Targeting mitochondrial one-carbon enzyme MTHFD2 together with pemetrexed confers therapeutic advantages in lung adenocarcinoma.

Metabolic remodeling is the fundamental molecular feature of malignant tumors. Cancer cells require sufficient energy supplies supporting their high proliferative rate. MTHFD2, a mitochondrial one-carbon metabolic enzyme, is dysregulated in several malignancies and may serve as a promising therapeutic candidate in cancer treatment. Here, our data confirmed that MTHFD2 gene and protein was upregulated in the cancerous tissues of LUAD patients and was correlated with a poor survival in LUAD. MTHFD2 was involved in lung cancer cell proliferation, migration, and apoptosis by mediating its downstream molecules, such as DNA helicases (MCM4 and MCM7), as well as ZEB1, Vimentin and SNAI1, which contributed to tumor cell growth and epithelial-to-mesenchymal transition (EMT) process. Moreover, we identified that miRNA-99a-3p appeared to be an upstream mediator directly regulating MTHFD2 and MCM4 expression. Moreover, specific inhibition of MTHFD2 functions by siRNA or a chemical compound, improved anti-tumor sensitivities induced by pemetrexed in LUAD. Taken together, our study revealed the underlying molecular mechanisms of MTHFD2 in regulating cell proliferation and identified a novel therapeutic strategy improving the treatment efficacies in LUAD.

Diagnostic and prognostic value of MATN3 expression in gastric carcinoma: TCGA database mining.

BACKGROUNDS: Globally, the high morbidity and mortality of gastric carcinoma (GC) have been one of the great challenges facing humanity. However, the early diagnosis of GC is still unknown. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. Previous studies have reported a correlation between the expression of MATN3 and bone disease. However, the role of MATN3 in GC has not been reported in depth, which can have a possible far-reaching implication for GC. METHODS: We explored the diagnostic and prognostic value and pathway enrichment of MATN3 expression in GC. Limma package conducted by R was used to analysis the difference expression data of MATN3 from The Cancer Genome Atlas (TCGA). The receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic value of MATN3 expression. univariate and multivariate analysis were used to assess the prognostic value of MATN3, and gene set enrichment analysis (GSEA) to identify the enriched signaling pathways. RESULTS: MATN3 was found to be significantly higher in GC tissue samples. GC patients with high MATN3 expression had poor prognosis. Then, GSEA showed that the gene sets were correlated with signaling pathways including ECM receptor interaction, hypertrophic cardiomyopathy (HCM), and glycosaminoglycan biosynthesis chondroitin sulfate, among others. CONCLUSIONS: The study suggests that MATN3 can serve as a potential diagnostic and prognostic biomarker for GC.

Nonradiative Triplet Loss Suppressed in Organic Photovoltaic Blends with Fluoridated Nonfullerene Acceptors.

In organic photovoltaic (OPV) blends, photogenerated excitons dissociate into charge-separated electrons and holes at donor/acceptor interfaces. The bimolecular recombination of spin-uncorrelated electrons and holes may cause nonradiative loss by forming the low-lying triplet excited states (T1) via the intermediate charge-transfer triplet states. Here, we show that such a spin-related loss channel can be suppressed in the OPV blends with fluorinated nonfullerene acceptors (NFAs). By combining ultrafast optical spectroscopy and triplet sensitization measurements, the T1 states at the acceptors have been observed to generate from the charge-separated electrons and holes in the OPV blends with a same polymer donor and two sets of NFAs with and without fluorination. The triplet formation is largely suppressed and the lifetime of charge carrier is markedly prolonged in the blends with fluorinated NFAs. The fluorination effect on the charge dynamics can be ascribed to the modified energy alignment between the triplet excited states of charge-transfer and locally excited characters as supported by quantum chemical computation. Our findings explain the mechanism responsible for the improved photocurrent generation in the OPV blends with fluorinated NFAs, suggesting that manipulating the energy landscape of triplet excited states is a promising strategy for further optimizing OPV devices.

Hole Transfer Promoted by a Viscosity Additive in an All-Polymer Photovoltaic Blend.

Viscosity modifiers are widely applied to improve the mechanical compliance of organic optoelectronic devices. However, the effect of the viscosity additives on the charge dynamics remains poorly understood. Here, we report the observation of markedly different effects of a high-viscosity polymeric additive on the electron- and hole-transfer dynamics in all-polymer organic photovoltaic blends. By using ultrafast transient absorption spectroscopy, we determine that hole transfer from charge-transfer excitations in the acceptor is markedly promoted while the electron transfer from local excitations in the donor remains nearly unchanged upon introduction of viscosity additives into the blends. We argue that the modification of dielectric screening is the mechanism underlying the effect of the additive on the charge dynamics. This finding suggests a new strategy for designing high-performance flexible organic photovoltaic devices by manipulating the dielectric environment.

A Comparative Study on Hole Transfer Inversely Correlated with Driving Force in Two Non-Fullerene Organic Solar Cells.

We report a faster rate of hole transfer under a smaller ΔHOMO in a comparative study of two group organic solar cells (OSCs) consisting of IT-4F as an acceptor and PBDBT and PBDBT-SF as donors. In the OSCs based on PBDBT-SF:IT-4F, a higher short-circuit current (JSC) was observed with a ΔHOMO of 0.31 eV compared to a lower JSC in PBDBT:IT-4F OSCs with a larger ΔHOMO (0.45 eV). Intensive investigation indicates that the rate of transfer of a hole from IT-4F to PBDBT-SF or PBDBT is inversely proportional to the ΔHOMO between IT-4F and donors. The larger JSC in the PBDBT-SF:IT-4F device is attributed to a synergy of faster hole transfer, slower recombination, and rapid charge extraction enabled by desired morphology and balanced charge carrier mobilities with PBDBT-SF, suggesting that under a sufficiently high ΔHOMO, comprehensive considerations of the transport, film morphology, and energy levels are needed when designing new materials for high-performance OSCs.

Highly Flexible and Efficient All-Polymer Solar Cells with High-Viscosity Processing Polymer Additive toward Potential of Stretchable Devices.

Considering the potential applications of all-polymer solar cells (all-PSCs) as wearable power generators, there is an urgent need to develop photoactive layers that possess intrinsic mechanical endurance, while maintaining a high power-conversion efficiency (PCE).Herein a strategy is demonstrated to simultaneously control the intercalation behavior and nanocrystallite size in the polymer-polymer blend by using a newly developed, high-viscosity polymeric additive, poly(dimethylsiloxane-co-methyl phenethylsiloxane) (PDPS), into the TQ-F:N2200 all-PSC matrix. A mechanically robust 10wt% PDPS blend film with a great toughness was obtained. Our results provide a feasible route for producing high-performance ductile all-PSCs, which can potentially be used to realize stretchable all-PSCs as a linchpin of next-generation electronics.

The Scarier the Better: Maximizing Exposure Therapy Outcomes for Spider Fear.

BACKGROUND: While exposure therapy effectively reduces anxiety associated with specific phobias, not all individuals respond to treatment and some will experience a return of fear after treatment ceases. AIMS: This study aimed to test the potential benefit of increasing the intensity of exposure therapy by adding an extra step that challenged uncontrollability (Step 15: allowing a spider to walk freely over one's body) to the standard fear hierarchy. METHOD: Fifty-one participants who had a severe fear of spiders completed two 60-min exposure sessions 1 week apart in a context that was either the same or different from the baseline and follow-up assessment context. Participants were categorized into groups based on the last hierarchy step they completed during treatment (Step 14 or fewer, or Step 15). RESULTS: Those who completed Step 15 had greater reductions in fear and beliefs about the probability of harm from baseline to post-treatment than those who completed fewer steps. Although completing Step 15 did not prevent fear from returning after a context change, it allowed people to maintain their ability to tolerate their fear, which earlier steps did not. Despite some fear returning after a context change, individuals who completed Step 15 tended to report greater reductions in fear from baseline to the follow-up assessment than participants who completed 14 or fewer steps. CONCLUSIONS: Overall, these results suggest that more intensive exposure that directly challenges harm beliefs may lead to greater changes in fear and fear beliefs than less intensive exposure.

Side Chain Engineering on Medium Bandgap Copolymers to Suppress Triplet Formation for High-Efficiency Polymer Solar Cells.

Suppression of carrier recombination is critically important in realizing high-efficiency polymer solar cells. Herein, it is demonstrated difluoro-substitution of thiophene conjugated side chain on donor polymer can suppress triplet formation for reducing carrier recombination. A new medium bandgap 2D-conjugated D-A copolymer J91 is designed and synthesized with bi(alkyl-difluorothienyl)-benzodithiophene as donor unit and fluorobenzotriazole as acceptor unit, for taking the advantages of the synergistic fluorination on the backbone and thiophene side chain. J91 demonstrates enhanced absorption, low-lying highest occupied molecular orbital energy level, and higher hole mobility, in comparison with its control polymer J52 without fluorination on the thiophene side chains. The transient absorption spectra indicate that J91 can suppress the triplet formation in its blend film with n-type organic semiconductor acceptor m-ITIC (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(3-hexylphenyl)-dithieno[2,3-d:2,3'-d']-s-indaceno[1,2-b:5,6-b']-dithiophene). With these favorable properties, a higher power conversion efficiency of 11.63% with high VOC of 0.984 V and high JSC of 18.03 mA cm-2 is obtained for the polymer solar cells based on J91/m-ITIC with thermal annealing. The improved photovoltaic performance by thermal annealing is explained from the morphology change upon thermal annealing as revealed by photoinduced force microscopy. The results indicate that side chain engineering can provide a new solution to suppress carrier recombination toward high efficiency, thus deserves further attention.

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.

Diode-end-pumped Ho, Pr:LiLuF4 bulk laser at 2.95 µm.

A diode-end-pumped continuous-wave (CW) and passively Q-switched Ho, Pr:LiLuF4 (Ho, Pr:LLF) laser operation at 2.95 µm was demonstrated for the first time, to the best of our knowledge. The maximum CW output power was 172 mW. By using a monolayer graphene as the saturable absorber, the passively Q-switched operation was realized, in which regimes with the highest output power, the shortest pulse duration, and the maximum repetition rate were determined to be 88 mW, 937.5 ns, and 55.7 kHz, respectively. The laser beam quality factor M2 at the maximum CW output power were measured to be Mx2=1.48 and My2=1.47.

Composite Nd:YAG-SiC-bonding laser with orthogonal-linear-polarization output.

We report a multiple-gain-element Nd:YAG laser where the gain media (three pieces of slab crystal) are alternately bonded to two optical quality 4H-SiC wafers. Such composite gain configuration can efficiently remove waste heat from the gain medium, preventing thermal lensing and heat-induced birefringence/distortion under high power laser operation. Through near Brewster's angles incidence designing and polarization discrimination, two orthogonally linearly polarized (P and S polarized) laser beams are generated simultaneously from different parts of the same system. Based on a T = 3% output coupler, this continuous wave laser produces maximum power of 5.34 W (0.83 W) with a slope efficiency of 21.1% (3.6%) for the S (P) polarized laser beam. At the 5-W level, the S polarized beam has a beam quality of M2~1.2. The wavelengths of these two perpendicularly polarized laser beams differ about 0.6 nm (1063.7 and 1064.3 nm). Polarized output behavior dependent on the output-coupler transmission is also studied, and it is found that increasing the transmission leads to steady growth of the P polarized laser beam; when a T = 1.3% output coupler is adopted, more than 99% of the output is the S polarized beam. The highest total output power is 6.75 W obtained with the T = 1.3% output coupler, corresponding to slope efficiency of 25.7%. This composite laser scheme, bonding multiple gain media with high-thermal-conductivity materials, opens a new avenue for high-power high-beam-quality solid-state lasers with multiple-polarization output beams.

Developing carbon-nitride nanosheets for mode-locking ytterbium fiber lasers.

Graphitic carbon nitrides (CNs) have appeared as a new type of photocatalyst for water splitting, but their optical properties (e.g., nonlinear absorption), to the best of our knowledge, have been seldom explored. Here, we report the saturable absorption effects of novel 2D carbon-nitride-type nanosheets and use them as saturable absorbers to passively mode-lock Yb-doped fiber lasers. The CN-based saturable absorber is manufactured by solution coating of 2D CN nanosheets on a gold mirror and has a modulation depth and saturation intensity of 12.5% and 7.5 MW/cm2, respectively. Two different output couplers are employed to construct ring laser cavities. With the 10% coupler, the mode-locked fiber laser produces pulses with duration of ∼310 ps, average power of 1.24 mW, and repetition rate of 7.65 MHz. The laser spectrum is centered at 1066 nm with a bandwidth of 2.4 nm. Increasing the coupling ratio to 50% improves the output power to 2.58 mW but at the same time broadens the pulse width to 420 ps. As a new kind of 2D material with strong saturable absorption, CN nanosheets will open a new way for novel photonic and optoelectronic devices.

Precise manipulation on spike train of uneven duration or delay pulses with a time grating system.

In this paper, we proposed a time grating system to achieve spike train of uneven duration or delay (STUD) pulses, and theoretically study their features under various modulation conditions. This time grating scheme, which is a temporal analogy of spatial grating, introduces great degree of freedom for controlling the output pulse characteristics (pulse width, repetition rate, pulse shape, etc.) through simply tuning the electronics elements and the programmable phase modulation function. The narrowest pulse width is highly determined by the modulation parameters and the branch number N, and the numerically obtained value is around tens of femtoseconds in the current case. When super-Gaussian pulses are modulated with an optimized and modified trapezoidal function, the pulse rising/falling edge can be greatly compressed to form a clean nearly-square wave (with edges less than 10 fs). STUD pulses generated with this time grating system have high-degree controllability and are very beneficial for suppressing parametric instabilities in laser driven inertial confinement fusion.

Developing high-power hybrid resonant gain-switched thulium fiber lasers.

In this paper, we propose hybrid-pumped resonant gain-switched thulium fiber lasers to realize high-average-power and high-pulse-energy 2-µm laser emissions. Based on numerical simulation, laser dynamics (pulse peak power, pulse energy, pulse duration, etc.) of this kind of laser system are investigated in detail. By taking advantages of the 793 nm continuous wave pump and the 1900 nm pulsed pump, performance of the laser emission can be significantly improved, with the highest average power of 28 W, peak power of 3.5 kW, pulse energy of 281 µJ, and narrowest pulse duration of 92 ns, all of which can be further optimized through designing the cavity parameters and the pumping circumstance. Compared with the pump pulses, two times improvement in pulse energy and average power has been achieved. This hybrid resonant gain-switched system has an all-fiber configuration and high efficiency (low heat load), and can be steadily extended into the cladding pump scheme, thus paving a new way to realize high power (>100 W average power) and high pulse energy (>1 mJ) 2 µm thulium fiber lasers.

Developing high energy dissipative soliton fiber lasers at 2 micron.

While the recent discovered new mode-locking mechanism--dissipative soliton--has successfully improved the pulse energy of 1 µm and 1.5 µm fiber lasers to tens of nanojoules, it is still hard to scale the pulse energy at 2 µm due to the anomalous dispersion of the gain fiber. After analyzing the intracavity pulse dynamics, we propose that the gain fiber should be condensed to short lengths in order to generate high energy pulse at 2 µm. Numerical simulation predicts the existence of stable 2 µm dissipative soliton solutions with pulse energy over 10 nJ, comparable to that achieved in the 1 µm and 1.5 µm regimes. Experimental operation confirms the validity of the proposal. These results will advance our understanding of mode-locked fiber lasers at different wavelengths and lay an important step in achieving high energy ultrafast laser pulses from anomalous dispersion gain media.

High power tandem-pumped thulium-doped fiber laser.

We propose a cascaded tandem pumping technique and show its high power and high efficient operation in the 2-µm wavelength region, opening up a new way to scale the output power of the 2-µm fiber laser to new levels (e.g. 10 kW). Using a 1942 nm Tm(3+) fiber laser as the pump source with the co- (counter-) propagating configuration, the 2020 nm Tm(3+) fiber laser generates 34.68 W (35.15W) of output power with 84.4% (86.3%) optical-to-optical efficiency and 91.7% (92.4%) slope efficiency, with respect to launched pump power. It provides the highest slope efficiency reported for 2-µm Tm(3+)-doped fiber lasers, and the highest output power for all-fiber tandem-pumped 2-µm fiber oscillators. This system fulfills the complete structure of the proposed cascaded tandem pumping technique in the 2-µm wavelength region (~1900 nm → ~1940 nm → ~2020 nm). Numerical analysis is also carried out to show the power scaling capability and efficiency of the cascaded tandem pumping technique.

A random Q-switched fiber laser.

Extensive studies have been performed on random lasers in which multiple-scattering feedback is used to generate coherent emission. Q-switching and mode-locking are well-known routes for achieving high peak power output in conventional lasers. However, in random lasers, the ubiquitous random cavities that are formed by multiple scattering inhibit energy storage, making Q-switching impossible. In this paper, widespread Rayleigh scattering arising from the intrinsic micro-scale refractive-index irregularities of fiber cores is used to form random cavities along the fiber. The Q-factor of the cavity is rapidly increased by stimulated Brillouin scattering just after the spontaneous emission is enhanced by random cavity resonances, resulting in random Q-switched pulses with high brightness and high peak power. This report is the first observation of high-brightness random Q-switched laser emission and is expected to stimulate new areas of scientific research and applications, including encryption, remote three-dimensional random imaging and the simulation of stellar lasing.

High signal-to-noise ratio, single-frequency 2 µm Brillouin fiber laser.

A high optical signal-to-noise ratio (OSNR) single-frequency 2 µm Brillouin fiber laser (BFL) with watt-level output and high transfer efficiency is demonstrated for the first time to the best of our knowledge. The Brillouin pump is constructed with a two-stage thulium-doped fiber amplifier (TDFA) seeded by a 2 µm laser diode, providing 4.02 W average power with 1 MHz linewidth. Using an optimized length of 14 m for the Brillouin ring cavity, the BFL works stably in single-mode region with 8 kHz linewidth because of the linewidth narrowing effect. The transfer efficiency is 51% with 1.08 W output power and 62 dB OSNR for 3.22 W pump power.

Efficient dual-wavelength Nd:LuLiF4 laser.

We report an efficient continuous-wave (CW) and passively Q-switched dual-wavelength Nd:LuLiF4 laser at 1314 and 1321 nm for the first time. Maximum CW output power of 6.08 W is obtained, giving an optical-to-optical conversion efficiency of 30.2% and a slope efficiency of 32.1%. Even using high doping V3+:YAG as the saturable absorber to passively Q-switch the laser, stable dual-wavelength operation remains. Maximum pulse energy extracted from the resonator is 108.7 µJ at 17.2 kHz pulse-repetition rate, and maximum peak power is 885 W.