Lp-PLA2 silencing ameliorates inflammation and autophagy in nonalcoholic steatohepatitis through inhibiting the JAK2/STAT3 pathway.

Background: Nonalcoholic steatohepatitis (NASH), a common cause of liver-related morbidity and mortality worldwide, is characterized by inflammation and hepatocellular injury. Our research focuses on lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammation-related biomarker that has recently garnered interest in the context of NASH due to its potential roles in disease pathogenesis and progression. Methods: We established a NASH mouse model using a high-fat diet (HFD) and treated it with sh-Lp-PLA2 and/or rapamycin (an mTOR inhibitor). Lp-PLA2 expression in NASH mice was detected by qRT-PCR. Serum levels of liver function parameters and inflammatory cytokines were detected using corresponding assay kits. We examined pathological changes in liver using hematoxylin-eosin, oil red O, and Masson staining, and observed autophagy through transmission electron microscopy. The protein levels of Lp-PLA2, mTOR, light chain 3 (LC3) II/I, phosphorylated Janus kinase 2 (p-JAK2)/JAK2, and phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/STAT3 were determined by western blotting. Kupffer cells extracted from C57BL/6J mice were treated to replicate NASH conditions and treated with sh-Lp-PLA2, rapamycin, and/or a JAK2-inhibitor to further verify the roles and mechanisms of Lp-PLA2 in NASH. Results: Our data indicate an upregulation of Lp-PLA2 expression in HFD-induced NASH mice. Silencing Lp-PLA2 in NASH mice reduced liver damage and inflammation markers (aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)), while increasing IL-10 levels, an anti-inflammatory cytokine. Additionally, Lp-PLA2 silencing decreased lipid and collagen accumulation and promoted autophagy. The beneficial effects of sh-Lp-PLA2 on NASH were enhanced by rapamycin. Furthermore, Lp-PLA2 silencing resulted in the downregulation of the expression of p-JAK2/JAK2 and p-STAT3/STAT3 in NASH mice. Similar results were observed in Kupffer cells treated under NASH conditions; Lp-PLA2 silencing promoted autophagy and repressed inflammation, effects which were potentiated by the addition of rapamycin or a JAK2-inhibitor. Conclusion: Our findings suggest that silencing Lp-PLA2 promotes autophagy via deactivating the JAK2/STAT3 signaling pathway, thereby restraining NASH progression. This highlights the potential therapeutic value of targeting Lp-PLA2, adding a new dimension to our understanding of NASH pathogenesis and treatment strategies.

Anterior mediastinal tumor surgery applying single-port thoracoscopy using the subxiphoid approach.

Background: This study aims to investigate the effectiveness of application of single-port thoracoscopy using the subxiphoid approach in anterior mediastinal tumor surgery. Methods: Between June 2014 and June 2016, a total of 108 patients (59 males, 49 females; mean age: 64.9±7.5 years; range, 45 to 79 years) with anterior mediastinal tumors were randomized into subxiphoid (experimental) or right chest (control) groups. Single-port thoracoscopy using the subxiphoid approach was performed in the subxiphoid group, while thoracoscopy using the right thoracic approach was performed in the control group. Preand postoperative pain stress indicators, Visual Analog Scale scores, quality of life scores, postoperative tumor recurrence, and five-year survival rates were compared between the groups. Results: There were no mortality or serious complications in either group. The mean Visual Analog Scale pain scores on postoperative Days 1 and 7 were 6.5±0.8 and 2.9±0.8 in the subxiphoid group, respectively, compared to 7.2±0.8 and 3.4±0.8 in the control group (p<0.05 for all), respectively. The mean quality of life scores on postoperative Days 1 and 7 were 81.5±5.0 and 79.3±7.7, respectively, in the subxiphoid group compared to 72.4±4.3 and 71.3±4.8 in the control group, respectively (p<0.05 for all). Postoperative pain and pain mediator indexes were lower in the subxiphoid group (p<0.05 for all). The postoperative tumor recurrence rates were 3.70% and 20.37% in the subxiphoid and control groups, respectively (p=0.008). The five-year survival rates were 85.2% and 63.0% in the subxiphoid and control groups, respectively (p=0.008). Conclusion: Single-port thoracoscopy using the subxiphoid approach is technically feasible, safe, and effective in performing surgery for anterior mediastinal tumors with an intact capsule and a tumor diameter of ≤5 cm.

A Case of Adult Acute B-Cell Lymphoblastic Leukemia with Hypercalcemia and Osteolytic Bone Lesions.

BACKGROUND: We report a rare case of adult acute B-lymphoblastic leukemia (B-ALL) with hypercalcemia and osteolytic bone lesions in a 53-year-old man who died after chemotherapy. METHODS: The bone marrow examination was evaluated by Wright-Giemsa staining, tissue biopsy, immunohistochemical staining, and flow cytometry. Bone imaging was performed using positron emission tomography/computed tomography (PET/CT) technology. Total calcium levels were measured by biochemical analyzer. RESULTS: The result of PET/CT indicated the patient with B-ALL with severe osteolytic bone lesions. The serum total calcium level was as high as 4.09 mmol/L, and the cytokines interleukin-6 and 17A were significantly elevated. The patient was resistant to chemotherapy and had a poor prognosis. CONCLUSIONS: Hypercalcemia and osteolytic bone lesions are rare complications of adult B-ALL, and their co-occurrence may be an indicator of poor prognosis in patients with B-ALL.

Spectrally flat mid-infrared supercontinuum pumped by a high power 2 µm noise-like pulse.

We demonstrate spectrally flat high-power mid-infrared supercontinuum (MIR SC) generation with record-breaking power of 33.1 W and power conversion efficiency of 75.06%. It is pumped by a 2 µm master oscillator power amplifier system consisting of a figure-8 mode-locked noise-like pulse seed laser and dual-stage Tm-doped fiber amplifiers with repetition rate of 4.08 MHz. Through cascading a piece of ZBLAN fiber with 13.5 µm large core diameter by direct-low-loss fusion splicing, SCs with spectral ranges of 1.9-3.68 µm, 1.9-3.84 µm, 1.9-4.02 µm and average powers of 33.1 W, 29.8 W, 25.9 W are generated. To the best of our knowledge, all of them have achieved the highest output power under the same condition of MIR spectrum range. This high-power all-fiber MIR SC laser system has relatively simple architecture, high efficiency and flat spectrum, demonstrating the advantages of 2 µm noise-like pulse pump in high-power MIR SC generation.

Research on the Roundness Approximation Search Algorithm of Si3N4 Ceramic Balls Based on Least Square and EMD Methods.

This paper aims to obtain the best shape accuracy evaluation algorithm for silicon nitride ceramic balls after lapping, and to extract the initial signal of the ball surface to improve the accuracy and reliability of the algorithm. The research methods of this paper are as follows: Firstly, an analysis of the uniform envelope of the lapping trajectory of ceramic balls is carried out to verify whether the lapping trajectory after processing can achieve a consistent envelope on the balls' surface. On this basis, it is found through experiments that the standard deviation SD between the roundness deviations of different contour sections is small. The value is maintained at approximately 0.03 µm, and the roundness deviation can approximately replace the spherical deviation. Then the different contour sections of the sphere are sampled by the Taylor roundness instrument. Considering the uncertainty, the sampling points of different contour sections are averaged and used as the original signal of the sphere surface. Then the EMD method is used to process the signal to be detected on the sphere surface. The initial signal of the sphere surface is extracted by judging whether the number of ripples Kc obtained by decomposition is greater than the critical value. Then the initial signal is used as the input value of the approximation algorithm. Through the roundness deviation approximation algorithm based on the least square method, the given minimum approximation domain range is finely processed. The divided fine points are used as the center of the circle to intersect with the initial signal. The maximum, minimum, and range of each circle are calculated to obtain the roundness error based on the minimum circumscribed circle, the maximum inscribed circle, and the minimum region method. Finally, the calculated values are compared with those obtained by the traditional algorithm. The experimental results of this paper show that the algorithm is consistent with the roundness error measured by the instrument, compared with the mainstream evaluation criteria. In summary, the conclusions can be drawn as follows: Through a large number of experimental cases and comparative experiments, the algorithm has high accuracy and reliability. The research results of this paper have essential reference significance for accurately evaluating the shape accuracy of ceramic balls in actual production.

Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells.

Exosomes containing various biological cargoes have potential to be novel diagnostic biomarkers for metabolic diseases. In this study, retinol-binding protein 4 (RBP4) was found to be enriched in serum exosomes, and its increased levels could be considered as an independent risk factor for the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Exosomal RBP4 (exo-RBP4), primarily derived from hepatocytes, significantly enhanced the M1-like polarization of Kupffer cells (KCs) via promoting the activation of NOX2 and NF-κB and reactive oxygen species (ROS) accumulation, resulting in the over-production of inflammatory cytokines including TNF-α. Subsequently, those excess cytokines remarkably increased the levels of intracellular free fatty acid uptake and lipogenesis-related genes (FAS and SREBP-1c) but decreased fatty acid degradation-related genes (CPT-1 and PPARα) in palmitic acid-treated LO2 cells. More notably, TNF-α significantly elevated RBP4 transcription by activating STAT3 in hepatocytes, playing a positive role in NAFLD development. Intravenous injection with RBP4 (50 µg/kg) potentiated hepatic lipid accumulation, M1-type KC proportion, and serum pro-inflammatory cytokine levels in the hepatic tissues of high-fat-diet-fed mice. Collectively, these data indicated that exo-RBP4 converted KCs to M1 subtype by mediating the NOX2/ROS/NF-κB pathway, subsequently promoting de novo lipogenesis in hepatocytes by TNF-α secretion to activate the JAK2/STAT3 signaling pathway. Therefore, this study uncovered a novel intercellular communication between the inflammatory microenvironment and lipid metabolism for fostering NAFLD progression and found the potential of exo-RBP4 as a novel diagnostic biomarker and therapeutic target for NAFLD.

Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications.

The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the "second genome" of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis via alteration of bile acid metabolism pathway. Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.

The Biological Functions and Clinical Values of Exosomal Circular RNAs in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) exacts a heavy disease burden and is currently the second most common cause of cancer-related deaths worldwide. HCC usually lacks obvious symptoms in the early stage, and most HCC patients are diagnosed at advanced stages with poor prognosis. Circular RNAs (circRNAs) are single-stranded RNAs that form covalently closed loops and are stable in exosomes. Exosomes are known as important messengers of the cross-talk between tumor and immune cells. Accumulating studies have demonstrated the promoter or suppressor roles of exosomal circRNAs in the carcinogenesis, progression, and metastasis of HCC. In this review, we summarized the current studies on the biological functions and diagnostic and prognostic values of exosomal circRNAs in HCC progression.

Mid-infrared supercontinuum generation in an all-fiberized Er-doped ZBLAN fiber amplifier.

A high power mid-infrared (MIR) supercontinuum (SC) is demonstrated in a strictly all-fiberized Er-doped ZBLAN fiber amplifier (EDZFA). The EDZFA is seeded by a 2.0-3.5 µm fiber-based SC laser and pumped at 976 nm. At pulse repetition rate of 500 kHz, the output SC spanning from 2.7 to 4.2 µm reaches a record output power of 4.96 W with an overall slope efficiency of 17.3%. This Letter, to the best of our knowledge, demonstrates the first all-fiberized in-amplifier SC generation in the MIR region, which has significant potential for further power scaling.

Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site.

The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.

1.2-15.2 µm supercontinuum generation in a low-loss chalcohalide fiber pumped at a deep anomalous-dispersion region.

A novel low-loss selenium-based chalcohalide fiber, with a low zero-dispersion wavelength, was prepared by an innovative preparation process. The composition optimized fiber has a wide transmission range of up to 11.5 µm, a lowest fundamental mode zero-dispersion wavelength of 4.03 µm, and a minimum optical loss of 1.12 dB/m at 6.4 µm, which provides a possibility to replace As2S3 and As2Se3 in a cascade of ZrF4-BaF2-LaF3-AlF3-NaF(ZBLAN)-As2S3-As2Se3 fiber in the practical all-fiberized supercontinuum (SC) source. Meanwhile, the broadest SC spectrum, ∼1.2 to 15.2 µm, was achieved by pumping a 12-cm-long fiber with a femtosecond laser at a deep anomalous-dispersion region. Furthermore, simulations are adopted to interpret the results as well as to demonstrate spectral evolution along the fiber. To the best of our knowledge, this is the broadest SC spectrum reported in any selenium-based chalcogenide fiber.

Association between Serum Ferritin Level and Nonalcoholic Fatty Liver Disease in a Non-Obese Chinese Population: a Cross-Sectional Study.

BACKGROUND: The aim of the study is to evaluate the cross-sectional association between serum ferritin level and nonalcoholic fatty liver disease (NAFLD) in a non-obese Chinese population. METHODS: A cross-sectional study was performed among 1,020 non-obese subjects (body mass index < 25 kg/m2) who took their annual health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University. Serum ferritin level and other clinical and laboratory parameters were measured in the population. Liver ultrasound examinations were performed to diagnose NAFLD. RESULTS: Of the 1,020 enrolled participants, 148 (14.51%) fulfilled the diagnostic criteria for NAFLD. Subjects with NAFLD had a higher level of serum ferritin than individuals without NAFLD in non-obese subjects. Serum ferritin level was significantly and positively correlated with parameters of MS (BMI, SBP, TG and FPG) in NAFLD group. Stepwise logistic regression analysis showed that serum ferritin level was significantly associated with the risk factor for NAFLD. After adjusting for confounders, serum ferritin level was an independent factor predicting advanced fibrosis (FIB-4 ≥ 1.3) in NAFLD participants. CONCLUSIONS: Increased serum ferritin level is significantly associated with NAFLD, and elevated serum ferritin level is an independent factor predicting advanced fibrosis for NAFLD in a non-obese Chinese population.

Use of autologous platelet rich fibrin-based bioactive membrane in pressure ulcer healing in rats.

OBJECTIVE: To verify the feasibility of treating pressure ulcers (PUs) with autologous platelet-rich fibrin-based (PRF) bioactive membrane, both in vitro and in vivo. METHOD: An animal model using adult male Sprague-Dawley rats was used. Pressure was periodically exerted on the skin to induce localised ischaemia by using an external magnet and transplanted metal disc. After a PU developed, the rats were divided into two groups: a treatment group and a control group. Rats in the treatment group were then treated with PRF bioactive membrane every three days. RESULTS: A total of 20 rats were used in this study. At days three and seven, the PU area in the PRF bioactive membrane-treated group was significantly smaller than that in the control group, and after 14 days of treatment, the PUs in the PRF bioactive membrane treatment group had healed. Haemotoxylin and eosin staining, immunohistochemistry and Western blot results indicated that PRF bioactive membrane induced wound healing by increasing the thickness of the regenerated epidermis and by upregulating vascular endothelial growth factor expression. Further, we found that different concentrations of rat autologous PRF soluble factors extraction components could significantly promote rat aortic endothelial cell proliferation, wound healing and migration ability in vitro. CONCLUSION: Overall, results indicate that PRF bioactive membrane promotes PU healing in rats. Thus, it may represent a natural and effective wound-healing tool for use in the treatment of clinical skin PUs in humans in the future.

Mid-infrared flattened supercontinuum generation in all-normal dispersion tellurium chalcogenide fiber.

We have prepared a well-structured tellurium chalcogenide (ChG) fiber with a specialized double cladding structure by an improved extrusion method, and experimentally demonstrated an ultra-flat mid-infrared (MIR) supercontinuum (SC) generation in such a fiber. The step-index fiber had an optical loss of <1 dB/m in a range from 7.4 to 9.7 µm with a minimum loss of 0.69 dB/m at 7.87 µm. Simulation showed that an all-normal dispersion profile can be realized in this double cladding tellurium fiber. An ultra-flat MIR SC spectrum (~3.2-12.1µm at -10 dB, ~2-14 µm at -30 dB) was generated from a 22-cm long fiber pumped with a femtosecond laser at 5 µm (~150 fs, 1 kHz). Then the degree of coherence was calculated out based on a simulation, showing that a high coherent MIR SC (from 2.9 to 13.1 µm) can be generated in this double-cladding tellurium fiber.

Association Between Serum Free Fatty Acids Levels and Gestational Diabetes Mellitus: a Cross-Sectional Study.

BACKGROUND: This study aimed to assess the relationship between serum free fatty acid (FFA) levels and gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: A cross-sectional study was performed among 779 eligible pregnant women who underwent detailed prenatal visits in Hangzhou, China. RESULTS: Patients with GDM had significantly higher serum FFA levels than those without GDM. Spearman's correlation analysis showed that FFA levels were positively correlated with fasting plasma glucose, 1hPG, 2hPG, HOMA-IR, triglyceride, and sialic acid (p < 0.05) and negatively correlated with serum amylase level (all with p < 0.05). Stepwise logistic regression analysis further showed that elevated FFA levels significantly contributed to the risk for GDM. CONCLUSIONS: Our findings suggested that serum FFA levels were significantly associated with GDM.

1.9-3.6 µm supercontinuum generation in a very short highly nonlinear germania fiber with a high mid-infrared power ratio.

In this Letter, a high-power supercontinuum (SC) laser source which spanned from 1.9 to 3.6 µm with an all-fiber configuration was reported. This SC laser was obtained by concatenating a thulium-doped fiber amplifier (TDFA) and a 12 cm long highly nonlinear germania fiber. A 1.9-2.7 µm SC laser from the TDFA was spectrally broadened continuously into the mid-infrared region (>3 µm) in the following germania fiber. When the repetition rate was 2 MHz, the obtained SC laser had a maximum output power of 6.12 W with an optical conversion efficiency of 15.3% with respect to the TDFA pump power. The SC laser had a spectral bandwidth of 1506 nm ranging from 1944 to 3450 nm at the -20 dB level. The SC power with wavelengths >3 µm was 2.9 W, corresponding to a high power ratio of 47.4% in the mid-infrared region. The achieved power ratio in the mid-infrared region, as well as the long wavelength cutoff, to the best of our knowledge, were the best results ever reported in germania fibers.

0.6-3.2 µm supercontinuum generation in a step-index germania-core fiber using a 4.4 kW peak-power pump laser.

An ultra-broadband supercontinuum was generated in a short piece of step-index germania-core fiber using a fiber laser with a peak power of 4.4 kW. The pure germania core made this fiber capable of propagating light towards the desirable mid-infrared region. The spectral broadening characteristics towards the mid-infrared region under different lengths of germania-core fiber were investigated using pump pulses of 4.4 kW and 1.1 ns at 1550 nm. The large nonlinear refractive index of germania and the small core size of germania-core fiber produced a nonlinear coefficient as high as 11.8 (W km)-1 at 1550 nm, which was beneficial for supercontinuum generation. The pump wavelength was located in the anomalous dispersion regime and close to the zero dispersion wavelength of this germania-core fiber, 1.426 µm. Eventually, an ultra-broadband supercontinuum source with a spectrum spanning from 0.6 to 3.2 µm was obtained and had a total output power of 350 mW at an optimized germania-core fiber length of 0.8 m. This work is the first demonstration, to the best of our knowledge, of a germania-core fiber-based ultra-broadband supercontinuum source that spans from the visible region to the mid-infrared region.

Mid-infrared supercontinuum generation based on cascaded Raman scattering in a few-mode As2S3 fiber pumped by a thulium-doped fiber laser.

By pumping a 1.7-m-long As2S3 fiber at 2050 nm directly, a fiber-based mid-infrared supercontinuum (SC) source with an output power of 366 mW is demonstrated. This is the first experimental demonstration to obtain such a mid-infrared SC in a piece of chalcogenide fiber pumped at 2 µm directly. The cut-off wavelength of the As2S3 fiber is 3.5 µm, indicating that it could support several modes at around 2 µm. It is found that nonlinear spectral broadening mechanisms in the few-mode chalcogenide fiber could be affected through adjusting the butt-coupling position. That is because different positions will excite different modes that correspondingly possess different nonlinearity and dispersion characteristics. When stimulated Raman scattering (SRS) corresponding to the excitation of the fundamental mode becomes dominant in this few-mode fiber, an efficient cascaded SRS-based SC is obtained with five Stokes peaks ranging from 2 µm to 3.4 µm. Results from numerical simulation are in accord with the experimental results, showing that it is feasible to obtain an SRS based mid-infrared SC in a step-index As2S3 fiber by using a 2 µm high peak power picosecond laser to pump directly.

Mid-infrared supercontinuum generation in step-index As2S3 fibers pumped by a nanosecond shortwave-infrared supercontinuum pump source.

A supercontinuum (SC) source spanning from 2 to 4 µm is demonstrated in As2S3-chalcogenide fibers pumped by a nanosecond supercontinuum pump source in the normal dispersion region. In this experiment, two pieces of 3-m-long step-index As2S3 fiber with different core diameters of 7 µm and 9 µm are pumped by a 1.9-2.5 µm nanosecond supercontinuum source. The zero dispersion wavelengths are both beyond 6.6 µm, thus cascaded stimulated Raman scattering is believed to be the dominant mechanism responsible for spectral broadening. With a low peak pump power of ~2.9 kW, both of the output spectra have extended to 4 µm with enhanced power distribution in the MIR region. The maximum output power of the mid-infrared supercontinua is ~140 mW. To the best of our knowledge, it is the first supercontinuum extenting to 4 µm in an As2S3 fiber pumped by shortwave-infrared SC pluses in the normal dispersion region.

Highly stable, monolithic, single-mode mid-infrared supercontinuum source based on low-loss fusion spliced silica and fluoride fibers.

A 0.8 to 4.5 µm highly stable all-fiber spliced mid-infrared supercontinuum (SC) source was presented. The joint between the single-mode (SM) pump silica fiber and the ZBLAN fiber (ZrF4 - BaF2 - LaF3 - AlF3 - NaF, a type of fluoride fiber) was fusion spliced, which greatly improved the SC's stability. The low-loss splicing was guaranteed by the similar mode field areas of the fundamental mode LP(01) of the silica and ZBLAN fibers. At the splicing joint the ZBLAN fiber enveloped the silica fiber, thus increasing the robustness of the splice. A low splicing loss of less than 0.1 dB was calculated, which ensured that the whole SC source was very reliable. The SC had a maximal average power of 550.8 mW with a 1.5 dB spectral bandwidth ranging from 2642 to 4065 nm. In particular, the SC power for λ>3.8 µm was measured to be 116.1 mW with a power ratio of ∼21.1% of the total SC power. Perfect Gaussian beam profiles of the SC source demonstrated its SM operation. Over 12 h of continuous operation of this SC source showed its outstanding power stability with a root mean square variation of 0.59%, which also demonstrated the high quality of the fusion spliced joint.