Symmetry breaking of A3M2X9-type perovskite derivatives induced by polar quaternary ammonium cations: achieving efficient nonlinear optical properties.

Low-dimensional organic-inorganic metal halides, especially lead-free perovskites, are attracting increasing attention because of their environmentally friendly processing, flexible structures, chemical stability, and promising nonlinear optical properties. Herein, we report a new stable polar 0D lead-free hybrid bismuth chloride to enable the second-harmonic generation (SHG) active material (BTA)3Bi2Cl9 (BTA = benzyltriethylammonium, C6H5CH2N(C2H5)3+) that was obtained by the antisolvent vapor diffusion method and crystallized in the polar Cc space group. Its structure features organic cations surrounded by face-sharing [Bi2Cl9]3- dimers. (BTA)3Bi2Cl9 exhibits a wide direct bandgap (3.21 eV) and a strong phase-matchable SHG conversion efficiency (1.39 × KDP). Theoretical calculation reveals that the SHG response is owing to the synergistic effect of distorted inorganic [Bi2Cl9]3- anions and polar organic BTA+ cations. This work not only enriches the family of organic-inorganic A3M2X9 (A = monovalent cations; M = trivalent metal ions; and X = halide ions) NLO crystals but also provides the possibilities for further designing novel lead-free semiconducting piezoelectric, pyroelectric and ferroelectric materials.

Infectivity and antigenicity of pseudoviruses with high-frequency mutations of SARS-CoV-2 identified in Portugal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more-virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs between regions, and this variation may have an impact on the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 spike protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y. The mutant pseudoviruses were used to infect four susceptible cell lines (Huh7, hACE2-293T-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity against these pseudoviruses was evaluated using mouse serum and 11 monoclonal antibodies. The neutralizing activity of immunized mouse serum was not significantly reduced with the mutant strains, but the mutant strains from Portugal could evade nine of the 11 monoclonal antibodies tested. Neutralization resistance was mainly caused by the mutations S477N, N439K, and N501Y in the spike-receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control.

Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage.

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1ß, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.

Feasibility and Safety of Using Supraglottic Airway Devices for Pediatric Patients Undergoing Magnetic Resonance Imaging: A Case Series of High-Risk Patients.

BACKGROUND: General anesthesia or sedation is commonly required for pediatric patients undergoing magnetic resonance imaging (MRI) scans, and airway management during the procedure is the highest concern for anesthesiologists owing to the limited access to the patient in the MRI unit. The use of supraglottic airway devices (SADs) has recently become more popular than endotracheal tubes; however, the feasibility of using SADs for children in MRI suites was reported only in a few studies that involved healthy patients. METHODS: We present a successful case series of 30 pediatric patients, and the majority are high-risk patients, including patients with aromatic L-amino acid decarboxylase (AADC) deficiency, mitochondrial disease, and tuberous sclerosis, using either i-gel or laryngeal masks for airway maintenance during MRI examination. RESULTS: A total of 38 MRI exams were conducted; the patients' median age was 4 (range 1.6-17.0 years), and the mean examination time was 50.87 minutes. No patient experienced oxygen desaturation, and only 1 patient with AADC deficiency had an episode of hypotension. The MRI scans were completed without interruption with an adequate image quality according to a specialized radiologist. CONCLUSION: From the clinical point of view, this case series demonstrated a broader application of SADs for airway maintenance during MRI scans for pediatric patients with a high risk during anesthesia rather than only for a healthy patient population.

Cognition and transcranial sonography in Parkinson's disease patients with or without orthostatic hypotension.

BACKGROUND: Orthostatic hypotension (OH) is a common nonmotor symptom in patients with Parkinson's disease (PD), with an incidence ranging from 14% to 54%. AIMS: This study explored changes in cognition and transcranial sonography (TCS) findings in patients with PD and OH. METHODS: We enrolled PD patients who visited the outpatient or inpatient department from 2017 to 2020. Blood pressure was measured in different positions, and demographic data were collected. Motor and nonmotor symptoms were evaluated using standard scales. A subset of 107 patients underwent TCS. RESULTS: We enrolled 66 PD-OH patients and 92 PD-no orthostatic hypotension (NOH) patients. There were no significant differences in gender, age, disease duration, or Hoehn and Yahr stage between groups. Binary logistic regression revealed age as an independent risk factor for OH in PD patients. There were statistically significant group differences in visuospatial and executive function and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores (p < .05). Among PD-OH patients, there was a statistically significant difference in UPDRS II and III scores between patients with or without clinical symptoms (p < .05). The substantia nigra (SN) area was significantly larger in PD-NOH patients (0.45 ± 0.18 cm2 ) than PD-OH patients (0.34 ± 0.16 cm2 ) (p < .05). CONCLUSIONS: PD-OH patients had poorer visuospatial and executive function and lower UPDRS I and II scores compared with PD-NOH patients. Within the PD-OH group, there was no significant difference in cognition between patients with or without clinical symptoms. The difference in the SN area may indicate different subtypes of PD or a tendency to develop parkinsonism syndrome.

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study.

BACKGROUND: Retinal abnormalities measured by optical coherence tomography (OCT) have been detected in both Parkinson's disease (PD) and Alzheimer's disease (AD). Cognitive impairment is not only found in AD, but 75-90% of PD patients will also develop dementia in the late stage of disease. We assessed whether baseline retinal nerve fiber layer (RNFL) thickness predicted worsening of cognitive status over time and the correlation between RNFL thickness and the detailed impaired cognitive domains in PD. METHODS: RNFL thickness was measured using high-definition OCT in 78 non-dementia PD patients. Clinical and cognitive assessments were performed at baseline and at 3.61 ± 0.65 years follow-up. Linear mixed-effects models were used to examine associations between RNFL thickness and the changes in cognitive test scores, after adjusting for age, sex, disease duration and education. RESULTS: Analysis of outcomes according to baseline RNFL tertiles showed worse performance in global cognitive tests, delayed memory, and executive functions in patients with a thin RNFL. During follow-up, greater cognitive deterioration was found in thin RNFL tertile patients. Lower baseline average RNFL thickness was associated with greater annualized decline in Mini-Mental State Examination and Montreal Cognitive Assessment. CONCLUSION: The correlation between RNFL thickness and cognitive dysfunction suggests that OCT may be useful for predicting cognitive dysfunction in PD patients.

Low-Frequency Repetitive Transcranial Magnetic Stimulation over Right Dorsolateral Prefrontal Cortex in Parkinson's Disease.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic tool for Parkinson's disease (PD), and many stimulation targets have been implicated. We aim to explore whether low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) improves motor and nonmotor symptoms of individuals with PD. METHODS: We conducted a randomized, single-blind, sham-controlled parallel trial to compare the effect of 10 consecutive daily sessions of 1 Hz rTMS over right DLPFC on individuals with idiopathic PD between active and sham rTMS group. Primary outcomes were changes in Unified Parkinson's Disease Rating Scale (UPDRS) part III and Nonmotor Symptom Questionnaire (NMSQ). Secondary outcomes were changes in UPDRS total score, Hamilton Rating Scale for Depression (HRSD), Pittsburgh Sleep Quality Index (PSQI), and Montreal Cognitive Assessment (MoCA). Assessments were completed at baseline, after treatment, and at 1 month, 3 months, and 6 months after treatment. RESULTS: A total of 33 participants with PD were randomized. All participants completed the study and no severe adverse effect was noticed. Compared to baseline, active rTMS showed significant improvements in UPDRS part III and NMSQ at 1 month. Change of scores on UPDRS part III, HRSD, and PSQI persisted for 3 months after rTMS intervention. The beneficial effect on cognitive performance assessed by MoCA was maintained for at least 6 months in the follow-up. No significant changes were observed in the group with sham rTMS. CONCLUSIONS: Low-frequency rTMS of right DLPFC could be a potential selection in managing motor and nonmotor symptoms in PD.

Reduced cortical arousability to nocturnal apneic episodes in patients with wake-up ischemic stroke.

STUDY OBJECTIVES: Sleep breathing disorders (SBD) have been linked to wake-up stroke (WUS). Respiratory arousals have an important role in responding to danger during sleep, yet currently no studies have investigated respiratory arousability in WUS. In this study, we used a clinical tool to predict low respiratory arousal threshold (ArTH), and then compared respiratory arousability in patients with WUS and non-WUS. METHODS: We enrolled 119 patients with acute ischemic stroke and assigned them into WUS (n = 34) and non-WUS (n = 85) groups. All participants underwent polysomnography (PSG) during the acute phase of stroke. The respiratory ArTH predictive tool assigns one point for each of the following: apnea-hypopnea index (AHI) < 30/h, nadir oxygen saturation (SaO2) > 82.5%, and fraction of hypopneas > 58.3%. An ArTH score ≥2 represents low respiratory ArTH. RESULTS: Our results reconfirmed the association between moderate-to-severe sleep apnea syndrome and WUS (OR 2.879, 95% CI 1.17-7.089, p = 0.021). Significantly fewer participants with obstructive sleep apnea (AHI ≥ 5/h) had low respiratory ArTH in the WUS group than in the non-WUS group (34.8% vs. 68.1%, respectively, p = 0.008). High respiratory ArTH was independently associated with WUS (OR 5.556, 95% CI 1.959-15.761, p = 0.001). CONCLUSIONS: The correlation between SBD and WUS suggests that sleep apnea might induce acute physiological changes that trigger the onset of stroke. We show that reduced respiratory arousability is associated with WUS, and hypothesize that reduced cortical capability to generate respiratory arousal may have a role in triggering stroke during sleep.

Author Correction: CRISPR/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Causality test of ambient fine particles and human influenza in Taiwan: Age group-specific disparity and geographic heterogeneity.

Influenza is a major global public health problem, with serious outcomes that can result in hospitalization or even death. We investigate the causal relationship between human influenza cases and air pollution, quantified by ambient fine particles <2.5µm in aerodynamic diameter (PM2.5). A modified Granger causality test is proposed to ascertain age group-specific causal relationship between weekly influenza cases and weekly adjusted accumulative PM2.5 from 2009 to 2015 in 11 cities and counties in Taiwan. We examine the causal relationship based on posterior probabilities of the log-linear integer-valued GARCH (generalized autoregressive conditional heteroscedastic) model with covariates, which enable us to handle characteristics of influenza data such as integer-value, lagged dependence, and over-dispersion. The resulting posterior probabilities show that the adult age group (25-64) and the elderly group in New Taipei in the north and cities in southwestern part of Taiwan are strongly affected by ambient fine particles. Moreover, the elderly group is clearly affected in all study sites. Globalization and economic growth have resulted in increased ambient air pollution (including PM2.5) and subsequently substantial public health concerns in the West Pacific region. Minimizing exposure to air pollutants is particularly important for the elderly and susceptible individuals with respiratory diseases.

CRISPR/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus.

CRISPR/Cas9 is a valuable tool for both basic and applied research that has been widely applied to different plant species. Nonetheless, a systematical assessment of the efficiency of this method is not available for the allotetraploid Brassica napus-an important oilseed crop. In this study, we examined the mutation efficiency of the CRISPR/Cas9 method for 12 genes and also determined the pattern, specificity and heritability of these gene modifications in B. napus. The average mutation frequency for a single-gene targeted sgRNA in the T0 generation is 65.3%. For paralogous genes located in conserved regions that were targeted by sgRNAs, we observed mutation frequencies that ranged from 27.6% to 96.6%. Homozygotes were readily found in T0 plants. A total of 48.2% of the gene mutations, including homozygotes, bi-alleles, and heterozygotes were stably inherited as classic Mendelian alleles in the next generation (T1) without any new mutations or reversions. Moreover, no mutation was found in the putative off-target sites among the examined T0 plants. Collectively, our results demonstrate that CRISPR/Cas9 is an efficient tool for creating targeted genome modifications at multiple loci that are stable and inheritable in B. napus. These findings open many doors for biotechnological applications in oilseed crops.

Visible light nonlinear absorption and optical limiting of ultrathin ZrSe3 nanoflakes.

The nonlinear absorption and nonlinear refractive properties of ZrSe3 nanoflakes were studied with a 6.5 ns pulse laser at 532 nm. Open-aperture Z-scan curves reveal that ZrSe3 nanoflakes have a strong reverse saturable absorption property, and close-aperture Z-scan curves show that ZrSe3 dispersions possess a positive nonlinear refractive index caused by self-focusing. The nonlinear absorption coefficient, the nonlinear refraction coefficient, and the figures of merit (FOM) of ZrSe3 dispersed in water with linear transmittances of 0.86 at input energy of 18 µJ are 6.35 × 10-10 m W-1 15.73 × 10-17 m2 W-1, and 10.09 × 10-11 esu · cm respectively. In addition, nonlinear optical (NLO) performance of ZrSe3 nanoflakes depends on organic solvent dispersions. ZrSe3 nanoflakes in water dispersions have the largest FOM of 10.27 × 10-11 esu · cm, while the FOM in ethanol dispersions is 5.41 × 10-11 esu · cm at the same input energy of 26.5 µJ. The optical limiting threshold Fth of ZrSe3 nanosheet is 2.2 J cm-2 under picosecond laser pulse. The Results imply that ZrSe3 nanoflakes are an extraordinarily promising material for novel nanophotonic devices like optical limiters.

Reverse saturable absorption and nonlinear refraction of ultrathin ZrS3 nanobelts.

The nonlinear optical (NLO) properties of a ZrS3 nanobelt were measured with a 6.5 ns pulse laser at 532 nm. Its optical response to the incident light exhibits good optical absorptive and refractive effects, with the nonlinear absorption coefficient ß = 4.42 × 10(-10) m W(-1) and the nonlinear refraction coefficient γ = 5.86 × 10(-17) m(2) W(-1) for the ZrS3 nanobelt in ethanol dispersions at an input energy of 34.25 µJ. In addition, the ß values and γ values have dependence on input energy. Results show that the ZrS3 nanobelts have an excellent reverse saturable absorption (RSA) performance in nanosecond pulses, demonstrating that ZrS3 nanobelts are an extraordinarily promising novel optical power limiting material. Meanwhile, compared to the pure ZrS3, graphene oxide (GO) and reduced graphene oxide (RGO), composites (ZrS3/GRO) exhibit an enhanced nonlinear absorption response at the same input energy.

Enhanced ultraviolet-visible light responses of phototransistors based on single and a few ZrS3 nanobelts.

Phototransistors based on single and three ZrS3 nanobelts were fabricated on SiO2/Si wafers by photolithography and the lift-off technique, respectively, and their light-induced electric properties were investigated in detail. Both the devices demonstrate a remarkable photoresponse from ultraviolet to near infrared light. The photoswitch current ratio (PCR) of the single-nanobelt phototransistor is 13 under the illumination of 405 nm light with an optical power of 10.5 mW cm(-2) at a bias of 5 V, while the PCR of the three-nanobelt device is 210 under the illumination of 405 nm light with an optical power of 5.57 mW cm(-2) at a bias of 1 V. On comparison of the photoresponses under the same conditions, the latter is found to be superior to the former, and both the devices show a much better photoresponse than the reported flexible ZrS3-nanobelt-film photodetector.

Dynamic source routing strategy for two-level flows on scale-free networks.

Packets transmitting in real communication networks such as the Internet can be classified as time-sensitive or time-insensitive. To better support the real-time and time-insensitive applications, we propose a two-level flow traffic model in which packets are labeled as level-1 or level-2, and those with level-1 have higher priority to be transmitted. In order to enhance the traffic capacity of the two-level flow traffic model, we expand the global dynamic routing strategy and propose a new dynamic source routing which supports no routing-flaps, high traffic capacity, and diverse traffic flows. As shown in this paper, the proposed dynamic source routing can significantly enhance the traffic capacity and quality of time-sensitive applications compared with the global shortest path routing strategy.

[CD4(+) T lymphocyte detection in renal transplant recipients and its clinical value for cytomegalovirus pneumonia treatment].

OBJECTIVE: To explore the clinical value of CD4(+)T lymphocyte detection in the treatment of cytomegalovirus(CMV) pneumonia following kidney transplantation. METHODS: From January 2005 to May 2008, 133 recipients of kidney transplantation were enrolled in this study. The number of CD4(+)T cells in peripheral blood was examined. According to the changes of CD4(+)T cell, immunosuppressive agents (CsA/FK506+MMF+Pred) were adjusted, and the effects of CMV pneumonia occurring were investigated. RESULTS: In the period of 45-72 day after renal transplantation, 36 cases were found to have significantly lower number of CD4(+)T cells than that before operation. Of the 133 recipients, 12(9.0%, 12/133) had severe pneumonia, during 58-118 days after operation, including 7 with acute respiratory distress syndrome(ARDS); 4 patients(33.3%, 4/12) died and 8(66.7%, 8/12) were cured. The incidence of CMV pneumonia(27.8%, 10/36) in the low- CD4(+)T cell recipients was significantly higher than that(2.1%, 2/97) in patients with normal T cell level(P<0.01). During the withdrawal of immunosuppressive agents, 34 patients had normal kidney function(serum creatinine 71-126 micromol/L), except 2 cases underwent mild acute rejection. In 24 non-pneumonia recipients, the number of CD4(+)T cell kept growing as the withdrawal, on 14, 21 day after the withdrawal increased markedly compared with that on 0 day. In 8 survival patients with CMV pneumonia, the number of CD4(+)T cell rose slowly,on 21 day after the withdrawal increased to the normal level. But in 4 non-survival patients, the number of CD4(+)T cell kept continuously in lower level. CONCLUSION: CMV pneumonia is associated with lower CD4(+)T cell level in kidney transplant recipients. Determination of CD4(+) T cell could reflect the status of cellular immunity and give directions of the withdrawal. Discontinuance of immunosuppressive agents in severe CMV pneumonia patients was safe. However, it may be helpful to guide the clinical treatment.

Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor.

DPP-IV (EC 3.4.14.5) is a validated drug target for human type II diabetes. DPP-IV inhibitors without DPP8/9 inhibitory activity have been sought because a possible association has been reported between a "DPP8/9 inhibitor" and severe toxicity in animals. However, at present, it is not known whether the observed toxicity is associated with DPP8/9 inhibition, or an off-target effect induced by the compound. We investigated whether the inhibition of DPP8/9 is the cause of the severe toxicity in animals using a very potent and selective DPP8/9 inhibitor with different pharmacophore, 1G244. By Ki measurement, 1G244 is 15- and 8-fold more potent against DPP8 and DPP9, respectively, than the "DPP8/9 inhibitor". Strikingly, the "DPP8/9 inhibitor" does not penetrate the plasma membrane but remains outside the cells, whereas 1G244 readily enters the cells, even at low doses. By repeatedly exposing Sprague-Dawley rats to 1G244 by intravenous injection for a period of 14 days, we observed no significant toxicological symptoms associated with 1G244. Blood and serum chemistry parameters were all within the normal ranges for the treated animals. Because of the high potency, good membrane penetration and adequate tissue distribution of 1G244, the mild symptoms observed are probably associated with DPP8/9 inhibition.