[Analysis of clinical manifestations and imaging characteristics of in vivo confocal microscopy for Nocardia keratitis].

Objective: To analyze the clinical manifestations and imaging characteristics of in vivo confocal microscopy (IVCM) for Nocardia keratitis. Methods: It was a retrospective case series study. Medical records of 16 consecutive patients (16 eyes) with Nocardia keratitis were collected from the Department of Ophthalmology at Beijing Tongren Hospital, Capital Medical University between 2018 and 2022. The group consisted of 11 males and 5 females. The inclusion criteria for the study were the presence of typical clinical manifestations of Nocardia keratitis and at least one positive pathogenic test (corneal scraping or microbial culture) indicating Nocardia infection. The medical history, clinical and microbiological examination data of the patients were analyzed, including risk factors, diagnosis time, clinical manifestations, diagnostic methods, strain isolation, cure time, and best corrected visual acuity before and after treatment. This study utilized techniques such as slit lamp microscopy, in vivo confocal microscopy (IVCM), scraping cytology, microbial culture, and mass spectrometry identification. Results: The main risk factors for Nocardia keratitis included plant or foreign body injuries (5 out of 16 cases), contact lens use (4 out of 16 cases), and surgery (2 out of 16 cases). The average time to diagnosis was (20.8±11.8) days, with the shortest time being 8 days and the longest being 60 days. The best corrected visual acuity was less than 0.05 in 7 patients, between 0.05 to 0.3 in 7 patients, and greater than or equal to 0.3 in 2 patients. The typical symptoms included superficial gray-white infiltration in a wreath-like pattern on the cornea, corneal ulcers with dry and gray-white necrotic tissue coverage, and in severe cases, corneal ulcer perforation. Nocardia corneal infection was identified in 12 out of 16 cases by scraping cytology, 9 out of 16 cases by mass spectrometry, and 8 out of 16 cases by both methods. IVCM showed the presence of fine and moderately reflective filamentous hyphae in the subepithelial and superficial stromal layer of the cornea, arranged in elongated, beaded, and branched structures. Infiltration of many hyper-reflective round inflammatory cells was also seen around the hyphae. Fourteen cases were treated with medication and 2 cases were treated with corneal transplantation. The average cure time was (37.5±25.2) days and there were no cases of recurrence during the follow-up period (all greater than 6 months). Conclusions: Nocardia keratitis is primarily characterized by dense, round, or wreath-like infiltration in the early stage, and by gray-white dry necrotic secretion and hypopyon on the surface of corneal ulcers in the middle and late stages. Fine, branched or beaded, and moderately reflective filamentous structures are the hallmark of the corneal lesion on the IVCM images.

[A case of bilateral corneal ulcer after left eye cataract extraction surgery].

The patient is a 73-year-old female who developed bilateral corneal ulcers one month after cataract surgery in her left eye. The diagnosis is bilateral conjunctival pemphigoid. She underwent a left-eye amniotic membrane transplant and a right-eye lamellar corneal transplant, and was treated with oral immunosuppressants. The patient's condition is stable.

[A case report of congenital osteogenesis imperfacta with corneal ectasia].

An 8-year-old male patient was admitted to ophthalmology for bilateral progressive blurred vision for 5 years. He had a history of multiple spontaneous fractures. Ocular examination revealed best-corrected visual acuity (BCVA) of 0.5 in the right eye and 0.6 in the left eye. Slitlamp examination showed bilateral blue sclerae, thining of the entire cornea and corneal ectasia. General physical examination demonstrated multi-site ligamentous laxity. The diagnosis of osteogenesis imperfacta was made. The patient was advised to wear rigid gas permeable contact lens with large diameter and stabilized peripheral curve, and the BCVA achieved 0.8 for both eyes.

[A case of bacterial keratitis after lamellar keratoplasty for pterygium].

A 48-year-old man presented to Beijing Tongren Hospital Ophthalmology Department with redness, increased secretions and vision loss in his right eye. He had been treated with pterygium excision and lamellar keratoplasty due to recurrent pterygium in the right eye. After corneal scraping and microbial culture, he was diagnosed as bacterial keratitis after pterygium lamellar keratoplasty in the right eye. After applying topical antibiotic eye drops, removing corneal graft and conducting amniotic membrane transplantation, corneal infection was controlled and his vision was recovered.

[Detection of the spontaneous blinking pattern of dry eye patients using the machine learning method].

Objective: To establish a method to record the spontaneous blink pattern with a machine learning model, and to clarify the spontaneous blink pattern in patients with dry eye. Methods: It was a cross-setional study.We selected 357 dry eye patients (102 males and 255 females), aged (46.2±13.3) years, who visited corneal specialist clinics of Beijing Tongren Eye Center in 2019, as the dry eye group. The control group enrolled 152 normal controls, including 32 males and 120 females, aged (48.1±13.9) years. All participants completed the Ocular Surface Disease Index questionnaire, blink video capture, lipid layer thickness measurement, tear break-up time measurement, corneal fluorescein staining, and Schirmer Ⅱ test. Based on the assembled model built using UNet image segmentation algorithm and ResNet image classification algorithm, single frames of the blink video were analyzed, and then the palpebral opening height of each frame was obtained in order to establish a spontaneous blink wave. Finally, the characteristics of spontaneous blinks in dry eye patients were analyzed based on different types of complete blinks (types A, B and C) and partial blinks (types Ⅰ, Ⅱ and Ⅲ). Independent sample t test and Wilcoxon rank-sum test were used to judge if there was significant difference between the dry eye group and the normal group. Results: The accuracy of the segmentation model and the classification model was 96.3% and 96.0%, respectively, and the consistency with the manual analysis was 97.9%. In dry eye patients, the number of blinks was 30 (18, 42)/min, which was higher than that in normal controls [20 (9, 46)/min] (U=18 132.50, P=0.002). The number of complete blinks in dry eye cases was significantly lower than that in normal controls [6 (3, 24)/min vs. 12 (3,33)/min; U=12 361.00, P=0.016], and the number of partial blinks was significantly higher than that in normal controls [15 (6, 27)/min vs. 3 (0, 10)/min; U=22 839.00, P<0.001]. In complete blinks, the proportion of type A blinks in dry eye patients was significantly higher than that in normal controls [53.7% (2 796/5 177) vs. 39.3% (633/1 698); χ²=101.83, P<0.001]; in partial blinks, the proportion of type Ⅱ blinks in dry eye patients was significantly higher than that in normal controls [36.0%(2 334/6 477) vs. 29.6%(126/426); χ²=6.99, P=0.007]. The average interblink interval of dry eye patients was 1.2 s, which was not significantly different from that of normal controls (1.1 s; U=15 230.00, P=0.093). The eyelid closed phase of dry eye patients was 0.8 s, which was significantly shorter than that of normal controls (1.3 s; U=16 291.50, P=0.006). There were no significant differences in eyelid closing phase, early opening phase and late opening phase between the two groups (all P>0.05). Conclusions: In dry eye patients, the number of partial blinks increased, the number of complete blinks decreased, and the duration of eyelid closed phase shortened significantly. The main blink patterns of dry eye patients included type Ⅱ partial blinks with a reduced closure amplitude and type A complete blinks with a shortened closure time.

[A randomized controlled trial study of immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in different immunization schedules].

Objective: To compare the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine used for the vaccination in public security officers with different immunization schedules. Methods: From January to February, 2021, 405 public security officers in Taiyuan were randomly divided into 3 groups. Two doses of SARS-CoV-2 inactivated vaccine were injected according to the immunization schedule of 0-14 days, 0-21 days or 0-28 days, respectively. The nucleic acid of SARS-CoV-2 was detected by reverse transcription polymerase chain reaction. The neutralizing antibodies to SARS-CoV-2 were tested by microdose cytopathogenic efficiency assay of live virus. The GMT, seroconversion rate of SARS-CoV-2 neutralizing antibody and safety of the vaccine were analyzed for the 3 groups. Results: The seroconversion rate of SARS-CoV-2 neutralizing antibody was 100% in all the 3 groups. The SARS-CoV-2 neutralizing antibody level of 0-21 day group [166.70 (95%CI: 148.30-185.10)] was similar to that of 0-28 day group [179.50 (95%CI: 156.50-202.60)] (P>0.05), significantly higher than that of 0-14 day group [86.08 (95%CI: 72.36-99.80)] (P<0.001). The incidence rates of adverse reaction in the 3 groups were 1.48% (2/135), 0.74% (1/136) and 1.49% (2/134) respectively (P=0.750), all the adverse reactions were mild. Conclusions: The vaccination of inactivated SARS-CoV-2 vaccine with different immunization schedules in public security officers showed good safety and high seroconversion rate, and the GMTs of SARS-CoV-2 neutralizing antibody in 0-21 day group and 0-28 day group were higher than that in 0-14 day group.

[Correlation of inflammatory cells and corneal nerve damage in fungal keratitis on in vivo confocal microscopy].

Objective: To investigate the relationship between inflammatory cell infiltration and nerve damage in patients with fungal keratitis at different degrees of severity. Methods: Retrospective study. A total of 44 consecutive patients (44 eyes) with fungal keratitis in Beijing Tongren Hospital Affiliated to Capital Medical University from January 2017 to December 2019 were selected as the patient group, including 30 males and 14 females, with an age of (58.3±11.5) years old. Twenty healthy people (20 eyes) were included as control group. Slit-lamp microscopy was performed to observe the corneal ulcer. According to the diameter of corneal ulcer, patients were divided into mild, moderate and severe groups. With in vivo confocal microscopic ,the images were obtained from the epithelial layer to the endothelial layer in the central cornea and superior, inferior, nasal and temporal peripheral cornea. Parameters of the maximum density of fungal hyphae, the maximum depth of hyphal infiltration, the density, area and length of dendritic cells (DCs), the nerve density, and the number and curvature of nerve trunks were collected. The Kruskal-Wallis test, Wilcoxon test, and Spearman correlation analysis were used for analyses. Results: On confocal microscopy, many uniform, highly reflective, segment-like structures in parallel or staggered rows were detected in the cornea, with a certain degree of physiological curvature and branching. Quantitative analysis of hyphal density found that the median rating of hyphal density was 2.6 (2.0, 3.0), mainly with medium to large amounts of hyphae. Most hyphae were 100-150 µm in depth (18 cases, 40.9%), and the maximum depth of hyphae in 95.5% (42 cases) of patients was within 300 µm. The hyphal invasion depth in the mild group was 89.4 (50.5, 106.8) µm, in the moderate group was 133 (122, 203) µm, and in the severe group was 135 (74, 151) µm. As the severity of the disease increased, the depth of hyphal invasion increased (F=4.248, P=0.001). Compared with the control group, the DC density [166 (81.3, 212.5) vs. 24.0 (20.8, 32.3) cells/µm2], area [441.3 (291.9, 529.5) vs. 63.7 (47.7, 70.3) µm2] and length [68.3 (39.4, 91.0) vs. 9.2 (7.0, 11.3) µm] increased in patients (W=493.5, 500.0, 500.0; P<0.01). The nerve density [5 398.3 (3 202.7, 6 828.3) vs. 19 171.8 (17 558.8, 21 550.4) µm/mm2; t=-14.448, P<0.01] and the length [692.7 (402.0, 925.1) vs.2 138.4 (1 940.4, 2 597.2) µm; t=-11.930, P<0.01] and number [2.9 (2.0,3.0) vs. 6.0 (5.5,7.0); t=-8.282, P<0.01] of nerve trunks in patients decreased. There were strong negative correlations between the nerve density, the number of nerve trunks, and the DC density (r=-0.555, -0.466; P<0.01). Conclusions: The depth of fungal hypha invasion in patients with fungal keratitis is mainly concentrated in the epithelial layer and superficial stroma layer. The density of mature dendritic cells in the lesion area was negatively correlated with the density and number of subbasal nerves. The density of subbasal nerves decreased as the increase of the severity of the lesion. (Chin J Ophthalmol, 2021, 57: 580-588).

[In vivo confocal microscopic characteristics of limbal stem cell deficiency].

Objective: To investigate the cellular changes and quantitative analysis of basal cell density (BCD) and corneal epithelial thickness (CET) in limbal stem cell deficiency (LSCD) by in vivo confocal microscopy (IVCM). Methods: Prospective case-control study. A total of 35 eyes of 23 patients diagnosed with LSCD and 25 eyes from normal subjects were included in this study. Based on slit-lamp presentation and the global consensus on classification, the LSCD patients were classified into LSCD Ⅰ, LSCD Ⅱ and LSCD Ⅲ. Confocal images of the central cornea, and the superior, inferior, nasal and temporal limbus were inspected by IVCM. Morphologic characteristics of LSCD were summarized. The BCD and CET in all locations were measured. ANVOA or Kruskal-Wallis test was used for analysis when appropriate. A receiver operating characteristic was used to detect the diagnosis efficiency of BCD and CET. Results: The characteristics in the corneal epithelium of LSCD on IVCM included nested corneal epithelial cells, goblet cells with hyper-reflective spots, irregular basal cells and decreasing subbasal nerve density. The mean BCD of the LSCD group was (8 976±1 096) cells/mm2 in the central cornea. Compared to the control group, the BCD in the central cornea, superior, inferior, nasal and temporal limbus decreased by 30.2%, 26.0%, 28.7%, 29.3% and 30.2%, respectively (all P<0.007). The CET in the central cornea was (47.3±8.1) µm. The CET in the central cornea, superior, inferior, nasal and temporal limbus decreased by 27.9%, 23.7%, 20.6%, 26.9% and 23.1%, respectively, compared to the control group (all P<0.007). There was a decline of BCD and CET in more serious LSCD. Additionally, the decline of BCD and CET was shown in the unaffected region. The receiver operating characteristic showed the diagnosis efficiency of BCD in the corneal center and limbus (0.931 and 0.916) was superior to CET (0.853 and 0.817). Conclusions: There was a series of characteristic cellular changes in LSCD on IVCM. Both BCD and CET decreased significantly in LSCD. The BCD had higher diagnostic efficiency for LSCD.(Chin J Ophthalmol, 2020, 56:447-455).

[Identification of pathogens in the vitreous of patients with infectious uveitis by metagenomic sequencing].

Objective: To investigate the role of metagenomic sequencing in the diagnosis of infectious uveitis. Methods: Cross-sectional study. A total of 19 vitreous specimens of patients with suspected infectious uveitis from March 2016 to July 2018 in Beijing Tongren Hospital were collected, including 8 males and 11 females, 19 to 68 years old. There were 10 cases in the right eye, 8 cases in the left eye and 1 case in both eyes. Acute retinal necrosis was clinically diagnosed in 8 patients (9 eyes), and the diagnosis was unknown in 11 patients (11 eyes). About 1 ml of the vitreous fluid was reserved for each specimen, 800 µl for metagenomic sequencing and 200 µl for real-time fluorescence quantitative PCR verification. The TIANamp Micro DNA Kit was used to extract the sample DNA for metagenomic sequencing, and the ultrasonic fragment was broken to 200-300 bp. The BGISEQ-500 platform was used for sequencing. The data with low quality and length less than 35 bp were cleared from the sequencing data to obtain high-quality data. Through biological authentication software, the reference human genome sequence and low complexity were removed from high-quality data. The data obtained were compared with a special microorganism database regarding the percentage of microbial sequences, the number of unique sequences, coverage and sequencing depth, so as to determine positive sequencing parameters, which were classified into bacteria, viruses, fungi and parasites. Real-time fluorescence quantitative PCR was performed to validate the accuracy. Results: A variety of microorganisms were detected by metagenomic sequencing in 19 specimens, including 3 cases of varicella zoster virus, 2 cases of Candida albicans, 1 case of Propionibacterium acnes and 1 case of Haemophilus parainfluenzae. The percentage of microbial sequences was 77.93% （1 794/2 302）, 99.98% （12 843/12 845） and 98.88%（5 733/5 798）, and the number of unique sequences was 1 794, 12 843 and 57 33 in varicella zoster virus cases, respectively. The verification of varicella zoster virus by PCR was consistent with that by metagenomic sequencing. Conclusion: Metagenomic sequencing can be used as an alternative method for laboratory diagnosis of infectious uveitis. (Chin J Ophthalmol, 2020, 56: 519-523).

[Progress of clinical diagnosis and treatment in fungal keratitis].

Fungal keratitis is an important cause of corneal blindness in China. Delayed diagnosis and treatment contribute to its poor prognosis. In recent years, with the advancement of laboratory test techniques, imaging diagnostic techniques and treatment methods, the diagnosis and treatment of fungal keratitis has constantly improved. This article reviews the recent progress of the laboratory and imaging diagnosis, medicine and surgical treatment in fungal keratitis. It may be helpful to promote the application of the new technologies in China and to improve the prognosis of fungal keratitis.(Chin J Ophthalmol, 2020, 56: 631-636).

[Mechanism of transcriptional regulation of Meox1 by transforming growth factor ß (1) and its effect on cell migration of adult human dermal fibroblasts].

Objective: To explore the transcriptional regulation mechanism of transforming growth factor ß(1) (TGF-ß(1)) on Meox1 and its effect on cell migration of adult human dermal fibroblasts (HDF-a). Methods: (1) HDF-a cells were cultured in RPMI 1640 complete medium (hereinafter referred to as routinely cultured). The cells were divided into TGF-ß(1) stimulation group and blank control group. The cells in TGF-ß(1) stimulation group were stimulated with 10 µL TGF-ß(1) in the mass concentration of 1 mg/µL, while the cells in blank control group were stimulated with the equal volume of phosphate buffer solution. After 72 hours in culture, partial cells in both groups were collected for transcriptome sequencing. The genes with differential expression ratio greater than or equal to 2 and P<0.01 between the two groups were selected to perform enrichment analysis and analysis of metabolic pathways of the Kyoto Gene and Genome Encyclopedia with, and the expression value of Meox1 per million transcripts (TPM) was recorded (n=3). Partial cells from the two groups were used to detect the Meox1 mRNA expression by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) (n=3). (2) Cultured HDF-a cells in the logarithmic growth phase (the same growth phase of cells below) were divided into empty plasmid group, Smad2 overexpression (OE) group, Smad3 OE group, and Smad4 OE group, which were transfected respectively with 2 µg empty pcDNA3.1 plasmid and pcDNA3.1 plasmids separately carrying Smad2, Smad3, and Smad4 for 6 hours, and then were routinely cultured for 48 hours. The Meox1 mRNA expression in the transfected cells of each group was detected by real-time fluorescent quantitative RT-PCR (n=3). (3) HDF-a cells were routinely cultured and grouped the same as in experiment (1). After 72 hours in culture, the enrichment of Smad2, Smad3, and Smad4 protein on the Meox1 promoter in the cells of each group was detected by chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) (n=3). (4) HDF-a cells were routinely cultured and divided into negative interference group, small interference RNA (siRNA)-Smad2 group, siRNA-Smad3 group, siRNA-Smad4 group, empty plasmid group, Smad2 OE group, Smad3 OE group, and Smad4 OE group, which were transfected respectively with 50 µmol/L random siRNA, siRNA-Smad2, siRNA-Smad3, siRNA-Smad4, 2 µg empty pcDNA3.1 plasmid and pcDNA3.1 plasmids separately carrying Smad2, Smad3, and Smad4 for 6 hours and then routinely cultured for 48 hours. The enrichment of Smad2, Smad3, and Smad4 protein on the Meox1 promoter in the cells of corresponding group was detected by ChIP-qPCR (n=3). (5) Two batches of HDF-a cells were cultured and divided into negative interference group, siRNA-Meox1 group, empty plasmid group, and Meox1 OE group, which were transfected respectively with 50 µmol/L random siRNA, siRNA-Meox1, 2 µg empty pcDNA3.1 plasmid and pcDNA3.1 plasmid carrying Meox1 for 6 hours and then routinely cultured for 24 hours. One batch of cells were subjected to scratch test with the scratch width being observed 24 hours after scratching and compared with the initial width for scratch wound healing; the other batch of cells were subjected to Transwell assay, in which the migrated cells were counted after being routinely cultured for 24 hours (n=3). (6) From January 2018 to June 2019, 3 hypertrophic scar patients (2 males and 1 female, aged 35-56 years) were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University) 8-12 months after burns. The scar tissue and normal skin tissue along the scar margin resected during surgery were taken, and immunohistochemical staining was performed to observe the distribution of Meox1 protein expression. Data were statistically analyzed with one-way analysis of variance and independent sample t test. Results: (1) After 72 hours in culture, a total of 843 genes were obviously differentially expressed between the two groups, being related to tissue repair, cell migration, inflammatory cell chemotaxis induction process and potential signaling pathways such as tumor necrosis factor, interleukin 17, extracellular matrix receptor. The TPM value of Meox1 in the cells of blank control group was 45.9±1.9, which was significantly lower than 163.1±29.5 of TGF-ß(1) stimulation group (t=6.88, P<0.01) with RNA-sequencing. After 72 hours in culture, the Meox1 mRNA expression levels in the cells of blank control group was 1.00±0.21, which was significantly lower than 11.00±3.61 of TGF-ß(1) stimulation group (t=4.79, P<0.01). (2) After 48 hours in culture, the Meox1 mRNA expression levels in the cells of Smad2 OE group, Smad3 OE group, and Smad4 OE group were 198.70±11.02, 35.47±4.30, 20.27±2.50, respectively, which were significantly higher than 1.03±0.19 of empty plasmid group (t=31.07, 13.80, 13.12, P<0.01). (3) After 72 hours in culture, the enrichment of Smad2, Smad3, and Smad4 protein on the promoter of Meox1 in the cells of TGF-ß(1) stimulation group was significantly higher than that of blank control group respectively (t=12.99, 41.47, 29.10, P<0.01). (4) After 48 hours in culture, the enrichment of Smad2 protein on the promoter of Meox1 in the cells of negative interference group was (0.200 000±0.030 000)%, significantly higher than (0.000 770±0.000 013)% of siRNA-Smad2 group (t=11.67, P<0.01); the enrichment of Smad2 protein on the promoter of Meox1 in the cells of empty plasmid group was (0.200 000±0.040 000)%, significantly lower than (0.700 000±0.090 000)% of Smad2 OE group (t=8.85, P<0.01). The enrichment of Smad3 protein on the promoter of Meox1 in the cells of negative interference group was (0.500 0±0.041 3)%, significantly higher than (0.006 0±0.001 3)% of siRNA-Smad3 group (t=17.79, P<0.01); the enrichment of Smad3 protein on the promoter of Meox1 in the cells of empty plasmid group was (0.470 0±0.080 0)%, which was significantly lower than (1.100 0±0.070 0)% of Smad3 OE group (t=9.93, P<0.01). The enrichment of Smad4 protein on the promoter of Meox1 in the cells of negative interference group was similar to that of siRNA-Smad4 group (t=2.11, P>0.05); the enrichment of Smad4 protein on the promoter of Meox1 in the cells of empty plasmid group was similar to that of Smad4 OE group (t=0.60, P>0.05). (5) Twenty-four hours after scratching, the scratch healing width of cells in siRNA-Meox1 group was narrower than that of negative interference group, while that of Meox1 OE group was wider than that of empty plasmid group. After 24 hours in culture, the number of migration cells in negative interference group was significantly higher than that in siRNA-Meox1 group (t=9.12, P<0.01), and that in empty plasmid group was significantly lower than that in Meox1 OE group (t=8.99, P<0.01). (6) The expression of Meox1 protein in the scar tissue was significantly higher than that in normal skin of patients with hypertrophic scars. Conclusions: TGF-ß(1) transcriptionally regulates Meox1 expression via Smad2/3 in HDF-a cells, thus promoting cell migration.

Synthesis of high quality silver nanowires and their applications in ultrafast photonics.

Silver nanowires are widely used in catalysts, surface enhanced Raman scattering, microelectronic equipment, thin film solar cells, microelectrodes and biosensors for their excellent conductivity, heat transfer, low surface resistance, high transparency and good biocompatibility. However, the optical nonlinearity of silver nanowires has not been further explored yet. In this paper, three silver nanowire samples with different concentrations are produced via a typical hydrothermal method. Their applications to fiber lasers are implemented to prove the optical nonlinearity of silver nanowires for the first time. Based on three kinds of silver nanowires, the mode-locked operation of fiber lasers is successfully realized. Moreover, the fiber laser based on the silver nanowire with a concentration of 2 mg/L demonstrates the shortest pulse duration of 149.3 fs. The experiment not only proves the optical nonlinearity of silver nanowires, but also has some enlightenment on the selection of the optimum concentration of silver nanowires in the consideration of ultrashort pulse output.

Nonlinear optical properties of MoS2-WS2 heterostructure in fiber lasers.

As a saturable absorption material, the heterostructure with the van der Waals structure has been paid much attention in material science. In general, the heterogeneous combination is able to neutralize, or even exceed, the individual material's advantages in some aspects. In this paper, which describes the magnetron sputtering deposition method, the tapered fiber is coated by the MoS2-WS2 heterostructure, and the MoS2-WS2 heterostructure saturable absorber (SA) is fabricated. The modulation depth of the prepared MoS2-WS2 heterostructure SA is measured to be 19.12%. Besides, the theoretical calculations for the band gap and carrier mobility of the MoS2-WS2 heterostructure are provided. By employing the prepared SA, a stable and passively erbium-doped fiber laser is implemented. The generated pulse duration of 154 fs is certified to be the shortest among all fiber lasers based on transition mental dichalcogenides. Results in this paper provide the new direction for the fabrication of ultrafast photon modulation devices.

Methylmercury-l-Cysteine targeting L-type amino acid transporter conjugate cytotoxicity on C6 glioma cells.

Glioma is the most common primary tumor in the brain, accounting for about 40~50% of intracranial primary tumors. Most chemotherapeutic drugs have difficulty in penetrating the blood-brain barrier, and their clinical applications are greatly limited. We evaluated the effects of methylmercury-L-cysteine (MeHg-L-cys) and methylmercury chloride (MMC) on apoptosis of C6 glioma cells. L-type amino acid transporter (LAT1) was used to investigate the targeted transport function and cytotoxicity of MeHg- L-cys in glioma. MeHg-L-cys enhanced the ability of targeting glioma cells and reduced the adverse reactions to normal brain tissues. Therefore, it is significantly important to develop new anti-glioma drugs targeting the blood-brain barrier.

Identifying the molecular targets of Salvia miltiorrhiza (SM) in ox-LDL induced macrophage-derived foam cells based on the integration of metabolomics and network pharmacology.

The identification of network targets is one of the core issues used to reveal the molecular mechanism of traditional Chinese medicine (TCM) and is also the grand challenge of modernization of TCM. In this study, a protein-protein interaction (PPI) network was constructed based on the integration of network pharmacology and metabolomics, which was used as an effective approach to elucidate the relationship between disease pathway proteins and the targets of active small-molecule compounds. The intermolecular transfer process of the drug effect of active compounds in Salvia miltiorrhiza (SM) was revealed and visualized using the PPI network. Our study indicates that PTGS2 was the most important disease protein regulated by the active compounds in SM. Furthermore, the drug targets that can be linked to PTGS2 were regarded as direct targets and the direct targets of the active compounds were identified, respectively. Western blot and co-immuno precipitation (Co-IP) were used to verify the results of the network analysis and reveal the intermolecular transfer process of the effect of Tan IIA. Biological validation revealed that Tan IIA-EDN1-PTGS2-anandamide was a major intervention way of Tan IIA on early atherosclerosis (AS). This work provides a new perspective for the discovery of drug targets and the specific approaches regulated by the active compounds in SM on disease pathway proteins, which is beneficial for understanding the mechanism of action of bioactive compounds and expanding their clinical applications.

Coherent Generation of Photo-Thermo-Acoustic Wave from Graphene Sheets.

Many remarkable properties of graphene are derived from its large energy window for Dirac-like electronic states and have been explored for applications in electronics and photonics. In addition, strong electron-phonon interaction in graphene has led to efficient photo-thermo energy conversions, which has been harnessed for energy applications. By combining the wavelength independent absorption property and the efficient photo-thermo energy conversion, here we report a new type of applications in sound wave generation underlined by a photo-thermo-acoustic energy conversion mechanism. Most significantly, by utilizing ultrafast optical pulses, we demonstrate the ability to control the phase of sound waves generated by the photo-thermal-acoustic process. Our finding paves the way for new types of applications for graphene, such as remote non-contact speakers, optical-switching acoustic devices, etc.

Generation of quasi-monoenergetic electron beams with small normalized divergences angle from a 2 TW laser facility.

We report the generation of a 6 pC, 23 MeV electron bunch with the energy spread ± 3.5% by using 2 TW, 80 fs high contrast laser pulses interacting with helium gas targets. Within the optimized experimental condition, we obtained quasi-monoenergetic electron beam with an ultra-small normalized divergence angle of 92 mrad, which is at least 5 times smaller than the previous LPA-produced bunches. We suggest the significant decrease of the normalized divergence angles is due to smooth transfer from SM-LWFA to LWFA. Since the beam size in LPA is typically small, this observation may explore a simple way to generate ultralow normalized emittance electron bunches by using small-power but high-repetition-rate laser facilities.

Note: A new angle-resolved proton energy spectrometer.

In typical laser-driven proton acceleration experiments Thomson parabola proton spectrometers are used to measure the proton spectra with very small acceptance angle in specific directions. Stacks composed of CR-39 nuclear track detectors, imaging plates, or radiochromic films are used to measure the angular distributions of the proton beams, respectively. In this paper, a new proton spectrometer, which can measure the spectra and angular distributions simultaneously, has been designed. Proton acceleration experiments performed on the Xtreme light III laser system demonstrates that the spectrometer can give angle-resolved spectra with a large acceptance angle. This will be conductive to revealing the acceleration mechanisms, optimization, and applications of laser-driven proton beams.