On-Chip Topological Photonic Crystal Nanobeam Filters.

We present an on-chip filter with a broad tailorable working wavelength and a single-mode operation. This is realized through the application of topological photonic crystal nanobeam filters employing synthesis parameter dimensions. By introducing the translation of air holes as a new synthetic parameter dimension, we obtained nanobeams with tunable Zak phases. Leveraging the bulk-edge correspondence, we identify the existence of topological cavity modes and establish a correlation between the cavity's interface morphology and working wavelength. Through experiments, we demonstrate filters with adjustable filtering wavelengths ranging from 1301 to 1570 nm. Our work illustrates the use of the synthetic translation dimension in the design of on-chip filters, and it holds potential for applications in other devices such as microcavities.

Visible-Light-Induced and Iodoform-Promoted Functionalization of Ether with Secondary Sulfonyl Amides.

An iodoform-promoted functionalization of ether with secondary sulfonyl amides under visible-light irradiation was developed toward synthesis of hemiaminal skeleton with good to excellent isolated yields. The characterization of the isolated ether and iodoform complex revealed regioselective hydrogen atom transfer to initiate carbon radical formation and enabled the amination reaction with the sulfonamide.

Suppressed Voltage Deficit and Degradation of Perovskite Solar Cells by Regulating the Mineralization of Lead Iodide.

Both the uncoordinated Pb2+ and excess PbI2 in perovskite film will create defects and perturb carrier collection, thus leading to the open-circuit voltage (VOC ) loss and inducing rapid performance degradation of perovskite solar cells (PSCs). Herein, an additive of 3-aminothiophene-2-carboxamide (3-AzTca) that contains amide and amino and features a large molecular size is introduced to improve the quality of perovskite film. The interplay of size effect and adequate bonding strength between 3-AzTca and uncoordinated Pb2+ regulates the mineralization of PbI2 and generates low-dimensional PbI2 phase, thereby boosting the crystallization of perovskite. The decreased defect states result in suppressed nonradiative recombination and reduced VOC loss. The power conversion efficiency (PCE) of modified PSC is improved to 22.79% with a high VOC of 1.22 V. Moreover, the decomposition of PbI2 and perovskite films is also retarded, yielding enhanced device stability. This study provides an effective method to minimize the concentration of uncoordinated Pb2+ and improve the PCE and stability of PSCs.

Visible-Light Photoredox Catalyzed Regioselective 1,4-Hydroalkylation of 1,3-Enyne.

Described herein is a visible-light photoredox-catalyzed regioselective 1,4-hydroalkylation of 1,3-enynes. Various of di- and tri-substituent allenes were really accessible under the present reaction conditions. The visible-light photoredox activation of the carbon nucleophile to generate its radical species, allowing the addition with un-activated enynes. The synthetic utility for the present protocol was demonstrated by a large-scale reaction, as well as the derivatization of the allene product.

Microglia-dependent excessive synaptic pruning leads to cortical underconnectivity and behavioral abnormality following chronic social defeat stress in mice.

Synapse loss in medial prefrontal cortex (mPFC) has been implicated in stress-related mood disorders, such as depression. However, the exact effect of synapse elimination in the depression and how it is triggered are largely unknown. Through repeated longitudinal imaging of mPFC in the living brain, we found both presynaptic and postsynaptic components were declined, together with the impairment of synapse remodeling and cross-synaptic signal transmission in the mPFC during chronic stress. Meanwhile, chronic stress also induced excessive microglia phagocytosis, leading to engulfment of excitatory synapses. Further investigation revealed that the elevated complement C3 during the stress acted as the tag of synapses to be eliminated by microglia. Besides, chronic stress induced a reduction of the connectivity between the mPFC and neighbor regions. C3 knockout mice displayed significant reduction of synaptic pruning and alleviation of disrupted functional connectivity in mPFC, resulting in more resilience to chronic stress. These results indicate that complement-mediated excessive microglia phagocytosis in adulthood induces synaptic dysfunction and cortical hypo-connectivity, leading to stress-related behavioral abnormality.

Visible-Light-Mediated Radical Hydroalkylative Cyclization of 1,6-Enynes.

A radical hydroalkylative cyclization approach accessing various alkenyl heterocyclic compounds was developed using dimethyl malonate and 1,6-enynes in the presence of visible-light photoredox catalysis. The use of Ir(dtbbpy)(ppy)2PF6 as a photosensitizer enables carbon atom radical formation and initiates the cascade cyclization reaction under mild conditions.

Photoinduced Copper-Catalyzed 1,2-Difunctionalization of 1,3-Dienes with Aryl Diselenides.

Described herein is a photoinduced copper-catalyzed 1,2-difunctionalization of 1,3-dienes. The selenium atom radical was generated by the visible light irradiation of diselenides, triggering radical addition with 1,3-dienes to form allyl radical intermediate. Subsequent rapid Z/E isomerization allowed for thermodynamically favorable intermediate formation and enabled copper catalyzed stereoselective functionalization with various nucleophiles.

Copper-Catalyzed Bromo-cyanomethylative Cyclization of Enynes.

A copper-catalyzed bromo-cyanomethylative cyclization of 1,6-enynes is demonstrated. The treatment of 2-bromoacetonitrile with CuI enables the alkyl radical generation and triggers the radical addition/cyclization/bromination sequence, giving various vinyl C-Br bonds containing functionalized heterocycles in good yields.

Copper-Catalyzed Oxidative Dearomatized Oxyalkylation of Indoles with Alcohols: Synthesis of 3-Alkoxy-2-Oxindoles.

Described herein is a copper-catalyzed efficient oxidative dearomatized functionalization of indoles by using alcohols as the nucleophiles. Various 3-alkoxy-2-oxindoles were accessible with good isolated yields. The synthetic potential applications are demonstrated by the large-scale reaction, as well as the derivatization of the desired 3-alkoxy substituted-2-oxindole products.

Prolonged ST segment and T-wave alternans with torsade de pointes secondary to hypocalcemia due to hypoparathyroidism: A case report.

Hypoparathyroidism predisposes patients to hypocalcemia. Patients with hypoparathyroidism are thus at risk of electrocardiographic abnormalities, including T-wave alternans. T-wave alternans is poorly understood and lacks uniform diagnostic criteria. Its presence suggests myocardial electrical instability, and it has become an important sign for identifying patients at high risk of malignant arrhythmias and sudden cardiac death. We report a rare case of T-wave alternans with torsade de pointes due to hypocalcemia. The etiology of T-wave alternans may easily be overlooked. It should thus be thoroughly investigated to avoid misdiagnosis and poor outcomes.

[Study on regulation of CYP450 enzyme system to reduce liver toxicity through compatibility of Aconiti Kusnezoffii Radix Cocta with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma].

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.

α-Acylation of Alkenes by a Single Photocatalyst.

A direct strategy for the difunctionalization of alkenes, with acylation occurring at the more substituted alkene position, would be attractive for complex ketone synthesis. We report herein a reaction driven by a single photocatalyst that enables α-acylation in this way with the introduction of a fluoromethyl, alkyl, sulfonyl or thioether group at the ß-position of the alkene with high chemo- and regioselectivity under extremely mild conditions. Crucial to the success of this method are rate differences in the kinetics of radical generation through single-electron transfer (SET) between different radical precursors and the excited photocatalyst (PC*). Thus, the ß-position of the alkene is first occupied by the group derived from the radical precursor that can be generated most readily, and α-keto acids could be used as an electrophilic reagent for the α-acylation of alkenes.

Full-color photon-counting single-pixel imaging.

We propose and experimentally demonstrate a high-efficiency single-pixel imaging (SPI) scheme by integrating time-correlated single-photon counting (TCSPC) with time-division multiplexing to acquire full-color images at an extremely low light level. This SPI scheme uses a digital micromirror device to modulate a sequence of laser pulses with preset delays to achieve three-color structured illumination, then employs a photomultiplier tube into the TCSPC module to achieve photon-counting detection. By exploiting the time-resolved capabilities of TCSPC, we demodulate the spectrum-image-encoded signals, and then reconstruct high-quality full-color images in a single round of measurement. Based on this scheme, strategies such as single-step measurement, high-speed projection, and undersampling can further improve imaging efficiency.

Distinct effects of asthma and COPD comorbidity on disease expression and outcome in patients with COVID-19.

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections.

BACKGROUND: The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. MEASURE: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. RESULTS: A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. CONCLUSION: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.

Visible-Light Mediated Diarylselenylative Cyclization of 1,6-Enynes.

We herein described a selenylative cyclization reaction of enynes by the utilization of diselenides as radical sources. The visible-light irradiation of the reaction mixture enables the generation of the selenium atom radical to trigger the radical addition/cyclization/selenation sequences. Both terminal alkyne and internal alkyne derived 1,6-enynes were tested and suitable for the current synthetic protocol, delivering various kinds of selenium-containing cycles in good yields.

Direct 1,2-Dicarbonylation of Alkenes towards 1,4-Diketones via Photocatalysis.

1,4-Dicarbonyl compounds are intriguing motifs and versatile precursors in numerous pharmaceutical molecules and bioactive natural compounds. Direct incorporation of two carbonyl groups into a double bond at both ends is straightforward, but also challenging. Represented herein is the first example of 1,2-dicarbonylation of alkenes by photocatalysis. Key to success is that N(n-Bu)4+ not only associates with the alkyl anion to avoid protonation, but also activates the α-keto acid to undergo electrophilic addition. The α-keto acid is employed both for acyl generation and electrophilic addition. By tuning the reductive and electrophilic ability of the acyl precursor, unsymmetric 1,4-dicarbonylation is achieved for the first time. This metal-free, redox-neutral and regioselective 1,2-dicarbonylation of alkenes is executed by a photocatalyst for versatile substrates under extremely mild conditions and shows great potential in biomolecular and drug molecular derivatization.

Restriction of Intramolecular Vibration in Aggregation-Induced Emission Luminogens: Applications in Multifunctional Luminescent Metal-Organic Frameworks.

Butterfly-like molecules of oxacalix[2]arene[2]pyrazine (OAP) are reported, which exhibit the typical characteristics of aggregation-induced emission (AIE) via the restriction of intramolecular vibration (RIV) mechanism. Unlike any of the reported RIV-type AIE molecules, the synthetic procedures of which are complicated and have associated high costs, OAP AIEgens can be synthesized in a facile manner by a one-step catalyst-free reaction using commercially available materials. Notably, OAP AIEgens are ideal ligands for constructing metal-organic frameworks (MOFs) due to their built-in pyrazine coordination sites. OAP-based MOFs exhibit multiple potential applications in reversible gas response, encrypted information storage, and construction of white light-emitting devices. This work builds on RIV-type AIEgens, offers additional selections of bridging ligands for constructing luminescent MOFs and provides a visualized prototype to understand the effect of the RIV process on the luminescence properties of MOFs.

Knockdown of LINC00657 inhibits ox-LDL-induced endothelial cell injury by regulating miR-30c-5p/Wnt7b/ß-catenin.

Long noncoding RNAs (lncRNAs) play pivotal roles in the pathogenesis, development, and treatment of atherosclerosis (AS). The endothelial cell injury is a feature of AS. However, the role and mechanism of lncRNA LINC00657 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury remain unclear. The serum samples were collected from 32 AS patients and normal volunteers. Ox-LDL-treated human umbilical vein endothelial cells (HUVEC) were used for the experiments in vitro. The levels of LINC00657, microRNA (miR)-30c-5p and Wnt family member 7B (Wnt7b) were measured by quantitative real-time polymerase chain reaction or western blot. The expression levels of proteins in Wnt7b/ß-catenin pathway or endothelial-mesenchymal transition (EndMT) were detected by western blot. The secretion of inflammatory cytokine was examined by enzyme linked immunosorbent assay (ELISA). Cell viability and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, flow cytometry, and western blot. The target association of miR-30c-5p and LINC00657/Wnt7b was analyzed via dual-luciferase reporter assay and RNA pull-down assay. LINC00657 expression was increased in AS serum and ox-LDL-treated HUVEC cells. LINC00657 knockdown suppressed ox-LDL-induced Wnt7b/ß-catenin activation, EndMT, inflammatory response, and apoptosis in HUVEC cells. MiR-30c-5p was bound to LINC00657 and it knockdown reversed the role of LINC00657 inhibition in ox-LDL-induced HUVEC cell injury. MiR-30c-5p targeted Wnt7b to inhibit ox-LDL-induced Wnt7b/ß-catenin activation, EndMT, inflammatory response, and apoptosis in HUVEC cells. Silence of LINC00657 repressed ox-LDL-induced injury via inhibiting EndMT, inflammatory response, and apoptosis in HUVEC cells by regulating miR-30c-5p/Wnt7b/ß-catenin, indicating a potential target for treatment of AS.

Copper-Catalyzed Bromodifluoroacetylative Cyclization of Enynes.

A copper-catalyzed bromodifluoroacetylative cyclization reaction is described. The treatment of bromodifluoroacete derivatives by CuI and B2Pin2 enables difluoroalkyl radical generation and triggers the radical addition/cyclization/bromination sequences. Bromodifluoroacetyl-derived ester, amide, and ketone were compatible and gave various vinyl C-Br bonds containing functionalized heterocycles in good yields.