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Objective: To compare effectiveness of topical 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA PDT) and loop electrosurgical excision procedure (LEEP) among patients with cervical intraepithelial neoplasia (CIN). Methods: We retrospectively identified patients who underwent either 5-ALA PDT or LEEP from Sep. 2012 to Dec. 2019 in Chinese PLA general hospital. Patients' outcomes were compared according to the HPV genotyping, cytological tests within 3–6-month follow-up post-treatment, the pathological examination would be performed if the cytological results indicated the risk of CIN. Propensity score matching (PSM) was adapted to pair the baseline. Complete remission (CR), partial remission (PR) and the remission rate of HPV infections were used to evaluate the efficacy of 5-ALA PDT versus LEEP. Results: In total, 30 pairs were matched as the matching tolerance was set as 0.03. There was no significant difference about the CR and PR between 5-ALA PDT and LEEP group (73.33% vs 84.00%, P = 0.340; 3.33% vs 4.00%, P = 1.000). Among different CIN group, there was no statistic difference between 5-ALA PDT and LEEP. Moreover, in terms of HPV remission rate, 5-ALA PDT showed the same efficacy as LEEP (59.26% vs 53.85%, P = 0.691). Conclusions: In essence, topical 5-ALA PDT emerges as a non-invasive, repeatable procedure with minimal side effects for cervical lesions, preserving cervical structure. Overall, the efficacy of 5-ALA PDT is comparable to LEEP in achieving successful outcomes. [ABSTRACT FROM AUTHOR]

The preparation of cellular metabolomics samples and how to achieve comprehensive coverage of different polar metabolites in cell samples in the analysis pose a challenge for cellular metabolomics. In this study, we optimized a metabolomics protocol based on ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC/HRMS) for the extraction and detection of metabolites in A549 cells and exploration of the intervention effect of Qi-Yu-San-Long decoction (QYSLD) on A549 cells. The results indicate that the lowest level of ATP leakage was observed when A549 cells were quenched under liquid nitrogen. MeOH/chloroform/H2O (1:2:1) extraction yielded more chromatographic peaks and excellent reproducibility, and the relative extraction efficiency of most target metabolites was also high. And we optimized the chromatographic separation conditions in both HILIC and RPLC modes, enabling comprehensive detection and analysis of metabolites with varying polarities. Then, we applied the optimized method to UPLC-Q-TOF/MS-based metabolomics of A549 cells to study the mechanism of QYSLD intervention in non-small cell lung cancer (NSCLC). The CCK-8, EdU staining, and cell cycle assay showed that QYSLD inhibited the proliferation of A549 cells by interfering with the cell cycle and blocking them in the G1 phase. A total of 36 differential metabolites associated with the antitumor effects of QYSLD on NSCLC were identified, mainly involving nicotinate and nicotinamide metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. And western blotting confirmed that the change in 1-methylnicotinamide levels after QYSLD intervention was associated with the inhibition of nicotinamide N-methyltransferase expression in A549 cells. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a major global health concern, with its prevalence increasing steadily. While plasma proteins have been implicated in NAFLD, establishing causal relationships has been challenging due to confounding factors in observational studies. This study aims to explore the causal relationships between plasma proteins and NAFLD using Mendelian randomization (MR) analysis. We utilized genome-wide association study (GWAS) data from multiple sources to conduct MR analyses. Plasma protein data were obtained from the deCODE open database, and NAFLD data were sourced from the Finnish genetic sample collection (FinnGen). We performed MR analysis to identify plasma proteins causally related to NAFLD and explored the potential mediation effect of antibody-immune responses. Our MR analysis identified three plasma proteins—KNG1, MICB, and PKD2—with significant causal relationships to NAFLD. Mediation analysis further revealed that KNG1 negatively mediated the risk of NAFLD through Epstein-Barr virus EA-D antibody levels, while MICB and PKD2 positively mediated NAFLD risk through the same antibody levels. This study provides novel genetic evidence of causal relationships between specific plasma proteins and NAFLD risk. Measuring the levels of KNG1, MICB, PKD2, and Epstein-Barr virus EA-D antibody levels in patients may help clinicians assess NAFLD risk more accurately. Further clinical research is warranted to validate these findings and explore their potential therapeutic implications. [ABSTRACT FROM AUTHOR]

In the hard turning process of AISI M2, due to its high hardness and high strength, the tool wear is serious. Tool wear seriously restricts the economic feasibility of hard turning and the machining quality of workpiece. Therefore, it is very necessary to take optimization measures of cutting parameters to reduce tool wear. In this research, 15 groups of hard turning experiments were carried out based on BBD. The relative wear of tool flank in hard turning per unit material volume was taken as the optimization objective, and the prediction model of relative wear of tool flank was established. The research results were as follows: (1) the wear forms of CBN tool were crater wear of tool rake, abrasive wear of tool flank and cutting edge wear; (2) the correlation coefficient R2 of the prediction model was 0.9922, and the adjusted correlation coefficient R adj 2 was 0.9843; and (3) the contribution of feed rate to the relative wear of tool flank was 48.83%, and that of depth of cut was 22.05%. A = 81.17 m/min, B = 0.15 mm/rev and C = 0.2 mm were the optimal cutting parameters. This research is helpful to reduce the tool wear in hard turning and improve the economic feasibility of hard turning precision machining. [ABSTRACT FROM AUTHOR]

Background and Objectives: Smoothened (SMO), a key component of the hedgehog signaling pathway, represents a therapeutic target for triple negative breast cancer (TNBC), yet the chemotherapy response rate in TNBC patients is only 40–50%, underscoring the urgent need for the development of novel drugs to effectively treat this condition. The novel compound TPB15, an SMO inhibitor derived from [1,2,4] triazolo [4,3-α] pyridines, demonstrated superior anti-TNBC activity and lower toxicity compared to the first SMO inhibitor vismodegib in both in vitro and in vivo. However, the compound's pharmacokinetic properties remain unclear. The present work aims to develop a simple HPLC-MS/MS method to profile the pharmacokinetics and bioavailability of TPB15 in rats as a ground work for further clinical research. Methods: Separation was performed on an Agilent ZORBAX StableBond C18 column by gradient elution using acetonitrile and 0.1% formic acid as mobile phase at a flow rate of 0.3 mL/min. Multiple reaction monitoring(MRM) in positive mode with the transitions of m/z 454.2 → 100.0, 248.1 → 121.1 was employed to determine TPB15 and internal standard tinidazole, respectively. The specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover of the method was validated. The pharmacokinetics and bioavailability study of TPB15 were carried out on rats through intravenous injection at the dose of 5 mg/kg and oral gavage at the dose of 25 mg/kg, and the pharmacokinetics parameters were calculated by the non-compartment analysis using the pharmacokinetics software DAS 2.1.1. Results: The values of specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover satisfied the acceptable limits. The lower limit of quantification of this method was 10 ng/mL with a linear range of 10–2000 ng/mL. The validated method was then applied to pharmacokinetics and bioavailability studies in rat by dosing with gavage (25 mg/kg) and intravenous injection(5 mg/kg), and the oral bioavailability of TBP15 in rat was calculated as 16.4 ± 3.5%. The pharmacokinetic parameters were calculated as following: maximum of plasma concentration (Cmax) (PO: 2787.17 ± 279.45 µg/L), Time to maximum plasma concentration (Tmax) (PO: 4.20 ± 0.90 h), the area under the concentration-time curve 0 to time (AUC0–t) (PO: 17,373.03 ± 2585.18 ng/mL·h, IV: 21,129.79 ± 3360.84 ng/mL·h), the area under the concentration-time curve 0 to infinity (AUC0–∞) (PO: 17,443.85 ± 2597.63 ng/mL·h, IV: 17,443.85 ± 2597.63 ng/mL·h), terminal elimination half-life (t1/2) (PO: 7.26 ± 2.16 h, IV: 4.78 ± 1.09 h). Conclusions: TPB15, a promising candidate for treating TNBC, has demonstrated outstanding efficacy and safety in vitro and in vivo. This study established a simple, sensitive, and rapid HPLC-MS/MS bioanalytical method, developed and validated in accordance with FDA and EMA guidelines, for conducting pharmacokinetic and bioavailability studies of TPB15. The results revealed a favorable pharmacokinetic profile owing to its long t1/2. Nevertheless, the next phase of research should include formulation screening to enhance bioavailability, as well as clinical trials, metabolism pathway analysis, and assessment of potential drug-drug interactions. [ABSTRACT FROM AUTHOR]

In this paper, the lattice constants, elastic anisotropies, and elastic constants (C11, C12 and C44) of three Cs halide materials, CsCl, CsBr and CsI have been investigated for the first time by using first-principles-based calculations, and the bulk modulus (B), shear modulus (G), and Young's modulus (E) of the materials have been obtained based on the calculated elastic constants, and the mechanical properties of the materials have been analysed. The elastic anisotropy of the material is calculated and the corresponding three-dimensional surface diagram is drawn. The generalized stacking fault energy (GSFE) curves of CsCl, CsBr and CsI were calculated and the generalized stacking fault energy (GSFE) surfaces were fitted. The calculations show that the elastic constant results for CsCl, CsBr and CsI are fully consistent with the Born stability criterion, i.e., all three materials are consistent with good mechanical stability. The 3D surface images representing the dependence of the elastic properties on the crystal orientation more intuitively reflect the degree of anisotropy of the materials in agreement with the information reflected by the anisotropy factor. By comparing the generalized stacking fault energy (GSFE) surfaces in the three directions of the materials, it is found that the slip of CsI intermetallic is the hardest and the generalized stacking fault energy (GSFE) on the {110} plane has the laws of CsI > CsCl > CsBr along the < 100>, < 110 > and < 111 > directions. [ABSTRACT FROM AUTHOR]

Intermetallic compounds with B2 structure are used in aviation and aerospace, but lower ductilities are required for these materials. Here, to better understand the properties of this class of compound, the lattice constants of the intermetallic compounds AlSc and MgSc with B2 structure were calculated via first-principles methods, along with the their phase transition pressures. The generalized stacking energy curves of AlSc and MgSc at different pressures were also calculated, and the generalized stacking energy surface was fitted. The results reveal that, under pressure, < 111>{110} remains the sliding system of B2-type AlSc and MgSc. As the pressure increases, the antiphase boundary energies and unstable stacking fault energies of the two materials in all directions gradually increase. This means that the more energy required for dislocation in the process of sliding, the lower the ductility of the material. Comparing the phase change pressures of the two materials, it can be seen that AlSc has greater compressive resistance than MgSc, but for MgSc, at pressures lower than the phase change pressure, its ductility is greater than that of AlSc. [ABSTRACT FROM AUTHOR]

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, accounting for the overwhelming majority of malignant liver tumors. Therefore, how to effectively prevent and cure HCC has become a research hotspot. Many studies have shown that arenobufagin can induce apoptosis, ferroptosis, and autophagy of tumor cells. An increasing number of studies have shown that autophagy is closely linked to ferroptosis. In this study, HepG2 cells and BALB/c nude mice were used as research objects to explore the effect and preliminary mechanism of hepatoma cell autophagy and ferroptosis induced by arenobufagin. We found that arenobufagin can significantly inhibit tumor growth in vivo, and interestingly, we found that arenobufagin inhibited ferroptosis-related proteins Nrf2 and COX-2 in a dose-dependent manner and decreased the levels of reduced glutathione (GSH) and superoxide dismutase (T-SOD) in tissues, while increased the level of reduced malondialdehyde (MDA). In addition, we found that arenobufagin increased the levels of COX-2 and MDA in cells, decreased the levels of Nrf2, GSH, and T-SOD, increased the levels of tissue reactive oxygen species (ROS) and lipid ROS in a dose-dependent manner, and promoted ferroptosis in HepG2 cells. HepG2 cells were preprotected by autophagy inhibitor chloroquine (CQ) and ferroptosis inhibitor deferoxamine (DFO), and then treated with arenobufagin. It was found that CQ partially reversed the changes of COX-2 and Nrf2 expression and lipid peroxidation induced by arenobufagin-induced autophagy and HepG2 cells. Interestingly, CQ partially reversed the inhibition of arenobufagin on cytoplasmic junction protein (Keap1) and heme oxygenase-1 (HO-1) in p62-Keap1-Nrf2 pathway. At the same time, we found that the effect of arenobufagin on oxidative stress of HepG2 cells overexpressed by Nrf2 was significantly less than that of the control group. To sum up, arenobufagin promotes autophagy-dependent ferroptosis of HepG2 cells by inducing autophagy and regulating p62-Keap1-Nrf2 pathway. It is suggested that arenobufagin can be used as a potential intervention therapy. [ABSTRACT FROM AUTHOR]

Current studies do not provide a consensus on whether digital technology innovation can reduce enterprise carbon intensity despite the rise of the digital economy. This paper examines the role and influence pathway of digital technology innovation on enterprise carbon intensity using data from A-share listed enterprises in China's manufacturing industry from 2012 to 2021. The findings indicate that (1) digital technology innovation has been found to significantly reduce enterprise carbon intensity, as confirmed by numerous robustness and endogeneity tests. However, its inhibitory effect on carbon intensity shows a marginal decreasing trend. (2) In the heterogeneity analysis, it was found that digital technology innovation significantly reduces the carbon intensity of consuming coal, coke, kerosene, and diesel. From various perspectives, including enterprise, industry, and external environment, there are significant differences in the carbon reduction effects of digital technology innovation. (3) The analysis of impact paths reveals that digital technology innovation can affect enterprise carbon intensity through three paths: improving productivity, enhancing green innovation efficiency, and adjusting energy consumption. (4) Upon further analysis, it was discovered that the spillover effect of digital technology innovation is more pronounced in the industry cohort of enterprises. Additionally, digital technology innovation plays a positive role in enhancing enterprise ESG performance. The paper's findings offer empirical evidence and decision-making references for the government to develop reasonable policies for reducing carbon emissions, promoting green and low-carbon enterprise transformation, and actively and steadily achieving the goal of carbon peaking and carbon neutrality. [ABSTRACT FROM AUTHOR]

Regarding the impact of microplastics (MPs) on the male reproductive system, previous studies have identified a variety of MPs in both human semen and testicular samples. These studies have put forward the hypothesis that small particles can enter the semen through the epididymis and seminal vesicles. Here, we performed qualitative and quantitative analyses of MPs in human testis, semen, and epididymis samples, as well as in testis, epididymis, seminal vesicle, and prostate samples from mice via pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The goal of this approach was to comprehensively characterize the distribution of MPs within the male reproductive system. Additionally, we aimed to evaluate potential sources of MPs identified in semen, as well as to identify possible sources of overall MP exposure. Our results highlighted a general atlas of MPs in the male reproductive system and suggested that MPs in semen may originate from the epididymis, seminal vesicles, and prostate. An exposure questionnaire, coupled with the characteristics of the MPs detected in the male reproductive system, revealed that high urbanization, home-cooked meals, and using scrub cleansers were important sources of MP exposure in men. These findings may provide novel insights into alleviating the exposure of men to MPs. [ABSTRACT FROM AUTHOR]

Background: High tumor mutation burden (TMB) failed to serve as a favorable prognostic biomarker for immunotherapy across all tumors. This study aimed to explore TMB-sensitive tumors on a pan-cancer level and construct their immune infiltration phenotypes in TMB-high groups. Methods: Pan-cancer patients were separated into TMB-high and TMB-low groups based on the median TMB values per tumor. TMB-related genes were identified using differently expressed genes (DEGs) and differently mutated genes (DMGs) between the above two TMB groups. CIBERSORT algorithm was used to estimate the abundance of 22 tumor immune infiltrating cells (TIICs). Consensus clustering analysis was applied to predict molecular subtypes. Cox regression analysis was performed to evaluate the correlations between hub genes and TIICs and immunomodulator genes. Results: Nine TMB-sensitive tumors were identified by high-frequency of TMB-related genes. A total of 126 tumor-specific hub genes (1 in BLCA, 19 in BRCA, 4 in COAD, 4 in HNSC, 25 in LUAD, 2 in LUSC, 27 in SKCM, 37 in STAD, and 7 UCEC) were identified. In five out of nine TMB-sensitive tumors, the molecular subtypes based on hub gene expression were characterized by TMB values, prognostic values and tumor-specific TIICs levels. In TMB-high groups, hub genes associated immune infiltration phenotypes were constructed with key TIICs and immunomodulators spanning TMB-sensitive tumors. Conclusions: Our tumor-specific analysis revealed hub genes associated immune infiltration features may serve as potential therapeutic targets and prognostic markers of immunotherapy, providing the potential underlying mechanism of immune infiltration in TMB-high groups across TMB-sensitive tumors. [ABSTRACT FROM AUTHOR]

Purpose: Poor ovarian response (POR) affects approximately 9% to 24% of women undergoing in vitro fertilization (IVF) cycles, resulting in fewer eggs obtained and increasing clinical cycle cancellation rates. The pathogenesis of POR is related to gene variations. Our study included a Chinese family comprising two siblings with infertility born to consanguineous parents. Poor ovarian response (POR) was identified in the female patient who had multiple embryo implantation failures occurring in subsequent assisted reproductive technology cycles. Meanwhile, the male patient was diagnosed with non-obstructive azoospermia (NOA). Methods: Whole-exome sequencing and rigorous bioinformatics analyses were conducted to identify the underlying genetic causes. Moreover, the pathogenicity of the identified splicing variant was assessed using a minigene assay in vitro. The remaining poor-quality blastocyst and abortion tissues from the female patient were detected for copy number variations. Results: We identified a novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings. Apart from NOA and POI, biallelic variants in HFM1 were also associated with recurrent implantation failure (RIF). Additionally, we demonstrated that splicing variants caused abnormal alternative splicing of HFM1. Using copy number variation sequencing, we found that the embryos of the female patients had either euploidy or aneuploidy; however, both harbored chromosomal microduplications of maternal origin. Conclusion: Our results reveal the different effects of HFM1 on reproductive injury in males and females, extend the phenotypic and mutational spectrum of HFM1, and show the potential risk of chromosomal abnormalities under the RIF phenotype. Moreover, our study provides new diagnostic markers for the genetic counseling of POR patients. [ABSTRACT FROM AUTHOR]

This study explored the role of P2X7 receptors in spinal cord astrocytes in the electroacupuncture-induced inhibition of visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS). Visceral hypersensitivity of IBS was intracolonically induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Visceromotor responses to colorectal distension (CRD-20,40,60,80 mmHg) and abdominal withdrawal reflex scoring (AWRs) were recorded after electroacupuncture at bilateral Zusanli (ST36) and Sanyinjiao (SP6) acupoints to evaluate the analgesic effect of electroacupuncture on visceral pain in rats with IBS. Fluorocitric acid (FCA), an astrocyte activity inhibitor, was injected intrathecally before electroacupuncture intervention and AWRs were recorded. Western blot and real-time qPCR were used to detect the expression of NMDA and P2X7 receptor to observe the regulation effect of electroacupuncture on NMDA receptor in the spinal cord of rats with visceral hypersensitivity. Intrathecal injection of P2X7 agonist or antagonist was administered before electroacupuncture treatment. To observe the effect of P2X7 receptor in spinal astrocytes on the inhibition of visceral hyperalgesia by electroacupuncture, the changes of AWR score, NMDA receptor in the spinal cord, and GFAP expression in astrocytes were detected. Inflammation of the colon had basically subsided at day 21 post-TNBS; persistent visceral hypersensitivity could be suppressed by electroacupuncture. This analgesic effect could be inhibited by FCA. The analgesic effect, downregulation of NMDA receptor NR1 subunit, and P2X7 protein of electroacupuncture were all reversed by FCA. P2X7 receptor antagonist A740003 can cooperate with EA to carry out analgesic effect in rats with visceral pain and downregulate the expression of NR1, NR2B, and GFAP in spinal dorsal horn. However, the P2X7 receptor agonist BzATP could partially reverse the analgesic effect of EA, inhibiting the downregulatory effect of EA on the expression of NR1, NR2B, and GFAP. These results indicate that EA may downregulate the expression of the NMDA receptor by inhibiting the P2X7 receptor in the spinal cord, thereby inhibiting spinal cord sensitization in IBS rats with visceral pain, in which astrocytes are an important medium. [ABSTRACT FROM AUTHOR]

Background: ADAM metallopeptidase domain 12 (ADAM12) is generally upregulated in tissues of various tumors, emerging as a prognostic biomarker. However, the clinical significance of serum ADAM12 in tumors still remains to be fully elucidated. The present study aimed to investigate the expression and prognostic value of serum ADAM12 in tumor patients. Materials and methods: Serum samples were collected from healthy doners (HDs; n = 87) and patients (n = 238) with a clinical diagnosis of breast, liver, lung, stomach and esophageal (STES) and thyroid cancer. Serum ADAM12 protein and mRNA expression was detected by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), respectively. Receiver–operator characteristic (ROC) analysis was performed to explored the prognostic value of serum ADAM12 expression. Results: The expression of serum ADAM12 in breast and liver cancer patients was significantly upregulated compared with HDs. In patients with breast cancer, the levels of serum ADAM12 protein and mRNA were significantly higher in tumor stages than that in HDs (p < 0.05), with AUC value of 0.82. In liver cancer, elevated levels of serum ADAM12 protein were significantly correlated with clinical stage (r = 0.74; p = 6.9e−4) and T stage (r = 0.74, p = 7.6e−4), and attained AUC value of 1. However, the clinical significance of serum ADAM12 expression in lung, STES and thyroid cancer had not been found. Conclusions: Serum ADAM12 expression showed high degree of tumor heterogeneity, and may be a valuable noninvasive diagnostic and prognostic biomarker for breast and liver cancer. [ABSTRACT FROM AUTHOR]

High pressure represents extreme environments and provides opportunities for materials discovery1–8. Thermal transport under high hydrostatic pressure has been investigated for more than 100 years and all measurements of crystals so far have indicated a monotonically increasing lattice thermal conductivity. Here we report in situ thermal transport measurements in the newly discovered semiconductor crystal boron arsenide, and observe an anomalous pressure dependence of the thermal conductivity. We use ultrafast optics, Raman spectroscopy and inelastic X-ray scattering measurements to examine the phonon bandstructure evolution of the optical and acoustic branches, as well as thermal conductivity under varied temperatures and pressures up to 32 gigapascals. Using atomistic theory, we attribute the anomalous high-pressure behaviour to competitive heat conduction channels from interactive high-order anharmonicity physics inherent to the unique phonon bandstructure. Our study verifies ab initio theory calculations and we show that the phonon dynamics—resulting from competing three-phonon and four-phonon scattering processes—are beyond those expected from classical models and seen in common materials. This work uses high-pressure spectroscopy combined with atomistic theory as a powerful approach to probe complex phonon physics and provide fundamental insights for understanding microscopic energy transport in materials of extreme properties.Competition between three- and four-phonon scattering processes is shown to be the source of a unique anomalous thermal conductivity in boron arsenide at high pressures. [ABSTRACT FROM AUTHOR]

Non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) represent the most serious forms of human infertility caused by gametogenic failure. Although whole-exome sequencing (WES) has uncovered multiple monogenic causes of human infertility, our knowledge of the genetic basis of human gametogenesis defects remains at a rudimentary stage. Coiled-coil-domain-containing protein 155 (CCDC155) encodes a core component of the linker of the nucleoskeleton and cytoskeleton complex that is essential for modulating telomere-led chromosome movements during the meiotic prophase of mice. Additionally, Ccdc155 deficiency in mice causes infertility in both sexes with meiotic arrest. In this study, we applied WES to identify the pathogenic genes for 15 NOA and POI patients whose parents were consanguineous and identified a novel homozygous missense mutation in CCDC155 [c.590T>C (p.Leu197Pro)] in a pair of familial NOA and POI patients whose parents were first cousins. The affected spermatocytes were unable to complete meiotic division coupled with unresolved repair of the DNA double-strand break. This rare missense mutation with lesions in the conserved CC domain of CCDC155 blocked nuclear envelope (NE) distribution and subsequently prevented NE-specific enrichment of Sad1- and UNC84-domain-containing 1 either ex vivo or in vitro, eventually leading to disruptive NE anchoring of chromosome-induced meiotic arrest in both sexes. This study presents the first evidence of the necessity of the SUN1–CCDC155 complex during human meiosis and provides insight into the CCDC155 CC domain, thereby expanding the genetic spectrum of human NOA and POI and promoting adequate genetic counselling and appropriate fertility guidance for these patients. [ABSTRACT FROM AUTHOR]

This study investigated whether singleton pregnancies conceived after preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are associated with a higher risk of adverse perinatal outcomes than singleton pregnancies conceived after intracytoplasmic sperm injection (ICSI). We collected data on singleton live births after PGT-SR (n = 107) and ICSI (n = 585) in our hospital from January 2017 to August 2020. Multivariable analyses were used to adjust for maternal age, body mass index, gravidity and parity, paternal age, ovulatory disorder, and recurrent spontaneous abortion. The unadjusted results showed a significantly higher risk of hypertensive disorders of pregnancy (HDP) (odds ratio (OR) = 2.47; 95% confidence interval (CI): 1.10–5.54; P = 0.029) associated with PGT-SR singleton pregnancies than with ICSI singleton pregnancies. However, after adjusting for potential confounders, there were no longer any significant differences in the risk of HDP (adjusted OR = 2.24; 95% CI: 0.92–5.48; P = 0.077) between PGT-SR and ICSI singleton pregnancies. There were no significant differences between PGT-SR and ICSI singleton pregnancies in terms of gestational diabetes, preterm premature rupture of membranes, placenta previa, cesarean delivery, gestational age (weeks), preterm delivery (< 37 weeks), very preterm delivery (≥ 28 weeks and < 32 weeks), birth weight (g), low birth weight (< 2500 g), very low birth weight (< 1500 g), birth height (cm), birth defects, and 1-min and 5-min Apgar scores. In conclusion, for single frozen-thawed blastocyst cycles, there were no significant differences in adverse perinatal outcomes between PGT-SR and ICSI singleton pregnancies. However, due to the limited sample size, these conclusions need to be confirmed by further studies. [ABSTRACT FROM AUTHOR]

Nanosized tungsten carbide (WC)/carbon (C) catalyst was synthesized via a novel ultra-rapid confinement combustion synthesis method. The amount of activated carbon (AC) plays an important role in the morphology and structure, controlling both the precursor and final powder. The WC particles synthesized inside the pores of the AC had been 10–20 nm because of the confinement of the pore structure and the large specific surface area of AC. When used for oxygen reduction performance, the half-wave potential was −0.24 V, and the electron transfer number was 3.45, indicating the main reaction process was the transfer of four electrons. The detailed electrocatalytic performance and underlying mechanism were investigated in this work. Our study provides a novel approach for the design of catalysts with new compositions and new structures, which are significant for promoting the commercialization of fuel cells. [ABSTRACT FROM AUTHOR]

The effect of hydrocarbon (HC) concentration on particulate deposition and the microstructure of the deposit in exhaust gas recirculation (EGR) cooler was investigated. The EGR cooler inlet gas temperature was 300 °C and the coolant temperature was 85 °C throughout the test, and the HC concentration was fixed at 200 ppm, 450 ppm, and 850 ppm respectively. The results indicated that there is a HC concentration region in which the effect of HC condensation on particle deposition in EGR cooler was enhanced. The HC concentration is not only affecting the particulate regeneration and deposition but also affecting the deposit microstructure. The deposit that built up under low HC concentration has two layers, of which the top layer is a thinner loose flocculent dendrite layer and the bottom layer is a thicker dense layer. The deposit in the EGR cooler that built up under high HC concentration conditions is mainly a dense layer, and with clusters of flocculent particles scattered on the surface of it. Due to the large amount of HC volatilized in the deposit layer, the structure of deposit in the EGR cooler that built up under extreme high HC concentration finally becomes coarser and the density decreases. [ABSTRACT FROM AUTHOR]

Anthriscus sylvestris L. Hoffm. Gen (A. sylvestris) is a perennial herb widely used for antitussive and diuretic purposes in traditional Korean and Chinese medicine. Lignans are critical secondary metabolites with widely pharmacological activities in A. sylvestris. Using transcriptome data of A. sylvestris, we identified genes related to lignan biosynthesis. In all, 123,852 unigenes were obtained from the flowers, leaves, roots, and stems of A. sylvestris with the Illumina HiSeq 4000 platform. The average length of unigenes was 1,123 bp and 91,217 (73.65%) of them were annotated in public databases. Differentially expressed genes and root-specific genes were analyzed between roots and the other three tissue types by comparing gene expression profiles. Specifically, the key enzyme genes involved in lignan biosynthesis were identified and analyzed. The expression levels of some of these genes were highest in the roots, consistent with the accumulation of deoxypodophyllotoxin. These expression levels were experimentally verified via quantitative real-time polymerase chain reaction (qRT-PCR). This research provides valuable information on the transcriptome data of A. sylvestris and the identification of candidate genes associated with the biosynthesis of lignans, laying the foundation for further research on genomics in A. sylvestris and related species. [ABSTRACT FROM AUTHOR]

With the widespread use of agile software development methods, such as agile and scrum, software is iteratively updated more frequently. To ensure the quality of the software, regression testing is conducted before new versions are released. Moreover, to improve the efficiency of regression testing, testing efforts should be concentrated on the modified and impacted parts of a program. However, the costs of manually constructing new test cases for the modified and impacted parts are relatively expensive. Fuzz testing is an effective method for generating test data automatically, but it is usually devoted to achieving higher code coverage, which makes fuzz testing unsuitable for direct regression testing scenarios. For this reason, we propose a fuzz testing method based on the guidance of historical version information. First, the differences between the program being tested and the last version are analyzed, and the results of the analysis are used to locate change points. Second, change impact analysis is performed to find the corresponding impacted basic blocks. Finally, the fitness values of test cases are calculated according to the execution traces, and new test cases are generated iteratively by the genetic algorithm. Based on the proposed method, we implement a prototype tool DeltaFuzz and conduct experiments on six open-source projects. Compared with the fuzzing tool AFLGo, AFLFast and AFL, DeltaFuzz can reach the target faster, and the time taken by DeltaFuzz was reduced by 20.59%, 30.05% and 32.61%, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Multiple morphological abnormalities in the sperm flagella (MMAF) comprise a severe phenotype of asthenoteratozoospermia with reduced or absent spermatozoa motility. Whereas dozens of candidate pathogenic genes for MMAF have been identified, the genetic cause in a large proportion of patients is unknown. We attempted to identify novel genetic explanations for MMAF. Methods: We performed whole-exome sequencing of patients with MMAF to identify pathogenic variants. The phenotypes of spermatozoa in patients carrying DNAH10 variants were investigated using haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy. The expression and location of DNAH10 and other spermatozoa structure–related proteins were analyzed using immunofluorescence assays. Results: We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant (NM_207437: c.10820 T > C:p.M3607T; c.12692C > T:p.T4231I) in two patients with MMAF. These variants were absent or rare in the general population. Haematoxylin and eosin staining and scanning electron microscopy revealed the significant disruption of sperm flagella in the patients. In addition, ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella. Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1. Conclusions: We identified putative novel pathogenic variants in DNAH10 for MMAF, which might advance the genetic diagnosis and clinical genetic counselling for male infertility. [ABSTRACT FROM AUTHOR]

Spermatozoa are polarized cells with a head and a flagellum joined together by the connecting piece. Flagellum integrity is critical for normal sperm function, and flagellum defects consistently lead to male infertility. Multiple morphological abnormalities of the flagella (MMAF) is a distinct sperm phenotype consistently leading to male infertility due to a reduced or absent sperm motility associated with severe morphological and ultrastructural flagellum defects. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analyzed remain unresolved, suggesting that many yet uncharacterized gene defects account for this phenotype. By performing a retrospective exome analysis of the unsolved cases from our initial cohort of 167 infertile men with a MMAF phenotype, we identified one individual carrying a homozygous frameshift variant in CFAP206, a gene encoding a microtubule-docking adapter for radial spoke and inner dynein arm. Immunostaining experiments in the patient's sperm cells demonstrated the absence of WDR66 and RSPH1 proteins suggesting severe radial spokes and calmodulin and spoke-associated complex defects. Using the CRISPR–Cas9 technique, we generated homozygous Cfap206 knockout (KO) mice which presented with male infertility due to functional, structural and ultrastructural sperm flagellum defects associated with a very low rate of embryo development using ICSI. Overall, we showed that CFAP206 is essential for normal sperm flagellum structure and function in human and mouse and that bi-allelic mutations in CFAP206 cause male infertility in man and mouse by inducing morphological and functional defects of the sperm flagellum that may also cause ICSI failures. [ABSTRACT FROM AUTHOR]

We present a new self-supervised monocular depth estimation method with multi-scale texture detail enhancement. Based on the observation that the image texture detail and the semantic information have essential significance on the depth estimation, we propose to provide them to the network to learn more sharpness and structural integrity of depth. Firstly, we generate the filtered images and detail images by multi-scale decomposition and use a deep neural network to automatically learn their weights to construct the texture detail enhanced image. Then, we consider the semantic features by putting deep features from the VGG-19 network into a self-attention network, guide the depth decoder network to focus on the integrity of objects in the scene. Finally, we propose a scale-invariant smooth loss to improve the structural integrity of the predicted depth. We evaluate our method on the KITTI 2015 and Make3D datasets and apply the predicted depth to novel view synthesis. The experimental results show that it has achieved satisfactory results compared with the existing methods. [ABSTRACT FROM AUTHOR]

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Purpose: To evaluate the association between the DNA methylation of specific genes and sperm DNA integrity status in human sperm samples. Methods: A total of 166 semen samples were evaluated (86 controls and 80 cases with impaired sperm DNA integrity). We detected the methylation status of 257 CpG sites among two imprinted genes (H19 and SNRPN) and four non-imprinted genes related to male infertility (MTHFR, GSTM1, DAZL, and CREM) by using a targeted next-generation sequencing method. Results: Differential methylation was found in 43 CpG sites of the promoters of the six candidate genes. H19, SNRPN, MTHFR, DAZL, GSTM1, and CREM contained 22, 12, 1, 4, 0, and 4 differentially methylated CpG sites (P<0.05), respectively. The imprinting genes were associated with relatively higher rates of differentially methylated CpG sites (28.21% in H19 and 41.38% in SNRPN) than the non-imprinting genes. One CpG site in H19 remained significant after performing strict Bonferroni correction. Conclusion: In this study, we found that different site-specific DNA methylation signatures were correlated with sperm DNA integrity status. Further studies are needed to investigate the specific mechanisms leading to the epigenetic modifications. [ABSTRACT FROM AUTHOR]

The LOX genes have been identified and characterized in many plant species, but studies on the banana LOX genes are very limited. In this study, we respectively identified 18 MaLOX, 11 MbLOX, and 12 MiLOX genes from the Musa acuminata, M. balbisiana and M. itinerans genome data, investigated their gene structures and characterized the physicochemical properties of their encoded proteins. Banana LOXs showed a preference for using and ending with G/C and their encoded proteins can be classified into 9-LOX, Type I 13-LOX and Type II 13-LOX subfamilies. The expansion of the MaLOXs might result from the combined actions of genome-wide, tandem, and segmental duplications. However, tandem and segmental duplications contribute to the expansion of MbLOXs. Transcriptome data based gene expression analysis showed that MaLOX1, 4, and 7 were highly expressed in fruit and their expression levels were significantly regulated by ethylene. And 11, 12 and 7 MaLOXs were found to be low temperature-, high temperature-, and Fusarium oxysporum f. sp. Cubense tropical race 4 (FocTR4)-responsive, respectively. MaLOX8, 9 and 13 are responsive to all the three stresses, MaLOX4 and MaLOX12 are high temperature- and FocTR4-responsive; MaLOX6 and MaLOX17 are significantly induced by low temperature and FocTR4; and the expression of MaLOX7 and MaLOX16 are only affected by high temperature. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression levels of several MaLOXs are regulated by MeJA and FocTR4, indicating that they can increase the resistance of banana by regulating the JA pathway. Additionally, the weighted gene co-expression network analysis (WGCNA) of MaLOXs revealed 3 models respectively for 5 (MaLOX7-11), 3 (MaLOX6, 13, and 17), and 1 (MaLOX12) MaLOX genes. Our findings can provide valuable information for the characterization, evolution, diversity and functionality of MaLOX, MbLOX and MiLOX genes and are helpful for understanding the roles of LOXs in banana growth and development and adaptations to different stresses. [ABSTRACT FROM AUTHOR]

Thermal management is the most critical technology challenge for modern electronics. Recent key materials innovation focuses on developing advanced thermal interface of electronic packaging for achieving efficient heat dissipation. Here, for the first time we report a record-high performance thermal interface beyond the current state of the art, based on self-assembled manufacturing of cubic boron arsenide (s-BAs). The s-BAs exhibits highly desirable characteristics of high thermal conductivity up to 21 W/m·K and excellent elastic compliance similar to that of soft biological tissues down to 100 kPa through the rational design of BAs microcrystals in polymer composite. In addition, the s-BAs demonstrates high flexibility and preserves the high conductivity over at least 500 bending cycles, opening up new application opportunities for flexible thermal cooling. Moreover, we demonstrated device integration with power LEDs and measured a superior cooling performance of s-BAs beyond the current state of the art, by up to 45 °C reduction in the hot spot temperature. Together, this study demonstrates scalable manufacturing of a new generation of energy-efficient and flexible thermal interface that holds great promise for advanced thermal management of future integrated circuits and emerging applications such as wearable electronics and soft robotics. Well-developed prototype interface materials for electronics thermal management are limited to a low thermal conductivity or high elastic modulus. Here, the authors report flexible thermal interfaces through self-assembled manufacturing of polymetric composites based on the high thermal conductivity of cubic boron arsenide. [ABSTRACT FROM AUTHOR]

Flash floods can be characterized by several variables. Of these, soil moisture (SM) is an important environmental factor that plays a key role in hydrological and ecological processes and affects the mechanisms that cause flash floods. To more accurately determine the occurrence probability of flash floods, the combined effects of soil moisture and rainfall indexes were considered in this paper, and the copula function approach was explored for use in joint probability analyses of flash flood risks. The results showed that (1) the Clayton copula function offered the best fit for the bivariate joint distribution and captured the occurrence probability of the combination of both peak flow (PF) and SM, while the t-copula function achieved the best fit for the multivariate joint distribution, which presented different combinations of characteristic flash flood parameters. (2) The joint distribution probability of flash floods increased with increasing risk parameter thresholds. Return period analysis indicated that the return periods of the bivariate joint distribution were smaller than those of the multivariate joint distribution. (3) If PF and SM are fixed, the occurrence probability of flash floods is higher in regions where the maximum 1-h rainfall is higher. This study provides an effective and quantitative approach to improving flash flood prediction and advances the application of this approach for the management of future flash flood risks. [ABSTRACT FROM AUTHOR]

Purpose: Cystic fibrosis transmembrane conductance regulator (CFTR) and adhesion G protein-coupled receptor G2 (ADGRG2) have been identified as the main pathogenic genes in congenital bilateral absence of the vas deferens (CBAVD), which is an important cause of obstructive azoospermia. This study aimed to identify the disease-causing gene in two brothers with CBAVD from a Chinese consanguineous family and reveal the intracytoplasmic sperm injection (ICSI) outcomes in these patients. Methods: Whole-exome sequencing and Sanger sequencing were used to identify the candidate pathogenic genes. Real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to assess the expression of the mutant gene. Moreover, the ICSI results from both patients were retrospectively reviewed. Results: A novel hemizygous loss-of-function mutation (c.G118T: p.Glu40*) in ADGRG2 was identified in both patients with CBAVD. This mutation is absent from the human genome databases and causes an early translational termination in the third exon of ADGRG2. Expression analyses showed that both the ADGRG2 mRNA and the corresponding protein were undetectable in the proximal epididymal tissue of ADGRG2-mutated patients. ADGRG2 expression was restricted to the apical membranes of non-ciliated epithelia in human efferent ducts, which was consistent with a previous report in mice. Both ADGRG2-mutated patients had normal spermatogenesis and had successful clinical outcomes following ICSI. Conclusions: Our study verifies the pathogenic role of ADGRG2 in X-linked CBAVD and broadens the spectrum of ADGRG2 mutations. In addition, we found positive ICSI outcomes in the two ADGRG2-mutated CBAVD patients. [ABSTRACT FROM AUTHOR]

Background: Asthenoteratospermia with multiple morphological abnormalities in the sperm flagella (MMAF) is a significant cause of male infertility. WDR19 is a core component in the IFT-A complex and has a critical role in intraflagellar transport. However, the role of WDR19 mutations in male infertility has yet to be examined. Methods and results: We performed whole exome sequencing (WES) for 65 asthenoteratospermia individuals and identified a proband who carried a homozygous WDR19 (c.A3811G, p.K1271E) mutation from a consanguineous family. Systematic examinations, including CT scanning and retinal imaging, excluded previous ciliopathic syndromes in the proband. Moreover, semen analysis of this patient showed that the progressive rate decreased to zero, and the sperm flagella showed multiple morphological abnormalities. Scanning and transmission electron microscopy assays indicated that the ultrastructure of sperm flagella in the patient was completely destroyed, while immunofluorescence revealed that WDR19 was absent from the sperm neck and flagella. Moreover, IFT140 and IFT88, predicted to interact with WDR19 directly, were mis-allocated in the WDR19-mutated sperm. Notably, the MMAF subject harboring WDR19 variant and his partner successfully achieved clinical pregnancy through intracytoplasmic sperm injection (ICSI). Conclusions: We identified WDR19 as a novel pathogenic gene for male infertility caused by asthenoteratospermia in the absence of other ciliopathic phenotypes, and that patients carrying WDR19 variant can have favorable pregnancy outcomes following ICSI. [ABSTRACT FROM AUTHOR]

Doping control has been a key challenge for electronic applications of van der Waals materials. Here, we demonstrate complementary doping of black phosphorus using controlled ionic intercalation to achieve monolithic building elements. We characterize the anisotropic electrical transport as a function of ion concentrations and report a widely tunable resistivity up to three orders of magnitude with characteristic concentration dependence corresponding to phase transitions during intercalation. As a further step, we develop both p-type and n-type field effect transistors as well as electrical diodes with high device stability and performance. In addition, enhanced charge mobility from 380 to 820 cm2/(V·s) with the intercalation process is observed and explained as the suppressed neutral impurity scattering based on our ab initio calculations. Our study provides a unique approach to atomically control the electrical properties of van der Waals materials, and may open up new opportunities in developing advanced electronics and physics platforms. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relation between mutations in ciliopathy-related SPAG6 and RSPH3 and male infertility with severe asthenoteratospermia characterized by multiple flagellar malformations and reveal the intracytoplasmic sperm injection (ICSI) outcomes of those primary ciliary dyskinesia (PCD) patients. Methods: Whole-exome sequencing was applied to identify the pathogenic genes for the five PCD patients. The ICSI outcomes of those patients were compared with eight DNAH1-mutated patients and 215 oligo-asthenospermia (OAT) patients. Results: We identified, for the first time, the compound heterozygous SPAG6 mutations (c.143_145del: p.48_49del, c.585delA: p.Lys196Serfs*6) in a sporadic PCD patient. Further, a novel homozygous nonsynonymous RSPH3 mutation (c.C799T: p.Arg267Cys) was identified in another PCD patient with consanguineous parents. The pathogenicity of these mutations in the assembly of sperm flagella was confirmed by flagellar ultrastructure analysis, immunofluorescence, and quantitative real-time PCR. All five patients underwent six ICSI cycles. The fertilization rate, blastocyst development rate, and clinical pregnancy rate were 69.3%, 50.0%, and 66.7%, respectively. Four of the five couples, including the subjects carrying mutations in SPAG6 or RSPH3, got healthy children born after ICSI. Additionally, the ICSI outcomes of the five PCD couples were statistically comparable with those of the eight DNAH1-mutated couples and the 215 OAT couples. Conclusions: Mutations in ciliopathy-related SPAG6 and RSPH3 cause severe asthenoteratospermia characterized by multiple flagellar malformations, resulting in sterility. ICSI is an optimal management with a positive pregnancy outcome. [ABSTRACT FROM AUTHOR]

Purpose: To identify the pathogenic PLCZ1 mutation involved in male infertility and fertilization failure. Methods: All coding regions of PLCZ1 were sequenced by Sanger sequencing. The expression and localization of PLCZ1 in sperm was determined by Western blotting and immunofluorescence. To promote the fertilization rate, the infertile man with PLCZ1 mutation was treated with intracytoplasmic sperm injection (ICSI) accompanied by assisted oocyte activation (AOA) in the following cycle. Result: We identified a novel homozygous PLCZ1 nonsense mutation, c.588C>A (p.Cys196Ter) in an infertile man from a consanguineous family. No PLCZ1 protein was detected by Western blotting and immunofluorescence in ejaculated sperm from the patient. The treatment of ICSI + AOA avoided fertilization failure but did not result in pregnancy in the following cycle. Conclusion: Our study confirmed the essential role of PLCZ1 in fertilization and male fertility, which indicated the potential prognostic value of testing for PLCZ1 mutations in primary infertile men with sperm-derived fertilization failure. [ABSTRACT FROM AUTHOR]

We state and study a discrete SIR epidemic model with bilinear incidence rate and constant recovery. We obtain conditions for the existence of the disease-free equilibrium and endemic equilibria. Theoretic analysis shows that the disease-free equilibrium is globally asymptotically stable when the basic reproduction number is less than unity, and the numerical simulations illustrate that it is asymptotically stable when the number is greater than unity. We also obtain conditions for the stability of the endemic equilibria. More attention is paid to the existence of the saddle-node bifurcation, the flip bifurcation, the 1 : 1 resonance, and the Neimark–Sacker bifurcation. We obtain sufficient conditions for those bifurcations. Our numerical simulations demonstrate our theoretical results and the complexity of the model. [ABSTRACT FROM AUTHOR]

Photosynthetic efficiency depends on equal light energy conversion by two spectrally distinct, serially-connected photosystems. The redox state of the plastoquinone pool, located between the two photosystems, is a key regulatory signal that initiates acclimatory changes in the relative abundance of photosystems. The Chloroplast Sensor Kinase (CSK) links the plastoquinone redox signal with photosystem gene expression but the mechanism by which it monitors the plastoquinone redox state is unclear. Here we show that the purified Arabidopsis and Phaeodactylum CSK and the cyanobacterial CSK homologue, Histidine kinase 2 (Hik2), are iron-sulfur proteins. The Fe-S cluster of CSK is further revealed to be a high potential redox-responsive [3Fe-4S] center. CSK responds to redox agents with reduced plastoquinone suppressing its autokinase activity. Redox changes within the CSK iron-sulfur cluster translate into conformational changes in the protein fold. These results provide key insights into redox signal perception and propagation by the CSK-based chloroplast two-component system. Ibrahim et al. show that the Arabidopsis and Phaeodactylum Chloroplast Sensor Kinase (CSK) and the cyanobacterial CSK homologue, Histidine kinase 2, are iron sulfur proteins. This study provides insights into how the CSK-based chloroplast two-component system perceives and propagates the plastoquinone redox signals. [ABSTRACT FROM AUTHOR]

Disinfection byproducts (DBPs) in swimming pool have elicited increasing worldwide concern due to their potential health risks. However, only trihalomethanes (THMs) are regulated by several local governing bodies. Studies indicated that specific unregulated DBP classes would drive disinfected water toxicity in addition to THMs. Halobenzoquinones (HBQs), a type of emerging unregulated DBPs, have been shown to be possible bladder cancer carcinogens. This study aimed to determine the distribution and formation of HBQs in indoor and outdoor swimming pool waters of Nanning City, Southwest China. Seven HBQs in water from seven public indoor and outdoor swimming pools were examined using an effective ultra-performance liquid chromatography–tandem mass spectrometry method. Results suggest the presence of 2,6-dichloro-1,4-benzoquinone in all the swimming pool waters in the range of 4.56–45.30 ng/L. Furthermore, 2,6-dibromo-1,4-benzoquinone and 3,4,5,6-tetrachloro-1,2-benzoquinone (TetraC-1,2-BQ) were detected in two pools at concentrations of < 0.38–14.20 and < 0.54–2.60 ng/L, respectively. The swimming pool water featured higher HBQs than input tap water, and TetraC-1,2-BQ was only detected in pool water. Higher HBQ levels were observed in the indoor pools than in the outdoor pools. These findings demonstrate that low NH3–N, high chloride, humic acid, chemical oxygen demand, and UV254 in the indoor pools increased the HBQ formation. This study is the first to reveal the occurrence and formation of HBQs in water from Chinese indoor and outdoor swimming pools. The findings should be useful in the management of these governing factors and HBQ controls in swimming pools. [ABSTRACT FROM AUTHOR]

Few spatial ecological studies on hair selenium (Se) and Keshan disease (KD) have been reported. To investigate the relationships of hair Se with KD and economic indicators and to visualize the evidence for KD precise prevention. An ecological study design was employed. The levels of hair Se of 636 adult men (≥ 18 years old) living in rural, general cities and developed cities in 15 KD endemic provinces and 11 KD non-endemic provinces in mainland China were measured using hydride generation atomic fluorescence spectrometry. Spatial description and spatial analysis of hair Se were conducted. The subjects were adults aged. The hair Se level of the residents of KD endemic areas was 0.30 mg/kg, statistically significantly lower than that of non-endemic areas 0.34 mg/kg (Mann–Whitney U test, p = 0.007). The hair Se level of the 636 people was 0.33 mg/kg. The hair Se levels of the residents of the developed cities, general cities, and rural were 0.35 mg/kg, 0.33 mg/kg, and 0.32 mg/kg, respectively, with statistical significance (Kruskal–Wallis H test, P = 0.032). Spatial regression analysis showed that the spatial distribution of hair Se was positively correlated with per capita GDP. Selenium deficiency may still exist among residents living in the KD endemic areas. The results of spatial description and analysis of hair Se provided visualized evidence for targeting key provinces for precise prevention of Keshan disease, including assessment of KD elimination. The hair Se level of the mainland Chinese males was probably between 0.31 and 0.33 μg/g in 2015. [ABSTRACT FROM AUTHOR]

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Background: Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (参术冠心方颗粒, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients.Methods: A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up.Discussion: This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504) [ABSTRACT FROM AUTHOR]

Objective: To analyze the meridian and acupoint-selection patterns in acupuncture-moxibustion treatment of polycystic ovarian syndrome (PCOS) by data mining technique, for exploring acupoints that could be effective for PCOS and providing suggestion and reference in selecting acupoints for the acupuncture-moxibustion treatment of PCOS.Methods: Literatures related to the acupuncture-moxibustion treatment of PCOS published before April 2018 were collected. By a self-made data mining program developed using Microsoft Excel 2007, a database of acupuncturemoxibustion treatment of PCOS was then established. The correlation analysis was performed for the frequency of use of acupoints and acupoint groups. Cluster analysis was also conducted.Results: A total of 92 articles were recruited finally. Sanyinjiao (SP 6), Conception Vessel and chest-abdomen region ranked the top on the list of the most frequently used acupoints, meridians and regions, respectively. Correlation analysis showed that the acupoint group with the highest confidence was Sanyinjiao (SP 6) and Zusanli (ST 36), and the group with the highest support was Sanyinjiao (SP 6) and Guanyuan (CV 4). Cluster analysis revealed five effective clusters: Guanyuan (CV 4) and Sanyinjiao (SP 6); Zhongwan (CV 12) and Tianshu (ST 25); Zhongji (CV 3), Zusanli (ST 36) and Qihai (CV 6); Xuehai (SP 10), Shenshu (BL 23), Taichong (LR 3) and Guilai (ST 29); Ganshu (BL 18), Taixi (KI 3), Yinlingquan (SP 9) and Pishu (BL 20).Conclusion: According to the confidence and support report, Sanyinjiao (SP 6) and Zusanli (ST 36) or Sanyinjiao (SP 6) and Guanyuan (CV 4) are recommended in acupuncture-moxibustion treatment of PCOS, with adjunct points selected for different patterns, e.g. Zhongwan (CV 12) and Tianshu (ST 25) for tonifying spleen and expelling dampness; Zhongji (CV 3) and Qihai (CV 6) for supplementing qi and cultivating blood; Xuehai (SP 10), Shenshu (BL 23), Taichong (LR 3) and Guilai (ST 29) for tonifying kidney and dissolving stasis; Ganshu (BL 18), Taixi (KI 3), Yinlingquan (SP 9) and Pishu (BL 20) for tonifying kidney and spleen and regulating liver. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggest that aberrations of neurotrophic factors are involved in the etiology and pathogenesis of Alzheimer’s disease (AD), but clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic factor levels in AD is necessary. We performed a systematic review of blood, CSF, and post-mortem brain neurotrophic factor levels in patients with AD compared with controls and quantitatively summarized the clinical data in blood and CSF with a meta-analytical technique. A systematic search of PubMed and Web of Science identified 98 articles in this study (with samples more than 9000). Random effects meta-analysis demonstrated that peripheral blood BDNF levels were significantly decreased in AD patients compared with controls. However, blood NGF, IGF, and VEGF did not show significant differences between cases and controls. In CSF, random effects meta-analysis showed significantly deceased BDNF and increased NGF levels in patients with AD, whereas IGF and VEGF did not show significant differences between the AD group and control group. In addition, 23 post-mortem studies were included in the systematic review. Although data from post-mortem brains were not always consistent across studies, most studies suggested decreased BDNF and increased (pro)NGF levels in hippocampus and neocortex of patients with AD. These results provide strong clinical evidence that AD is accompanied by an aberrant neurotrophin profile, and future investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and therapeutic targets for AD may be warranted. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of electroacupuncture (EA) and mild-warm moxibustion (Mox) therapies for constipation-predominant irritable bowel syndrome (C-IBS) patients.Methods: Sixty C-IBS patients were assigned to 2 groups by simple randomized method, i.e. EA group (30 cases) and Mox group (30 cases). Both EA and Mox treatments were performed on bilateral Tianshu (ST 25) and Shangjuxu (ST 37) for 30 min each time, 6 times per week, for 4 consecutive weeks. The gastrointestinal symptoms and psychological symptoms of the two groups were scored before and after treatment. The effects on the corresponding functional brain areas, namely the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging (fMRI) before and after treatment.Results: Compared with the Mox group, greater improvements in abdominal distension, defecation frequency, diffificulty in defecation and stool features were observed in the EA group (all P<0.01), both Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores were signifificantly decreased in the EA group (all P<0.01). Finally, decreased activated voxel values were observed in the ACC, right IC and PFC brain regions of EA group with 150 mL colorectal distension stimulation (P<0.05 or P<0.01).Conclusions: Both EA and Mox could signifificantly improve some of the most intrusive symptoms of C-IBS patients, and EA was more effective than Mox. The therapeutic effect of these two therapies might through modulating of the brain-gut axis function. (Registration No. ChiCTRTRC-11001349). [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is the leading cause of fatality worldwide. Our study aimed to investigate the dysregulated long non-coding RNA (lncRNA) in MI and elucidate the mechanism of it in MI. The lncRNA and mRNA expression profiling of the whole left ventricular tissue of MI mice model (8 mice) and Sham group (8 mice) was obtained based on microarray analysis. Differentially expressed lnRNAs/mRNA (DELs/DEMs) were identified in MI. DELs/DEMs co-expression network construction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to predict the biological functions of DEMs. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate the abnormally expressed DELs in left ventricular tissues of MI mice model. Total of 168 DELs (37 up- and 131 down-regulated) and 126 DEMs (87 up- and 39 down-regulated) were identified in MI compared with Sham group. The co-expression network of candidate DELs and DEMs was constructed, which covered 219 nodes and 1775 edges. The qRT-PCR validation results indicated that ENSMUST00000124047 was significantly down-regulated in MI group and AK166279 was significantly up-regulated in MI group. ENSMUST00000121611 and NR_015515 had the up-regulated tendency in MI group compared with Sham group. The DEMs in MI were significantly enriched in 41 signaling pathways including complement and coagulation cascades, cytokine-cytokine receptor interaction and chemokine signaling pathway. The expression profiling of dysregulated DELs in MI was identified. Our results might provide useful information for exploring the pathogenesis mechanism of MI. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)