A self-starting bi-chromatic LiNbO_3 soliton microcomb

The wide range of functions that are possible with lithium niobate (LN) waveguide devices, including phase and intensity modulation, second-harmonic generation, and difference-frequency generation, makes it attractive as a potential microcomb material. LN microcombs would combine essential comb self-referencing and control functions with the pulse generation process in a single microresonator device. Here, we demonstrate a soliton microcomb in a monolithic high-Q LN resonator. Direct frequency doubling of the soliton spectrum is observed inside the same cavity. The LN soliton mode-locking process also self-starts and allows bi-directional switching of soliton states, effects that are shown to result from the LN photorefractive effect. The Kerr solitons exhibit a self-frequency shift resulting from the Raman effect of LN. This microcomb platform can dramatically simplify miniature time keeping, frequency synthesis/division, and spectroscopy systems. Moreover, direct generation of femtosecond timescale pulses within LN microresonators can benefit quantum photonics and signal processing systems

A self-starting bi-chromatic LiNbO_3 soliton microcomb

The wide range of functions that are possible with lithium niobate (LN) waveguide devices, including phase and intensity modulation, second-harmonic generation, and difference-frequency generation, makes it attractive as a potential microcomb material. LN microcombs would combine essential comb self-referencing and control functions with the pulse generation process in a single microresonator device. Here, we demonstrate a soliton microcomb in a monolithic high-Q LN resonator. Direct frequency doubling of the soliton spectrum is observed inside the same cavity. The LN soliton mode-locking process also self-starts and allows bi-directional switching of soliton states, effects that are shown to result from the LN photorefractive effect. The Kerr solitons exhibit a self-frequency shift resulting from the Raman effect of LN. This microcomb platform can dramatically simplify miniature time keeping, frequency synthesis/division, and spectroscopy systems. Moreover, direct generation of femtosecond timescale pulses within LN microresonators can benefit quantum photonics and signal processing systems

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Enhanced Thermal Stability of Polyphosphate-Dependent Glucomannokinase by Directed Evolution

Polyphosphate-dependent glucomannokinase (PPGMK) is able to utilize inorganic polyphosphate to synthesize mannose-6-phosphate (M6P) instead of highly costly ATP. This enzyme was modified and designed by combining error-prone PCR (EP-PCR) and site-directed saturation mutagenesis. Two mutants, H92L/A138V and E119V, were screened out from the random mutation library, and we used site-specific saturation mutations to find the optimal amino acid at each site. Finally, we found the optimal combination mutant, H92K/E119R. The thermal stability of H92K/E119R increased by 5.4 times at 50 °C, and the half-life at 50 °C increased to 243 min. Moreover, the enzyme activity of H92K/E119R increased to 16.6 U/mg, and its enzyme activity is twice that of WT. We analyzed the structure of the mutant using molecular dynamics simulation. We found that the shortening of the hydrogen bond distance and the formation of salt bridges can firmly connect the α-helix and β-sheet and improve the stability of the PPGMK structure

Enhanced Thermal Stability of Polyphosphate-Dependent Glucomannokinase by Directed Evolution

Polyphosphate-dependent glucomannokinase (PPGMK) is able to utilize inorganic polyphosphate to synthesize mannose-6-phosphate (M6P) instead of highly costly ATP. This enzyme was modified and designed by combining error-prone PCR (EP-PCR) and site-directed saturation mutagenesis. Two mutants, H92L/A138V and E119V, were screened out from the random mutation library, and we used site-specific saturation mutations to find the optimal amino acid at each site. Finally, we found the optimal combination mutant, H92K/E119R. The thermal stability of H92K/E119R increased by 5.4 times at 50 °C, and the half-life at 50 °C increased to 243 min. Moreover, the enzyme activity of H92K/E119R increased to 16.6 U/mg, and its enzyme activity is twice that of WT. We analyzed the structure of the mutant using molecular dynamics simulation. We found that the shortening of the hydrogen bond distance and the formation of salt bridges can firmly connect the α-helix and β-sheet and improve the stability of the PPGMK structure

Reversible On-Off Photoswitching of DNA Replication Using a Dumbbell Oligodeoxynucleotide

In most organisms, DNA extension is highly regulated; however, most studies have focused on controlling the initiation of replication, and few have been done to control the regulation of DNA extension. In this study, we adopted a new strategy for azODNs to regulate DNA extension, which is based on azobenzene oligonucleotide chimeras regulated by substrate binding affinity, and the conformation of the chimera can be regulated by a light source with a light wavelength of 365 nm. The results showed that the primer was extended with Taq DNA polymerase after visible light treatment, and DNA extension could be effectively hindered with UV light treatment. We also verify the reversibility of the photoregulation of primer extension through photoswitching of dumbbell asODNs by alternate irradiation with UV and visible light. Our method has the advantages of fast and simple, green response and reversible operations, providing a new strategy for regulating gene replication

Study on Permeability Characteristics of Porous Transparent Gels Based on Synthetic Materials

Advanced knowledge of the permeability characteristics of transparent gels play a key role in providing a rational basis for the study of porous polymer permeability and the research on the migration behavior of superpolymer solutions. Thus, a new type of transparent gel was prepared to simulate porous media, with aim to observe and analyze the permeability characteristics of transparent gel under the conditions of our experimental design by combining a transparent soil test and simple particle image velocimetry. The experimental results showed that the permeability of the transparent gel was similar to that through actual soil. The permeability coefficients of the transparent gel under different pressure gradients varied greatly early in the experimental cycle, while changing only slightly afterward, showing an overall trend of decreasing first and then stabilizing. With the increase of the mass ratio, the permeability coefficient of the sample decreased, the distribution of the low-velocity zone of the intercepted section became wider and tended to move upward. Differences in spatial position also caused different patterns of velocity and direction. The findings presented in this paper contribute to providing a new direction for the study of porous polymer permeability and the porous migration of superpolymer solutions