Enantiodivergent Cyclization of Racemic Cyclohexadienones via Parallel Kinetic Asymmetric Transformation.

Strategies that fully convert available racemic substrates into valuable enantioenriched products are urgently needed in organic synthesis. Reported herein is the first parallel kinetic asymmetric transformation of racemic cyclohexadienones. Racemic cyclohexadienones are first diastereoselectively converted into a new pair of racemic transient dienol intermediates, which are then parallel protonated by chiral phosphoric acid to deliver two sets of hydroindole products bearing a quaternary stereocenter with generally excellent enantioselectivity.

Ultrasound sensing with optical microcavities.

Ultrasound sensors play an important role in biomedical imaging, industrial nondestructive inspection, etc. Traditional ultrasound sensors that use piezoelectric transducers face limitations in sensitivity and spatial resolution when miniaturized, with typical sizes at the millimeter to centimeter scale. To overcome these challenges, optical ultrasound sensors have emerged as a promising alternative, offering both high sensitivity and spatial resolution. In particular, ultrasound sensors utilizing high-quality factor (Q) optical microcavities have achieved unprecedented performance in terms of sensitivity and bandwidth, while also enabling mass production on silicon chips. In this review, we focus on recent advances in ultrasound sensing applications using three types of optical microcavities: Fabry-Perot cavities, π-phase-shifted Bragg gratings, and whispering gallery mode microcavities. We provide an overview of the ultrasound sensing mechanisms employed by these microcavities and discuss the key parameters for optimizing ultrasound sensors. Furthermore, we survey recent advances in ultrasound sensing using these microcavity-based approaches, highlighting their applications in diverse detection scenarios, such as photoacoustic imaging, ranging, and particle detection. The goal of this review is to provide a comprehensive understanding of the latest advances in ultrasound sensing with optical microcavities and their potential for future development in high-performance ultrasound imaging and sensing technologies.

Analysis of the expression level and predictive value of CLEC16A|miR-654-5p|RARA regulatory axis in the peripheral blood of patients with ischemic stroke based on biosignature analysis.

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

Comprehensive genomic profiling of breast cancers characterizes germline-somatic mutation interactions mediating therapeutic vulnerabilities.

Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population.

Implementation of Individualized Low-Dose Computed Tomography-Guided Hook Wire Localization of Pulmonary Nodules: Feasibility and Safety in the Clinical Setting.

Background: CT-guided hook-wire localization is an essential step in the management of small pulmonary nodules. Few studies, however, have focused on reducing radiation exposure during the procedure. Purpose: This study aims to explore the feasibility of implementing a low-dose computed tomography (CT)-guided hook wire localization using tailored kVp based on patients' body size. Materials and Methods: A total of 151 patients with small pulmonary nodules were prospectively enrolled for CT-guided hook wire localization using individualized low-dose CT (LDCT) vs. standard-dose CT (SDCT) protocols. Radiation dose, image quality, characteristics of target nodules and procedure-related variables were compared. All variables were analyzed using Chi-Square and Student's t-test. Results: The mean CTDIvol was significantly reduced for LDCT (for BMI ≤ 21 kg/m2, 0.56 ± 0.00 mGy and for BMI > 21 kg/m2, 1.48 ± 0.00 mGy) when compared with SDCT (for BMI ≤ 21 kg/m2, 5.24 ± 0.95 mGy and for BMI > 21 kg/m2, 6.69 ± 1.47 mGy). Accordingly, the DLP of LDCT was significantly reduced as compared with that of SDCT (for BMI ≤ 21 kg/m2, 56.86 ± 4.73 vs. 533.58 ± 122.06 mGy.cm, and for BMI > 21 kg/m2, 167.02 ± 38.76 vs. 746.01 ± 230.91 mGy.cm). In comparison with SDCT, the effective dose (ED) of LDCT decreased by an average of 89.42% (for BMI ≤ 21 kg/m2) and 77.68% (for BMI > 21 kg/m2), respectively. Although the images acquired with the LDCT protocol yielded inferior quality to those acquired with the SDCT protocol, they were clinically acceptable for hook wire localization. Conclusions: LDCT-guided localization can provide safety and nodule detection performance comparable to SDCT-guided localization, benefiting radiation dose reduction dramatically, especially for patients with small body mass indexes.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

Controllable spin-resolved photon emission enhanced by a slow-light mode in photonic crystal waveguides on a chip.

We report the slow-light enhanced spin-resolved in-plane emission from a single quantum dot (QD) in a photonic crystal waveguide (PCW). The slow light dispersions in PCWs are designed to match the emission wavelengths of single QDs. The resonance between two spin states emitted from a single QD and a slow light mode of a waveguide is investigated under a magnetic field with Faraday configuration. Two spin states of a single QD experience different degrees of enhancement as their emission wavelengths are shifted by combining diamagnetic and Zeeman effects with an optical excitation power control. A circular polarization degree up to 0.81 is achieved by changing the off-resonant excitation power. Strongly polarized photon emission enhanced by a slow light mode shows great potential to attain controllable spin-resolved photon sources for integrated optical quantum networks on chip.

[Characteristics and Source Apportionment of Atmospheric Ion Deposition During Winter and Spring in the Core Area of Beijing].

In recent years, the Ministry of Ecology and Environment and the Beijing Municipal Government have continuously strengthened the control indicators of dustfall. In order to grasp the characteristics and sources of ion deposition in dustfall, the filtration method and ion chromatography were used to determine the dustfall and ion deposition during winter and spring in the core area of Beijing, and the PMF model was carried out to analyze the sources of ion deposition. The results indicated:① the average values of ion deposition and its proportion in dustfall were 0.87 t·(km2·30 d)-1 and 14.2%, respectively. The dustfall and ion deposition on working days were 1.3 times and 0.7 times that on rest days, respectively. ② The coefficient of determination in the linear equations between ion deposition and precipitation, relative humidity, temperature, and average wind speed were 0.54, 0.16, 0.15, and 0.02, respectively. In addition, the coefficient of determination in the linear equations between ion deposition and PM2.5 concentration and dustfall were 0.26 and 0.17, respectively. Therefore, controlling the concentration of PM2.5 was crucial to treating ion deposition. ③ Anions and cations accounted for 61.6% and 38.4%, respectively, in the ion deposition, and SO42-, NO3-, and NH4+ accounted for 60.6% in total. The ratio of anion and cation charge deposition was 0.70, and the dustfall was alkaline. The ρ(NO3-)/ρ(SO42-) in the ion deposition was 0.66, which was higher than that of 15 years ago. ④ The contribution rates of secondary sources, fugitive dust sources, combustion sources, snow-melting agent sources, and other sources were 51.7%, 17.7%, 13.5%, 13.5%, and 3.6%, respectively.

Trichosporon asahii Infection in an Extremely Preterm Infant in China.

Trichosporon asahii is an uncommon cause of fungal sepsis among neonates, but it is an important life-threatening opportunistic systemic pathogen. We report a case of T. asahii sepsis in a 980-g female baby born at 27 weeks of gestation. The extremely preterm initially presented with recurrent feeding intolerance and bloating; she subsequently developed oxygen saturation fluctuations, apnea, and a decreased heart rate. Blood culture was positive, and the causative agent was identified as T. asahii by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). According to reported minimum inhibitory concentration (MIC) values, the infant received a high dose of fluconazole (FLC, 12 mg/kg, qod) and was successfully treated.

Legacy and alternative per- and polyfluoroalkyl substances (PFASs) in the West River and North River, south China: Occurrence, fate, spatio-temporal variations and potential sources.

Poly- and perfluoroalkyl substances (PFASs) are contaminants of global concern. Studies in Pearl River, south China have focused on the delta area, while the upstream contributions are unclear. Here, we systematically investigated the fate, trends and potential sources of 57 PFASs in river water, sediment and fish of the North and West Rivers of the Pearl River system. Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2Cl-PFESA) were frequently found compounds in waters, sediments and fish, suggesting their wide usage in this area and potential for bioaccumulation. Waters showed a higher ∑PFASs in the wet season compared to the dry season, but sediments did not. The North River contributed higher PFAS loads to the Pearl River Delta. Our results also reflect the current shift in PFAS usage from legacy substances to alternatives. This study, for the first time, reports data on PFASs in two upstream rivers of the Pearl River and on alternative PFASs such as PFESA in this area, which can better the understanding of their use, fate, risk assessment and further controls and management.

Enhanced emission from a single quantum dot in a microdisk at a deterministic diabolical point.

We report on controllable cavity modes by controlling the backscattering by two identical scatterers. Periodic changes of the backscattering coupling between two degenerate cavity modes are observed with the changing angle between two scatterers and elucidated by a theoretical model using two-mode approximation and numerical simulations. The periodically appearing single-peak cavity modes indicate mode degeneracy at diabolical points. Interactions between single quantum dots and cavity modes are then investigated. Enhanced emission of a quantum dot with a six-fold intensity increase is obtained in a microdisk at a diabolical point. This method to control cavity modes allows large-scale integration, high reproducibility and flexible design of the size, the location, the quantity and the shape for scatterers, which can be applied for integrated photonic structures with scatterer-modified light-matter interaction.

Timolol induces necroptosis, apoptosis and senescence concentration-dependently in rabbit Limbal stem cells in vitro.

Limbal stem cells (LSCs) are crucial for corneal transparency and vision. Any damages to LSCs might lead to limbal stem cell deficiency resulting in corneal opacification and even blindness. Here, we investigated the cytotoxicity of timolol and its underlying mechanisms in rabbit LSCs (rLSCs) in vitro. High concentrations of 0.5% and 0.25% timolol induced necroptosis in rLSCs to upregulate receptor interacting protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL) and phosphorylated MLKL along with downregulation of caspase-8 and caspase-2 within 4 h. While, median concentrations of 0.125% to 0.0625% timolol induced apoptosis in the rLSCs within 28 h. The apoptotic mechanism in the median-concentration timolol-treated rLSCs is probably via extrinsic apoptosis pathway by activating caspase-2, caspase-8 and caspase-3 and intrinsic apoptosis pathway triggered by excessive generation of ROS and subsequent DNA damage to upregulate Bax and Bad, downregulate Bcl-2 and Bcl-xL, subsequently disrupt mitochondrial membrane potential, cytosolically translocate cytochrome c and apoptosis-inducing factor, and activate caspase-9. In addition, low concentration of 0.03125% timolol induced senescence in the rLSCs by elevating ROS level and increasing number of senescence associated ß-galactosidase positive cells at 28 h. Our findings reveal that timolol induces necroptosis, apoptosis and senescence concentration-dependently in rLSCs in vitro.

Lineage-specific plastid degradation in subtribe Gentianinae (Gentianaceae).

The structure and sequence of plastid genomes is highly conserved across most land plants, except for a minority of lineages that show gene loss and genome degradation. Understanding the early stages of plastome degradation may provide crucial insights into the repeatability and predictability of genomic evolutionary trends. We investigated these trends in subtribe Gentianinae of the Gentianaceae, which encompasses ca. 450 species distributed around the world, particularly in alpine and subalpine environments. We sequenced, assembled, and annotated the plastomes of 41 species, representing all six genera in subtribe Gentianinae and all main sections of the species-rich genus Gentiana L. We reconstructed the phylogeny, estimated divergence times, investigated the phylogenetic distribution of putative gene losses, and related these to substitution rate shifts and species' habitats. We obtained a strongly supported topology consistent with earlier studies, with all six genera in Gentianinae recovered as monophyletic and all main sections of Gentiana having full support. While closely related species have very similar plastomes in terms of size and structure, independent gene losses, particularly of the ndh complex, have occurred in multiple clades across the phylogeny. Gene loss was usually associated with a shift in the boundaries of the small single-copy and inverted repeat regions. Substitution rates were variable between clades, with evidence for both elevated and decelerated rate shifts. Independent lineage-specific loss of ndh genes occurred at a wide range of times, from Eocene to Pliocene. Our study illustrates that diverse degradation patterns shape the evolution of the plastid in this species-rich plant group.

Hepatoprotective effect of total flavonoids from Glycyrrhiza uralensis Fisch in liver injury mice.

This work aimed to investigate the hepatoprotective effect of total flavonoids from Glycyrrhiza uralensis. The main compounds in licorice total flavonoids (LTF) were isolated from Glycyrrhiza uralensis and their total content in LTF were more than 60%. Hepatoprotective effects of LTF were investigated in three kinds of hepatic injury mice model induced by high-fat emulsion, Chinese liquor and tetrachloromethane. Serum ALT, AST and ALP levels and hepatic MDA, TG, cholesterol, and hydroxyproline of hepatic injury mice were reduced by LTF. Simultaneously, hepatic SOD and glutathione were increased by LTF. These results suggested that LTF can repair liver tissue and reduce hepatic injury via alleviating inflammation, improving antioxidant enzyme activity and reducing oxidative stress in liver tissue and it may be a valuable natural source of hepatoprotective activity.

[Localization of Soil Wind Erosion Dust Emission Factor in Beijing].

Soil wind erosion dust is one of the primary sources of fine particulate matter (PM2.5). Compared with the fugitive dust emission inventory of typical domestic provinces and cities, we found that the maximum among the contribution rates of soil wind erosion dust to the local total fugitive dust PM2.5 emission inventory was about 4 orders of magnitude higher than the minimum. This study provided a wind erosion equation and a determination method of parameter values. The remote sensing interpretation, China soil dataset, and meteorological data of each district in Beijing were used to achieve the spatial distribution of the vegetation coverage factor (V), soil erodibility index (I), and climatic factors (C) in the plain area of Beijing. This study also estimated the emission factor of soil wind erosion dust and its spatial distribution. The main conclusions are as follows: ① Taking 2017 and Beijing city as an example, it was found that the climatic factor (C) was underestimated to different extents by domestic scholars, and PM2.5 emission factors were overestimated or underestimated. ② V, I, and C showed apparent spatial differences and the average values of them were 0.63±0.09, 188±73, and 0.029±0.009, respectively. The maximum values of V, I, and C were 1.5, 2.1, and 4.5 times the minimum among all districts, respectively. ③ The PM2.5 emission factor of soil wind erosion dust in Beijing showed a high spatial distribution in the northwest and southeast. The average emission factor of the city was (0.0018±0.0008) t·(hm2·a)-1, which is 0.54 times the highest emission factor (Xicheng District) and 3.12 times the lowest (Pinggu District). The area proportions of standardized emission factors with higher intensity (0.6 to 0.8] and high intensity (0.8 to 1.0] was 0.72% and 0.04%, respectively.

Contamination profile of antibiotic resistance genes in ground water in comparison with surface water.

Dissemination of antibiotic resistance genes (ARGs) in the water environment has become an increasing concern. There have been many reports on ARGs in surface water, but little is known about ARGs in groundwater. In this study, we investigated the profiles and abundance of ARGs in groundwater in comparison with those in surface water of Maozhou River using high-throughput quantitative PCR (HT-qPCR). Totally 127 ARGs and 10 MGEs were detected by HT-qPCR, and among them the sulfonamides, multidrug and aminoglycosides resistance genes were the dominant ARG types. According to the results of HT-qPCR, 18 frequently detected ARGs conferring resistance to 6 classes of antibiotics and 3 MGEs were further quantified by qPCR in the wet season and dry season. The absolute abundance ranged from 1.23 × 105 to 8.89 × 106 copies/mL in wet season and from 8.50 × 102 to 2.65 × 106 copies/mL in the dry season, with sul1 and sul2 being the most abundant ARGs. The absolute abundance of ARGs and MGEs has no significant difference between the wet season and dry season while the diversity of ARGs in the dry season was higher than that in the wet season (p < 0.05). Totally 141 and 150 ARGs were detected in the water and sediments of Maozhou River, respectively. A total of 116 ARGs were shared among the groundwater, river water, and sediment, which accounted for 67.1% of all detected genes. Redundancy analysis further demonstrated that the environmental factors contributed 70.7% of the total ARG variations. The findings of large shared ARGs, abundant Total Coliforms and large wastewater burden in the groundwater provide a clear evidence that anthropogenic activities had a significant impact on groundwater.

Diabolical points in coupled active cavities with quantum emitters.

In single microdisks, embedded active emitters intrinsically affect the cavity modes of the microdisks, resulting in trivial symmetric backscattering and low controllability. Here we demonstrate macroscopic control of the backscattering direction by optimizing the cavity size. The signature of the positive and negative backscattering directions in each single microdisk is confirmed with two strongly coupled microdisks. Furthermore, diabolical points are achieved at the resonance of the two microdisks, which agrees well with theoretical calculations considering the backscattering directions. Diabolical points in active optical structures pave the way for an implementation of quantum information processing with geometric phase in quantum photonic networks.

Indoleamine 2,3-dioxgenase-transfected mesenchymal stem cells suppress heart allograft rejection by increasing the production and activity of dendritic cells and regulatory T cells.

Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based transgenic system was used to generate bone marrow stem cells (BMSC) which stably expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A heterotopic heart transplant model in rats was used to evaluate allograft rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated immunosuppression were investigated by evaluating levels of proinflammatory and anti-inflammatory cytokines, and production of Tregs. A significant decrease in DC marker-positive cells and a significant increase in Tregs were observed in IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated with significantly prolonged graft survival. Compared with the control groups, transplanted animals treated with IDO-BMSCs had a (1) significantly higher ejection fraction and fractional shortening, (2) significantly lower expression of CD86, CD80, and MHCII, and significantly higher expression in CD274, and Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), transforming growth factor beta-1 (TGF-ß1), TGF-ß2, and TGF-ß3, and significantly lower levels of IL-2 and interferon gamma. Our results expand our understanding of the molecular mechanisms underlying suppression of heart allograft rejection via IDO-expressing BMSCs.

Contamination profiles and health risks of PFASs in groundwater of the Maozhou River basin.

Per-and polyfluoroalkyl substances (PFASs) are a group of chemicals with a wide range of industrial and commercial applications, but little is known about the contamination of PFASs in groundwater and their linkage to surface water. Here we investigated the occurrence of PFASs in groundwater and surface water at the Maozhou River basin in order to understand their contamination profiles and potential health risks. The results showed that total PFASs concentrations ranged from 9.9 to 592.2 ng/L, 50.2-339.9 ng/L and 3.7-74.3 ng/g in groundwater, river water and sediment, respectively. The detection frequencies of C4-C8 chains (C4-C8) PFASs were higher than C9-C14 chains PFASs in the river and groundwater. Statistical analysis showed an obvious correlation between the major contaminants in the river and those in the groundwater, indicating the potential linkage of PFASs in the groundwater to the surface water. The wastewater indicator found in groundwater suggested domestic wastewater was only one of the source for the PFASs in the river and groundwater of Maozhou River basin. Moreover, human health risk assessment showed low risks from the PFASs to the residents by drinking groundwater.