Overexpressing lipid raft protein STOML2 modulates the tumor microenvironment via NF-κB signaling in colorectal cancer.

Colorectal cancer (CRC) is characterized by a complex tumor inflammatory microenvironment, while angiogenesis and immunosuppression frequently occur concomitantly. However, the exact mechanism that controls angiogenesis and immunosuppression in CRC microenvironment remains unclear. Herein, we found that expression levels of lipid raft protein STOML2 were increased in CRC and were associated with advanced disease stage and poor survival outcomes. Intriguingly, we revealed that STOML2 is essential for CRC tumor inflammatory microenvironment, which induces angiogenesis and facilitates tumor immune escape simultaneously both in vitro and in vivo. Moreover, tumors with STOML2 overexpression showed effective response to anti-angiogenesis treatment and immunotherapy in vivo. Mechanistically, STOML2 regulates CRC proliferation, angiogenesis, and immune escape through activated NF-κB signaling pathway via binding to TRADD protein, resulting in upregulation of CCND1, VEGF, and PD-L1. Furthermore, treatment with NF-κB inhibitor dramatically reversed the ability of proliferation and angiogenesis. Clinically, we also observed a strong positive correlation between STOML2 expression and Ki67, CD31, VEGFC and PD-1 of CD8+T cell expression. Taken together, our results provided novel insights into the role of STOML2 in CRC inflammatory microenvironment, which may present a therapeutic opportunity for CRC.

ß-hydroxybutyrate resensitizes colorectal cancer cells to oxaliplatin by suppressing H3K79 methylation in vitro and in vivo.

BACKGROUND: Ketone ß-hydroxybutyrate (BHB) has been reported to prevent tumor cell proliferation and improve drug resistance. However, the effectiveness of BHB in oxaliplatin (Oxa)-resistant colorectal cancer (CRC) and the underlying mechanism still require further proof. METHODS: CRC-Oxa-resistant strains were established by increasing concentrations of CRC cells to Oxa. CRC-Oxa cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were checked following BHB intervention in vitro. The subcutaneous and metastasis models were established to assess the effects of BHB on the growth and metastasis of CRC-Oxa in vivo. Eight Oxa responders and seven nonresponders with CRC were enrolled in the study. Then, the serum BHB level and H3K79me, H3K27ac, H3K14ac, and H3K9me levels in tissues were detected. DOT1L (H3K79me methyltransferase) gene knockdown or GNE-049 (H3K27ac inhibitor) use was applied to analyze further whether BHB reversed CRC-Oxa resistance via H3K79 demethylation and/or H3K27 deacetylation in vivo and in vitro. RESULTS: Following BHB intervention based on Oxa, the proliferation, migration, invasion, and EMT of CRC-Oxa cells and the growth and metastasis of transplanted tumors in mice were suppressed. Clinical analysis revealed that the differential change in BHB level was associated with drug resistance and was decreased in drug-resistant patient serum. The H3K79me, H3K27ac, and H3K14ac expressions in CRC were negatively correlated with BHB. Furthermore, results indicated that H3K79me inhibition may lead to BHB target deletion, resulting in its inability to function. CONCLUSIONS: ß-hydroxybutyrate resensitized CRC cells to Oxa by suppressing H3K79 methylation in vitro and in vivo.

Fusobacterium nucleatum-derived small extracellular vesicles facilitate tumor growth and metastasis via TLR4 in breast cancer.

BACKGROUND: The contributive role of the microbiome in tumor progression has been reported in multiple studies, such as the Fusobacterium nucleatum (F. nucleatum) in breast cancer (BC). This study aimed to explore the role of F. nucleatum-derived small extracellular vesicles (Fn-EVs) in BC and preliminarily uncover the mechanism. METHODS: Ten normal and 20 cancerous breast tissues were harvested to investigate the gDNA expression of F. nucleatum and its relation with the clinical characteristics of BC patients. After isolating Fn-EVs by ultracentrifugation from F. nucleatum (ATCC 25,586), both MDA-MB-231 and MCF-7 cells were treated with PBS, Fn, or Fn-EVs, followed by being subjected to CCK-8, Edu staining, wound healing, and Transwell assays to detect their cell viability, proliferation, migration, and invasion. TLR4 expression in BC cells with diverse treatments was assessed by western blot. In vivo experiments were performed to verify its role in tumor growth and liver metastasis. RESULTS: The F. nucleatum gDNA levels of breast tissues in BC patients were significantly higher than those in normal subjects, and positively associated with tumor size and metastasis. Fn-EVs administration significantly enhanced the cell viability, proliferation, migration, and invasion of BC cells, while knocking down TLR4 in BC cells could block these effects. Furthermore, in vivo study verified the contributive role of Fn-EVs in tumor growth and metastasis of BC, which might rely on its regulation of TLR4. CONCLUSIONS: Collectively, our results suggest that F. nucleatum plays an important role in BC tumor growth and metastasis by regulating TLR4 through Fn-EVs. Thus, a better understanding of this process may aid in the development of novel therapeutic agents.

Theoretical and experimental investigations on doubly Q-switched Tm:YAP laser with EOM and Sb2Te3 nanosheets.

In this paper, two-dimensional material Sb2Te3 nanosheets are fabricated and the optical nonlinear response is investigated. A laser diode (LD) end-pumped doubly Q-switched Tm:YAP laser with electro-optic modulator (EOM) and Sb2Te3 nanosheets based saturable absorber (SA) is presented. The shortest pulse duration of 38 ns is achieved at the pulse repetition frequency of 100 Hz, corresponding to the highest peak power of 111.8 kW. The double Q-switching technique shows the advantages of pulse duration compression and peak power improvement. The coupled rate equations for the doubly Q-switched laser are developed and the corresponding numerical simulation agrees with the experimental results. We believe that the Sb2Te3 is a potential nanomaterial for the application in optoelectronic field.

Theoretical and experimental investigations on Nb2CTxMXene Q-switched Tm:YAP laser at 2µm for the nonlinear optical response.

In this paper, the Nb2CTxMXene nanosheets were fabricated and the corresponding microstructures were investigated. The nonlinear optical response was illustrated by open aperture Z-scan and I-scan methods. The ground and the excited state absorption cross-sections of 2D Nb2CTxMXene were also investigated. As the saturable absorber (SA), the Nb2CTxMXene was applied in the passively Q-switched Tm:YAP laser. 1.96µs Q-switched pulses with 3.97 W peak power were achieved at the repetition frequency of 80 kHz. Further theoretical model was built by using the coupled rate equations in simulating the dynamic process of the passively Q-switched Tm:YAP laser. The numerical simulation results are fundamentally in agreement with the experimental results, which proves the Nb2CTxMXene can be a good potential nanomaterial for further optoelectronic applications.

Passively Q-switched Tm:CaLu0.1Gd0.9AlO4 laser at 2†µm with hematite nanosheets as the saturable absorber.

We report the first passive Q-switching operation at 1.95 µm utilizing the disordered Tm:CaLu0.1Gd0.9AlO4 (Tm:CLGA) crystal and the hematite (α-Fe2O3) nanosheets as the saturable absorber. The nonlinear saturable absorption properties of the hematite nanosheets were investigated by the conventional Z-scan technology. The modulation depth of 14.3% with the low saturation intensity of 205 kW/cm2 was obtained, indicating that the hematite could be a suitable saturable absorber for the mid-infrared pulse generation. Using the disordered Tm:CLGA crystal as the gain medium, the passive Q-switching operation could be realized with the hematite nanosheets as the saturable absorber, producing the shortest pulse duration of 402 ns with a repetition rate of 76 kHz. The experimental results convinced us that the hematite nanosheets could be of great interest in the optical pulse generation in the mid-infrared region.

Comparison of antimicrobial efficacy of eravacycline and tigecycline against clinical isolates of Streptococcus agalactiae in China: In vitro activity, heteroresistance, and cross-resistance.

AIMS: The aims of this study were to compare the antimicrobial efficacy of Eravacycline (Erava) versus tigecycline (Tig) in vitro against clinical isolates of S. agalactiae from China and further to evaluate the heteroresistance risk and resistance mechanisms of Erava. METHODS: 162 clinical isolates of S. agalactiae were collected retrospectively and the minimal inhibitory concentrations (MICs) of Erava and Tig were determined by agar dilution. Moreover, Tetracycline (Tet) specific resistance genes, genetic mutations in Tet target sites, and sequence types (ST) profiles of clinical isolates of S. agalactiae were investigated with polymerase chain reaction (PCR) experiments. The heteroresistance frequency of Erava and Tig in S. agalactiae was analyzed by population analysis profiling. Furthermore, the resistance mechanisms of both Erava and Tig were investigated in antibiotic-induced resistant S. agalactiae isolates in vitro. RESULTS: The MIC values of Erava and Tig were shown with ≤0.25 mg/L and ≤0.5 mg/L, respectively, against clinical S. agalactiae isolates, including that harboring the Tet-specific resistance genes tet(K), tet(M), or tet(O). The heteroresistance frequency of Tig among the clinical isolates of S. agalactiae was 1.84% (3/162), whereas no positive Erava heteroresistance was found. The enhanced MIC values of both Erava and Tig in the heteroresistance-derivative S. agalactiae clones could be reversed by the efflux pump inhibition experiments. Genetic mutations affecting 30S ribosome units (16SrRNA copies or 30S ribosome protein S10) could result in the cross resistance toward Erava and Tig in the antibiotic-induced resistant S. agalactiae isolates in vitro. CONCLUSIONS: Erava MIC values were nearly half of that of Tig against the clinical isolates of S. agalactiae from China and genetic mutations in the 30S ribosome units of Tet target sites (16SrRNA copies or 30S ribosome protein S10) participated in the resistance evolution of both Erava and Tig under the antibiotic pressure.

Passively Q-switched Er:Lu2O3 laser with MXene material Ti4N3Tx (T = F, O, or OH) as a saturable absorber.

In this Letter, we report a titanium nitride (Ti4N3Tx) passive Q-switched Er:Lu2O3 laser. The homemade two-dimensional Ti4N3Tx saturable absorber shows excellent passive Q-switching performance around a 2.85 µm wavelength region. Under the absorbed pump power of 7.4 W, the passive Q-switching laser yields a maximum output power of 0.778 W at a pulse repetition rate of 113.7 kHz, corresponding to a single pulse energy of 6.84 µJ and peak power of 24.57 W.

Nonlinear optical properties of colloidal CdSe/ZnS quantum dots in PMMA.

The colloidal CdSe/ZnS quantum dots (QDs) in the PMMA polymer film with different QDs concentrations were fabricated. The influence of QDs concentration and excitation pump energy on nonlinear optical (NLO) properties of PMMA capped CdSe/ZnS QDs was investigated by the Z-scan technique with nanosecond laser pulses in the near-infrared spectral band. A large effective nonlinear absorption coefficient (ß eff  âˆ¼ -10-13 esu) due to the saturable absorption was observed. It was found that the appropriate concentration could lead to the reinforcement of NLO effect. In addition, the impact of the excitation energy on the nonlinear refractive index n 2, real and imaginary parts of the third-order nonlinear optical susceptibility was also performed. This study involving the light-matter interactions in the colloidal quantum dots will benefit potential NLO-based applications of optoelectronics, optical modulation and photonics.

Passively Q-switched Er:Lu2O3 laser at 2.8 µm with TiC saturable absorber.

Titanium carbide (TiC) nanosheets of two-dimensional multilayer structure were prepared by the liquid-phase exfoliation method. By using the TiC as a saturable absorber, a stable passively Q-switched Er:Lu2O3 laser at 2.85 µm was realized. Under an absorbed pump power of 7.32 W, the obtained maximum output power was 896 mW with a slope efficiency of 15.6%. The Q-switched pulse duration was measured to be 266.8 ns with repetition rates of 136.9 kHz, corresponding to a peak power of 24.6 W.

GaAs Q-switched Nd:CNGG lasers: operating at 4F3/2 → 2I11/2 and 4F3/2 → 2I13/2 transitions.

The nonlinear absorption properties of GaAs were measured at 1.06 and 1.34 µm by the open aperture Z-scan technique in this paper. Based on a neodymium doped calcium niobium gallium garnet (Nd:CNGG) disordered crystal grown by the Czochralski method, passively Q-switched lasers with the conventional GaAs wafer as the saturable absorber were demonstrated, operating on the transitions of 4F3/2 → 2I11/2 and 4F3/2 → 2I13/2. For the 4F3/2 → 2I11/2 transition, the laser operated at 1063 nm with a pulse duration of 546 ns and a repetition rate of 98.5 kHz. While for the 4F3/2 → 2I13/2 transition operating at 1340 nm, the minimum pulse width was 499.6 ns with the pulse repetition rate of 110.7 kHz.

Optical modulation characteristics of zeolitic imidazolate framework-67 (ZIF-67) in the near infrared regime.

We report the passively Q-switched (PQS) operation in the near infrared (NIR) regime with as-prepared zeolitic imidazolate framework-67 (ZIF-67) as saturable absorbers (SAs) for the first time, to the best of our knowledge. Based on the excellent saturable absorption properties of the as-prepared ZIF-67, passively Q-switched Nd:GdVO4 lasers were achieved operating at 4F3/2→2I11/2 and 4F3/2→2I13/2 transitions. The stable Q-switched laser's pulses with a pulse width of 120 ns at a repetition rate of 566 kHz and a pulse width of 108 ns at a repetition rate of 415 kHz were obtained, corresponding to the transition 4F3/2→2I11/2 at 1 µm and the transition 4F3/2→2I13/2 at 1.3 µm, respectively. The results indicate that the ZIF-67 saturable absorber with the advantages of large modulation depth and high thermal stability is a promising saturable absorber candidate for the NIR pulse generation.

Pulse characteristics from a MoSe2Q-switched Nd:GdVO4 laser at 1.3 µm.

Few-layered ${{\rm MoSe}_2}$MoSe2 nanosheets were prepared by the low-cost, simple liquid-phase exfoliation method. The ${{\rm MoSe}_2}$MoSe2 nanosheets possessed the modulation depth of 16.5% with a saturation intensity of ${0.84}\;{{\rm MW/cm}^2}$0.84MW/cm2 at 1.34 µm, indicating the performance as the saturable absorber. The passively $Q$Q-switched c-cut ${\rm Nd}:{{\rm GdVO}_4}$Nd:GdVO4 laser at 1.34 µm was demonstrated with the few-layered ${{\rm MoSe}_2}$MoSe2 saturable absorber for the first time. The minimum pulse duration of 420 ns at a repetition rate of 238 kHz could be obtained. In order to significantly reduce the pulse duration, dual-loss modulation simultaneously using both ${{\rm V}^{3 + }}:{\rm YAG}$V3+:YAG and ${{\rm MoSe}_2}$MoSe2 saturable absorbers was implemented. The pulse duration was compressed to a 82.4 ns pulse at a repetition rate of 409.3 kHz at the pump power of 10.66 W. The experimental results provide a solid fundament for the short pulse generation with ${{\rm MoSe}_2}$MoSe2 saturable absorber at 1.34 µm.

An optimization model of sewage discharge in an urban wetland based on the multi-objective wolf pack algorithm.

The Longfeng Wetland of Daqing City in China was taken as the research object to determine a reasonable sewage reduction scheme and resolve the pollution of urban wetland ecosystems. First, the main pollutants, including dichromate oxidizability (CODCr), ammonia nitrogen (NH3-N), total phosphorus (TP), and petroleum, were selected as indices. A two-dimensional hydrodynamic and water quality coupling model was established using MIKE 21. An optimal regulation method to improve the water quality of the wetland was then proposed following the numerical simulation method, and a multi-objective optimization model is established. The model establishes two objective functions based on wetland pollutant and water quality requirements. The model's constraints include hydrodynamic conditions and water quality conditions, and it considers the control point of the sewage concentration, sewage outfall processing capacity, depth of treatment, and changes in the water cycle. The wolf pack algorithm is introduced to resolve the multi-objective problem of sewage outfall optimization, and an optimal sewage scheme is obtained. According to the results of the scheme, some measures are proposed to manage the pollutants in urban wetland waters.

Eravacycline activity against clinical S. aureus isolates from China: in vitro activity, MLST profiles and heteroresistance.

BACKGROUND: Mortality rates for patients with Staphylococcus aureus (S. aureus) infections have improved only modestly in recent decades and S. aureus infections remain a major clinical challenge This study investigated the in vitro antimicrobial activity of erevacycline (erava) against clinical S. aureus isolates from China, as well as the heteroresistance frequency of erava and sequence types (STs) represented in the sample. RESULTS: A sample of 328 non-duplicate clinical S. aureus isolates, including 138 methecillin-resistant (MRSA) and 190 methecillin-sensitive (MSSA) isolates, were collected retrospectively in China. Erava exhibited excellent in vitro activity (MIC50 ≤ 0.25 mg/L) against MRSA and MSSA, including isolates harboring Tet specific resistance genes. The frequency of erava heteroresistance in MSSA with erava MICs = 0.5 mg/L was 13.79% (4/29); no MRSA with erava MICs ≤0.5 mg/L exhibited heteroresistance. Heteroresistance- derived clones had no 30S ribosome subunit mutations, but their erava MICs (range, 1-4 mg/L) were suppressed dramatically in the presence of efflux protein inhibitors. CONCLUSIONS: Conclusively, erava exhibited excellent in vitro activity against S. aureus, however hints of erava heteroresistance risk and MIC creep were detected, particularly among MSSA with MICs of 0.5 mg/L.

Nonlinear optical property of a Bi-doped GaAs semiconductor saturable absorber.

By using an Open-Aperture Z-scan technique with both femtosecond and nanosecond laser pulses at 1064nm, the nonlinear optical properties of GaAs and Bi-doped GaAs, including the saturable absorption property and reverse saturable absorption property are systematically measured and analyzed directly in detail. Compared to pure GaAs, Bi-doped GaAs has a lower saturation intensity, wider saturable absorption energy region, lower two-photon absorption coefficient, better saturable absorption response and stronger optical limiting response. The results suggest that the incorporation of Bismuth in GaAs is an effective way of improving the nonlinear optical properties of GaAs, which provide crucial experimental evidence for that the characteristics of the passively Q-switched laser with Bi-doped GaAs saturable absorber is better than pure GaAs.

Continuous wave and ReS2 passively Q-switched Er : SrF2 laser at ∼3 µm.

We report on an efficient Er:SrF2 laser at 2.79 µm. A continuous wave output power of 1.06 W was obtained with a slope efficiency of 41%, significantly exceeding the Stokes efficiency of 35%. Stable Q-switched laser operation was realized by using an ReS2 saturable absorber, generating an average output power of 0.58 W with a pulse duration of 508 ns at a repetition rate of 49 kHz, corresponding to a pulse energy of 12.1 µJ.

Passively Q-switched Ho,Pr:LiLuF4 laser with graphitic carbon nitride nanosheet film.

A few-layer graphitic carbon nitride (g-CN) nanosheet film on an yttrium aluminum garnet substrate was fabricated and employed as saturable absorber for a passively Q-switched Ho,Pr:LiLuF4 laser at 2.95 µm. Under an absorbed pump power of 3.89 W at a pump wavelength of 1.15 µm, a maximum average output power of 101 mW was realized with a pulse duration of 420 ns and a repetition rate of 93 kHz. Even shorter pulse durations of 385 ns were obtained at a reduced output coupler transmission.

Hybrid Q-switched laser with MoS2 saturable absorber and AOM driven sub-nanosecond KTP-OPO.

Two-dimensional (2D) materials, especially transition-metal dichalcogenides, such as molybdenum disulfide (MoS2) and tungsten disulfide (WS2), have attracted great interests due to their exceptional optical properties as saturable absorbers in laser systems. In this work, at first, we presented a diode-pumped passively Q-switched laser with MoS2 saturable absorber (MoS2-SA). At an incident pump power of 6.54 W, a maximum output power of 1.15 W with a minimum pulse duration of 70.6 ns was obtained, which is the shortest pulse duration of diode pumped passively Q-switched laser with MoS2-SA to the best of our knowledge. Then, by using a hybrid Q-switched laser with a MoS2-SA and an acousto-optic modulator (AOM) as pumping fundamental laser, a sub-nanosecond KTiOPO4 (KTP) based intracavity optical parametric oscillation (IOPO) was realized. With an incident pump power of 10.2 W and AOM repetition rate of 10 kHz, the maximum output power of 183 mW with minimum pulse duration of 850 ps was obtained. The experimental results indicate that the IOPO pumped by the hybrid Q-switched laser with AOM and MoS2-SA can generate signal wave with shorter pulse duration than those IOPOs pumped by hybrid Q-switched laser with AOM and Cr4+:YAG or single-walled carbon nanotube saturable absober (SWCNT-SA) or monolayer graphene SA.

Graphitic C3N4 as a new saturable absorber for the mid-infrared spectral range.

The saturable absorption properties of few-layer graphitic carbon nitride (g-C3N4) nanosheets near 3 µm were investigated. A stable Q-switched Er:Lu2O3 laser at 2.84 µm was realized by using a home-made g-C3N4 saturable absorber (SA), generating a pulse duration of 351 ns and an average output power of 1.09 W at a repetition rate of 99 kHz, corresponding to a pulse energy of 11.1 µJ. Our result indicates a great potential of g-C3N4 as a new SA in the 3 µm wavelength range.