Mechanism of bufalin inhibition of colon cancer liver metastasis by regulating M2-type polarization of Kupffer cells induced by highly metastatic colon cancer cells.

Patients with metastatic colorectal cancer often have poor outcomes, primarily due to hepatic metastasis. Colorectal cancer (CRC) cells have the ability to secrete cytokines and other molecules that can remodel the tumor microenvironment, facilitating the spread of cancer to the liver. Kupffer cells (KCs), which are macrophages in the liver, can be polarized to M2 type, thereby promoting the expression of adhesion molecules that aid in tumor metastasis. Our research has shown that huachanshu (with bufalin as the main active monomer) can effectively inhibit CRC metastasis. However, the underlying mechanism still needs to be thoroughly investigated. We have observed that highly metastatic CRC cells have a greater ability to induce M2-type polarization of Kupffer cells, leading to enhanced metastasis. Interestingly, we have found that inhibiting the expression of IL-6, which is highly expressed in the serum, can reverse this phenomenon. Notably, bufalin has been shown to attenuate the M2-type polarization of Kupffer cells induced by highly metastatic Colorectal cancer (mCRC) cells and down-regulate IL-6 expression, ultimately inhibiting tumor metastasis. In this project, our aim is to study how high mCRC cells induce M2-type polarization and how bufalin, via the SRC-3/IL-6 pathway, can inhibit CRC metastasis. This research will provide a theoretical foundation for understanding the anti-CRC effect of bufalin.

Requirements on double-cladding Yb-doped fiber for power scaling of diffraction-limited fiber amplifiers.

Requirements on the double-cladding Yb-doped fiber (DCYF) for power scaling of diffraction-limited fiber amplifiers are studied in this paper. By considering the limitations of thermal lens and transverse mode instability separately, it is found that the power scaling limit can be enlarged to more-than 100 kW and 80 kW, respectively, with the proper selection of pump and signal wavelengths. It is also found that the requirements on DCYF strongly depend on the wavelength and brightness of pump light. It is predicted that smaller-than 20-µm core diameter is required to achieve the 20-kW output power, as long as the 976-nm pump brightness can be high enough. The requirements on the inner-cladding diameter and cladding-to-core ratio of DCYF are also investigated.

Demonstration of hundred-watt-level near-diffraction-limited monolithic fiber laser near 980 nm with step-index double-cladding Yb-doped fiber.

In this paper, a hundred-watt-level near-diffraction-limited step-index Yb-doped fiber (YDF) laser near 980 nm is demonstrated firstly, to the best of our knowledge. By using the 11.7-W 979-nm single-mode seed light, the in-band amplified spontaneous emission (ASE) is well suppressed and the maximum output power of 101.5 W with the beam quality (M2 factor) of 1.285 was obtained. This work does not only propose an effective method for the suppression of in-band ASE, but also provides a cost-effective solution of hundred-Watt-level near-diffraction-limited fiber lasers near 980 nm.

5†kW power-level 1050†nm narrow-linewidth fiber amplifier enabled by biconical-tapered active fiber.

Effective wavelength extension is vital in the applications of high-power narrow-linewidth fiber lasers. In this work, we demonstrate a 5-kW power-level narrow-linewidth fiber amplifier at 1050 nm utilizing a homemade biconical-tapered Yb-doped fiber (BT-YDF). Up to ∼4.96 kW fiber laser is achieved with a 3 dB linewidth of ∼0.54 nm and a beam quality factor of Mx 2 = 1.46, My 2 = 1.6. The experimental comparisons reveal that BT-YDF has the advantages of improving a stimulated Raman scattering threshold and balancing transverse mode instability suppression in the fiber amplifier. This work could provide a good reference for extending the operating wavelength of high-power fiber amplifiers.

Bufalin reverses cancer-associated fibroblast-mediated colorectal cancer metastasis by inhibiting the STAT3 signaling pathway.

At present, recurrence and metastasis are still important factors that lead to a poor prognosis among colorectal cancer (CRC) patients. Cancer-associated fibroblasts (CAFs) can promote tumorigenesis and development. Bufalin is the main active monomer of the clinical drug cinobufacini, which exhibits antitumor activity in various cancers. But few research have investigated the effect of bufalin in inhibiting metastasis from the perspective of the tumor microenvironment. We first isolated CAFs from freshly resected colorectal cancer patient specimens and observed the effect of CAFs on CRC cell invasion through a series of experiments. We explored the effect of bufalin on the physiological activity of CRC mediated by CAFs through experiments. In our study, we found that CAFs could promote CRC cell activity through the STAT3 pathway. Bufalin reversed CAF-mediated CRC invasion and metastasis by inhibiting the STAT3 pathway. Overexpression of STAT3 attenuated the inhibitory function of bufalin on invasion and metastasis. Taken together, bufalin can reverse CAF-mediated colorectal cancer metastasis based on inhibiting the STAT3 signaling pathway.

Increasing the Photocatalytic Hydrogen Generation Activity of CdS Nanorods by Introducing Interfacial and Polarization Electric Fields.

Cadmium sulfide (CdS) is a photocatalyst widely used for efficient H2 production under visible light irradiation, due to its narrow bandgap and suitable conduction band position. However, the fast recombination of carriers results in their low utilization. In order to improve photocatalytic hydrogen production, it reports the successful introduction of metallic Cd and S vacancies on CdS nanorods (CdS NRs) by a facile in situ chemical reduction method, using a thermal treatment process. This procedure generates interfacial and polarization electric fields, that significantly improve the photocatalytic hydrogen production performance of CdS NRs in sodium sulfide and sodium sulfite aqueous solutions, under visible light irradiation (λ >420 nm). The introduction of these electric fields is believed to improve charge separation and facilitate faster interfacial charge migration, resulting in a significantly optimized catalyst, with a photocatalytic hydrogen evolution rate of up to 10.6 mmol-1  g-1  h-1 with apparent quantum efficiency (AQE) of 12.1% (420 nm), which is 8.5 times higher than that of CdS. This work provides a useful method to introduce metallic and S vacancies on metal sulfide photocatalysts to build local polarization and interfacial electric fields for high-performance photocatalytic H2 production.

High power mid-infrared fiber amplifier at 3.1†µm by acetylene-filled hollow-core fibers.

We characterized high-power continuous-wave (CW) and pulsed mid-infrared (mid-IR) fiber amplifiers at a wavelength of 3.1 µm in acetylene-filled hollow-core fibers (HCFs) with a homemade seed laser. A maximum CW power of 7.9 W was achieved in a 4.2-m HCF filled with 4-mbar acetylene, which was 11% higher than the power without the seed. The maximum average power of the pulsed laser was 8.6 W (pulse energy of 0.86 µJ) at 7-mbar acetylene pressure, a 16% increase over the power without the seed. To the best of our knowledge, backward characteristics are reported for the first time for fiber gas lasers, and the backward power accounted for less than 5% of the forward power. The optimum acetylene pressure and HCF length for the highest mid-IR output are discussed based on theoretical simulations. This study provides significant guidance for high-power mid-infrared (mid-IR) output in gas-filled HCFs.

Raman suppression in high-power fiber oscillators by femtosecond-written chirped and tilted fiber Bragg gratings.

Realizing stimulated Raman scattering (SRS) suppression is a key topic for high-power fiber lasers. Here, we report an effective and simple strategy for SRS suppression using chirped and tilted fiber Bragg gratings (CTFBGs) in high-power fiber oscillators while maintaining the compactness and stability of the system. The CTFBG is inserted on the side of a cavity mirror FBG without cutting the gain fiber. To improve power handling capability, the CTFBG and cavity mirror FBGs are inscribed by femtosecond (fs) lasers. The optimal SRS suppression effect can be realized when the CTFBG is inserted into the resonant cavity and on the side of the output coupler FBG. The SRS threshold is increased by approximately 11% with an SRS suppression ratio of nearly 14 dB. Moreover, the output power of the fiber oscillator is improved to 3.5 kW, which is the maximum power achieved in fiber oscillators with SRS suppression using CTFBGs, to the best of our knowledge. The temperature of the air-cooled CTFBG is 50.2 °C, which has the potential to handle higher power. This work provides new insights for suppressing SRS in fiber oscillators, promoting the application of CTFBGs in high-power lasers.

Femtosecond laser fabrication of chirped and tilted fiber Bragg gratings for stimulated Raman scattering suppression in kilowatt-level fiber lasers.

Chirped and tilted fiber Bragg gratings (CTFBGs) are important all-fiber filtering components in high-power fiber lasers for stimulated Raman scattering (SRS) suppression. The fabrication of CTFBGs in large-mode-area double-cladding fibers (LMA-DCFs) by femtosecond (fs) laser is reported for the first time to the best of our knowledge. The chirped and tilted grating structure is obtained by scanning the fiber obliquely and moving the fs-laser beam relative to the chirped phase mask at the same time. By this method, the CTFBGs with different chirp rates, grating lengths, and tilted angles are fabricated, and the maximum rejection depth and bandwidth are ∼25 dB and ∼12 nm, respectively. To test the performance of the fabricated CTFBGs, one is inserted between the seed laser and the amplifier stage of a 2.7 kW fiber amplifier, and an SRS suppression ratio of ∼4 dB is achieved with no reduction in laser efficiency and degradation in beam quality. This work provides a highly fast and flexible method to fabricate large-core CTFBGs, which is of great significance to the development of high-power fiber laser systems.

Robust femtosecond-written chirped and tilted fiber Bragg gratings for Raman filtering in multi-kW fiber lasers.

We present a robust chirped and tilted fiber Bragg grating (CTFBG) in a large-mode-area double-cladding fiber (LMA-DCF) written by a femtosecond (fs) laser. By implementing the fs-CTFBG into the output end of a high-power fiber laser for Raman filtering, a power handling capability of 4 kW is achieved with a Raman filtering ratio of ∼13 dB. To the best of our knowledge, this is the maximum handling power of a CTFBG for Raman filtering. The signal loss of the fs-CTFBG is 0.03 dB, which has little effect on the output laser beam quality. The air-cooled fs-CTFBG has a minimum temperature slope of 7.8°C/kW due to a self-annealing effect. This work proves the excellent performance of the fs-CTFBG, promoting the development of high-power CTFBGs.

Mid-infrared fiber gas amplifier in acetylene-filled hollow-core fiber.

We report here the first, to the best of our knowledge, demonstration of a mid-infrared (mid-IR) fiber gas amplifier based on acetylene-filled hollow-core fibers. A quasi-all-fiber structure fiber acetylene laser in a single-pass configuration is used as a seed. The injection of the seed removes the threshold and increases the laser efficiency, which are more pronounced at high pressure. In a 3.1-m HCF filled with 2.5 mbar of acetylene, the fiber gas amplifier shows a conversion efficiency (relative to the coupled pump power) of 22.2% at 3.1 µm, which is increased by 35% compared with that without the seed. Both the seed laser and the amplifier laser have good beam quality with M2 < 1.1. It is predictable that such a fiber gas amplifier can achieve a more efficient and higher power mid-IR output for other selected molecular species compared with the single-pass structure, which is beneficial to the development of high-power mid-IR fiber gas lasers.

Fiber laser source of 8 W at 3.1 µm based on acetylene-filled hollow-core silica fibers.

We report here the characteristics of a nanosecond high-power mid-infrared (mid-IR) light source based on an anti-resonant hollow-core fiber (AR-HCF) filled with acetylene gas. It is a single-pass configuration with 9.3-m HCFs, pumped by a modulated and amplified diode laser. A maximum average power of approximately 8 W (pulse energy of ∼0.8 µJ and peak power of ∼40 W) at 3.1 µm is achieved with a laser slope efficiency of ∼22.8% at 6 mbar of acetylene, which is, to the best of our knowledge, a record output power for such mid-IR HCF lasers. This work demonstrates the great potential of fiber gas lasers for high-power output in the mid-IR.

Minocycline Pretreatment Prevents Blood-Brain Barrier Disruption in Septic Rats.

INTRODUCTION: The aim of the study was to explore the mechanism by which minocycline protects the blood-brain barrier (BBB) in septic rats. METHODS: A sepsis rat model was generated in healthy, male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were randomly divided into four groups and treated as follows: sham-operated plus normal saline (Sham + S group), CLP plus normal saline (CLP + S group), CLP plus minocycline pretreatment (CLP + M1 group), and CLP plus minocycline treatment (CLP + M2 group). Rats in the CLP + M1 group received 45 mg/kg minocycline by intraperitoneal injection every 12 h for 72 h. Rats in the Sham + S and CLP + S groups were injected with the same volume of normal saline every 12 h for 72 h. Rats in the CLP + M2 group were intraperitoneally injected with 45 mg/kg minocycline immediately after CLP and once every 12 h for 72 h. All rats were sacrificed at 72 h after operation. Tumor necrosis factor α and interleukin 6 levels, the expression of ionized calcium-binding adaptor molecule-1 (Iba-1), and the permeability of the BBB were measured. The expression of matrix metalloproteinases-9 (MMP-9) and the tight junction proteins zonula occludens-1 (ZO-1) and occludin was detected by Western blot. In addition, Evans blue (EB) staining, immunohistochemistry, and ELISA analysis were carried out. RESULTS: Minocycline pretreatment significantly inhibited microglial activation, decreased the sepsis-induced expression of MMP-9, increased the expression of ZO-1 and occludin, and improved the permeability of the BBB. Minocycline treatment failed to inhibit microglial activation, decrease the sepsis-induced expression of MMP-9, increase the expression of ZO-1 or occluding, or improve the permeability of the BBB. CONCLUSIONS: Minocycline pretreatment can effectively improve the altered permeability of the BBB caused by sepsis. The mechanism may be related to the inhibition of microglial activation and MMP-9 expression and increased expression of ZO-1 and occludin.

Investigation of the pump coupling efficiency of a side-pumping combiner based on tapered-fused method.

Side-pumping combiner is used for pumping double-clad fiber in various fiber laser schemes. However, its coupling efficiency and temperature characteristics suffer when pumped via a large numerical aperture (NA) pump light. We investigated the method of optimizing the coupling efficiency of a (2 + 1) ×1 combiner under a large NA pump light injection. After optimization of taper ratio and length of the pump fiber and fusion area between pump and signal fiber, the coupling efficiency increased and the temperature characteristic improved, which could be useful for fabrication of a side-pumping combiner for high-power fiber laser applications.

Demonstration of kilowatt monolithic Yb-doped fiber laser operation near 980 nm.

In this Letter, to the best of our knowledge, the first kilowatt monolithic Yb-doped fiber laser operating near 980 nm is demonstrated. The fiber laser is achieved with the help of an all-fiber amplifier fabricated with a 105/250-µm core/cladding-diameter double-cladding Yb-doped fiber. With 11-W seed light, about 1.11-kW output power was obtained with 65.3% slope efficiency. The center wavelength was around 978 nm with a 10-dB bandwidth of about 0.6 nm. About 34-dB suppression of 1030-nm amplified spontaneous emission was realized, and the output beam quality (M2 factor) was about 16.2 at maximum output power. Better beam quality can be expected by optimizing the seed light and active fiber. This work can provide significant guidance for the study and designation of high-power fiber lasers operating near 980 nm and other three-level fiber sources.

5 kW monolithic fiber amplifier employing homemade spindle-shaped ytterbium-doped fiber.

We have demonstrated a 5 kW high-power monolithic fiber amplifier employing a homemade spindle-shaped ytterbium-doped fiber (YDF) based on the main oscillator power amplifier configuration. The YDF consists of a spindle-shaped core and cladding along the fiber length, with a core/cladding diameter of 27/410 µm at both ends and 39.5/600 µm in the middle. An output power of over 5 kW and beam quality of about 1.9 and an optical-to-optical conversion efficiency of 66.6% were achieved in the amplifier under a bidirectional pump scheme. While operating at the maximum power, the laser performance was evaluated, and the transverse mode instability and stimulated Raman scattering effects were well mitigated. To the best of our knowledge, this is the highest power demonstration in a continuous-wave fiber laser employing a tapered fiber. Further power scaling is promising by optimizing the structure of the YDF.

Use of volume controlled vs. pressure controlled volume guaranteed ventilation in elderly patients undergoing laparoscopic surgery with laryngeal mask airway.

BACKGROUND: The peak inspiratory pressure (PIP) is crucial in mechanical ventilation with supraglottic airway device (SAD). Pressure-controlled ventilation volume-guaranteed (PCV-VG), delivering a preset tidal volume with the lowest required airway pressure, is being increasingly used during general anesthesia. In this study, we compared respiratory mechanics and circulatory parameters between volume-controlled ventilation (VCV) and PCV-VG in elderly patients undergoing laparoscopic surgery using the laryngeal mask airway supreme (LMA). METHODS: Eighty participants scheduled for laparoscopic surgery were enrolled in this prospective, randomized clinical trial. The participants were randomly assigned to receive VCV or PCV-VG. PIP, dynamic compliance (Cdyn) and mean inspiratory pressure (Pmean) were recorded at 5 min after induction of anesthesia (T1), 5 min after pneumoperitoneum(T2), 30 and 60 min after pneumoperitoneum (T3 and T4). Data including other respiratory variables, hemodynamic variables, and arterial blood gases were also collected. The difference in PIP between VCV and PCV-VG was assessed as the primary outcome. RESULTS: PIP was significantly lower at T2, T3, and T4 in both groups compared with T1 (all P <  0.0001), and it was significantly lower in the PCV-VG group than the VCV group at T2, T3, and T4 (all P <  0.001). Cydn was decreased at T2, T3, and T4 in two groups compared with T1 (all P <  0.0001), but it was higher in PCV-VG group than in VCV group at T2, T3, and T4 (all P <  0.0001). There were on statistically significant differences were found between the groups for other respiratory and hemodynamic variables. CONCLUSION: In elderly patients who underwent laparoscopic surgery using an LMA, PCV-VG was superior to VCV in its ability to provide ventilation with lower peak inspiratory pressure and greater dynamic compliance.

Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: A double-blind, randomised clinical trial.

BACKGROUND: Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce. OBJECTIVE: To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Single-centre, tertiary care hospital, November 2016 to September 2018. PATIENTS: Eligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90). INTERVENTIONS: Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 µg kg-1), over 15 min, followed by a continuous infusion at a rate of 0.1 µg kg-1 h-1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol. OUTCOME MEASURES: The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile. RESULTS: All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P < 0.0001). CONCLUSION: Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881.

Comparison of two treatments in the presence of competing risks.

Competing risks data arise frequently in clinical trials, and a common problem encountered is the overall homogeneity between two groups. In competing risks analysis, when the proportional subdistribution hazard assumption is violated or two cumulative incidence function (CIF) curves cross; currently, the most commonly used testing methods, for example, the Gray test and the Pepe and Mori test, may lead to a significant loss of statistical testing power. In this article, we propose a testing method based on the area between the CIF curves (ABC). The ABC test captures the difference over the whole time interval for which survival information is available for both groups and is not based on any special assumptions regarding the underlying distributions. The ABC test was also extended to test short-term and long-term effects. We also consider a combined test and a two-stage procedure based on this new method, and a bootstrap resampling procedure is suggested in practice to approximate the limiting distribution of the combined test and two-stage test. An extensive series of Monte Carlo simulations is conducted to investigate the power and the type I error rate of the methods. In addition, based on our simulations, our proposed TS, Comb, and ABC tests have a relatively high power in most situations. In addition, the methods are illustrated using two different datasets with different CIF situations.

Differential motility parameters and identification of proteomic profiles of human sperm cryopreserved with cryostraw and cryovial.

BACKGROUND: Although sperm cryopreservation has been widely used in human reproductive medicine as an integral infertility management in infertility clinics and for banking sperm in sperm banks, the freezing/thawing protocols are not optimal. The freezing and thawing processes result in changes at both structural and molecular levels, some even detrimental, in human sperm when compared with fresh sperm. The change of sperm proteins after cryopreservation may play negative roles for fertilization and early embryo development. Conventionally, cryostraws (CS) and cryovials (CV) are the most widely used cryopreservation carriers (CPCs) for human sperm cryopreservation accompanied with the use of egg yolk free commercial media. However, the influence of cryopreservation on the proteomic profile of human sperm preserved with the two CPCs is unknown. Therefore the purpose of the present study was to compare the frozen-thawed motility, investigate the proteomic profile of human sperm cryopreserved with the two types of CPCs, and identify the susceptible proteins that play key roles for sperm function and fertility. METHODS: The present study compared the cryosurvival of human sperm frozen with the two different CPCs and identified the sperm proteomic changes by using the isobaric tags for relative and absolute quantification labeling technique coupled with 2D LC-MS/MS analysis after freezing and thawing. RESULTS: Our results indicated that sperm cryopreserved with CV showed higher values for percentage of motile sperm and forward activity rate than those with CS. Compared to fresh sperm, 434 and 432 proteins were differentially identified in human sperm cryopreserved with CS and CV, respectively. CONCLUSION: The proteomic profiles of human sperm are greatly affected by cryopreservation with either type of CPC. GO analysis revealed that most of the differentially identified sperm proteins enriched in the extracellular membrane-bounded organelles, cytoplasm and cytosol. In addition, 106 susceptible proteins having known identities related to sperm functions were identified. In general, cryovial seems to be the preferred CPC for human sperm cryopreservation based on the post-thaw motility parameters and the effect on sperm proteomic profiles. These results are beneficial for the insight into the understanding of the cryoinjury mechanism of sperm and the development of human sperm cryopreservation strategies.