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Double-cone ignition [Zhang et al., Phil. Trans. R. Soc. A 378, 20200015 (2020)] was proposed recently as a novel path for direct-drive inertial confinement fusion using high-power lasers. In this scheme, plasma jets with both high density and high velocity are required for collisions. Here we report preliminary experimental results obtained at the Shenguang-II upgrade laser facility, employing a CHCl shell in a gold cone irradiated with a two-ramp laser pulse. The CHCl shell was pre-compressed by the first laser ramp to a density of 3.75 g/cm3 along the isentropic path. Subsequently, the target was further compressed and accelerated by the second laser ramp in the cone. According to the simulations, the plasma jet reached a density of up to 15 g/cm3, while measurements indicated a velocity of 126.8 ± 17.1 km/s. The good agreements between experimental data and simulations are documented.

Pointing fluctuations of beams reduce the possibility of incoherent or coherent addition for ultrahigh peak power in a multi-beam picosecond–petawatt laser system. Pointing fluctuations on the target were observed on Shenguang Upgrade Petawatt (SGII-UP-Petawatt) beam using a high-speed and high-resolution active pointing stabilization control system. The maximum frequency of the pointing fluctuations was less than 50 Hz, and the amplitude was approximately 2.8 µrad (RMS). An online test of pointing fluctuations with active stabilization control demonstrated that pointing fluctuations could be reduced to 0.63 µrad (RMS), approximately one-quarter of that without active stabilization control. The benefits of reduced pointing fluctuation were estimated using a multi-beamlet petawatt laser system; the results demonstrated that peak power could be increased by 51.7% when active stabilization control was used in an eight-beamlet picosecond–petawatt laser system.

The Zeeman splitting effect is observed in a strong magnetic field generated by a laser-driven coil. The expanding plasma from the coil wire surface is concentrated at the coil center and interacts with the simultaneously generated magnetic field. The Cu I spectral lines at wavelengths of 510.5541, 515.3235, and 521.8202 nm are detected and analyzed. The splittings of spectral lines are used to estimate the magnetic field strength at the coil center as ∼31.4 ± 15.7 T at a laser intensity of ∼5.6 × 1015 W/cm2, which agrees well with measurements using a B-dot probe. Some other plasma parameters of the central plasma disk are also studied. The temperature is evaluated from the Cu I spectral line intensity ratio, while the electron density is estimated from the Stark broadening effect.

The driving mechanism of solar flares and coronal mass ejections is a topic of ongoing debate, apart from the consensus that magnetic reconnection plays a key role during the impulsive process. While present solar research mostly depends on observations and theoretical models, laboratory experiments based on high-energy density facilities provide the third method for quantitatively comparing astrophysical observations and models with data achieved in experimental settings. In this article, we show laboratory modeling of solar flares and coronal mass ejections by constructing the magnetic reconnection system with two mutually approaching laser-produced plasmas circumfused of self-generated megagauss magnetic fields. Due to the Euler similarity between the laboratory and solar plasma systems, the present experiments demonstrate the morphological reproduction of flares and coronal mass ejections in solar observations in a scaled sense, and confirm the theory and model predictions about the current-sheet-born anomalous plasmoid as the initial stage of coronal mass ejections, and the behavior of moving-away plasmoid stretching the primary reconnected field lines into a secondary current sheet conjoined with two bright ridges identified as solar flares.

Abstract Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index’s prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P

One new alkaloid, 6, 7-dimethoxyisoquinoline-N-oxide (1), one new benzofuran derivative, 3,7-dimethyl-6-acetyl-8-benzofuranol (2) and one new lignan, salsolains A (3), along with seven known compounds (4–10), were isolated from the whole plant of Salsola collina Pall. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1 D and 2 D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. The activities of compounds 1–10 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, especially, compound 5 (50 μM) exhibited the most significant anti-inflammatory activity with the secretion levels of IL-6 and TNF-α at 3.87% and 4.03%, respectively. [ABSTRACT FROM AUTHOR]

Abstract The high sequencing error rate has impeded the application of long noisy reads for diploid genome assembly. Most existing assemblers failed to generate high-quality phased assemblies using long noisy reads. Here, we present PECAT, a Phased Error Correction and Assembly Tool, for reconstructing diploid genomes from long noisy reads. We design a haplotype-aware error correction method that can retain heterozygote alleles while correcting sequencing errors. We combine a corrected read SNP caller and a raw read SNP caller to further improve the identification of inconsistent overlaps in the string graph. We use a grouping method to assign reads to different haplotype groups. PECAT efficiently assembles diploid genomes using Nanopore R9, PacBio CLR or Nanopore R10 reads only. PECAT generates more contiguous haplotype-specific contigs compared to other assemblers. Especially, PECAT achieves nearly haplotype-resolved assembly on B. taurus (Bison×Simmental) using Nanopore R9 reads and phase block NG50 with 59.4/58.0 Mb for HG002 using Nanopore R10 reads.

C26H41NO8, orthorhombic, P212121 (no. 19), a = 8.24370(10) Å, b = 13.1867(2) Å, c = 22.8490(4) Å, V = 2483.85(6) Å3, Z = 4, Rgt(F) = 0.0357, wRref(F2) = 0.0975, T = 169.99(10) K. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: A phytochemical investigation on the seeds of Sophora alopecuroides led to obtaining fourteen structurally diverse matrine‐based alkaloids (1—14), including eight new ones (1, 6, 8—12, 14). Notably, alopecuroide F (1) represents the first dimeric matrine‐type skeleton assembled via unprecedent C‐13–C‐12' connection. The new structures were determined through extensive spectroscopic data (UV, OR, HRESIMS, 1D, and 2D NMR), ECD calculations, and three instances, verified by X‐ray crystallography. Biologically, all alkaloids were evaluated for cytotoxicity against four human cancer cell lines (HepG2, A549, THP‐1, and MCF‐7) and anti‐inflammatory activities for two pro‐inflammatory cytokines (TNF‐α and IL‐6). Alopecuroide F (1) can inhibit TNF‐α and IL‐6 productions in a dose‐dependent manner, with IC50 values of 35.6 ± 0.5 and 41.7 ± 0.8 μmol/L, respectively. [ABSTRACT FROM AUTHOR]

Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine Nβ-oxide (1), 6S,6aS-N-nantenine Nα-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one Nβ-oxide (10) and (+)-10-O-methylhernovine Nβ-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay. [ABSTRACT FROM AUTHOR]

Abstract Long single-molecular sequencing technologies, such as PacBio circular consensus sequencing (CCS) and nanopore sequencing, are advantageous in detecting DNA 5-methylcytosine in CpGs (5mCpGs), especially in repetitive genomic regions. However, existing methods for detecting 5mCpGs using PacBio CCS are less accurate and robust. Here, we present ccsmeth, a deep-learning method to detect DNA 5mCpGs using CCS reads. We sequence polymerase-chain-reaction treated and M.SssI-methyltransferase treated DNA of one human sample using PacBio CCS for training ccsmeth. Using long (≥10 Kb) CCS reads, ccsmeth achieves 0.90 accuracy and 0.97 Area Under the Curve on 5mCpG detection at single-molecule resolution. At the genome-wide site level, ccsmeth achieves >0.90 correlations with bisulfite sequencing and nanopore sequencing using only 10× reads. Furthermore, we develop a Nextflow pipeline, ccsmethphase, to detect haplotype-aware methylation using CCS reads, and then sequence a Chinese family trio to validate it. ccsmeth and ccsmethphase can be robust and accurate tools for detecting DNA 5-methylcytosines.

ObjectivesThe present study used publicly available genome-wide association study (GWAS) summary data to perform three two-sample Mendelian randomization (MR) studies, aiming to examine the causal links between gut microbiome and BCC, melanoma skin cancer, ease of skin tanning.MethodsSNPs associated with exposures to basal cell carcinoma, melanoma skin cancer and ease of skin tanning from the genome-wide association study data of UK Biobank and MRC-IEU (MRC Integrative Epidemiology Unit), and the meta-analysis data from Biobank and MRC-IEU were used as instrumental variables (IVs). The casual estimates were assessed with a two-sample Mendelian randomisation test using the inverse-variance-weighted (IVW) method, Wald ratio, MR-Egger method, maximum likelihood, weighted median, simple mode, and weighted mode.ResultsAfter the application of MR analysis, diffirent effects of multiple groups of gut microbiota was observed for BCC, melanoma skin cancer and ease of skin tanning. The relationships between the gut microbiome and BCC, melanoma skin cancer, ease of skin tanning were supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between between the gut microbiome and BCC, melanoma skin cancer, ease of skin tanning.ConclusionOur study initially identified potential causal roles between the gut microbiome and BCC, melanoma skin cancer, ease of skin tanning, and highlighted the role of gut microbiome in the progression of basal cell carcinoma, melanoma skin cancer, ease of skin tanning.

Main observation and conclusion: Sophaloseedlines A—G (1—7), seven new matrine‐based alkaloids along with two known analogues, were isolated from the seeds of Sophora alopecuroides. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism calculations, and X‐ray crystallography. Notably, sophaloseedline A (1) represents a novel rearranged 6(5→17)‐abeo‐matrine alkaloid featuring unprecedented highly constructed 7/6/5/6 tetracyclic fused ring skeleton. The hypothetical biosynthetic pathways for sophaloseedlines A—F were proposed based on co‐existing precursors. Additionally, all the isolated alkaloids were screened for their antiviral activities against hepatitis B virus, and new alkaloids 1 and 2 displayed more potent activities than those of matrine (a parent alkaloid of title plant) and positive control (lamivudine). [ABSTRACT FROM AUTHOR]

A new sesquiterpene pyridine alkaloid (1), along with four known compounds (2-5), were isolated from the stems and leaves of Euonymus fortunei. The new structure was determined by extensive spectroscopic analyses (IR, UV, NMR, HRESIMS and ECD). In addition, compound 3 showed a stronger anti-respiratory syncytial virus (RSV) activity with an IC50 value of 1.20 ± 0.10 µM than the positive control ribavirin with an IC50 value of 5.62 ± 0.49 µM. [ABSTRACT FROM AUTHOR]

A new isopropylpyrone, hypemonone F (1), and a new phenylpyrone, hypemonone G (2), along with five known phenylpyrones, peplidiforone B (3), hypemonone C (4), hypemonone B (5), 3‐(1,1‐dimethyl‐2‐propen‐1‐yl)‐4‐methoxy‐6‐phenyl‐2H‐pyran‐2‐one (6), hyperenone A (7) were isolated from the leaves of Hypericum monogynum. Their structures were identified on the basis of the spectral data (IR, UV, HRESIMS, and NMR). The absolute configurations of 1−4 were determined by electronic circular dichroism and single crystal X‐ray analyses. All isolated compounds (1−7) were evaluated for their cytotoxic activities on tumor cells (HeLa and HepG2). Compounds 1−7 showed cytotoxic activities against HeLa cells with IC50 values of 28.27 ± 2.65 to 89.02 ± 2.30 μM, and compounds 2, 3, 6, 7 showed cytotoxic activities against HepG2 cells with IC50 values of 68.44 ± 1.45 to 80.7 ± 1.66 μM. [ABSTRACT FROM AUTHOR]

BackgroundIn China, the risk of stroke is higher than that in developed countries such as Europe and North America. Informal caregivers play a major role in providing support to stroke survivors. Currently, only limited studies on changes in psychological state of the caregivers at different stages of stroke have been published.PurposeTo investigate the stress and psychological state of informal caregivers of stroke patients in different periods and to explore the factors that affect their states.Methods202 informal caregivers of stroke patients were selected in a 3a-grade hospital in Chengdu, Sichuan. Follow-up was conducted by face-to-face interviews, telephone calls, or home visits on days 3, 2 months, and 1 year after onset. We investigated the basic information about the caregivers, including their anxiety, depression and social support conditions. We analyzed the pressure and psychological conditions of informal caregivers at different stages of stroke and analyzed its influencing factors. The data were displayed by the number and percentage of the cases; the continuous variables were described by means and standard deviation. In addition, the data were compared by Pearson correlation analysis and logistic regression analysis.Results(1) Within 3 days after the onset of stroke, the informal caregivers had the highest stress, the most severe anxiety and depression, the heaviest burden, and the lowest score of medical-social support. Over time, the pressure and burden of the caregivers are gradually decreasing, anxiety and depression are increasing, and social support is also increasing. (2) The stress and psychological status of informal stroke caregivers are affected by multiple factors, including the caregiver’s age, relationship with the patient, patient’s age, and patient’s physical conditions.ConclusionThe stress and psychological status of informal caregivers varied in the different stages of stroke, and they were affected by several factors. Medical staff should pay attention to informal caregivers while providing care for patients. Relevant interventions may be developed based on the results to improve the health of informal caregivers and thus to promote the health of patients.

Three new prenylated acetophenone derivatives, acronyculatin P (1), acronyculatin Q (2), and acronyculatin R (3) were isolated from the leaves of Acronychia oligophlebia. Their structures were identified by extensive analyses of spectroscopic data (IR, UV, ESI-HRMS, 1D and 2D NMR) and comparison with the literatures. In addition, the cytotoxic activity against MCF-7 cells of the compounds were evaluated by the MTT assay and the IC50 values were 56.8, 40.4 and 69.1 μM, respectively. [ABSTRACT FROM AUTHOR]

Existing methods cannot profile genome-wide cytosine DNA methylations (5mCs) in all three contexts with acceptable accuracy. Here, the authors develop a deep learning tool to detect genome-wide 5mCs of all three contexts in plants with high accuracy from Nanopore reads.

Three new diterpenoids, including one labdane diterpenoid (1) and two cembrane diterpenoids (2–3), were isolated from the aerial parts ofCroton laui, along with four known analogues (4–7). Their structures were elucidated by spectroscopic analysis and comparison with literature data. All compounds were evaluated for their cytotoxicity against two tumour cell lines. [ABSTRACT FROM PUBLISHER]

Three novel sesquiterpenoid-based meroterpenoids, drychampones A-C (1-3, respectively), were isolated from Dryopteris championii. Compounds 1 and 3 possessed a novel carbon skeleton which was constructed by an 11/6/6 ring system coupled with a pyronone moiety, and 1-3 were three racemates. Their structures and absolute configurations were elucidated by NMR, MS, and computational methods. The hypothetical biosynthetic pathways of these meroterpenoids and their antibacterial activities were also discussed. [ABSTRACT FROM AUTHOR]

In an unbiased genome-wide screen for copy number variants (CNVs) on a cohort of Parkinson's disease (PD) patients, we identified in one patient a complex chromosomal rearrangement involving the nucleotide binding protein-like (NUBPL) gene on chromosome 14q12. We noted that mutations in the NUBPL gene had been reported as causing autosomal recessive (AR) mitochondrial Complex I (CI) deficiency in children. The precise breakpoints of the rearrangement in our PD case were found to be identical to those described in a patient with AR CI deficiency who also harbored a second pathogenic mutation in NUBPL. Mitochondrial dysfunction has long been considered a strong contributor to PD, and there is substantial evidence that decreased CI activity plays a central role in PD pathogenesis. We hypothesize that pathogenic NUBPL variants may increase the risk for PD analogous to variants in the glucosylceramidase beta (GBA) gene that increase the risk of developing PD in heterozygous carriers.

Three new diterpenoids, including one clerodane diterpenoid and two linear diterpenoids 2 and 3, were isolated from the aerial parts of Croton laui, along with four known compounds 4-7. Structural elucidation of the isolates was performed by spectral methods such as 1D and 2D NMR, IR, UV, and HRESIMS. Compound 1 exhibited cytotoxic activities against Hela and MCF-7 cells with IC50 values of 14.5 and 62.5 µM, respectively [ABSTRACT FROM AUTHOR]

Three new eudesmanolides, prostrolides A-C(1-3), along with six known compounds were isolated from the herbs of Wedelia prostrata (Asteraceae). The structures were determined by extensive analysis of their spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolated compounds were evaluated for their cytotoxic activity on human hepatocellular carcinoma HepG2 cells. All isolates exhibited cytotoxic activities with IC50 values of 4.60 ± 0.17 to 27.23 ± 0.36 μM. [ABSTRACT FROM AUTHOR]

Two new triterpenoids, tomentoids A and B (1 and 2), along with five known ones were isolated from the roots of Rhodomyrtus tomentosa. Their structures were elucidated via extensive spectro-scopic methods including HR-ESI-MS, UV, IR, and NMR. In addition, compounds 1 and 3-7 exhibited potent inhibitory effects on three tumor cell lines: BGC823, SGC7901, and SK-MEL-110. [ABSTRACT FROM AUTHOR]

Aim: To find human dopamine receptors, especially D1 -like receptor specific agonists from Chinese herbs as potential antihypertension drug leads. Methods: Two D 1-like receptor cell lines carrying a β-lactamase reporter gene, and a D2 receptor cell line coexpressing a promiscuous G protein G1 5 were constructed using HEK293 cells. A natural compound library made from fractionated samples of herbal extracts was used for high-throughput screening (HTS) against one of the cell lines, HEK/D5R/CRE-blax. The interested hits were evaluated for their activities against various dopamine receptors. Results: Fourteen hits were identified from primary screening, of which 2 of the better hit samples, HD0522 and HD0059, were selected for further material and activity analysis, and to obtain 2 compounds that appeared as 2 single peaks in HPLC, HD0522H01 and HD0059H01. HD0059H01 could activate D1, D2, and D5 receptors, with EC50 values of 2.28 μg/mL, 0.85 μg/mL, and 1.41 μg/mL, respectively. HD0522H01 could only activate D1R and D5R with EC50 values of 2.95 μg/mL and 8.38 μg/mL. Conclusion: We established cell-based assays for 3 different human dopamine receptors and identified specific agonists HD0522H01 and HD0059H01 through HTS. The specific agonist to D1-like receptors, HD0522H01, may become a new natural product-based drug lead for antihypertension treatment. [ABSTRACT FROM AUTHOR]

Two new sesquiterpenoids, strophanthoids A and B (1 and 2), along with seven known cardiac glycosides were isolated from the roots of Strophanthus divaricatus. Their structures were elucidated on the basis of extensive analyses by IR, HR-ESIMS, NMR, and single-crystal X-ray diffraction. And the new compounds were tested cytotoxic activities on the tumor cells SK-MEL-110 and SK-MEL-28. [ABSTRACT FROM AUTHOR]