CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway.

BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

Correlation between dysphagia and serum albumin levels and prognosis: a retrospective study / Correlación entre la disfagia y los niveles de albúmina sérica y el pronóstico: un estudio retrospectivo

Introduction: dysphagia is a common complication of stroke, and serum albumin is widely recognized as a strong prognostic marker of healthand/or disease status. However, the correlation between dysphagia and serum albumin levels has not been established.Objectives: to observe the correlation between dysphagia and serum albumin levels and prognosis in patients with stroke.Methods: we performed a retrospective study of patients hospitalized between June 1, 2018, and June 1, 2022. A total of 1,370 patients wereenrolled. The patients were divided into two groups: dysphagia and non-dysphagia. Binary logistic regression and multiple linear regressionmodels were used to analyze the correlation between dysphagia, albumin, modified Rankin Scale (mRS), activities of daily living (ADL), andlength of hospital stay (LOS).Results: after adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.417 times higher than that in the non-dysphagia group (OR = 2.417, 95 % CI: 1.902-3.072, p = 0.000). The risk of mRS ≥ 3 and modified Barthel index (MBI) < 60 in patients with dysphagia was 3.272-fold (OR = 3.272, 95 % CI: 2.508-4.269, p < 0.001) and 1.670-fold (OR = 1.670, 95 % CI: 1.230-2.268, p < 0.001), respectively; and the risk of hypoproteinemia was 2.533 times higher (OR = 2.533, 95 % CI: 1.879-3.414, p = 0.000). Stepwise linear regression showed that dysphagia was significantly correlated with lower albumin levels and higher mRS, lower ADL, and longer LOS in patients with stroke (β = -0.220, β = 0.265, β = -0.210, and β = 0.147, respectively; p < 0.001). Conclusions: dysphagia in patients with stroke is associated with decreased albumin levels and has an impact on its prognosis. (AU)

Introducción: la disfagia es una complicación común del accidente cerebrovascular, y la albúmina sérica es ampliamente reconocida como un fuerte marcador pronóstico del estado de salud y/o enfermedad. Sin embargo, no se ha establecido la correlación entre la disfagia y los niveles de albúmina sérica. Objetivos: observar la correlación entre la disfagia y los niveles de albúmina sérica y el pronóstico en pacientes con accidente cerebrovascular. Métodos: realizamos un estudio retrospectivo de pacientes hospitalizados entre el 1 de junio de 2018 y el 1 de junio de 2022. Se inscribieron untotal de 1.370 pacientes, los cuales fueron divididos en dos grupos: con disfagia y sin disfagia. Se utilizaron modelos de regresión logística binaria y de regresión lineal múltiple para analizar la correlación entre la disfagia, la albúmina, la escala de Rankin modificada (ERm), las actividades de la vida diaria (AVD) y el tiempo de estancia hospitalaria (TEH). Resultados: después de ajustar por factores de confusión, el riesgo de neumonía en el grupo de disfagia fue 2,417 veces mayor que en el gruposin disfagia (OR = 2,417, IC 95 %: 1,902-3,072, p = 0,000). El riesgo de ERm ≥ 3 y el índice de Barthel modificado (MBI) < 60 en pacientes condisfagia se multiplicó por 3,272 veces (OR = 3,272, IC 95 %: 2,508-4,269, p < 0,001) y 1,670 veces (OR = 1,670, IC 95 %: 1,230-2,268, p <0,001), respectivamente; el riesgo de hipoproteinemia fue 2,533 veces mayor (OR = 2,533, IC 95 %: 1,879-3,414, p = 0,000). La regresión linealpor pasos mostró que la disfagia se correlacionó significativamente con niveles más bajos de albúmina y ERm más altos, AVD más bajos y TEHmás prolongados en pacientes con accidente cerebrovascular (β = -0,220, β = 0,265, β = -0,210 y β = 0,147, respectivamente; p < 0,001).Conclusiones: la disfagia en pacientes con accidente cerebrovascular se asocia a una disminución de los niveles de albúmina y repercute ensu pronóstico. (AU)

A heterozygous ZP2 mutation causes zona pellucida defects and female infertility in mouse and human.

The zona pellucida (ZP) is an extracellular glycoprotein matrix surrounding mammalian oocytes. Recently, numerous mutations in genes encoding ZP proteins have been shown to be possibly related to oocyte abnormality and female infertility; few reports have confirmed the functions of these mutations in living animal models. Here, we identified a novel heterozygous missense mutation (NM_001376231.1:c.1616C>T, p.Thr539Met) in ZP2 from a primary infertile female. We showed that the mutation reduced ZP2 expression and impeded ZP2 secretion in cell lines. Furthermore, we constructed the mouse model with the mutation (Zp2T541M) using CRISPR-Cas9. Zp2WT/T541M female mice had normal fertility though generated oocytes with the thin ZP, whereas Zp2T541M female mice were completely infertile due to degeneration of oocytes without ZP. Additionally, ZP deletion impaired folliculogenesis and caused female infertility in Zp2T541M mice. Our study not only expands the spectrum of ZP2 mutation sites but also, more importantly, increases the understanding of pathogenic mechanisms of ZP2 mutations.

Correlation between dysphagia and serum albumin levels and prognosis: a retrospective study.

Introduction: Introduction: dysphagia is a common complication of stroke, and serum albumin is widely recognized as a strong prognostic marker of health and/or disease status. However, the correlation between dysphagia and serum albumin levels has not been established. Objectives: to observe the correlation between dysphagia and serum albumin levels and prognosis in patients with stroke. Methods: we performed a retrospective study of patients hospitalized between June 1, 2018, and June 1, 2022. A total of 1,370 patients were enrolled. The patients were divided into two groups: dysphagia and non-dysphagia. Binary logistic regression and multiple linear regression models were used to analyze the correlation between dysphagia, albumin, modified Rankin Scale (mRS), activities of daily living (ADL), and length of hospital stay (LOS). Results: after adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.417 times higher than that in the non-dysphagia group (OR = 2.417, 95 % CI: 1.902-3.072, p = 0.000). The risk of mRS ≥ 3 and modified Barthel index (MBI) < 60 in patients with dysphagia was 3.272-fold (OR = 3.272, 95 % CI: 2.508-4.269, p < 0.001) and 1.670-fold (OR = 1.670, 95 % CI: 1.230-2.268, p < 0.001), respectively; and the risk of hypoproteinemia was 2.533 times higher (OR = 2.533, 95 % CI: 1.879-3.414, p = 0.000). Stepwise linear regression showed that dysphagia was significantly correlated with lower albumin levels and higher mRS, lower ADL, and longer LOS in patients with stroke (ß = -0.220, ß = 0.265, ß = -0.210, and ß = 0.147, respectively; p < 0.001). Conclusions: dysphagia in patients with stroke is associated with decreased albumin levels and has an impact on its prognosis.

Introducción: Introducción: la disfagia es una complicación común del accidente cerebrovascular, y la albúmina sérica es ampliamente reconocida como un fuerte marcador pronóstico del estado de salud y/o enfermedad. Sin embargo, no se ha establecido la correlación entre la disfagia y los niveles de albúmina sérica. Objetivos: observar la correlación entre la disfagia y los niveles de albúmina sérica y el pronóstico en pacientes con accidente cerebrovascular. Métodos: realizamos un estudio retrospectivo de pacientes hospitalizados entre el 1 de junio de 2018 y el 1 de junio de 2022. Se inscribieron un total de 1.370 pacientes, los cuales fueron divididos en dos grupos: con disfagia y sin disfagia. Se utilizaron modelos de regresión logística binaria y de regresión lineal múltiple para analizar la correlación entre la disfagia, la albúmina, la escala de Rankin modificada (ERm), las actividades de la vida diaria (AVD) y el tiempo de estancia hospitalaria (TEH). Resultados: después de ajustar por factores de confusión, el riesgo de neumonía en el grupo de disfagia fue 2,417 veces mayor que en el grupo sin disfagia (OR = 2,417, IC 95 %: 1,902-3,072, p = 0,000). El riesgo de ERm ≥ 3 y el índice de Barthel modificado (MBI) < 60 en pacientes con disfagia se multiplicó por 3,272 veces (OR = 3,272, IC 95 %: 2,508-4,269, p < 0,001) y 1,670 veces (OR = 1,670, IC 95 %: 1,230-2,268, p < 0,001), respectivamente; el riesgo de hipoproteinemia fue 2,533 veces mayor (OR = 2,533, IC 95 %: 1,879-3,414, p = 0,000). La regresión lineal por pasos mostró que la disfagia se correlacionó significativamente con niveles más bajos de albúmina y ERm más altos, AVD más bajos y TEH más prolongados en pacientes con accidente cerebrovascular (ß = -0,220, ß = 0,265, ß = -0,210 y ß = 0,147, respectivamente; p < 0,001). Conclusiones: la disfagia en pacientes con accidente cerebrovascular se asocia a una disminución de los niveles de albúmina y repercute en su pronóstico.

Insights into the adverse effects of prepubertal chronic ethanol exposure on adult female reproduction.

Heavy drinking in women is known to adversely affect pregnancy and fertility. However, pregnancy is a complex process, and the adverse effects of ethanol on pregnancy does not mean that ethanol will have adverse effects on all stages from gamete to fetal formation. Similarly, the adverse effects of ethanol before and after adolescence cannot be generalized. To focus on the effects of prepubertal ethanol on female reproductive ability, we established a mouse model of prepubertal ethanol exposure by changing drinking water to 20% v/v ethanol. Some routine detections were performed on the model mice, and details such as mating, fertility, reproductive organ and fetal weights were recorded day by day after discontinuation of ethanol exposure. Prepubertal ethanol exposure resulted in decreased ovarian weight and significantly reduced oocyte maturation and ovulation after sexual maturation, however, normal morphology oocytes with discharged polar body showed normal chromosomes and spindle morphology. Strikingly, oocytes with normal morphology from ethanol exposed mice showed reduced fertilization rate, but once fertilized they had the ability to develop to blastocysts. RNA-seq analysis showed that the gene expression of the ethanol exposed oocytes with normal morphology had been altered. These results show the adverse effects of prepubertal alcohol exposure on adult female reproductive health.

T817MA Regulates Mitochondrial Dynamics via Sirt1 and Arc Following Subarachnoid Hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) is an acute neurologic emergency with poor outcomes, and mitochondrial dysfunction is known as one of the key pathological mechanisms underlying the SAH-induced early brain injury (EBI). 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate (T817MA) is a newly synthesized neurotrophic compound that has been demonstrated to exert protective effects against brain injury. Here, we investigated the effect of T817MA in neuronal injury following experimental SAH both in vitro and in vivo. Primary cultured cortical neurons were treated with oxyhemoglobin (OxyHb) to mimic SAH in vitro, and T817MA at concentrations higher than 0.1 µM reduced OxyHb-induced neuronal injury. T817MA treatment significantly inhibited lipid peroxidation, reduced neuronal apoptosis and attenuated mitochondrial fragmentation. The results of western blot showed that T817MA markedly reduced the expression of mitochondrial fission proteins, fission protein 1 (Fis-1) and dynamin-related GTPase-1 (Drp-1), but prolonged the expression of the postsynaptic protein activity-regulated cytoskeleton-associated protein (Arc). In addition, T817MA significantly increased the expression of sirtuin 1 (Sirt1), which was accompanied by preserved enzymatic of isocitrate dehydrogenase (IDH2) and superoxide dismutase (SOD). Knockdown of Sirt1 and Arc via small interfere RNA (siRNA) transfection partially prevented the T817MA-induced protection in cortical neurons. Furthermore, treatment with T817MA in vivo significantly reduced brain damage and preserved neurological function in rats. The decreased expression of Fis-1 and Drp-1, as well as the increased expression of Arc and Sirt1 were also observed in vivo. Taken together, these data indicate that the neuroprotective agent T817MA protects against SAH-induced brain injury via Sirt1- and Arc-mediated regulation of mitochondrial dynamics.

Effect of breathing exercises on oxidative stress biomarkers in humans: A systematic review and meta-analysis.

Background: Breathing exercises improve oxidative stress in healthy young adults and patients with diabetes, hypertension, and chronic obstructive pulmonary disease. Furthermore, the mechanism of respiratory intervention is controversial. Therefore, in this meta-analysis, we aimed to systematically evaluate the effects of breathing exercises on oxidative stress biomarkers in humans and provide evidence for the clinical application of breathing exercises. Methods: The Embase, PubMed, Cochrane Library, Web of Science, CNKI, and WANFANG databases were searched for studies about the effects of breathing exercises on human oxidative stress levels, with no restraints regarding time, race, or language. The experimental group included various breathing exercises, and the outcome index included malondialdehyde, superoxide dismutase, and glutathione, nitric oxide, vitamin C, or total antioxidant capacity levels from a randomized controlled trial. Data were extracted by more than two authors and reviewed by one author. Results: Ten studies were included from five countries. Data from patients with no disease, chronic obstructive pulmonary disease, hypertension, or diabetes were included. Participants who performed breathing exercises had greater changes in the included biomarkers than those who did not, suggesting that these biomarkers can be used to evaluate oxidative stress after respiratory interventions. Conclusion: Breathing exercises increased SOD and GSH activities and decreased MDA content. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337119, identifier CRD42022337119.

Reductive Aza-Pauson-Khand Reaction of Nitriles.

γ-Lactams are valuable heterocycles in synthetic chemistry and drug development. Here, we report a reductive aza-Pauson-Khand reaction (aza-PKR) of an alkyne, a nitrile, and Co2(CO)8. A wide array of bicyclic α,ß-unsaturated γ-lactams containing two adjacent stereocenters, including an all-carbon quaternary center, from alkyne-tethered malononitriles are efficiently accessed in high diastereoselectivity. Preliminary mechanistic investigations by experiments and DFT calculations reveal that the reaction undergoes an aza-PKR process followed by a in situ reduction. The reducing reagent generated in situ from water also provides a practical tool for deuterium incorporation into the γ-position of lactams using D2O as the deuterium source. This study represents a new mode for [2 + 2 + 1] cycloaddition that enables the direct use of nitrile in aza-heterocycle synthesis.

Source-independent quantum random number generator against tailored detector blinding attacks.

Randomness, mainly in the form of random numbers, is the fundamental prerequisite for the security of many cryptographic tasks. Quantum randomness can be extracted even if adversaries are fully aware of the protocol and even control the randomness source. However, an adversary can further manipulate the randomness via tailored detector blinding attacks, which are hacking attacks suffered by protocols with trusted detectors. Here, by treating no-click events as valid events, we propose a quantum random number generation protocol that can simultaneously address source vulnerability and ferocious tailored detector blinding attacks. The method can be extended to high-dimensional random number generation. We experimentally demonstrate the ability of our protocol to generate random numbers for two-dimensional measurement with a generation speed of 0.1 bit per pulse.

Isolation, Identification, and Biological Activity Analysis of Swim Bladder Polypeptides from Acipenser schrencki.

Swim bladder polypeptides (SBPs) of Acipenser schrencki were analyzed for their antioxidant activity and physicochemical properties. The results showed the optimal enzymatic conditions were alkaline protease with a solid-to-liquid ratio of 1:20, an incubation time of 4 h, a temperature of 55 °C, and an enzyme dosage of 5000 U/g. Three different molecular weight fractions (F1, F2, and F3) were obtained via ultrafiltration. F3 (912.44-2135.82 Da) showed 77.90%, 72.15%, and 66.25% removal of O2•-, DPPH•, and •OH, respectively, at 10 mg/mL, which was significantly higher than the F1 and F2 fractions (p < 0.05). F3 contained proline (6.17%), hydroxyproline (5.28%), and hydrophobic amino acids (51.39%). The UV spectrum of F3 showed maximum absorption at 224 nm. Peptide sequence analysis showed that F3 contained antioxidant peptides (MFGF, GPPGPRGPPGL, and GPGPSGERGPPGPM) and exhibited inhibitory activities on angiotensin-converting enzyme and dipeptidyl peptidase III/IV (FRF, FPFL and LPGLF). F3 was considered a good raw material for obtaining bioactive peptides.

Enantioselective Nickel-Catalyzed Reductive anti-Arylative Annulation of Alkyne-Tethered Malononitriles to Construct Quaternary Stereocenters.

A nickel-catalyzed reductive desymmetrizing annulation of alkyne-tethered malononitriles and (hetero)aryl iodides is reported for the access of cyclohexenones containing an α-all-carbon quaternary stereocenter. The use of a nickel catalyst derived from an electron-rich phosphinooxazoline ligand combined with iron powder as a reductant is crucial to the success of this transformation.

Discovery of novel N-benzylarylamide-dithiocarbamate based derivatives as dual inhibitors of tubulin polymerization and LSD1 that inhibit gastric cancers.

In this work, N-benzylarylamide-dithiocarbamate based derivatives were designed, synthesized, and their biological activities as anticancer agents were explored. Some of the 33 target compounds displayed significant antiproliferative activities with IC50 values at the double-digit nanomolar level. The representative compound I-25 (also named MY-943) not only showed the most effective inhibitory effects on three selected cancer cells MGC-803 (IC50 = 0.017 µM), HCT-116 (IC50 = 0.044 µM) and KYSE450 (IC50 = 0.030 µM), but also exhibited low nanomolar IC50 values from 0.019 to 0.253 µM against the other 11 cancer cells. Compound I-25 (MY-943) effectively inhibited tubulin polymerization and suppressed LSD1 at the enzymatic levels. Compound I-25 (MY-943) could act on the colchicine binding site of ß-tubulin, thus disrupting the construction of cell microtubule network and affecting the mitosis. In addition, compound I-25 (MY-943) could dose-dependently induce the accumulation of H3K4me1/2 (MGC-803 and SGC-7091 cells) and H3K9me2 (SGC-7091 cells). Compound I-25 (MY-943) could induce G2/M phase arrest and cell apoptosis, and suppress migration in MGC-803 and SGC-7901 cells. In addition, compound I-25 (MY-943) significantly modulated the expression of apoptosis- and cycle-related proteins. Furthermore, the binding modes of compound I-25 (MY-943) with tubulin and LSD1 were explored by molecular docking. The results of in vivo anti-gastric cancer assays using in situ tumor models showed that compound I-25 (MY-943) effectively reduced the weight and volume of gastric cancer in vivo without obvious toxicity. All these findings suggested that the N-benzylarylamide-dithiocarbamate based derivative I-25 (MY-943) was an effective dual inhibitor of tubulin polymerization and LSD1 that inhibited gastric cancers.

All-photonic quantum repeater for multipartite entanglement generation.

Quantum network applications such as distributed quantum computing and quantum secret sharing represent a promising future network equipped with quantum resources. Entanglement generation and distribution over long distances are critical and unavoidable when utilizing quantum technology in a fully connected network. The distribution of bipartite entanglement over long distances has seen some progress, while the distribution of multipartite entanglement over long distances remains unsolved. Here we report a two-dimensional quantum repeater protocol for the generation of multipartite entanglement over long distances with an all-photonic framework to fill this gap. The entanglement generation yield remains proportional to the transmission efficiency regardless of the number of network users and shows long transmission distance under various numbers of network users. With the improved efficiency and flexibility of extending the number of users, we anticipate that our protocol can work as a significant building block for quantum networks in the future.

A multimodal machine learning system in early screening for toddlers with autism spectrum disorders based on the response to name.

Background: Reduced or absence of the response to name (RTN) has been widely reported as an early specific indicator for autism spectrum disorder (ASD), while few studies have quantified the RTN of toddlers with ASD in an automatic way. The present study aims to apply a multimodal machine learning system (MMLS) in early screening for toddlers with ASD based on the RTN. Methods: A total of 125 toddlers were recruited, including ASD (n = 61), developmental delay (DD, n = 31), and typical developmental (TD, n = 33). Procedures of RTN were, respectively, performed by the evaluator and caregiver. Behavioral data were collected by eight-definition tripod-mounted cameras and coded by the MMLS. Response score, response time, and response duration time were accurately calculated to evaluate RTN. Results: Total accuracy of RTN scores rated by computers was 0.92. In both evaluator and caregiver procedures, toddlers with ASD had significant differences in response score, response time, and response duration time, compared to toddlers with DD and TD (all P-values < 0.05). The area under the curve (AUC) was 0.81 for the computer-rated results, and the AUC was 0.91 for the human-rated results. The accuracy in the identification of ASD based on the computer- and human-rated results was, respectively, 74.8 and 82.9%. There was a significant difference between the AUC of the human-rated results and computer-rated results (Z = 2.71, P-value = 0.007). Conclusion: The multimodal machine learning system can accurately quantify behaviors in RTN procedures and may effectively distinguish toddlers with ASD from the non-ASD group. This novel system may provide a low-cost approach to early screening and identifying toddlers with ASD. However, machine learning is not as accurate as a human observer, and the detection of a single symptom like RTN is not sufficient enough to detect ASD.

Tachykinin receptor 3 in the lateral habenula alleviates pain and anxiety comorbidity in mice.

The coexistence of chronic pain and anxiety is a common clinical phenomenon. Here, the role of tachykinin receptor 3 (NK3R) in the lateral habenula (LHb) in trigeminal neuralgia and in pain-associated anxiety was systematically investigated. First, electrophysiological recording showed that bilateral LHb neurons are hyperactive in a mouse model of trigeminal neuralgia made by partial transection of the infraorbital nerve (pT-ION). Chemicogenetic activation of bilateral LHb glutamatergic neurons in naive mice induced orofacial allodynia and anxiety-like behaviors, and pharmacological activation of NK3R in the LHb attenuated allodynia and anxiety-like behaviors induced by pT-ION. Electrophysiological recording showed that pharmacological activation of NK3R suppressed the abnormal excitation of LHb neurons. In parallel, pharmacological inhibition of NK3R induced orofacial allodynia and anxiety-like behavior in naive mice. The electrophysiological recording showed that pharmacological inhibition of NK3R activates LHb neurons. Neurokinin B (NKB) is an endogenous high-affinity ligand of NK3R, which binds NK3R and activates it to perform physiological functions, and further neuron projection tracing showed that the front section of the periaqueductal gray (fPAG) projects NKB-positive nerve fibers to the LHb. Optogenetics combined with electrophysiology recordings characterize the functional connections in this fPAG NKB → LHb pathway. In addition, electrophysiological recording showed that NKB-positive neurons in the fPAG were more active than NKB-negative neurons in pT-ION mice. Finally, inhibition of NKB release from the fPAG reversed the analgesic and anxiolytic effects of LHb Tacr3 overexpression in pT-ION mice, indicating that fPAG NKB → LHb regulates orofacial allodynia and pain-induced anxious behaviors. These findings for NK3R suggest the cellular mechanism behind pT-ION in the LHb and suggest that the fPAG NKB → LHb circuit is involved in pain and anxiety comorbidity. This previously unrecognized pathway might provide a potential approach for relieving the pain and anxiety associated with trigeminal neuralgia by targeting NK3R.

Formal Hydrotrimethylsilylation of Styrenes with Anti-Markovnikov Selectivity Using Hexamethyldisilane.

A combination of CsF and hexamethyldisilane in DMSO enabling an anti-Markovnikov formal hydrotrimethylsilylation of styrenes is reported. Mechanistic investigations detail the reaction pathways, including in situ generation of a silyl anion, the addition of this silyl anion onto the alkene to form a carbanion, and this carbanion is then protonated by DMSO. The choice of the solvent to match its reactivity with the carbanion and silyl anion is key to the success of this reaction.

DFT Study of Mechanism and Stereochemistry of Nickel-Catalyzed trans-Arylative Desymmetrizing Cyclization of Alkyne-Tethered Malononitriles.

Present here is a density functional theory (DFT) study of the mechanism and origin of enantioselectivity of Ni-catalyzed desymmetric cyclization of alkyne-tethered malononitriles and aryl boronic acids. The reaction starts from transmetalation and arylnickel addition, followed by trans to cis isomerization to give cis-alkenyl nickel species. The stereodetermining step is the CN insertion, which prefers a transition state with the bystander CN group staying away from the ligand to reduce steric repulsion, and gives the final (R)-product.

Simple security proof of coherent-one-way quantum key distribution.

Coherent-one-way quantum key distribution (COW-QKD), which requires a simple experimental setup and has the ability to withstand photon-number-splitting attacks, has been not only experimentally implemented but also commercially applied. However, recent studies have shown that the current COW-QKD system is insecure and can only distribute secret keys safely within 20 km of the optical fiber length. In this study, we propose a practical implementation of COW-QKD by adding a two-pulse vacuum state as a new decoy sequence. This proposal maintains the original experimental setup as well as the simplicity of its implementation. Utilizing detailed observations on the monitoring line to provide an analytical upper bound on the phase error rate, we provide a high-performance COW-QKD asymptotically secure against coherent attacks. This ensures the availability of COW-QKD within 100 km and establishes theoretical foundations for further applications.

The efficacy of Da Chaihu decoction combined with metformin tablets for type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone. METHODS: This systematic review and meta-analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3. RESULTS: Six randomized controlled trials comprising 516 participants were included. The meta-analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (-0.66 mmol/L; 95 % CI (confidence intervals) [- 1.28, - 0.04]), plasma glucose 2 h after meal (2-h PG) (-1.18 mmol/L; 95 % CI [-1.94, -0.42]) in six RCTs, body mass index (BMI) (-3.07 mmol/L; 95 % CI [-6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (-0.36 mmol/L; 95 % CI [-1.04, 0.31]) in three RCTs, and triglycerides (TG) (-0.76 mmol/L; 95 % CI [-1.37, -0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (-0.97 mmol/L; 95 % CI [-1.18, -0.76]). CONCLUSIONS: Very low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.

Diurnal changes of retinal microvascular circulation and RNFL thickness measured by optical coherence tomography angiography in patients with obstructive sleep apnea-hypopnea.

Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA). Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly. Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02). Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.