Background
Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut ...microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community‐dwelling healthy menopausal women.
Methods
Estimated SMM was derived from whole‐body dual‐energy X‐ray absorptiometry. We performed integrated analyses on whole‐genome sequencing, shotgun metagenomic sequencing, and serum short‐chain fatty acids (SCFAs), as well as available host SMM measurements among community‐dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome‐wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one‐sample and two‐sample Mendelian randomization (MR) analyses, respectively.
Results
In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels Spearman correlation coefficient (SCC) = 0.13, P = 0.02 and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate‐producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10−7) and Butyricimonas virosa (SCC = 0.15, P = 0.001) and for skeletal muscle index F. prausnitzii (SCC = 0.16, P = 6.2 × 10−4) and B. virosa (SCC = 0.17, P = 2.4 × 10−4). One‐sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two‐sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.06, 95% confidence interval 0 to 0.13, P = 0.06).
Conclusions
Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.
Coastal flooding catastrophes have affected human societies on coastal plains around the world on several occasions in the past, and are threatening 21st century societies under global warming and ...sea-level rise. However, the role of coastal flooding in the interruption of the Neolithic Liangzhu culture in the lower Yangtze valley, East China coast has been long contested. In this study, we used a well-dated Neolithic site (the Yushan site) close to the present coastline to demonstrate a marine drowning event at the terminal stage of the Liangzhu culture and discuss its linkage to relative sea-level rise. We analysed sedimentology, chronology, organic elemental composition, diatoms and dinoflagellate cysts for several typical profiles at the Yushan site. The field and sedimentary data provided clear evidence of a palaeo-typhoon event that overwhelmed the Yushan site at ∼2560 BCE, which heralded a period of marine inundation and ecological deterioration at the site. We also infer an acceleration in sea-level rise at 2560–2440 BCE from the sedimentary records at Yushan, which explains the widespread signatures of coastal flooding across the south Yangtze coastal plain at that time. The timing of this mid-Holocene coastal flooding coincided with the sudden disappearance of the advanced and widespread Liangzhu culture along the lower Yangtze valley. We infer that extreme events and flooding accompanying accelerated sea-level rise were major causes of vulnerability for prehistoric coastal societies.
•A catastrophic storm overwhelmed a Neolithic Liangzhu site at 2560 BCE.•Accelerated sea-level rise led to flooding on the Yangtze coast at 2560–2440 BCE.•Extreme events and floods were major causes of vulnerability for Liangzhu society.
•Novel donor–acceptor (D–A) covalent organic framework (COF), COF-BT was developed.•CoO was incorporated via a two-step impregnation and calcination method.•Co-COF-BT can be highly useful in the ...artificial photoreduction of CO2.•Superior catalytic performance attributed to the synergistic effect of D–A and CoO.
Artificial photoreduction of CO2 is considered an attractive solution for simultaneously achieving carbon neutrality goals and solving the energy shortage crisis. In this study, a donor–acceptor (D–A) covalent organic framework (COF), COF-BT, comprising (1,1′-biphenyl)-3,3′,5,5′-tetracarbaldehyde and 4,4′-(2,1,3-benzothiadiazole-4,7-diyl)bisbenzenamine was prepared, and cheap CoO was introduced into COF-BT via a two-step impregnation-calcination process to obtain Co-COF-BT with immobilized transition metals. Photoelectrochemical experimental and theoretical results indicate that the D–A structure of Co-COF-BT reduces the band gap, enhances visible light absorption, inhibits electron–hole recombination, and prolongs the life of photogenerated carriers. The introduction of CoO provides additional active sites, and the Co-S bond in Co-COF-BT provides an additional channel for ultrafast electron migration from the COF-BT unit to the CoO active center, which increases charge mobility and reduces the energy barrier formed by *COOH intermediates. Thus, the excellent photocatalytic CO2 reduction activity of Co-COF-BT is achieved with a CO yield of 2423 μmol g−1h−1 and selectivity > 99% under visible light. The superior photocatalytic performance is attributed to the synergistic effect of D–A moieties and CoO in Co-COF-BT. This study not only presents a novel COF-based photocatalyst with high charge transfer efficiency and high catalytic activity in CO2 reduction but also provides a potential strategy to fine-tune photoelectronic properties by adjusting the functional building blocks and additional metal active sites.
Monolayer Cr2Ge2Te6 (ML-CGT) has attracted broad interest due to its novel electronic and magnetic properties. However, there are still controversies on the origin of its intrinsic magnetism. Here, ...by exploring the electronic and magnetic properties of ML-CGT, we find that the magnetic shape anisotropy (MSA) is vital for establishing the long-range ferromagnetism, except for the contribution from magnetocrystalline anisotropy energy (MCA). Electronic band analysis, combined with atomic- and orbital-resolved magnetic anisotropy from a second-order perturbation theory, further reveals that the MCA of ML-CGT is mainly originated from hybridized Te-py and -pz orbitals. The MSA from magnetic Cr atoms in ML-CGT is larger than MCA, resulting in an in-plane magnetic anisotropy. Noticeably, by constructing a heterostructure (HTS) with ferroelectric Sc2CO2, CGT undergoes an in-plane to out-of-plane spin reorientation via ferroelectric polarization switching, accompanied with an electronic property transition from semiconductor to half-metal. The Curie temperature of CGT/Sc2CO2 HTS can be enhanced to 92.4 K under the ferroelectric polarization, which is much higher than that of pristine ML-CGT (34.7 K). These results not only clarify the contradiction of magnetic mechanism of ML-CGT in previous experimental and theoretical works, but also open the door for realizing nonvolatile magnetic memory devices based on a multifunctional ferromagnetic/ferroelectric HTS.
Background
Despite the clinical success of androgen receptor (AR)‐targeted therapies, prostate cancer (PCa) inevitably progresses to castration‐resistant prostate cancer (CRPC). Transcription factor ...6 α (ATF6α), an effector of the unfolded protein response (UPR) that modulates the cellular response to endoplasmic reticulum (ER) stress, has been linked to tumor development, metastasis, and relapse. However, the role of ATF6α in CRPC remains unclear.
Methods
The effect of ATF6α on the CRPC‐like phenotype in PCa cells was evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)−5‐(3‐carb‐Oxymethoxyphenyl)−2‐(4‐sulfophenyl)−2H‐tetrazolium inner salt (MTS), 5‐Bromo‐2‐deoxyUridine (BrdU) incorporation analysis, and cell death assay. Mechanistically, bioinformatic analysis was utilized to evaluate the potential of PLA2G4A as the target of ATF6α. Moreover, Western blot analysis, real‐time polymerase chain reaction, chromatin immunoprecipitation, arachidonic acid (AA), and prostaglandin E2 (PGE2) assays were performed to identify the regulatory effect of ATF6α on PLA2G4A.
Results
In this study, we found that the increase of ATF6α expression in response to androgen deprivation generates PCa cells with a CRPC‐like phenotype. PCa cells with high levels of ATF6α expression are resistant to ferroptosis, and genetic and pharmacological inhibition of ATF6α could, therefore, promote the ferroptotic death of tumor cells and delay PCa progression. Molecular analyses linked ATF6α regulation of ferroptosis to the PLA2G4A‐mediated release of AA and the resulting increase in PGE2 production, the latter of which acts as an antiferroptotic factor.
Conclusions
This study defines ATF6α as a novel antiferroptotic regulator that exacerbates PCa progression. In addition, our data establish ATF6α‐PLA2G4A signaling as an important pathological pathway in PCa, and targeting this pathway may be a novel treatment strategy.
Cholesterol is an important component of cell membranes, and also a precursor for the synthesis of sex hormones, playing an important role in reproduction. However, few studies have focused on ...cholesterol and reproductive health. To investigate the toxic effects of different cholesterol levels on the spermatogenesis of rare minnows, we regulate the cholesterol content in fish by feeding them a high-cholesterol diet and cholesterol inhibitor pravastatin, and cholesterol levels, sex hormone (T and 11KT) levels, testis histology, sperm morphology and function, and the expression of genes related to sex hormone synthesis were investigated. The research findings indicate that increasing cholesterol levels significantly increases the liver weight and hepatic-somatic index, as well as the total cholesterol and free cholesterol levels in the testis, liver, and plasma of rare minnow, while inhibiting cholesterol has the opposite effect (
< 0.05). However, both increasing and decreasing cholesterol levels can suppress rare minnow testicular development, as evidenced by a decrease in testis weight, lowered gonadosomatic index, suppressed sex hormone levels, and reduced mature sperm count. Further exploration revealed that the expression of sex hormone synthesis-related genes, including star, cyp19a1a, and hsd11b2, was significantly affected (
< 0.05), which may be an important reason for the decrease in sex hormone synthesis and consequent inhibition of testicular development. At the same time, the fertilization ability of mature sperm in both treatment groups significantly decreased. Scanning electron microscopy and fluorescence polarization tests showed that reducing cholesterol levels significantly increased the rate of sperm head cell membrane damage, while both increasing and decreasing cholesterol levels led to a reduction in sperm cell membrane fluidity, which may be the main reason for the decrease in sperm fertilization ability. This study demonstrates that both increasing and decreasing the levels of cholesterol are detrimental to the fish spermatogenesis, providing fundamental information for the study of fish reproduction and also a reference for the causes of male reproductive dysfunction.
Statistical features are commonly used in radar target recognition tasks using radar cross section as the data source. The traditional statistical feature extraction way may not make better use of ...the data information, making the target classification results slightly worse. Here, a new sliding window segmentation method is proposed for extracting statistical features to improve the accuracy of the radar target classification task and investigate the separability of the statistical features extracted after sliding window segmentation. The results show that the separability of the statistical features extracted by our method is better than other traditional ways. The classification accuracy of using BP neural network, SVM and KNN classification algorithms is improved by about 10% compared with the traditional way.
We propose a new sliding window segmentation method for extracting statistical features to improve the accuracy of the radar target classification task and investigate the separability of the statistical features extracted after sliding window segmentation. The results show that the separability of the statistical features extracted by our method is better than other traditional ways.
The access of new energy improves the flexibility of distribution network operation, but also leads to more complex mechanism of line loss. Therefore, starting from the nonlinear, fluctuating and ...multi-scale characteristics of line loss data, and based on the idea of decomposition prediction, this paper proposes a new method of line loss frequency division prediction based on wavelet transform and BIGRU-LSTM (Bidirectional Gated Recurrent Unit-Long Short Term Memory Network).Firstly, the grey relation analysis and the improved NARMA (Nonlinear Autoregressive Moving Average) correlation analysis method are used to extract the non-temporal and temporal influencing factors of line loss, and the corresponding feature data set is constructed. Then, the historical line loss data is decomposed into physical signals of different frequency bands by using wavelet transform, and the multi-dimensional input data of the prediction network is formed with the above characteristic data set. Finally, the BIGRU-LSTM prediction network is built to realize the probabilistic prediction of high-frequency and low-frequency components of line loss. The effectiveness and applicability of the method proposed in this paper were verified through numerical simulation. By dividing the line loss data into different frequency bands for frequency prediction, the mapping relationship between different line loss components and influencing factors was accurately matched, thereby improving the prediction accuracy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Determining the postmortem interval (PMI) is important in criminal, civil, and forensic cases. We examined the feasibility of using the transcript abundances of mRNAs, 18S rRNA, U6 snRNA, and ...microRNAs as a means to estimate the PMI. We removed spleen tissues from rats at different PMIs under 4°C or 25°C and examined gene transcript abundances in these samples by RT‐qPCR. Using the algorithm geNorm, we found that microRNAs to be appropriate control markers because they were less affected by PMI and temperature. We also characterized relationships between observed PMI and the transcript levels of the above‐mentioned RNAs. GAPDH1 and ACTB1 fluctuated slightly like cubic curves, while GAPDH2 and ACTB2 decreased rapidly. 18S rRNA transcript level exhibited a parabolic‐like trend at 25°C and exponential growth at 4°C, while U6 transcript level exhibited exponential decay at 25°C and a parabolic‐like trend at 4°C. Following validation, we conclude that GAPDH2, ACTB2, and 18S rRNA are suitable makers in the accurate determination of PMI.
Benzylic azides, an important class of active organic synthons, were synthesized in high yields from the easily accessible
-triftosylhydrazones with stable TMSN
under mild conditions. The reaction ...features high efficiency and excellent functional group tolerance, as illustrated by gram-scale synthesis and the synthesis of drug-like molecules. Mechanistic studies reveal that azidation occurs at the electron-deficient diazo-carbon
the elimination of N
by an azide ion.
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