Impact of third-order dispersion on the dynamics of dissipative solitons in an ultrafast fiber laser.

Dissipative solitons (DSs), due to the complex interplay among dispersion, nonlinear, gain and loss, illustrate abundant nonlinear dynamics behaviors. Especially, dispersion plays an important role in the research of DS dynamics in ultrafast fiber lasers. Previous studies have mainly focused on the effect of even-order dispersion, i.e., group velocity dispersion (GVD) and fourth-order dispersion. In fact, odd-order dispersions, such as third-order dispersion (TOD), also significantly influences the dynamics of DSs. However, due to the lack of dispersion engineering tools, few experimental researches in this domain have been reported. In this work, by employing a pulse shaper in ultrafast fiber laser, an in-depth exploration of the DS dynamics influenced by TOD was conducted. With the increase of TOD value, the stable single DS undergoes a splitting into two solitons and then enters explosion state, and ultimately evolves into a chaotic state. The laser operation state is correlated to dispersion profile, which could be controlled by TOD. Here, the positive dispersion at long-wavelength side will be gradually shifted to negative dispersion by increasing the TOD, where soliton effect will drive the transitions. These findings offer valuable insights into the nonlinear dynamics of ultrafast lasers and may also foster applications involving higher-order dispersion.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Periodically tunable multimode soliton pulsation in a spatiotemporal mode-locked fiber laser.

Multimode fiber lasers have become a new platform for investigating nonlinear phenomena since the report on spatiotemporal mode-locking. In this work, the multimode soliton pulsation with a tunable period is achieved in a spatiotemporal mode-locked fiber laser. It demonstrates that the pulsation period drops while increasing the pump power. Moreover, it is found that different transverse modes have the same pulsation period, asynchronous pulsation evolution and different dynamical characteristics through the spatial sampling technique and the dispersive Fourier transform technique. To further verify the experimental results, we numerically investigate the influences of the gain and the loss on the pulsation properties. It is found that within a certain parameter range, the pulsation period drops and rises linearly with the increase of the gain and the loss, respectively. The obtained results contribute to understanding the formation and regulating of soliton pulsations in fiber lasers.

Cutoffs of different body measurement indexes of central obesity in patients with type 2 diabetes.

Few research discuss whether the body measurement indexs of obesity in general populations is applicable to patients with type 2 diabetes. We explore the optimal cutoffs of visceral fat area (VFA) and subcutaneous fat area (SFA) in the diagnosis of central obesity and the cutoffs of corresponding waist circumference (WC) and body mass index (BMI) in patients with Type 2 Diabetes (T2D). Cross-sectional cohort study. 1057 patients with T2D (550 males and 507 females) aged 18 or above that satisfied the criteria were included. The definition and diagnostic criteria of Metabolic syndrome (Mets) were analyzed according to the 2020 Chinese Diabetes Society (CDS) Guideline. The VFA and SFA were measured by bioelectrical impedance analysis (BIA). The optimal VFA and SFA cutoffs and corresponding WC and BMI when two or more nonadipose components of MetS (without central obesity) were met were analyzed by ROC curve. Among all of the T2D patients, the optimal VFA cutoff for identifying two or more nonadipose components of MetS was 73.30 cm2 for females and 69.20 cm2 for males, while the optimal SFA cutoff was 186.70 cm2 for females and 123.30 cm2 for males. The ROC area under curve (AUC) of VFA for identifying two or more nonadipose components of MetS was higher than that of SFA (Female: 0.65 vs. 0.58, P = 0.01). The VFA cutoff of newly diagnosed T2D patients (females = 86.10 cm2, males = 69.00 cm2) was higher than that of non-newly diagnosed T2D patients (females = 73.30 cm2, males = 65.40 cm2). A stratification analysis of gender and whether newly diagnosed with T2D or not showed that the WCs corresponding to VFA were 85.00 cm and BMI was about 24.00 kg/m2. VFA measured by BIA can be a non-invasive method to detect central obesity in patients with T2D, the corresponding WC were 85.00 cm and BMI was 24.00 kg/m2.

Sub-50†fs, 0.5†W average power Nd-doped fiber amplifier at 920†nm.

We develop an all polarization-maintaining (PM) 920 nm Nd-doped fiber amplifier delivering a train of pulses with ∼0.53 W average power and sub-50 fs duration. The sub-50 fs pulse benefits from the pre-chirping management method that allows for over 60 nm broadening spectrum without pulse breaking in the amplification stage. By virtue of the short pulse duration, the pulse peak power can reach to ∼0.31 MW in spite of the moderate average power. These results represent a key step in developing high-peak-power pulse Nd-doped fiber laser systems at 920 nm, which will find important applications in fields such as biomedical imaging, ultrafast optical spectroscopy, and excitation of quantum-dot single photon sources.

Anti-phase pulsation of counter-propagating dissipative solitons in a bidirectional fiber laser.

Due to its unique geometric structure, the bidirectional ultrafast fiber laser is an excellent light source for dual-comb applications. However, sharing the same gain between the counter-propagating solitons also gives rise to complex dynamics. Herein, we report the anti-phase pulsation of counter-propagating dissipative solitons in a bidirectional fiber laser. The in-phase and anti-phase soliton pulsation can be manipulated by adjusting the intracavity birefringence. The periodic modulation of polarization-dependent gain (PDG) caused by polarization hole burning (PHB) in the gain fiber can be responsible for anti-phase pulsation of bidirectional dissipative solitons. These findings offer new, to the best of our knowledge, insights into the complex dynamics of solitons in dissipative optical systems and performance improvement of bidirectional ultrafast fiber lasers.

Revealing the pulse dynamics in a Mamyshev oscillator: from seed signal to oscillator pulse.

The Mamyshev oscillator (MO) is a promising platform to generate high-peak-power pulse with environmentally stable operation. However, rare efforts have been dedicated to unveil the dynamics from seed signal to oscillator pulse, particularly for the multi-pulse operation. Herein, we investigate the buildup dynamics of the oscillator pulse from the seed signal in a fiber MO. It is revealed that the gain competition among the successively injected seed pulses leads to higher pump power that is required to ignite the MO, hence resulting in the higher optical gain that supports buildup of multiple oscillator pulses. The multiple oscillator pulses are identified to be evolved from the multiple seed pulses. Moreover, the dispersive Fourier transform (DFT) technique is used to reveals the real-time spectral dynamics during the starting process. As a proof-of-concept demonstration, a highly intensity-modulated pulse bunch was employed as the seed signal to reduce the gain competition effect and avoid the multi-pulse starting operation. The experimental results are verified by numerical simulations. These findings would give new insights into the pulse dynamics in MO, which will be meaningful to the communities interested in ultrafast laser technologies and nonlinear optics.

Establishing artificial gene connections through RNA displacement-assembly-controlled CRISPR/Cas9 function.

Construction of synthetic circuits that can reprogram genetic networks and signal pathways is a long-term goal for manipulation of biosystems. However, it is still highly challenging to build artificial genetic communications among endogenous RNA species due to their sequence independence and structural diversities. Here we report an RNA-based synthetic circuit that can establish regulatory linkages between expression of endogenous genes in both Escherichiacoli and mammalian cells. This design employs a displacement-assembly approach to modulate the activity of guide RNA for function control of CRISPR/Cas9. Our experiments demonstrate the great effectiveness of this RNA circuit for building artificial connections between expression of originally unrelated genes. Both exogenous and naturally occurring RNAs, including small/microRNAs and long mRNAs, are capable of controlling expression of another endogenous gene through this approach. Moreover, an artificial signal pathway inside mammalian cells is also successfully established to control cell apoptosis through our designed synthetic circuit. This study provides a general strategy for constructing synthetic RNA circuits, which can introduce artificial connections into the genetic networks of mammalian cells and alter the cellular phenotypes.

A study of the types and manifestations of physicians' unintended behaviors in the DRG payment system.

Introduction: In recent years, China has implemented the Diagnosis Related Groups (DRG) payment system as part of its healthcare insurance reimbursement policy. Numerous studies have focused on the effectiveness of DRG payment system in controlling unreasonable growth in medical expenses. However, there has been no systematic report on the types of unintended behaviors exhibited by doctors under the DRG payment system. Methods: The study first utilized interrupted time series analysis to analyze medical records and insurance data from eight hospitals. It investigated the data changes in MDC and ADRG groups before and after the implementation of the DRG payment system. Subsequently, a semi-structured interview method was employed to conduct qualitative research on the unintended behaviors of physicians, aiming to gain a more accurate understanding of specific changes in physician behavior after the implementation of the DRG payment system. Results: This study discovered that doctors engage in unintended behaviors within the framework of the DRG payment system. Discussion: In the early implementation of the DRG payment system in China, the contradictions between the flawed DRG payment methods and supporting systems and the actual diagnostic and treatment work manifested in the form of unintended doctor behaviors. Most of these unintended behaviors can be considered reasonable feedback from doctors to cope with the existing system flaws. They are conducive to identifying the deficiencies in China's DRG payment system and suggesting directions for improvement.

Dissipative soliton resonance in a figure-eight multimode fiber laser.

We report, for the first time to the best of our knowledge, a spatiotemporal mode-locked (STML) multimode fiber laser based on nonlinear amplifying loop mirror (NALM), generating dissipative soliton resonance (DSR) pulses. Due to the complex filtering characteristics caused by the inherent multimode interference filtering structure and NALM in the cavity, the STML DSR pulse has wavelength tunable function. What's more, kinds of DSR pulses are also achieved, including multiple DSR pulses, and the period doubling bifurcations of single DSR pulse and multiple DSR pulses. These results contribute to further understand the nonlinear properties of STML lasers and may shed some light on improving the performance of the multimode fiber lasers.

Efficacy and safety of herbal medicine (Binafuxi granules) for the common cold with fever: A multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial.

Background: Binafuxi granules are a traditional Uighur medicine (TUM) for treating the common cold with fever. However, high-quality clinical studies supporting its efficacy and safety are lacking. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial, patients with common cold and fever were randomly assigned to a high-dose group, low-dose group, and placebo group in a 1:1:1 ratio. Outcomes were time to fever relief, time to fever clearance, proportion of afebrile patients, time to symptom disappearance, rate of symptom disappearance, effective rate, emergency drug usage and safety assessment. Results: A total of 235 patients were recruited. Of these, 234 were included in the full analysis set (FAS), and 217 were included in the per-protocol set (PPS). In the FAS analysis, the median time to fever relief was 6.00 h, 5.54 h and 10.65 h (P = 0.31) in the high-dose group, low-dose group and placebo group, respectively. The median time to fever clearance was 18.29 h, 20.08 h and 25.00 h (P = 0.0018), respectively, and the proportion of afebrile patients was 92.4%, 89.7% and 71.4% (P = 0.0002), respectively. There was a significant difference in the disappearance time and disappearance rate of all symptoms and of individual symptoms. No serious adverse events were found. Conclusions: Binafuxi granules can dose-dependently shorten the fever course and improve clinical symptoms in patients suffering from the common cold with fever. Trial Registration: This trial was registered at Chinese Clinical Trial Registry (ChiCTR-IIR-17013379).

Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study.

OBJECTIVE: Diminished ovarian reserve (DOR) can lead to early menopause, poor fecundity, and an increased risk of disorders such as osteoporosis, cardiovascular disease, and cognitive impairment, seriously affecting the physical and mental health of women. There is still no safe and effective strategy or method to combat DOR. We have developed a novel Chinese herbal formula, Tongji anti-ovarian aging 101 (TJAOA101), to treat DOR. However, its safety and efficacy need to be further validated. METHODS: In this prospective and pre-post clinical trial, 100 eligible patients aged 18-45 diagnosed with DOR will be recruited. All participants receive TJAOA101 twice a day for 3 months. Then, comparisons before and after treatment will be analyzed, and the outcomes, including anti-mullerian hormone (AMH) and follicle-stimulating hormone (FSH) levels and the antral follicle count (AFC), the recovery rate of menopause, and the Kupperman index (KMI), will be assessed at baseline, every month during medication (the intervention period), and 1, 3 months after medication (the follow-up period). Assessments for adverse events will be performed during the intervention and follow-up periods. CONCLUSION: A multicenter, prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

Adipose mesenchymal stem cell-derived extracellular vesicles reduce glutamate-induced excitotoxicity in the retina.

Adipose mesenchymal stem cells (ADSCs) have protective effects against glutamate-induced excitotoxicity, but ADSCs are limited in use for treatment of optic nerve injury. Studies have shown that the extracellular vesicles (EVs) secreted by ADSCs (ADSC-EVs) not only have the function of ADSCs, but also have unique advantages including non-immunogenicity, low probability of abnormal growth, and easy access to target cells. In the present study, we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate-induced damage to retinal morphology and electroretinography. In addition, R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate-induced overload of intracellular calcium, downregulation of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPAR) subunit GluA2, and phosphorylation of GluA2 and protein kinase C alpha in vitro. A protein kinase C alpha agonist, 12-O-tetradecanoylphorbol 13-acetate, inhibited the neuroprotective effects of ADSC-EVs on glutamate-induced R28 cells. These findings suggest that ADSC-EVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.

A systematic pharmacology-based in vivo study to reveal the effective mechanism of Yupingfeng in asthma treatment.

BACKGROUND: The clinical effect of Yupingfeng (YPF) has been confirmed in asthma patients, however, it lacks a study to verify its pharmacological mechanism. HYPOTHESIS/PURPOSE: To reveal the molecular basis and potential pharmacological mechanism of YPF in the treatment of asthma. STUDY DESIGN AND METHODS: First, a systems pharmacology-based method integrating pharmacokinetic screening, target prediction, network analyses, GO and KEGG analyses were used for the systematic deciphering of the mechanism of YPF in asthma. Second, differentially expressed genes (DEGs) between asthma patients and healthy controls were identified by GEO2R online tool. Third, based on systems pharmacology and DEGs results, molecular docking was performed utilizing the Discovery Studio 2020 Client version to detect the binding capacity between compounds and targets. Finally, ovalbumin (OVA)-challenged C57BL/6 mice were treated with YPF or its effective compound to assess the predictions. RESULTS: A total of 35 active compounds were filtered out, with 87 potential targets being identified for further analysis after target fishing and matching. Quercetin, kaempferol, and wogonin were identified as the main ingredients in YPF. The signaling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), tumor necrosis factor (TNF) and IL-17 were identified as the top signaling pathways in KEGG enrichment analysis. GEO2R tools of NCBI discovered five DEGs that overlapped with the therapeutic targets of YPF. Wogonin was proven to be the top active compound in YPF through the results of molecular docking. In vivo experiments indicated that YPF and wogonin significantly attenuated airway resistance and lung inflammation by decreasing the levels of inflammatory cytokines and key factors in PI3K/AKT, IL-17, and TNF signaling pathways. CONCLUSIONS: YPF and its main active compound wogonin may exert some therapeutic effects on asthma inflammation through multiple molecular targets and signaling pathways including PI3K/AKT, IL-17 and TNF-α.

Nutrition management by a multidisciplinary team for prevention of nutritional deficits and morbidity following esophagectomy.

This study evaluated the effects of perioperative nutrition management by a multidisciplinary team on nutrition and postoperative complications of patients with esophageal cancer. A total of 239 patients with esophageal cancer who underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between February 2019 and February 2020 were included in the study. They were divided into the experimental group (120 patients) and the control group (119 patients) using the random number table method. Control group patients received routine diet management and experimental group patients received perioperative nutrition management by a multidisciplinary team. The differences of nutriture and postoperative complications between the two groups were compared. At 3 and 7 days after surgery, the experimental group patients had higher total protein and albumin levels (P<0.05), shorter postoperative anal exhaust time (P<0.05), lower incidence of postoperative gastrointestinal adverse reactions, pneumonia, anastomotic fistula, hypoproteinemia (P<0.05), and lower hospitalization costs (P<0.05) than the control group. Nutrition management by a multidisciplinary team effectively improved the nutriture of patients, promoted the rapid recovery of postoperative gastrointestinal function, reduced postoperative complications, and reduced hospitalization costs.

Periodic transition between two evolving soliton pulsation states in an Yb-doped fiber laser.

Due to the fascinating features, pulsating solitons attract much attention in the field of nonlinear soliton dynamics and ultrafast lasers. So far, most of the investigations on pulsating soliton are conducted in Er-doped fiber lasers. In this work, we reported the periodic transition between two evolving pulsating soliton states in an Yb-doped fiber laser. By using the real-time measurement techniques, the spectral and temporal characteristics of this transition state were investigated. Two evolving soliton pulsation states have similar evolution process, i.e., from pulsating towards quasi-stable mode-locked states. However, the details of the two processes are different, such as the pulse energy levels, pulsating modulation depths, duration of quasi-stable mode-locked states. The transition between two evolving soliton pulsation states could be attributed to the interaction of the polarizer and the varying polarization states of the pulse inside the laser cavity. The experimental results will contribute to the further understanding of soliton pulsating dynamics in dissipative optical systems.

Assisting the mode-locking of a figure-9 fiber laser by thermal nonlinearity of graphene-decorated microfiber.

The self-starting performance of a figure-9 fiber laser is critically dependent on the phase shift difference between the counter-propagating beams. Herein, we propose an effective approach to dynamically control the phase shift difference in a figure-9 fiber laser by utilizing the thermal nonlinearity of graphene-decorated microfiber device. With the adjustment of the control laser power injected into the graphene-decorated microfiber, the self-starting mode-locked threshold of the figure-9 fiber laser can be attained in a flexible pump power range, i.e., from 300 mW to 390 mW. These findings demonstrated that the graphene-decorated microfiber could act as a dynamical control device of phase shift difference for improving the performance of figure-9 fiber lasers, and might also open up new possibilities for applications of microfiber photonic devices in the field of ultrafast optics.

Dopamine relieves inflammatory responses through the D2 receptor after electroacupuncture at ST36 in a mouse model of chronic obstructive pulmonary disease.

OBJECTIVE: To detect the role of dopamine in the anti-inflammatory effect of electroacupuncture (EA) at ST36 in a mouse model of chronic obstructive pulmonary disease (COPD). METHODS: Twenty-eight male BALB/c mice were randomly divided into the control group, model group, sham EA (sham) group or ST36 EA (ST36) group in a 1:1:1:1 ratio (n = 7 each). The COPD mouse model was established through cigarette smoke (CS) exposure for 12 weeks. During the last 2 weeks, EA was applied at a sham point location or ST36 before CS exposure. Lung function, histopathological changes, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), inflammatory cytokines in BALF, plasma, lung tissue homogenate (LTH), and plasma dopamine levels were detected in the different groups. Furthermore, the role of different dopamine receptors was explored through intraperitoneal injections of non-specific dopamine receptor antagonist chlorpromazine, specific dopamine D1 receptor antagonist SCH 23390 and specific dopamine D2 receptor antagonist eticlopride hydrochloride prior to ST36 EA and CS exposure. RESULTS: EA at ST36 improved lung function, alleviated lung and systemic inflammatory responses by reducing inflammatory cells and cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-8 and IL-1ß in BALF, plasma and lung tissue in this COPD mouse model. Plasma dopamine was greatly increased after EA at ST36, negatively correlated with lung histological lesions and inflammatory cytokine levels, and positively correlated with mice body weight and lung function indicators. Chlorpromazine and eticlopride hydrochloride inhibited the anti-inflammatory effect of EA at ST36, while SCH 23390 showed no neutralizing effect. CONCLUSION: EA at ST36 could alleviate inflammation in this mouse model of COPD through the dopamine D2 receptor pathway.

Nutrition management by a multidisciplinary team for prevention of nutritional deficits and morbidity following esophagectomy

This study evaluated the effects of perioperative nutrition management by a multidisciplinary team on nutrition and postoperative complications of patients with esophageal cancer. A total of 239 patients with esophageal cancer who underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between February 2019 and February 2020 were included in the study. They were divided into the experimental group (120 patients) and the control group (119 patients) using the random number table method. Control group patients received routine diet management and experimental group patients received perioperative nutrition management by a multidisciplinary team. The differences of nutriture and postoperative complications between the two groups were compared. At 3 and 7 days after surgery, the experimental group patients had higher total protein and albumin levels (P<0.05), shorter postoperative anal exhaust time (P<0.05), lower incidence of postoperative gastrointestinal adverse reactions, pneumonia, anastomotic fistula, hypoproteinemia (P<0.05), and lower hospitalization costs (P<0.05) than the control group. Nutrition management by a multidisciplinary team effectively improved the nutriture of patients, promoted the rapid recovery of postoperative gastrointestinal function, reduced postoperative complications, and reduced hospitalization costs.

Dissipative pure-quartic soliton fiber laser.

The evolution of ultrafast laser technology hinges partially on the understanding of the soliton nonlinear dynamics. Recently, the concept of pure-quartic soliton (PQS) that arises from the balance of pure negative fourth-order dispersion (FOD) and nonlinearity was proposed to generate high peak power pulse. Herein, we investigate the generation of dissipative pure-quartic soliton (DPQS) in a fiber laser, which is balanced among the positive FOD, nonlinearity, gain and loss. The DPQS features the shape-preserving propagation despite the asymmetrical temporal profile at higher pulse energy. It is found that the asymmetrical temporal profile of DPQS is resulted from the mismatching of the phase shift profiles caused by self-phase modulation and FOD. Moreover, it is demonstrated that the DPQS possesses a higher energy-scaling ability compared to conventional dissipative soliton, owing to the nonlinear relationship between the pulse energy and pulse duration. These findings demonstrated that the employment of positive FOD could be a promising way for manipulation of optical pulse as well as the improvement of laser performance.