Deprivation of methionine inhibits osteosarcoma growth and metastasis via C1orf112-mediated regulation of mitochondrial functions.

Osteosarcoma is a malignant bone tumor that primarily inflicts the youth. It often metastasizes to the lungs after chemotherapy failure, which eventually shortens patients' lives. Thus, there is a dire clinical need to develop a novel therapy to tackle osteosarcoma metastasis. Methionine dependence is a special metabolic characteristic of most malignant tumor cells that may offer a target pathway for such therapy. Herein, we demonstrated that methionine deficiency restricted the growth and metastasis of cultured human osteosarcoma cells. A genetically engineered Salmonella, SGN1, capable of overexpressing an L-methioninase and hydrolyzing methionine led to significant reduction of methionine and S-adenosyl-methionine (SAM) specifically in tumor tissues, drastically restricted the growth and metastasis in subcutaneous xenograft, orthotopic, and tail vein-injected metastatic models, and prolonged the survival of the model animals. SGN1 also sharply suppressed the growth of patient-derived organoid and xenograft. Methionine restriction in the osteosarcoma cells initiated severe mitochondrial dysfunction, as evident in the dysregulated gene expression of respiratory chains, increased mitochondrial ROS generation, reduced ATP production, decreased basal and maximum respiration, and damaged mitochondrial membrane potential. Transcriptomic and molecular analysis revealed the reduction of C1orf112 expression as a primary mechanism underlies methionine deprivation-initiated suppression on the growth and metastasis as well as mitochondrial functions. Collectively, our findings unraveled a molecular linkage between methionine restriction, mitochondrial function, and osteosarcoma growth and metastasis. A pharmacological agent, such as SGN1, that can achieve tumor specific deprivation of methionine may represent a promising modality against the metastasis of osteosarcoma and potentially other types of sarcomas as well.

Refractive Fresnel liquid crystal lenses driven by two voltages.

We propose and demonstrate a high-performance refractive Fresnel liquid crystal (LC) lens with a simple electrode design. The interconnected circular electrodes enable the creation of a parabolic voltage distribution within each Fresnel zone using only two driving voltages. By controlling these voltages within the linear response region of LC material, the desired parabolic phase profile can be achieved. We provide a detailed discussion on the electrode structure design methodology and operating principles of the lens. In our experiments, we constructed a four-zone Fresnel LC lens with a total aperture of 8 mm. The results show that the optical power of the lens can be continuously adjusted from -1.30 D to +1.33 D. Throughout the process of electrically tuning the optical power, the phase distribution within each Fresnel zone maintains a parabolic profile. These results demonstrate the high-performance of the proposed Fresnel LC lens.

True-color and super-resolution imaging using an optical axis shiftable liquid crystal lens.

This study explores the utilization of a liquid crystal lens with a shiftable axis for true-color and super-resolution imaging. By maintaining the optical power and shifting the axis of the liquid crystal lens, precise sub-pixel level shifts are applied to the images formed on the sensor, enabling the construction of true-color and super-resolution images. A comparative analysis with the traditional interpolation-based demosaicing method reveals that true-color imaging not only enhances clarity and effective pixel count, but also significantly reduces occurrences of false color, edge aliasing, and color moiré artifacts.

Method for increasing the utilization rate of birefringence in liquid crystal lenses.

We propose a method to increase the utilization rate of birefringence in liquid crystal (LC) lenses. The method involves designing electrode patterns based on the phase response curve of the LC material, enabling the lenses to operate across a wide range of driving voltages while generating the desired phase profile. The underlying principle of this technique is discussed in detail. Electrode patterns have been successfully designed for positive and negative cylindrical LC lenses. The experimental results demonstrate that the designed lenses generate a parabolic phase profile even when the driving voltage exceeds the linear response region. The utilization rate of LC birefringence for the positive lens has increased from 41.3% to 69.7%, indicating a 68.8% increase from the original. For the negative lens, the utilization rate has risen from 41.8% to 68.7%, representing a 64.4% increase from the original.

Eicosapentaenoic acid metabolites promotes the trans-differentiation of pancreatic α cells to ß cells.

Type 1 diabetes mellitus (T1DM) is characterized by life-threatening absolute insulin deficiency. Although ω-3 polyunsaturated fatty acids (PUFAs) displayed significant anti-hyperglycemic activity, the insulinotropic effects of their metabolites remain unknown. In this study, we took advantage of a transgenic model, mfat-1, that overexpresses an ω-3 desaturase and can convert ω-6 PUFAs to ω-3 PUFAs. Eicosapentaenoic acid (EPA) was sharply elevated in the pancreatic tissues of mfat-1 transgenic mice compared with wild-type (WT) mice. In contrast to the WT mice, the mfat-1 transgenics did not develop overt diabetes and still maintained normal blood glucose levels and insulin secretion following streptozotocin-treatment. Furthermore, under the condition of pancreatic ß-cell damage, co-incubation of the metabolites of EPA produced from the CYP 450 pathway with isolated islets promoted the overexpression of insulin as well as ß-cell specific markers, pdx1 and Nkx6.1 in pancreatic α-cells. Addition of EPA metabolites to the cultured glucagon-positive α-cell lines, a series of pancreatic ß-cell markers were also found significantly elevated. Combined together, these results demonstrated the effects of ω-3 PUFAs and their metabolites on the trans-differentiation from α-cells to ß-cells and its potential usage in the intervention of T1DM.

Liquid crystal lens with a shiftable optical axis.

A liquid crystal (LC) lens with a laterally shiftable optical axis is proposed and demonstrated. The optical axis of the lens can be driven to shift within the lens aperture without compromising its optical properties. The lens is constructed by two glass substrates with identical interdigitated comb-type finger electrodes on the inner surfaces, and they are oriented at 90° with respect to each other. The distribution of voltage difference between two substrates is determined by eight driving voltages, and is controlled within the linear response region of LC materials, thereby generating a parabolic phase profile. In experiments, an LC lens with an LC layer of 50 µm and an aperture of 2 mm × 2 mm is prepared. The interference fringes and focused spots are recorded and analyzed. As a result, the optical axis can be driven to shift precisely in the lens aperture, and the lens maintains its focusing ability. The experimental results are consistent with the theoretical analysis, and good performance of the LC lens is demonstrated.

Novel pharmaceutical salts of cephalexin with organic counterions: structural analysis and properties.

Three novel pharmaceutical salts of cephalexin (CPX) with 2,6-dihydroxybenzoic acid (DHBA), 5-chlorosalicylic acid (CSA) and 5-sulfosalicylic acid (SSA), which were obtained and thoroughly explored by various analytical techniques, were found to be crystallized invariably in hydrated forms. It is the proton transfer from carboxylic or sulfonic counterions to the CPX molecules that results in the salt formation. Crystal structure analyses reveal that the N-H⋯O and O-H⋯O hydrogen bonding interactions among the CPX, acidic guest molecules and water molecules play a crucial role in the packing motifs of crystal stabilization. All the salts exhibit higher solubility compared with the parent drug. These salts offer an alternative way of increasing the number of solid forms for CPX, which facilitates selection of a suitable form in the context of drug formulation development for further repurposing investigations.

Dielectric property and energy storage performance enhancement for iron niobium based tungsten bronze ceramic.

Ceramic dielectric capacitors have attracted increasing interest due to their wide applications in pulsed power electronic systems. Nevertheless, synchronously achieving the high energy storage density, high energy storage efficiency and good thermal stability in dielectric ceramics is still a great challenge. Herein, lead free Sr3SmNa2Fe0.5Nb9.5O30 (SSNFN) ceramic with tetragonal tungsten bronze structure was synthesized and characterized, high total energy storage density (2.1 J cm-3), recoverable energy storage density (1.7 J cm-3), energy storage efficiency (80%) and good thermal stability are obtained simultaneously in the compound, due to the contribution of high maximum polarization (P max), low remanent polarization (P r) and large breakdown strength (E b). The high P max is related with the intrinsic characteristic of Sr4Na2Nb10O30 (SNN) based system, while the small P r and good thermal stability stem from the significantly enhanced relaxor behavior. In addition, the large E b originates from the improved microstructure with fewer defects and decreased average grain size, and the reduction of electrical heterogeneity compared with SNN. The capacitive performance obtained in this work points out the great potential of tungsten bronze ceramic designed for energy storage applications and pave a feasible way to develop novel lead-free dielectric capacitors.

Liquid crystal lens array with positive and negative focal lengths.

A positive-negative tunable liquid crystal lens array is proposed by electrode design. The electrode structure consists of two main units, one of them is used to generate parabolic voltage profile and the other one distributes the voltage homogeneously across the lens aperture. The proposal features the advantages of high-quality performance, simple fabrication process (a single lithographic step), compact design, low voltages and simple driving method. In addition, the lens array can be driven as a square lens array or a rotatable cylindrical lens array. The voltage difference between the electrodes on the inner face of two substrates is controlled within the range that the phase of liquid crystal layer responds linearly to voltage difference, then the phase of the lens array maintains parabolic profile in the whole focus range. In experiments, a lens array with 30 µm liquid crystal layer is fabricated using the designed electrode. The size of the array area is 11 × 11 mm, and the side length of an individual square lens is 1.0 mm. The results show that the phase profile matches with the parabolic profile during focus tuning, and good focusing effect of the positive lens is observed. As a result, a liquid crystal lens array with high-quality performance is experimentally demonstrated, and the experimental results are consistent with the theoretical analyses.

Influence of Early Multidisciplinary Collaboration on Prevention of ICU-Acquired Weakness in Critically Ill Patients.

Objective: This study focused on elucidating the influence of early multidisciplinary collaboration on preventing intensive care unit- (ICU-) acquired weakness (AW) in critically ill patients (CIPs). Methods: Ninety-five CIPs admitted between December 2018 and December 2021 were selected and assigned to the following two groups according to the intervention pattern: the control group (the Con; n = 40) treated with routine early rehabilitation intervention, and the research group (the Res; n = 55) intervened by early multidisciplinary collaborative intervention. The incidence of complications (ICU-AW, deep vein thrombosis (DVT), and pressure ulcers (PSs)) and recovery indices (days of ventilator use, ICU treatment time, and length of hospital stay (LOS)) were recorded. Besides, patients' activity function and quality of life (QoL) were evaluated and compared, among which the former was evaluated by the Barthel Index (BI), ICU Mobility Scale (IMS), and Medical Research Council (MRC) Scale, and the latter was assessed by the World Health Organization Quality of Life Assessment (100-item version) (WHOQOL-100). Results: The data identified statistically a lower incidence of complications (ICU-AW, DVT, and PSs) and shorter time of ventilator use, ICU residence, and LOS in the Res compared with the Con. In addition, BI, IMS, MRC, and WHOQOL-100 scores in the Res elevated statistically after treatment and were higher than those of the Con. Conclusions: Early multidisciplinary collaboration can validly prevent ICU-AW in CIPs, reduce the incidence of DVT and PSs, and promote patients' rehabilitation, mobility, and QoL.

Efficiency of a Novel Light-Emitting Diode (LED) Trap for Trapping Rhyzopertha dominica (Coleoptera: Bostrichidae) in Paddy Rice Storehouses.

The lesser grain borer Rhyzopertha dominica is the major pest of stored paddy rice globally, including in Taiwan. It has strong phototaxis and is good at flying, suitable for developing a light-trapping method to monitor and control it. In the present study, a wavelength of light-emitting diodes (LEDs), i.e., 373 nm, was determined to be the most efficient to trap R. dominica using a dodecagon maze. Accordingly, an LED trap, named the Taiwan Agricultural Research Institute-LED (TARI-LED) trap, was invented, which comprised LEDs of two distinct wavelengths (373 and 408 nm), a wavelength switch, a suction fan, and an insect collector. The trapping efficiency was assessed in a 4-m3 laboratory arena and two paddy rice storehouses. An initial assessment was performed in the laboratory arena and showed that the TARI-LED trap with 373-nm wavelength for R. dominica rapidly increased in the first 30 min, reaching the highest trapping rate (68.5%) after 3 h. In addition, no significant difference was observed between the suction fan turned on or off. The field tests showed that the 373-nm wavelength had the highest effectiveness for trapping R. dominica in the two paddy rice storehouses, and no significant difference was observed in the number of R. dominica trapped by the 373-nm TARI-LED trap or the CDC-UV light trap. In conclusion, our TARI-LED trap 373 nm exhibited high efficiency in trapping R. dominica in paddy rice storehouses. Moreover, a suction fan-free design should benefit long-term and safe use in paddy rice storehouses trapping R. dominica.

Endogenous production of n-3 polyunsaturated fatty acids protects mice from carbon tetrachloride-induced liver fibrosis by regulating mTOR and Bcl-2/Bax signalling pathways.

NEW FINDINGS: What is the central question of this study? What is the protective benefit of n-3 polyunsaturated fatty acids (PUFAs) on liver fibrosis and what are the relevant signalling pathways in a transgenic mouse model overexpressing the mfat-1 enzyme? What is the main finding and its importance? n-3 PUFA elevation strongly prevented carbon tetrachloride (CCl4 )-induced hepatic damage and inhibited the activation of hepatic stellate cells. n-3 PUFAs suppressed CCl4 -induced activation of mTOR, elevated Bcl-2 expression, and reduced Bax level, suggesting that n-3 PUFAs can render strong protective effects against liver fibrosis and point to the potential of mfat-1 gene therapy as a treatment modality. ABSTRACT: Liver fibrosis is a reversible wound healing response with excessive accumulation of extracellular matrix proteins. It is a globally prevalent disease with ultimately severe pathological consequences. However, very few current clinical therapeutic options are available. Nutritional addition of n-3 polyunsaturated fatty acids (PUFAs) can delay and lessen the development of liver fibrosis. Herein, this study examined the protective benefit of n-3 PUFAs on liver fibrosis and the relevant signalling pathways using a transgenic mouse model overexpressing the mfat-1 enzyme that converts n-6 to n-3 PUFAs. Male C57BL/6 wild-type and mfat-1 transgenic mice were administered carbon tetrachloride (CCl4 ) or control corn oil by intraperitoneal injection. Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were subsequently measured. CCl4 -induced hepatic damage and fibrosis were assessed using haematoxylin-eosin and Masson's trichrome staining. Western blot assays were used to detect and quantify fibrosis-related proteins and mechanistic target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) signalling components. The direct effect of docosahexaenoic acid (DHA) on primary hepatic stellate cells (HSCs) was also investigated in a co-culture experiment. n-3 PUFAs, as a result of mfat-1 activity, had a strong protective effect on liver fibrosis. The elevation of ALT and AST induced by CCl4 was significantly lessened in the mfat-1 mice. Histological determination revealed the protective effects of n-3 PUFAs on liver inflammation and collagen deposition. Co-incubation with DHA reduced the expression of profibrogenic factors in the primary HSCs. Moreover, mfat-1 transgenic mice showed significant reduction of proteins that are involved in mTOR and Bcl-2/Bax signalling pathways. Collectively, these results suggest that n-3 PUFA elevation strongly prevents CCl4 -induced hepatic damage by directly inhibiting the activation of HSCs and regulating the basal activity of the mTOR and Bcl-2/Bax signalling pathways. Gene therapy applying mfat-1 and elevating n-3 PUFAs represents a promising treatment strategy to prevent liver fibrosis.

Design of a narrow-bandwidth refractive index sensor based on a cascaded few-mode long-period fiber grating.

This work presents a design of a cascaded few-mode long-period fiber grating (FM-CLPFG) refractive index sensor with a narrow bandwidth that is based on the feature of narrow-bandwidth loss peak of few-mode long-period fiber grating (FM-LPFG) and that further reduces the loss-peak bandwidth of a single FM-LPFG by cascading. On the basis of the coupled-mode theory of FM-LPFG, the mutual interference between the loss peaks of each mode is reduced, and the loss-peak coupling intensity is ensured by selecting the appropriate grating period and grating length. Furthermore, the influence of the cascaded fiber length and the number of cascaded grating segments on the loss-peak bandwidth are analyzed. Based on the above designed parameters, the FM-CLPFG narrow-bandwidth sensor with a bandwidth of about 1 nm is designed. The results show that the sensitivity of this sensor is available to 2410 nm/RIU, with the surrounding refractive index changing from 1.4445 to 1.4475.

Effect of imidacloprid exposure on life history traits in the agricultural generalist predator Paederus beetle: Lack of fitness cost but strong hormetic effect and skewed sex ratio.

A trade-off between life history traits in the evolution of insecticide resistance is common in insects because energy acquisition is mainly channeled for detoxification enzyme production. In addition, sublethal exposure to insecticides may have an effect on the physiology and behaviors of surviving insects. Similar to other agricultural pests, pesticide use may have led to insecticide resistance in populations of Paederus fuscipes Curtis. In this study, we determined the median lethal time of 10 field-collected strains in Taiwan for three insecticides that are commonly employed to manage agricultural pests. We determined that the susceptibility of these strains to cyhalothrin and fenitrothion were similar, with resistance ratios (RRs) ranging from 1 to 4; however, significantly different to imidacloprid (RRs: 1-16). The effect of imidacloprid resistance on the life history traits studied of Paederus beetles was limited; only a prolonged egg incubation period, and adult longevity decreased as imidacloprid resistance increased. Regarding sublethal exposure to imidacloprid, adult sex ratios were female biased in most combinations, though nonsignificant. The quality of offspring, particularly the length of eggs significantly decreased. In addition, a hormetic effect was apparent when the individual was exposed to LT25 and LT50; mean fecundity per female increased from 12.80 ±â€¯8.95 (±â€¯standard error [SE]) to 42.70 ±â€¯13.77 eggs compared with that of the control (7.10 ±â€¯1.32). However, the hormetic effect was inconsistent among the tested strains, possibly because of the difference in insecticide resistance levels given that reproductive compensation was absent among the resistant population.