Alkyl Cyclopropyl Ketones in Catalytic Formal [3 + 2] Cycloadditions: The Role of SmI2 Catalyst Stabilization.

Alkyl cyclopropyl ketones are introduced as versatile substrates for catalytic formal [3 + 2] cycloadditions with alkenes and alkynes and previously unexplored enyne partners, efficiently delivering complex, sp3-rich products. The key to effectively engaging this relatively unreactive new substrate class is the use of SmI2 as a catalyst in combination with substoichiometric amounts of Sm0; the latter likely acting to prevent catalyst deactivation by returning SmIII to the catalytic cycle. In the absence of Sm0, background degradation of the SmI2 catalyst can outrun product formation. For the most recalcitrant alkyl cyclopropyl ketones, catalysis is "switched-on" using these new robust conditions, and otherwise unattainable products are delivered. Combined experimental and computational studies have been used to identify and probe reactivity trends among alkyl cyclopropyl ketones, including more complex bicyclic alkyl cyclopropyl ketones, which react quickly with various partners to give complex products. In addition to establishing alkyl cyclopropyl ketones as a new substrate class in a burgeoning field of catalysis, our study provides vital mechanistic insight and robust, practical approaches for the nascent field of catalysis with SmI2.

Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

The double flower variant of yellowhorn is due to a LINE1 transposon-mediated insertion.

As essential organs of reproduction in angiosperms, flowers, and the genetic mechanisms of their development have been well characterized in many plant species but not in the woody tree yellowhorn (Xanthoceras sorbifolium). Here, we focused on the double flower phenotype in yellowhorn, which has high ornamental value. We found a candidate C-class gene, AGAMOUS1 (XsAG1), through bovine serum albumin sequencing and genetics analysis with a Long Interpersed Nuclear Elements 1 (LINE1) transposable element fragment (Xsag1-LINE1-1) inserted into its second intron that caused a loss-of-C-function and therefore the double flower phenotype. In situ hybridization of XsAG1 and analysis of the expression levels of other ABC genes were used to identify differences between single- and double-flower development processes. These findings enrich our understanding of double flower formation in yellowhorn and provide evidence that transposon insertions into genes can reshape plant traits in forest trees.

Multiple-access ultrastable frequency dissemination based on optical frequency combs via a fiber link.

We demonstrate an optical fiber-based, multiple-access frequency transmission using two optical frequency combs. The experimental results using the Allan deviation analysis show that with the phase compensation technique, the frequency instabilities at the remote site are 8.7 × 10-15/1 s and 1.0 × 10-17/103 s, and at the accessing node along the fiber link, the frequency instabilities are 6.9 × 10-15/1 s and 1.1 × 10-17/103 s. Similarly, the power spectral density of phase noise was analyzed in the frequency domain. These experimental results demonstrate that the compensation scheme improved the performance by two to three orders of magnitude. Thus, the proposed frequency transmission technique has potential application for disseminating ultrastable frequency references in the optical fiber network.

Highly stable power control for chip-based continuous-variable quantum key distribution system.

Quantum key distribution allows secret key generation with information theoretical security. It can be realized with photonic integrated circuits to benefit the tiny footprints and the large-scale manufacturing capacity. Continuous-variable quantum key distribution is suitable for chip-based integration due to its compatibility with mature optical communication devices. However, the quantum signal power control compatible with the mature photonic integration process faces difficulties on stability, which limits the system performance and causes the overestimation of a secret key rate that opens practical security loopholes. Here, a highly stable chip-based quantum signal power control scheme based on a biased Mach-Zehnder interferometer structure is proposed, theoretically analyzed, and experimentally implemented with standard silicon photonic techniques. Simulations and experimental results show that the proposed scheme significantly improves the system stability, where the standard deviation of the secret key rate is suppressed by an order of magnitude compared with the system using traditional designs, showing a promising and practicable way to realize a highly stable continuous-variable quantum key distribution system on chip.

Constrution of Quinazoline-Linked Covalent Organic Frameworks via a Multicomponent Reaction for Photocatalysis.

Quinazoline (Qz)-linked covalent organic frameworks (COFs) have been constructed via a three-component reaction of ortho-acylanilines, benzaldehydes and NH4OAc. The structure of Qz-COFs has been confirmed by solid-state nuclear magnetic resonance spectroscopy, Fourier transform infrared and powder X-ray diffraction patterns. The Qz-COFs possess high chemical stability, showing good endurance to strong acid, strong base, oxidant, reductant and other conditions. Particularly, Qz-COF-3 can catalyze the aerobic photooxidation of toluene and other compounds containing C(sp3)-H bonds.

Oxidative cascade cyclization of N-arylacrylamides with TMSN3.

An azido-radical-triggered cyclization of N-(o-cyanobiaryl)acrylamides with TMSN3via a C(sp3)-N/C(sp2)-C(sp3)/C(sp2)-N bond formation cascade is described. This reaction features mild conditions and high bond-forming efficiency, making it an efficient method for the construction of azide-substituted pyridophenanthridines.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

Glycemic Control and Oral Health Outcomes in Patients With Diabetes: Insights From a Nationwide Korean Survey.

BACKGROUND: Diabetes is recognized as a risk factor for various inflammatory conditions, including periodontitis. There exists a bidirectional relationship between glycemic control and oral health in individuals with diabetes. This study aimed to analyze the link between glycemic control and oral health status among Korean patients with diabetes. METHODS: Using data from a population-based nationwide survey conducted between 2007 and 2019, we identified 70,554 adults with diabetes-related information. The study population included 9,090 individuals diagnosed with diabetes and 61,164 healthy controls. The association between glycemic control, defined by mean glycated hemoglobin (HbA1c) values, and various oral health measures, such as tooth brushing frequency, periodontitis, denture wearing, Decayed, Missing, and Filled Teeth (DMFT) index, number of remaining teeth, and past-year dental clinic visits, was evaluated using multivariate logistic regression analyses. RESULTS: Compared to the control group, patients with diabetes exhibited a higher prevalence of periodontitis (88.6% vs. 73.3%), complete dentures (5.0% vs. 1.5%), and elevated DMFT index (33.2% vs. 26.7%) (all P < 0.001). Multivariate analyses revealed significant associations between diabetes and several oral health factors: denture status (No denture: adjusted odds ratio [aOR], 0.784; 95% confidence interval [CI], 0.627-0.979), and having fewer permanent teeth (0-19) (aOR, 1.474; 95% CI, 1.085-2.003). Additionally, a positive correlation was found between higher HbA1c levels and the risk of having fewer remaining teeth (0-19) (HbA1c < 6.5%: aOR, 1.129; 95% CI, 0.766-1.663; 6.5% ≤ HbA1c < 8.0%: aOR, 1.590; 95% CI, 1.117-2.262; HbA1c ≥ 8%: aOR, 1.910; 95% CI, 1.145-3.186) (P for trends = 0.041). CONCLUSION: We found a positive association between diabetes and poor oral health, as well as a noteworthy relationship between reduced permanent teeth (≤ 19) and glycemic control. These insights emphasize the critical role of oral health management in diabetic care and underscore the importance of maintaining effective glycemic control strategies for overall health and well-being in patients with diabetes.

Flavonoid Compounds in Hippophae rhamnoides L. Protect Endothelial Cells from Oxidative Damage Through the PI3K/AKT-eNOS Pathway.

Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT-eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4-2-1, Fr.4-2-2 and Fr.4-2-3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K-AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4-2-1 exerted its antioxidant effects by modulating the PI3K/AKT-eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress-induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.

Resveratrol alleviates fumonisin-induced intestinal cytotoxicity by modulating apoptosis, tight junction, and inflammation in IPEC-J2 porcine intestinal epithelial cells.

Fumonisins are common contaminants in the global food and environment, pose a variety of health risks to humans and animals. However, the method of mitigating fumonisin toxicity is still unclear. Resveratrol is a natural compound with antioxidant and anti-inflammatory properties. In this study, the protective effect of resveratrol against fumonisin-induced intestinal toxicity was investigated by the porcine intestinal epithelial cell line (IPEC-J2). The cells were treated with 0-40 µM fumonisin for 24 or 48 h with or without the 24 h resveratrol (15 µM) pretreatment. The data showed that resveratrol could alleviate the fumonisin B1 (FB1)-induced decrease in cell viability and amplify in membrane permeability. At the same time, it could reduce the accumulation of intracellular reactive oxygen species and increase the expression ranges of Nrf2 and downstream genes (SOD1 and NQO-1), thereby counteracting FB1-induced apoptosis. Furthermore, resveratrol was able to reduce the expression levels of inflammatory factors (TNF-α, IL-1ß, and IL-6), increase the expression levels of tight junction proteins (Claudin-1, Occludin, and ZO-1), and the integrity of the IPEC-J2 monolayer. Our data also showed that resveratrol could attenuate the toxicity of the co-occurrence of three fumonisins. It is implied that resveratrol represents a promising protective approach for fumonisin, even other mycotoxins in the future. This provided a new strategy for further blocking and controlling the toxicity of fumonisin, subsequently avoiding adverse effects on the human and animal health.

Common Bean (Phaseolus vulgaris L.) NAC Transcriptional Factor PvNAC52 Enhances Transgenic Arabidopsis Resistance to Salt, Alkali, Osmotic, and ABA Stress by Upregulating Stress-Responsive Genes.

The NAC family of transcription factors includes no apical meristem (NAM), Arabidopsis thaliana transcription activator 1/2 (ATAF1/2), and cup-shaped cotyledon (CUC2) proteins, which are unique to plants, contributing significantly to their adaptation to environmental challenges. In the present study, we observed that the PvNAC52 protein is predominantly expressed in the cell membrane, cytoplasm, and nucleus. Overexpression of PvNAC52 in Arabidopsis strengthened plant resilience to salt, alkali, osmotic, and ABA stresses. PvNAC52 significantly (p < 0.05) reduced the degree of oxidative damage to cell membranes, proline content, and plant water loss by increasing the expression of MSD1, FSD1, CSD1, POD, PRX69, CAT, and P5CS2. Moreover, the expression of genes associated with abiotic stress responses, such as SOS1, P5S1, RD29A, NCED3, ABIs, LEAs, and DREBs, was enhanced by PvNAC52 overexpression. A yeast one-hybrid assay showed that PvNAC52 specifically binds to the cis-acting elements ABRE (abscisic acid-responsive elements, ACGTG) within the promoter. This further suggests that PvNAC52 is responsible for the transcriptional modulation of abiotic stress response genes by identifying the core sequence, ACGTG. These findings provide a theoretical foundation for the further analysis of the targeted cis-acting elements and genes downstream of PvNAC52 in the common bean.

Phantom study of a fully automatic radioactive seed placement robot for the treatment of skull base tumours.

BACKGROUND: Interstitial brachytherapy is a form of intensive local irradiation that facilitates the effective protection of surrounding structures and the preservation of organ functions, resulting in a favourable therapeutic response. As surgical robots can perform needle placement with a high level of accuracy, our team developed a fully automatic radioactive seed placement robot, and this study aimed to evaluate the accuracy and feasibility of fully automatic radioactive seed placement for the treatment of tumours in the skull base. METHODS: A fully automatic radioactive seed placement robot was established, and 4 phantoms of skull base tumours were built for experimental validation. All the phantoms were subjected to computed tomography (CT) scans. Then, the CT data were imported into the Remebot software to design the preoperative seed placement plan. After the phantoms were fixed in place, navigation registration of the Remebot was carried out, and the automatic seed placement device was controlled to complete the needle insertion and particle placement operations. After all of the seeds were implanted in the 4 phantoms, postoperative image scanning was performed, and the results were verified via image fusion. RESULTS: A total of 120 seeds were implanted in 4 phantoms. The average error of seed placement was (2.51 ± 1.44) mm. CONCLUSION: This study presents an innovative, fully automated radioactive particle implantation system utilizing the Remebot device, which can successfully complete automated localization, needle insertion, and radioactive particle implantation procedures for skull base tumours. The phantom experiments showed the robotic system to be reliable, stable, efficient and safe. However, further research on the needle-soft tissue interaction and deformation mechanism of needle puncture is still needed.

The MYB transcription factor MYB103 acts upstream of TRICHOME BIREFRINGENCE-LIKE27 in regulating aluminum sensitivity by modulating the O-acetylation level of cell wall xyloglucan in Arabidopsis thaliana.

Modification of the O-acetylation level of xyloglucan (XyG) appears to affect aluminum (Al) sensitivity in Arabidopsis by modulating its binding capacity to Al. However, the transcriptional regulation of this process remains largely unknown. In our previous studies, we found that the expression of TRICHOME BIREFRINGENCE-LIKE27 (TBL27), which is responsible for the O-acetylation of XyG, was downregulated under Al stress. In the present study, we showed that the expression of an R2R3-type transcription factor-encoding gene, MYB103, was also inhibited by Al exposure and exhibited a co-expression pattern with TBL27 in roots and siliques, suggesting a potential link between MYB103 and TBL27. The loss of function of MYB103 resulted in increased Al sensitivity, as indicated by more inhibited root growth and elevated root Al content compared with the wild type. Moreover, we also detected increased Al accumulation in the root cell wall and the hemicellulose fraction, which was attributed to the changes in the O-acetylation level of XyG rather than the XyG content itself. In addition, further analysis revealed that MYB103 positively activated TBL27 expression by directly binding to the TBL27 promoter region, and TBL27 overexpression in the myb103 mutant rescued the Al-sensitive phenotype of the mutant to the wild-type level. Taken together, we conclude that MYB103 acts upstream of TBL27 to positively regulate Al resistance by modulating the O-acetylation of the cell wall XyG.

The NAC transcription factor ANAC017 regulates aluminum tolerance by regulating the cell wall-modifying genes.

Aluminum (Al) toxicity is one of the key factors limiting crop production in acid soils; however, little is known about its transcriptional regulation in plants. In this study, we characterized the role of a NAM, ATAF1/2, and cup-shaped cotyledon 2 (NAC) transcription factors (TFs), ANAC017, in the regulation of Al tolerance in Arabidopsis (Arabidopsis thaliana). ANAC017 was localized in the nucleus and exhibited constitutive expression in the root, stem, leaf, flower, and silique, although its expression and protein accumulation were repressed by Al stress. Loss of function of ANAC017 enhanced Al tolerance when compared with wild-type Col-0 and was accompanied by lower root and root cell wall Al content. Furthermore, both hemicellulose and xyloglucan content decreased in the anac017 mutants, indicating the possible interaction between ANAC017 and xyloglucan endotransglucosylase/hydrolase (XTH). Interestingly, the expression of XTH31, which is responsible for xyloglucan modification, was downregulated in the anac017 mutants regardless of Al supply, supporting the possible interaction between ANAC017 and XTH31. Yeast one-hybrid, dual-luciferase reporter assay, and chromatin immunoprecipitation-quantitative PCR analysis revealed that ANAC017 positively regulated the expression of XTH31 through directly binding to the XTH31 promoter region, and overexpression of XTH31 in the anac017 mutant background rescued its Al-tolerance phenotype. In conclusion, we identified that the tTF ANAC017 acts upstream of XTH31 to regulate Al tolerance in Arabidopsis.

Dual-comb fiber laser for stable frequency distribution.

A passive dual-comb laser can generate two optical frequency combs with different repetition frequencies. These repetition differences have high relative stability and mutual coherence through passive common-mode noise suppression without complex tight phase locking from a single-laser cavity. The comb-based frequency distribution requires the dual-comb laser to have a high repetition frequency difference. This paper presents a high repetition frequency difference bidirectional dual-comb fiber laser based on an all-polarization-maintaining cavity configuration and a semiconductor saturable absorption mirror with single polarization output. The proposed comb laser has a standard deviation of 69 Hz and an Allan deviation of 1.17 × 10-7 at τ = 1 s under different repetition frequencies of 12.815 MHz. Moreover, a transmission experiment has been conducted. Owing to the passive common-mode noise rejection capability of dual-comb laser, after passing an 84 km fiber link, the frequency stability of the repetition frequency difference signal is improved by two orders of magnitude than the repetition frequency signal at the receiver side.

Node-downloadable frequency transfer system based on a mode-locked laser with over 100 km of fiber.

To meet the requirements of time-frequency networks and enable frequency downloadability for nodes along the link, we demonstrated the extraction of stable frequency signals at nodes using a mode-locked laser under the condition of 100 km laboratory fiber. The node consists of a simple structure that utilizes widely used optoelectronic devices and enables plug-and-play applications. In addition, the node can recover frequency signals with multiple frequencies, which are useful for scenarios that require different frequencies. Here, we experimentally demonstrated a short-term frequency instability of 2.83 × 10-13@1 s and a long-term frequency instability of 1.18 × 10-15@10,000 s at the node, which is similar to that at the remote site of the frequency transfer system. At the same time, frequency signals with different frequencies also achieved stable extraction with the same performance at the node. Our results can support the distributed application under large-scale time-frequency networks.

Multi-nodes dissemination of stable radio frequency with 10-17 instability over 2000 km optical fiber.

To meet the demand of flexible access for high-precision synchronization frequency, we demonstrate multi-node stable radio frequency (RF) dissemination over a long-distance optical fiber. Stable radio frequency signals can be extracted at any node along the optical fiber, not just at the endpoint. The differential mixing structure (DMS) is employed to avoid the frequency harmonic leakage and enhance the precision. The phase-locked loop (PLL) provides frequency reference for the DMS while improving the signal to noise ratio (SNR) of dissemination signal. We measure the frequency instability of multi-node stable frequency dissemination system (MFDS) at different locations along the 2,000 km optical fiber. The measured short-term instability with average time of 1 s are 1.90 × 10-14 @ 500 km, 2.81 × 10-14 @ 1,000 km, 3.46 × 10-14 @ 1,500 km, and 3.84 × 10-14 @ 2,000 km respectively. The long-term instability with average time of 10,000 s are basically the same at any position of the optical fiber, which is about (6.24 ± 0.05) × 10-17. The resulting instability is sufficient for the propagation of precision active hydrogen masers.

Evolution of m6A-related genes in insects and the function of METTL3 in silkworm embryonic development.

N6-methyladenosine (m6A) plays a key role in many biological processes. However, the function and evolutionary relationship of m6A-related genes in insects remain largely unknown. Here we analysed the phylogeny of m6A-related genes among 207 insect species and found that m6A-related genes are evolutionarily conserved in insects. Subcellular localization experiments of m6A-related proteins in BmN cells confirmed that BmYTHDF3 was localized in the cytoplasm, BmMETTL3, BmMETTL14, and BmYTHDC were localized in the nucleus, and FL2D was localized to both the nucleus and cytoplasm. We examined the expression patterns of m6A-related genes during the embryonic development of Bombyx mori. To elucidate the function of BmMETTL3 during the embryonic stage, RNA sequencing was performed to measure changes in gene expression in silkworm eggs after BmMETTL3 knockdown, as well as in BmN cells overexpressing BmMETTL3. The global transcriptional pattern showed that knockdown of BmMETTL3 affected multiple cellular processes, including oxidoreductase activity, transcription regulator activity, and the cation binding. In addition, transcriptomic data revealed that many observed DEGs were associated with fundamental metabolic processes, including carbon metabolism, purine metabolism, amino acid biosynthesis, and the citrate cycle. Interestingly, we found that knockdown of BmMETTL3 significantly affected Wnt and Toll/Imd pathways in embryos. Taken together, these results suggest that BmMETTL3 plays an essential role in the embryonic development of B. mori, and deepen our understanding of the function of m6A-related genes in insects.

Experimental upstream transmission of continuous variable quantum key distribution access network.

Continuous variable quantum key distribution that can be implemented using only low-cost and off-the-shelf components reveals great potential in practical large-scale realization. Access networks, as a modern network necessity, connect many end-users to the network backbone. In this work, we first demonstrate upstream transmission quantum access networks using continuous variable quantum key distribution. A two-end-user quantum access network is then experimentally realized. Through phase compensation, data synchronization, and other technical upgrades, we achieve a secret key rate of the total network of 390 kbits/s. In addition, we extend the case of a two-end-user quantum access network to the case of a multiplicity of users, and analyze the network capacity in the case of a multiplicity of users by measuring the additive excess noise from different time slots.