Banana MaNAC1 activates secondary cell wall cellulose biosynthesis to enhance chilling resistance in fruit.

Chilling injury has a negative impact on the quantity and quality of crops, especially subtropical and tropical plants. The plant cell wall is not only the main source of biomass production, but also the first barrier to various stresses. Therefore, improving the understanding of the alterations in cell wall architecture is of great significance for both biomass production and stress adaptation. Herein, we demonstrated that the cell wall principal component cellulose accumulated during chilling stress, which was caused by the activation of MaCESA proteins. The sequence-multiple comparisons show that a cold-inducible NAC transcriptional factor MaNAC1, a homologue of Secondary Wall NAC transcription factors, has high sequence similarity with Arabidopsis SND3. An increase in cell wall thickness and cellulosic glucan content was observed in MaNAC1-overexpressing Arabidopsis lines, indicating that MaNAC1 participates in cellulose biosynthesis. Over-expression of MaNAC1 in Arabidopsis mutant snd3 restored the defective secondary growth of thinner cell walls and increased cellulosic glucan content. Furthermore, the activation of MaCESA7 and MaCESA6B cellulose biosynthesis genes can be directly induced by MaNAC1 through binding to SNBE motifs within their promoters, leading to enhanced cellulose content during low-temperature stress. Ultimately, tomato fruit showed greater cold resistance in MaNAC1 overexpression lines with thickened cell walls and increased cellulosic glucan content. Our findings revealed that MaNAC1 performs a vital role as a positive modulator in modulating cell wall cellulose metabolism within banana fruit under chilling stress.

1,25(OH)2 D3 inhibits Lewis lung cancer cell migration via NHE1-sensitive metabolic reprograming.

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.

Transcription factors KNAT3 and KNAT4 are essential for integument and ovule formation in Arabidopsis.

Integuments form important protective cell layers surrounding the developing ovules in gymno- and angiosperms. Although several genes have been shown to influence the development of integuments, the transcriptional regulatory mechanism is still poorly understood. In this work, we report that the Class II KNOTTED1-LIKE HOMEOBOX (KNOX II) transcription factors KNOTTED1-LIKE HOMEBOX GENE 3 (KNAT3) and KNAT4 regulate integument development in Arabidopsis (Arabidopsis thaliana). KNAT3 and KNAT4 were co-expressed in inflorescences and especially in young developing ovules. The loss-of-function double mutant knat3 knat4 showed an infertility phenotype, in which both inner and outer integuments of the ovule are arrested at an early stage and form an amorphous structure as in the bell1 (bel1) mutant. The expression of chimeric KNAT3- and KNAT4-EAR motif repression domain (SRDX repressors) resulted in severe seed abortion. Protein-protein interaction assays demonstrated that KNAT3 and KNAT4 interact with each other and also with INNER NO OUTER (INO), a key transcription factor required for the outer integument formation. Transcriptome analysis showed that the expression of genes related with integument development is influenced in the knat3 knat4 mutant. The knat3 knat4 mutant also had a lower indole-3-acetic acid (IAA) content, and some auxin signaling pathway genes were downregulated. Moreover, transactivation analysis indicated that KNAT3/4 and INO activate the auxin signaling gene IAA INDUCIBLE 14 (IAA14). Taken together, our study identified KNAT3 and KNAT4 as key factors in integument development in Arabidopsis.

Model-informed dose selection for an investigational human epidermal growth factor receptor 2 antibody-drug conjugate FS-1502 in patients with human epidermal growth factor receptor 2-expressing advanced malignant solid tumours.

AIMS: The dose-escalation phase (phase Ia study) of a novel human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) FS-1502 included a dose range from 0.1 to 3.5 mg/kg in HER2-expressing advanced malignant solid tumours. However, the defined maximum tolerated dose was not reached. This model-informed approach integrated population pharmacokinetic (PopPK) modelling and exposure-response (E-R) analysis to facilitate dose selection for phase II. METHODS: The PopPK model was constructed using PK data from 109 Chinese patients who received doses of 0.1-3.5 mg/kg FS-1502 every 3 (Q3W) or 4 weeks during a phase I dose-escalation and dose expansion trial. The structural model consisted of compartment models for FS-1502 and unconjugated monomethyl auristatin F. E-R was explored for the percentage change in tumour size, overall response rate and treatment-related adverse events. RESULTS: A semi-mechanistic 2-analyte PopPK model was developed. The FS-1502 PK data were best described by a 2-compartment PK model with parallel linear and nonlinear Michaelis-Menten eliminations. The PK of unconjugated monomethyl auristatin F was described by a 2-compartment model with first-order elimination. E-R analysis supported the clinically meaningful efficacy of FS-1502 at 2.3 mg/kg and above. However, 2.3 mg/kg Q3W was considered to have a better benefit-risk balance due to a lower incidence of safety events without a significant reduction in efficacy compared to 3.0 mg/kg Q3W. CONCLUSION: This PopPK and E-R analysis guided the recommended phase II dose selection of 2.3 mg/kg Q3W and supported body weight-based dosing for an investigational HER2 ADC FS-1502.

Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

Design, synthesis, and antifungal activity of novel pyrazole carboxamide derivatives containing benzimidazole moiety as potential SDH inhibitors.

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study.

Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results: 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion: Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.

Chromomycins from soil-derived Streptomyces sp. inhibit the growth of human non-small cell lung cancer cells by targeting c-FLIP.

Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.

Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.

Phase 1 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1-related unresectable plexiform neurofibromas.

BACKGROUND: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. METHODS: This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. RESULTS: Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug-related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. CONCLUSIONS: FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Functional Enrichment Analysis Identifying Regulatory Information Associated with Human Fracture.

Dozens of loci associated with fracture have been identified by genome-wide association studies (GWASs). However, most of these variants are located in the noncoding regions including introns, long terminal repeats, and intergenic regions. Although combining regulation information helps to identify the causal SNPs and interpret the involvement of these variants in the etiology of human fracture, regulation information which was truly associated with fracture was unknown. A novel functional enrichment method GARFIELD (GWAS Analysis of Regulatory of Functional Information Enrichment with LD correction) was applied to identify fracture-associated regulation information, including transcript factor binding sites, expression quantitative trait loci (eQTLs), chromatin states, enhancer, promoter, dyadic, super enhancer and Epigenome marks. Fracture SNPs were significantly enriched in exon (Bonferroni correction, p value < 7.14 × 10-3) at two GWAS p value thresholds through GARFIELD. High level of fold-enrichment was observed in super enhancer of monocyte and the enhancer of chondrocyte (Bonferroni correction, p value < 4.45 × 10-3). eQTLs of 44 tissues/cells and 10 transcription factors (TFs) were identified to be associated with human fracture. These results provide new insight into the etiology of human fracture, which might increase the identification of the causal SNPs through the fine-mapping study combined with functional annotation, as well as polygenic risk score.

Self-Consistent Quantum Mechanics/Embedded Charge Study on Aggregation-Enhanced Delayed Fluorescence of Cu(I) Complexes: Luminescence Mechanism and Molecular Design Strategy.

To elucidate the luminescence mechanism of highly efficient blue Cu(N^N)(POP)+-type thermally activated delayed fluorescence (TADF) materials, we have selected Cu(pytfmpz)(POP)+ (1) and Cu(pympz)(POP)+ (2) as targets to investigate the photophysical properties in both solution and solid phases. The self-consistent electrostatic potential (ESP) embedded charge within the quantum mechanics/molecular mechanics (QM/MM) method demonstrates a greater advantage over the charge equilibrium (QEQ) in accurately calculating atomic charges and reasonably describing the polarization effect, ultimately resulting in a favorable consistency between simulation and experimental measurements. After systematic and quantitative simulation, it has been found that complex 2, with an electron-donating group of -CH3, exhibits a much more blue-shifted spectrum and a significantly enhanced efficiency in comparison to complex 1 with -CF3. This is due to the widened HOMO-LUMO gap as well as the narrowed energy gap between the lowest singlet and triplet excited states (ΔEST), respectively. Then, the designed complex 3 is introduced with a stronger electron donor and larger tert-butyl group, which plays a key role in simultaneously suppressing the structural distortion and reducing the ΔEST. This leads to a faster reverse intersystem crossing process than that of the two experimental complexes in solution, turning out to be a new deep-blue-emitting material with excellent TADF performance.

Theoretical Studies and Design Strategies of Highly Efficient Two-Photon Excited Fluorescent Probes for Hydrogen Sulfide Detection through Simulation of Excited-State Dynamics.

Hydrogen sulfide (H2S) plays a critical role in numerous physiological and pathological processes, but an abnormal level of H2S in living systems can cause various diseases. To detect the level of endogenous H2S in a complicated biological system, the luminous mechanism of "turn-on" probe for H2S monitoring has been deeply explored through the simulation of excited-state dynamic processes, and the effect of different geometric modifications on optical properties has been minutely investigated based on molecular modeling. TD-DFT calculations demonstrate that line-type π-expanding in the molecular skeleton is beneficial for improving two-photon absorption (TPA) ability, but it can give rise to extremely large geometric relaxation, going against fluorescence emission. It is an effective way to suppress molecular skeleton scissoring vibration by introducing strong electron-withdrawing substituent groups (F, Cl, Br, CN) in benzopyran, and these compounds also have superior TPA properties in NIR. One of the potential materials in the application of biological imaging and H2S detection has been obtained, which simultaneously possesses easily distinguished spectra (with a Stokes shift as large as 77 nm), high luminous efficiency (with a quantum yield up to 20.07%), and large TPA cross section (952 GM at 950 nm).

Molecular Design of Highly Efficient Heavy-Atom-free NpImidazole Derivatives for Two-Photon Photodynamic Therapy and ClO- Detection.

Two-photon photodynamic therapy (TP-PDT), as a treatment technology with deep penetration and less damage, provides a broad prospect for cancer treatment. Nowadays, the development of TP-PDT suffers from the low two-photon absorption (TPA) intensity and short triplet state lifetime of photosensitizers (PSs) used in TP-PDT. Herein, we propose some novel modification strategies based on the thionated NpImidazole (the combination of naphthalimide and imidazole) derivatives to make efforts on those issues and obtain corresponding fluorescent probes for detecting ClO- and excellent PSs for TP-PDT. Density functional theory (DFT) and time-dependent DFT (TD-DFT) are used to help us characterize the photophysical properties and TP-PDT process of the newly designed compounds. Our results show that the introduction of different electron-donating groups at the position 4 of NpImidazole can effectively improve their TPA and emission properties. Specifically, 3s with a N,N-dimethylamino group has a large triplet state lifetime (τ = 699 µs) and TPA cross section value (δTPA = 314 GM), which can effectively achieve TP-PDT; additionally, 4s (with electron-donating group 2-oxa-6-azaspiro[3.3]heptane in NpImidazole) effectively realizes the dual-function of a PS for TP-PDT (τ = 25,122 µs, δTPA = 351 GM) and a fluorescent probe for detecting ClO- (Φf = 29% of the product 4o). Moreover, an important problem is clarified from a microscopic perspective, that is, why the transition property of 3s and 4s (1π-π*) from S1 to S0 is different from that of 1s and 2s (1n-π*). It is hoped that our work can provides valuable theoretical clues for the design and synthesis of heavy-atom-free NpImidazole-based PSs and fluorescent probes for the detection of hypochlorite.

Psittacosis caused severe community-acquired pneumonia accompanied by acute hypoxic respiratory failure: a multicenter retrospective cohort study from China.

INTRODUCTION: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). METHODS: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. RESULTS: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. CONCLUSION: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Theoretical study of the tuning role of ß-methylthio or ß-methylselenyl on the charge-transport properties of acenedithiophenes derivatives.

To date, the manipulation of intermolecular nonconjugation interactions in organic crystals is still a great challenge due to the complexity of weak intermolecular interactions. Here we designed molecules substituted by ß-methylselenyl on naphtho[1,2-b:5,6-b']dithiophene and anthra[2,3-b:6,7-b']dithiophene, respectively (anti-ß-MS-NDT, anti-ß-MS-ADT), which together with anti-ß-MS-BDT synthesized experimentally all exhibited 2D brickwork π-stacking. Moreover, their maximum molecular carrier mobilities reached 3.30 and 16.46 cm2 V-1 s-1. These results indicated that the substitution of ß-methylselenyl could be a strategy to directionally adjust the parent herringbone stacking into 2D brickwork π-stacking. Hirshfeld surface analysis and symmetry-adapted perturbation theory (SAPT) were used to investigate the nonconjugated interactions in the pitched π-stacking formed by the ß-methylthio-substituted acenedithiophene derivatives and the 2D brickwork π-stacking of the ß-methylselenyl-substituted ones; wherein, the steric hindrance caused by the introduction of the substituents promoted Csp2-Csp2⋯π interactions to replace Csp2-H⋯π to stabilize the face-to-face stacking. Moreover, by calculating the decomposition energy of the intermediate state model of the molecular stacking mode that may exist in the replacement conversion process, it was found that the energy of this intermediate state was larger than that of the actual ones, finally confirming the inevitability of the actual existence in this stacking. In addition, because of the reduction in intensity of the special vibration modes, it could be found that the ß-methylselenyl substitution showed better phonon assistance than ß-methylthio substitution in terms of dynamic disorder. This study is a further step toward fully understanding the relationship between intermolecular interactions and regulation of the molecular stacking.

Theoretical Research and Photodynamic Simulation of Aggregation-Induced Thermally Activated Delayed Fluorescence Materials for Organic Light-Emitting Diodes.

The discovery and utilization of pure organic thermally activated delayed fluorescence (TADF) materials provide a major breakthrough in obtaining high-performance and low-cost organic light-emitting diodes (OLEDs). In spite of recent research progress in TADF emitters, highly efficient and stable TADF emitters in high-concentration solutions and in the solid state have been rarely reported, and most of them suffer from aggregation-induced quenching (ACQ). To resolve this issue, the aggregation-induced delayed fluorescence (AIDF) mechanism was studied in depth by the simulation of excited-state dynamic processes, and the effect of geometric modifications on optical properties was minutely investigated based on molecular modeling. TD-DFT calculations demonstrate that it is the key point for the transformation between prompt fluorescence and TADF to effectively regulate singlet-triplet energy difference and electron-vibration coupling by the aggregation effect. Then, excellent green and red TADF materials with very small singlet-triplet energy differences of 0.05 and 0.06 eV, high TADF quantum yields up to 57.53% and 39.19%, and suitable fluorescence lifetimes of 0.99 and 1.67 us, respectively, were designed and obtained, which demonstrate the potential application of these two TADF materials in OLEDs.

Theoretical Study on the Formation and Decomposition Mechanisms of Coelenterazine Dioxetanone.

Bioluminescence has been drawing broad attention due to its high signal-to-noise ratio and high bioluminescence quantum yields, which has been widely applied in the fields of biomedicine, bioanalysis, and so on. Among numerous bioluminescent substrates, coelenterazine is famous for its wide distribution. However, the oxygenation reaction mechanism of coelenterazine is far from being completely understood. In this paper, the formation and decomposition mechanisms of coelenterazine dioxetanone were investigated via density functional theory (DFT) and time-dependent (TD) DFT approaches. The results showed that the oxygenation reaction first occurred along the triplet-state potential energy surface (PES), after the intersystem crossing (ISC), second jumped to the diradical-state PES, and ultimately formed coelenterazine dioxetanone. For the decomposition mechanism of dioxetanone, the computational results showed that the chemiexcitation of neutral dioxetanone was more efficient than that of other dioxetanone species. Moreover, the diradical properties and the degree of ionic character are modified by the counter ions.

Spin-selectivity effect of G-quadruplex DNA molecules.

Chirality-induced spin selectivity has been attracting extensive interest in recent years and is demonstrated in a variety of chiral molecules, all of which arise from inherent molecular chirality. Here, we first propose a theoretical model to study the spin-dependent electron transport along guanine-quadruplex (G4) DNA molecules, connected to two nonmagnetic electrodes, by considering the molecule-electrode contact and weak spin-orbit coupling. Our results indicate that the G4-DNA molecular junctions exhibit pronounced spin-selectivity effect, and the asymmetric contact-induced external chirality, instead of the inherent molecular chirality, dominates their spin filtration efficiency. Furthermore, the spin-selectivity effect is robust against the disorder and hold in a wide range of model parameters. These results could be checked by charge transport measurements and provide an alternative way to improve the spin-selectivity effect of chiral nanodevices.