019 to November 2021, we compared the results of ultrasound and mammography for breast lesion diagnosis in 2737 consecutive participants with suspected breast lesions; all patients underwent biopsies. We measured the sensitivity, specificity, and diagnostic accuracy separately. Results: Among the 2737 participants, 2844 breast lesions were detected, including 1935 (68.0%) breast cancers and 909 (32.0%) benign lesions. Of the breast cancers, ultrasound detected 1851 (95.7%), whereas mammography detected 1527 (78.9%). The sensitivity of ultrasound for breast cancer diagnosis was significantly higher than that of mammography (95.7% vs. 78.9%, p < 0.001), whereas the specificity was significantly lower than that of mammography (42.9% vs. 62.3%, p < 0.001). The receiver operating characteristic curves revealed that ultrasound was more accurate in detecting breast cancer than mammography (76.8% vs. 71.3%, p < 0.001). Age, body mass index, and breast density did not influence ultrasound sensitivity and accuracy. Conclusions: Ultrasound is more sensitive and accurate than mammography and detects more breast cancers with a lower specificity. [ABSTRACT FROM AUTHOR]

Testis-specific PRSS55 is a chymotrypsin-like serine protease that is highly conserved among mammalian species. The essential role of Prss55 in mouse male fertility has been established. What is the role of PRSS55 in human reproduction? Whole exome sequencing was used to identify the genetic cause in an infertile male with teratozoospermia. Papanicolaou staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to explore morphological defects in the patient's spermatozoa. Immunofluorescence staining and western blot analysis were conducted to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist the patient with fertilization. Sanger sequencing of the pedigree demonstrated that the infertile man carried a novel homozygous mutation in PRSS55 (c.575C>T [p.A192V]). Morphological defects in the sperm head, neck, midpiece and tail were demonstrated by Papanicolaou staining, SEM and TEM. Immunofluorescence staining and western blotting of the patient's spermatozoa showed that the point mutation changed the conformation of PRSS55 and caused a sharp decrease in the PRSS55 protein concentration. The expression and subcellular localization of PRSS55 in the testis and spermatozoa of mice and humans showed that PRSS55 was expressed in the head and flagella of spermatids and epididymal spermatozoa. Moreover, ICSI treatment for this kind of infertile patient was shown to be effective. These findings revealed a novel mutation in PRSS55 in an infertile patient, suggesting for the first time the crucial role of PRSS55 in human fertility. This study provides new insight into genetic counselling diagnoses and subsequent treatment for male infertility. [ABSTRACT FROM AUTHOR]

Summary: We designed a single-protein production (SPP) system in living E. coli cells that exploits the unique properties of MazF, a bacterial toxin that is an ssRNA- and ACA-specific endoribonuclease. In effect, MazF functions as an “mRNA interferase,” because it efficiently and selectively degrades all cellular mRNAs in vivo, resulting in a precipitous drop in total protein synthesis. Concomitant expression of MazF and a target gene engineered to encode an ACA-less mRNA results in sustained and high-level (up to 90%) target expression in the virtual absence of background cellular protein synthesis. Remarkably, target synthesis continues for at least 4 days, indicating that cells retain transcriptional and translational competence despite their growth arrest. SPP technology works well for E. coli (soluble and membrane), yeast, and human proteins. This expression system enables unparalleled signal to noise ratios that should dramatically simplify structural and functional studies of previously intractable but biologically important proteins. [Copyright &y& Elsevier]

Previous studies suggest that a reward-associated salient distractor can induce bottom-up attentional capture. Hitherto, the neurophysiological mechanisms underlying attentional allocation upon reward/loss associated nonsalient stimulus remain hardly investigated. The present study built the association between nonsalient stimuli and value, and tested it with a decision-making task. Consequently, we examined whether and how reward/loss-associated nonsalient stimuli (as distractors) influenced attentional allocation in a rapid serial visual presentation task. Behavioral analysis showed a significantly faster recognition of target in the loss condition compared to performance in the neutral/reward conditions. Electrophysiological results showed that reward-associated distractors induced a significant Pd component, while loss-associated distractors induced a significantly higher theta oscillation. These results demonstrated that subjects could proactively suppress reward-associated distractors. More importantly, we showed that attentional allocation upon reward/loss-associated nonsalient distractors is supported by distinct neural mechanisms. • Attentional allocation upon reward/loss-associated nonsalient distractors is supported by distinct neural mechanisms. • Reward-associated nonsalient distractor can be actively suppressed. • Theta oscillation was higher in Loss-associated condition. [ABSTRACT FROM AUTHOR]

The synergistic effect of enhanced low dose rate sensitivity and single-event transients (SETs) in the bipolar dual operational amplifier LM158 is studied. The test results show a significant reduction in the SET amplitude and broadening in the SET waveform upon exposure to total ionizing dose radiation. These results are much more prominent for a low dose rate (LDR) irradiation of 0.01 rad(Si)/s than for a high dose rate irradiation of 10 rad(Si)/s. The greater gain degradation in the LM158 with LDR irradiation could be the direct cause of the reduction in the SET amplitude and broadening in the SET waveform, and this is corroborated through HSPICE simulations. [ABSTRACT FROM AUTHOR]

Purpose: There are limited genes known to cause primary ciliary dyskinesia (PCD)–associated asthenozoospermia. In the present study, we aimed to expand the spectrum of mutations in PCD and to provide new information for genetic counseling diagnoses and the treatment of male infertility in PCD. Methods: One sterile patient with typical situs inversus was recruited to our center, and semen sample was collected. We performed whole-exome sequencing (WES) on the patient to identify the pathogenic mutations associated with PCD and used transmission electron microscopy to investigate spermatozoal ultrastructure. In addition, western blotting and immunofluorescence staining were used to confirm the untoward impact of the variant on the expression of LRRC6, as well as on the dynein arm proteins in the patient's spermatozoa. Results: We identified a homozygous nonsense variant c.749G>A (p.W250*) of LRRC6 in the PCD patient. This variant severely impaired LRRC6 expression and further led to negative effects on dynein arm protein expression in the spermatozoa of the affected individual, which eventually caused defects in sperm ultrastructure and motility. Moreover, we are the first to report a positive prognosis using intracytoplasmic sperm injection (ICSI) for LRRC6-associated male infertility. Conclusions: Our findings strongly implicated the homozygous mutation of c.749G>A (p.W250*) in LRRC6 as a new genetic cause of PCD, uncovering its involvement in defective sperm flagella and poor sperm motility. Furthermore, we posit that patients with LRRC6 mutations may have good outcomes with ICSI treatment. These findings add to the literature on the genetic diagnoses and treatment of male infertility associated with PCD. [ABSTRACT FROM AUTHOR]

In this paper, a temperature-switching approach (TSA) was used to evaluate low-dose-rate (LDR) ionizing radiation effects on single-event transients (SETs) in linear bipolar circuits. The experimental results show that the SET phenomenon of bipolar circuits after irradiation using a TSA with 3-rad(Si)/s dose rate is basically consistent with the SET phenomenon of bipolar circuits after LDR of 0.01-rad(Si)/s irradiation, which is obviously different from the SET phenomenon of bipolar circuits after the high-dose-rate of 10-rad(Si)/s irradiation. The TSA for evaluating the enhanced LDR sensitivity (ELDRS) of bipolar devices can be applied to the rapid evaluation of the SET effect of the bipolar circuits with LDR irradiation. [ABSTRACT FROM AUTHOR]

A temperature-switching irradiation (TSI) sequence has been developed that is based on a first-principles understanding of interface-trap buildup and annealing. The dynamics of interface-trap buildup and annealing during elevated temperature irradiation are described in detail to provide background, context, and enhanced understanding of the TSI method. The method is shown to be a practical and conservative test for enhanced low-dose-rate sensitivity (ELDRS) in linear bipolar devices and ICs. Examples of TSI sequences are shown for target doses up to 200 krad(Si), a range of great practical interest for space applications. The method can be adapted for higher dose applications via similar approaches. Devices that do not exhibit ELDRS respond similar to TSI and high-dose-rate irradiation. [ABSTRACT FROM AUTHOR]

Introduction: Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids. The pharmacokinetics of elagolix have been well-characterized in phase I studies; however, elagolix population pharmacokinetics have not been previously reported. Therefore, a robust model was developed to describe elagolix population pharmacokinetics and to evaluate factors affecting elagolix pharmacokinetic parameters.Methods: The data from nine clinical studies (a total of 1624 women) were included in the analysis: five phase I studies in healthy, premenopausal women and four phase III studies in premenopausal women with endometriosis.Results: Elagolix population pharmacokinetics were best described by a two-compartment model with a lag time in absorption. Of the 15 covariates tested for effect on elagolix apparent clearance (CL/F) and/or volume of distribution only one covariate, organic anion transporting polypeptide (OATP) 1B1 genotype status, had a statistically significant, but not clinically meaningful, effect on elagolix CL/F.Conclusion: Elagolix pharmacokinetics were not affected by patient demographics and were similar between healthy women and women with endometriosis. Clinical Trial Registration Numbers NCT01403038, NCT01620528, NCT01760954, NCT01931670, NCT02143713. [ABSTRACT FROM AUTHOR]

Biochar is an organic amendment used for soil remediation, there are only a few studies documenting the effects of nitrogen on the role of biochar in contaminated soils. A pot experiment was conducted to investigate the impacts of biochar (0%, 1%, and 2.5%, w/w) and nitrogen (0, 100, and 200 mg N kg−1) on plant growth, nutrient and cadmium (Cd) uptake of Cichorium intybus. N, P, Ca, Mg, and Cd concentrations increased with N level in 0% and 1% biochar treatments. In plants treated with 2.5% biochar, 200 mg N kg−1 addition caused significant reductions of N, P, Ca, Mg, and Cd concentrations in comparison to 100 mg N kg−1 treatments. Nitrogen promoted shoot biomass at all biochar treatments, while biochar had no effect on shoot biomass in 0 and 200 mg N kg−1 addition treatments. Nitrogen also significantly increased N, P, K, Ca, Mg, and Cd contents in the 0% and 1.5% biochar addition treatments. Although soil DTPA-extractable Cd concentration showed the lowest values in 1% biochar in combination with 100 and 200 mg N kg−1 addition treatments, lowest shoot Cd concentration, and relatively high shoot biomass occurred in the 2.5% biochar + 200 mg N kg−1 treatment. Based on these results, biochar application at its highest rate (2.5%) in combination with high N supply (200 mg N kg−1) contributed to both crop yield and agricultural product safety. N input alone might increase the risk of human health, and the optimum N dose should be determined during phytostabilization process. [ABSTRACT FROM AUTHOR]

Enhanced low-dose rate sensitivity (ELDRS) exhibited at low-dose rates (LDRs) by most bipolar devices is considered as one of the main concerns for spacecraft reliability. In this work, a time-saving and conservative approach – temperature-switching approach (TSA) – to simulate the ELDRS of bipolar devices is presented. Good agreement is observed between the predictive curve obtained with the TSA and the LDR data, and TSA provides us with a new insight into the test technique for ELDRS. Additionally, the mechanisms of TSA are analyzed in this paper. [ABSTRACT FROM PUBLISHER]