Oral Isavuconazole Combined with Nebulized Inhalation and Bronchoscopic Administration of Amphotericin B for the Treatment of Pulmonary Mucormycosis: A Case Report and Literature Review.

Pulmonary mucormycosis (PM) is an invasive and potentially fatal fungal infection, with Rhizopus microsporus (R. microsporus) being the most common pathogen. The routine therapy for this infection includes surgery and antifungal agents. However, the therapeutic effects of single agents are unsatisfactory due to the rapid progression of mucormycosis, while not all patients can tolerate surgery. Innovative treatment methods like combination therapy await validations of their clinical efficacy. We report a case of PM that was diagnosed via metagenomics next-generation sequencing (mNGS) of black drainage fluid from the patient's lung. The patient eventually recovered and was discharged after a combination therapy of oral isavuconazole, inhaled amphotericin B, and local perfusion of amphotericin B through bronchoscopy, which may be a promising strategy for the treatment of PM, especially for cases where surgery is not possible. A retrospective study of 297 cases in a literature review highlights the different treatment methods used in clinical practice.

Gastroesophageal reflux disease and non-alcoholic fatty liver disease: a two-sample Mendelian randomization combined with meta-analysis.

Accumulating evidence from observational studies have suggested an association between gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, due to that such studies are prone to biases, we imported Mendelian randomization (MR) to explore whether the causal association between two diseases exsit. Hence, we aimed to analysis the potential association with MR. The single nucleotide polymorphisms (SNPs) of GERD were retrieved from the genome-wide association study dataset as the exposure. The SNPs of NAFLD were taken from the FinnGen dataset as the outcome. The relationship was analyzed with the assistance of inverse variance weighted, MR-Egger, and weighted median. We also uitilized the MR-Egger intercept, Cochran's Q test, leave-one-out analysis, MR-PRESSO, and Steiger directionality test to evaluate the robustness of the causal association. The meta-analysis were also implemented to give an overall evaluation. Finally, our analysis showed a causal relationship between GERD and NAFLD with aid of MR and meta-analysis (OR 1.71 95% CI 1.40-2.09; P < 0.0001).

Comparing the impact of personal trainer guidance to exercising with others: Determining the optimal approach.

This study aimed to examine the effects of supervised fitness training under the guidance of a personal trainer and those of competitive fitness training with others and reveal the effects of specific differences between them in a detailed manner. The study's participants consisted of 66 healthy male adults (age: 29.2 ± 5.4 years). The participants were divided into three groups: the individual training group (n = 21), which served as the control group; the exercising with a partner group (n = 22); and the group trained by a personal trainer (n = 23). Each participant was subsequently assessed using one repetition maximum bench press, squats, skeletal muscle mass, fat mass, and a questionnaire regarding nutritional plan and injury to compare the effects of training sessions over a period of 12 weeks. Among the three groups, only the group trained by a personal trainer showed an obvious enhancement in fat reduction compared to baseline (-1.61 kg, p = 0.033), which was suggestive of a salient trend that far surpassed those of the individual training group and the exercising with a partner group. Regarding squats, only the group trained by a personal trainer showed a significant change compared to the individual training group (p = 0.003). Regarding the participants' consistent use of a nutritional plan, only the group trained by a personal trainer exhibited a palpable tendency (p < 0.001); furthermore, the effect of preventing injury in the group trained by a personal trainer was more notable than that in the individual training group and the exercising with a partner group. Our results indicate that a fitness personal trainer service is effective in expediting the process of achieving fitness goals in a relatively safe manner, thereby substantiating the diversified values of the fitness personal trainer service.

Heparanase-mediated histone 3 acetylation regulates VEGF gene transcription in the hyperglycemia and hypoxia human retinal endothelial cells.

Heparanase (HPA) is believed that might mediate histone 3 lysine 9 acetylation (H3K9ac) to regulate vascular endothelial growth factor (VEGF) gene expressions in the hyperglycemia and hypoxia human retinal endothelial cells (HRECs). Cultured human retinal endothelial cells (HRECs) in hyperglycemia, hypoxia, siRNA, and normal medium, respectively. Distributions of H3K9ac and HPA in HRECs were analyzed by immunofluorescence. Western blot and real-time PCR were respectively used to evaluate the expression of HPA, H3K9ac, and VEGF. The differences in occupancies of H3K9ac and RNA polymerase II at VEGF gene promoter among three groups were studied by Chromatin immunoprecipitation (ChIP) combined with real-time PCR. Co-immunoprecipitation (Co-IP) was used to measure the status of HPA and H3K9ac. Re-ChIP was used to verify whether HPA and H3K9ac associate to the transcription of VEGF gene. HPA was consistent with that of H3K9ac in the hyperglycemia and hypoxia groups. And the fluorescent lights of H3K9ac and HPA in siRNA groups were similar to the control group, fainter than that of hyperglycemia, hypoxia, and non-silencing groups. Western blot results showed that the expressions of HPA, H3K9ac, and VEGF in hyperglycemia and hypoxia HRECs were statistically higher than that of the control. HPA, H3K9ac, and VEGF expressions in siRNA groups were statistically lower than hyperglycemia and hypoxia HRECs. The same trends also were found in real-time PCR. ChIP exhibited the occupancies of H3K9ac and RNA Pol II at VEGF gene promoter in hyperglycemia and hypoxia groups were significantly more increased than in the control group. Co-IP revealed that HPA combined with H3K9ac in hyperglycemia and hypoxia groups; while it was not discovered in the control group. Re-ChIP showed that HPA combined with H3K9ac at VEGF gene promoter in the hyperglycemia and hypoxia HRECs nuclear. In our study HPA can influence expressions of H3K9ac and VEGF in the hyperglycemia and hypoxia HRECs. HPA can probably combine with H3K9ac and regulate the transcription of the VEGF gene in the hyperglycemia and hypoxia HRECs.

Aggregation-induced bimodal excitation of nitrogen-doped carbon dots for ratiometric sensing of new coccine and solid-state multicolor lighting.

Trace detection of foodstuff pigments have gained increasing attention because of their close association with biological and environmental processes. Herein, we propose an innovative bimodal excitation nitrogen-doped carbon dots (N-CDs) for ratiometric sensing of new coccine (NC) pigment, which are synthesized by using melamine and o-phenylenediamine as precursors via solvothermal treatment. With the increase of the N-CDs concentration, N-CDs exhibit not only a concentration-dependent tunable color behavior, but also a novel aggregation-induced bimodal excitation phenomenon. Considering this distinctive bimodal excitation behavior, a ratiometric sensor based on N-CDs has been developed for the detection of the NC in different organic solvents due to the inner filter effect and fluorescence resonance energy transfer. The intensity ratio of two excitation signals is linear with the NC concentration in the range of 0.032-100 µM, and the limit of detection is as low as 32.1 nM. Meanwhile, we realize the design of multicolor-emission N-CDs/polymer films. All in all, this work presents a novel kind view of the mechanism of distinctive bimodal excitation of N-CDs, and further proposes an innovative ratiometric method for the screening analysis of NC in food samples and environmental pollutants.

Activated cascade effect for dual-mode ratiometric and smartphone-assisted visual detection of curcumin and F- based on nitrogen-doped carbon dots.

The growing persistence of harmful ion or drug molecular residues has always been considered as a matter of concern due to its importance in biological and environmental processes, which requires taking measures to maintain environmental health sustainably and effectively. Inspired by the multi-system and visual quantitative detection of nitrogen-doped carbon dots (N-CDs), we develop a novel cascade nano-system based on dual emission carbon dots for on-site visual quantitative detection of curcumin and fluoride ion (F-). Herein, tris (hydroxymethyl) aminomethane (Tris) and m-dihydroxybenzene (m-DHB) are elected as reaction precursors to synthesize dual-emission N-CDs by a one-step hydrothermal method. The obtained N-CDs exhibit dual emission peaks at 426 nm (blue) and 528 nm (green) with quantum yields of 53 % and 71 %, respectively. Then, trace curcumin and F- intelligent off-on-off sensing probe is formed by taking advantage of the activated cascade effect. As for the occurrence of inner filter effect (IFE) and fluorescence resonance energy transfer (FRET), the green fluorescence of N-CDs quenches remarkably, called as OFF initial state. Then the curcumin-F- complex leads to the hypochromatic shift of the absorption band from 532 to 430 nm, which activates the green fluorescence of N-CDs, named as ON state. Meanwhile, the blue fluorescence of N-CDs is quenched due to the FRET, called as OFF terminal state. This system shows good linear relationships from 0 to 35 µM and 0 to 40 µM with low detection limits of 29 nM and 42 nM for curcumin and F- ratiometric detection, respectively. Moreover, a smartphone-assisted analyzer is developed for on-site quantitative detection. Furthermore, we design a logic gate for logistics information storage, which proves the possibility of a logic gate based on N-CDs in practical application. Thus, our work will provide an effective strategy for environmental quantitative monitoring and information storage encryption.

Revealing Intermolecular Electronic and Vibronic Coherence with Polarization-Dependent Two-Dimensional Beating Maps.

Two-dimensional electronic spectroscopy (2DES) has been widely employed as an efficient tool to reveal the impact of intermolecular electronic and/or vibronic quantum coherence on excitation energy transfer in light-harvesting complexes. However, intramolecular vibrational coherence would also contribute to oscillating signals in 2D spectra, along with the intermolecular coherence signals that are directly related to energy transfer. In this work, the possibility of screening the vibrational coherence signals is explored through polarization-dependent 2DES. The all-parallel (AP) and double-crossed (DC) polarization-dependent two-dimensional rephasing spectra (2DRS) are simulated for a minimalist heterodimer model with vibrational coupling. By combining the DC-2DRS and the 2D beating maps, we demonstrate that the population and vibrational coherence signals can be largely suppressed, resulting in highlighted intermolecular electronic and vibronic coherence signals. Moreover, the AP- and DC-2DBMs show rather different patterns at the vibrational frequency, indicating a possible way to identify pure vibrational coherence.

Assessing the effect of the coal-to-gas program on air pollution: evidence from China.

This paper studies the relationship between the coal-to-gas program and air pollution in China and provides micro-evidence of the mechanism from the perspective of households. Using daily air pollution and meteorological data between January 1, 2016, and January 1, 2020, we assessed the effect of the coal-to-gas program on air pollution by introducing the regression discontinuity designs in time (RDiT). We found that the coal-to-gas program significantly improved air quality and brought significant economic benefits. In the short term, the coal-to-gas program can lead to more than 10 units of reduction in SO2, PM2.5, and AQI in the treatment group, while it can lead to more than 50 units in the long term. Using the difference-in-differences approach, we found that the coal-to-gas program has significantly reduced air pollution. Combined with the micro-panel data of the China Health and Retirement Longitudinal Study from 2011 to 2018, we found that the coal-to-gas program changes the household heating energy choices and that the probability of coal-fired heating of households in pilot areas is decreasing. The study suggests that non-clean energy in households should be further replaced to continue improving air quality.

Vibrational and vibronic coherences in the energy transfer process of light-harvesting complex II revealed by two-dimensional electronic spectroscopy.

The presence of quantum coherence in light-harvesting complex II (LHCII) as a mechanism to understand the efficiency of the light-harvesting function in natural photosynthetic systems is still debated due to its structural complexity and weak-amplitude coherent oscillations. Here, we revisit the coherent dynamics and clarify different types of coherences in the energy transfer processes of LHCII using a joint method of the high-S/N transient grating and two-dimensional electronic spectroscopy. We find that the electronic coherence decays completely within 50 fs at room temperature. The vibrational coherences of chlorophyll a dominate over oscillations within 1 ps, whereas a low-frequency mode of 340 cm-1 with a vibronic mixing character may participate in vibrationally assisted energy transfer between chlorophylls a. Our results may suggest that vibronic mixing is relevant for rapid energy transfer processes among chlorophylls in LHCII.

Citizen participation and urban air pollution abatement: Evidence from environmental whistle-blowing platform policy in Sichuan China.

This study employs the environmental whistle-blowing platform policy adopted at Leshan City, Sichuan Province, China in July 2017 as the quasi-natural experiment and applies Synthetic Control Method (SCM) and Difference-in-Difference (DID) to examine the causal effect between citizen participation, median supervision, and air pollution abatement by government. The results show: first, the launch of the environmental whistle-blowing platform decreases daily AQI at Leshan City by 19 units; second, days with excellent air quality increase by 2.6 days each month on average at Leshan City; third, the probability for a day with excellent or good air quality at Leshan City increases by approximately 16.6%. Moreover, when the sample is expanded from neighboring prefecture level cities of Leshan City to prefecture level cities in Sichuan Province or across China, the results remain robust. Based on the panel data from China Family Panel Studies (CFPS), we find the launch of the environmental whistle-blowing platform improves individual's approval of government at primary level significantly and increases their life satisfaction. This demonstrates citizen participation and media supervision generate substantial effects on air pollution abatement. This study serves as a reference for solutions to improvement of air quality and governance capability of the government.

Characterization of the ultrafast spectral diffusion and vibronic coherence of TIPS-pentacene using 2D electronic spectroscopy.

TIPS-pentacene is a small-molecule organic semiconductor that is widely used in optoelectronic devices. It has been studied intensely owing to its ability to undergo singlet fission. In this study, we aim to develop further understanding of the coupling between the electronic and nuclear degrees of freedom of TIPS-pentacene (TIPS-Pn). We measured and analyzed the 2D electronic spectra of TIPS-Pn in solutions. Using center line slope (CLS) analysis, we characterized the frequency-fluctuation correlation function of the 0-0 vibronic transition. Strong oscillations in the CLS values were observed for up to 5 ps with a frequency of 264 cm-1, which are attributable to a large vibronic coupling with the TIPS-Pn ring-breathing vibrational mode. In addition, detailed analysis of the CLS values allowed us to retrieve two spectral diffusion lifetimes, which are attributed to the inertial and diffusive dynamics of solvent molecules. Amplitude beating analysis also uncovered couplings with another vibrational mode at 1173 cm-1. The experimental results can be described using the displaced harmonic oscillator model. By comparing the CLS values of the simulated data with the experimental CLS values, we estimated a Huang-Rhys factor of 0.1 for the ring-breathing vibrational mode. The results demonstrated how CLS analysis can be a useful method for characterizing the strength of vibronic coupling.

Development of interface-/surface-specific two-dimensional electronic spectroscopy.

Structures, kinetics, and chemical reactivities at interfaces and surfaces are key to understanding many of the fundamental scientific problems related to chemical, material, biological, and physical systems. These steady-state and dynamical properties at interfaces and surfaces require even-order techniques with time-resolution and spectral-resolution. Here, we develop fourth-order interface-/surface-specific two-dimensional electronic spectroscopy, including both two-dimensional electronic sum frequency generation (2D-ESFG) spectroscopy and two-dimensional electronic second harmonic generation (2D-ESHG) spectroscopy, for structural and dynamics studies of interfaces and surfaces. The 2D-ESFG and 2D-ESHG techniques were based on a unique laser source of broadband short-wave IR from 1200 nm to 2200 nm from a home-built optical parametric amplifier. With the broadband short-wave IR source, surface spectra cover most of the visible light region from 480 nm to 760 nm. A translating wedge-based identical pulses encoding system (TWINs) was introduced to generate a phase-locked pulse pair for coherent excitation in the 2D-ESFG and 2D-ESHG. As an example, we demonstrated surface dark states and their interactions of the surface states at p-type GaAs (001) surfaces with the 2D-ESFG and 2D-ESHG techniques. These newly developed time-resolved and interface-/surface-specific 2D spectroscopies would bring new information for structure and dynamics at interfaces and surfaces in the fields of the environment, materials, catalysis, and biology.

Hierarchical Equations of Motion Simulation of Temperature-Dependent Two-Dimensional Electronic Spectroscopy of the Chlorophyll a Manifold in LHCII.

We simulated two-dimensional electronic spectra (2DES) of the chlorophyll a manifold of light-harvesting complex II (LHCII) at various temperatures (77, 110, 150, 190, 230, 273, and 293 K) using the hierarchical equations of the motion-phase matching approach. We confirm the main excitation energy transfer pathways assignments within the chlorophyll a manifold of LHCII measured in a recent work (J. Phys. Chem. B 2019, 123, 6765-6775). The calculated transfer rates are also in general agreement with the measured rates. We also provided theoretical confirmation for the experimental assignments, as uphill and downhill energy transfer processes, of 2D spectral features that were reported in recent experimental reports. These temperature-dependent features were also ascertained to follow the detailed-balance principle.

Correction of spectral distortion in two-dimensional electronic spectroscopy arising from the wedge-based delay line.

Unlike the probe wavelength, which is spectrally resolved by monochromator, the excitation wavelength in two-dimensional electronic spectroscopy is retrieved by means of Fourier transform of the interference signal introduced by the coherence delay time between the first and second excitation laser pulses. Hence, the calibration of delay lines would determine its accuracy. In this work, we showed that an inaccurate calibration factor of wedge-based delay line would result in a global peak shift and asymmetric spectral twists along the excitation axis. Both theoretical analysis and experiments have shown that such spectral distortions can be corrected by an accurately predetermined calibration factor. The relative accuracy of calibration factor reaches 3 × 10-5 in our setup. The dispersion effect of wedges also has been considered for the broadband excitation.

Simulation of the Two-Dimensional Electronic Spectroscopy and Energy Transfer Dynamics of Light-Harvesting Complex II at Ambient Temperature.

We simulate the two-dimensional electronic spectra (2DES) of the light-harvesting complex II (LHCII) at room temperature by combining the hierarchical equations of motion method and the equation-of-motion phase-matching approach. The laser-excited population dynamics of LHCII is also calculated to help understanding the 2DES. Three different excitation schemes are studied, including (1) only the chlorophyll (Chl) b Q y states of LHCII are excited, (2) only the Chl a Q y states are excited, and (3) both the Chl b and Chl a states are excited. The energy transfer pathways and time scales revealed from the 2DES in schemes (1) and (2) agree with the recent experimental studies for the Chl b to Chl a energy transfer and the excitation energy relaxation process within the Chl a manifold. We also propose a different way to better present the signals of bottleneck states by investigating the diagonal peaks of the 2DES in scheme (3).

Heparanase mediates vascular endothelial growth factor gene transcription in high-glucose human retinal microvascular endothelial cells.

PURPOSE: To observe the nuclear expression and interaction of heparanase and RNA polymerase II (RNA Pol II), an enzyme that catalyzes the transcription of DNA in eukaryotic cells) in human retinal microvascular endothelial cells (HRECs) under high glucose condition and to investigate the association of heparanase with the transcription activity of the vascular endothelial growth factor (VEGF) gene promoter. METHODS: Cultured HRECs were maintained for 3 days in media with high or normal glucose. The expressions of heparanase and RNA Pol II in each group were analyzed with immunofluorescence. Co-immunoprecipitation was applied to detect the interaction of heparanase and Pol II proteins. Cells in both groups were used for chromatin immunoprecipitation (ChIP) with anti-heparanase and anti-RNA Pol II antibodies to identify high-confidence heparanase-binding regions across the entire VEGF gene promoter. Moreover, real-time PCR was used to demonstrate the interaction between heparanase and the VEGF gene promoter region. RESULTS: The immunofluorescence studies showed that the nuclear expression of heparanase was intense in high-glucose HRECs but faint in the normal group; RNA Pol II in the nucleus was also intense in high glucose HRECs, and the distribution of heparanase was consistent with that of RNA Pol II. The co-immunoprecipitation data showed that heparanase combined with RNA Pol II in HRECs cells treated with high glucose, and the molecular size of HPA interacted with RNA Pol II was 50 kDa, while no combination of two proteins was evident in normal HRECs cells. Real-time PCR-based ChIP results showed that the high-confidence HPA-binding region was -1155 to -1018 (containing hypoxia response element) in the VEGF gene promoter, and the cells treated with high glucose showed increases in heparanase and RNA Pol II in the VEGF gene promoter region compared with the normal glucose treated cells (t = -3.244, p = 0.032; t = -6.096, p = 0.004, respectively). CONCLUSIONS: Nuclear heparanase combines directly with the VEGF gene promoter and is involved in the regulation of VEGF gene transcription in high-glucose HRECs.

The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate the cytokine concentrations in the aqueous humor of patients with refractory polypoidal choroidal vasculopathy (PCV). METHODS: Three separate groups of patients were studied-refractory PCV (Group A, 41 eyes), stable PCV (Group B, 39 eyes) and senile cataract (Group C, 44 eyes). Aqueous humor samples were collected at two time points for Groups A and B-before the first intravitreal ranibizumab injection and before the last injection. Aqueous humor samples were collected prior to phacoemulsification in Group C. The cytokine concentrations of interleukin 2, 6, and 8 (IL-2, IL-6, and IL-8), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) were measured by cytometric bead array and flow cytometry. RESULTS: Before the first treatment, the MCP-1, VEGF, and TNF-α levels in Group A were significantly higher than those in Group C (P < 0.05), and the MCP-1 and VEGF levels in Group A were significantly higher than those in Group B (P < 0.05). Significantly higher MCP-1 and VEGF levels were seen in Group B compared to Group C (P < 0.05). Before the final treatment, the MCP-1, VEGF, and TNF-α concentrations in Group A were significantly higher than those in Group B (P < 0.05) and Group C (P < 0.05). IL-2 levels were significantly lower in Group A compared to Group B (P < 0.05) and Group C (P < 0.05). CONCLUSION: Inflammatory cytokines such as MCP-1, VEGF, and TNF-α may be associated with the pathogenesis of both stable and refractory PCV.

Simulation of two-dimensional electronic spectra of phycoerythrin 545 at ambient temperature.

By using a hierarchical equations-of-motion approach, we reproduce the two-dimensional electronic spectra of phycoerythrin 545 from Rhodomonas CS24 at ambient temperature (294 K). The simulated spectra are in agreement with the experimental results reported in Wong et al. (Nat. Chem. 2012, 4, 396). The evolutions of cross peaks for rephasing spectra and diagonal peaks for nonrephasing spectra have also been plotted. The peaks oscillate with the population times, with frequencies, phases, and amplitudes of the oscillating curves also being qualitatively consistent with the experimental results.