Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.

Supercapacitor Performance of Sulfonyldibenzene Derivative-Functionalized Graphene Aerogel.

3D aerogels incorporating functionalized reduced graphene oxide (SUL/rGO) were prepared as a hydrothermal method utilizing graphene oxide (GO) and a sulfonyldibenzene derivative (SUL) as raw materials. The aromatic compound SUL, which contains hydroxyl and sulfonyl groups, was bonded to reduced graphene oxide (rGO) through π-π connections. The obtained composite material exhibited porosity within its structure with improved hydrophilicity, along with excellent electrochemical characteristics. This improvement was ascribed to the specific rGO structure, as well as the pseudocapacitance inherent in SUL, both of which synergistically contribute to improvement in the characteristics of the prepared electrode materials. Also, an analysis was performed employing density functional theory from which the density of states and adsorption energy of SUL on the surface of rGO were computed to further investigate the charge storage process within the prepared composite. The prepared SUL/rGO-2 electrode exhibited the highest specific capacitance value of 388 F/g at a current density equal to 1 A/g. The constructed symmetrical supercapacitor, SUL/rGO-2//SUL/rGO-2, attained an energy density value of 14.55 Wh/kg at a power density equal to 350 W/kg with an exceptional galvanostatic charge-discharge (GCD) cyclic stability equal to 91% following 10 000 cycles. Therefore, this review presents a novel functionalized graphene-based material incorporating hydroxyl and sulfonyl groups, which holds promise in future energy storage applications.

Effects of Plyometric Training on Physical Fitness Attributes in Handball Players: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to examine the effects of plyometric training on physical fitness attributes in handball players. A systematic literature search across PubMed, SCOPUS, SPORTDiscus, and Web of Science identified 20 studies with 563 players. Plyometric training showed significant medium-to-large effects on various attributes: countermovement jump with arms (ES = 1.84), countermovement jump (ES = 1.33), squat jump (ES = 1.17), and horizontal jump (ES = 0.83), ≤ 10-m linear sprint time (ES = -1.12), > 10-m linear sprint time (ES = -1.46), repeated sprint ability with change-of-direction time (ES = -1.53), agility (ES = -1.60), maximal strength (ES = 0.52), and force-velocity (muscle power) (ES = 1.13). No significant impact on balance was found. Subgroup analysis indicated more pronounced agility improvements in players ≤ 66.6 kg compared to > 66.6 kg (ES = -1.93 vs. -0.23, p = 0.014). Additionally, greater improvements were observed in linear sprint and repeat sprint ability when comparing training durations of > 8 weeks with those ≤ 8 weeks (ES = -2.30 to -2.89 vs. ES = -0.92 to -0.97). In conclusion, plyometric training effectively improves various physical fitness attributes, including jump performance, linear sprint ability, maximal strength, muscle power and agility.

Electrolyte Engineering on Performance Enhancement of NiCo2 S4 Anode for Sodium Storage.

NiCo2 S4 is an attractive anode for sodium-ion batteries (SIBs) due to its high capacity and excellent redox reversibility. Practical deployment of NiCo2 S4 electrode in SIBs, however, is still hindered by the inferior capacity and unsatisfactory cycling performance, which result from the mismatch between the electrolyte chemistry and electrode. Herein, a functional electrolyte containing 1.0 m NaCF3 SO3 in diethylene glycol dimethyl ether (DEGDME) (1.0 m NaCF3 SO3 -DEGDME) is developed, which can be readily used for NiCo2 S4 anode with high initial coulomb efficiency (96.2%), enhanced cycling performance, and boosted capacities (341.7 mA h g-1 after 250 continuous cycles at the current density of 200 mA g-1 ). The electrochemical tests and related phase characterization combined with density functional theory (DFT) calculation indicate the ether-based electrolyte is more suitable for the NiCo2 S4 anode in SIBs due to the formation of a stable electrode-electrolyte interface. Additionally, the importance of the voltage window is also demonstrated to further optimize the electrochemical performance of the NiCo2 S4 electrode. The formation of sulfide intermediates during charging and discharging is predicted by combining DFT and verified by in situ XRD and HRTEM. The findings indicate that electrolyte engineering would be an effective way of performance enhancement for sulfides in practical SIBs.

Evaluation of the efficacy of ureteroscopic lithotripsy for proximal impacted ureter stones based on a new scoring standard: a bicentric matched-pair analysis.

OBJECTIVE: To evaluate the clinical efficacy of ureteroscopic lithotripsy (URSL) in the treatment of proximal impacted ureter stones (PIUS) based on a new scoring standard in two medical centers. METHODS: The data of 45 patients with Complicated PIUS (total stone score ≥ 3) and 350 with Simple PIUS (total stone score < 3) who underwent URSL were collected in this retrospective study between January 2015 and June 2022. The definition and scoring standards for preoperative high-risk factors associated with stones included whether the diameter of the stone was > 2 cm, stone density was > 1000 HU, there was a history of lithotripsy, the degree of hydronephrosis was greater than moderate, and there was an infection. Scores for stones were then assigned (yes = 1, no = 0), and the Complicated stone case was defined as a total stone score ≥ 3; the Simple stone case was defined as a total stone score < 3. During the same period, 45 patients were selected from the patients with Simple stone cases as the control group, matched at a 1:1 ratio to index Complicated stone cases with regard to age, sex, and BMI. Perioperative data were compared between the two groups. RESULTS: All 90 operations were successfully completed. Compared to the Simple cases group, the surgical duration of the Complicated group was significantly longer (59.69 ± 28.06 min vs. 73.46 ± 27.12 min, p < 0.05), and stone-free rate (SFR) was significantly lower (88.89 vs. 68.9%, p < 0.05). There was a significant difference in complication rate between the two groups regarding Clavien grade I, II, or III complications (20.0% in Complicated cases group vs. 8.9% in Simple cases group, p = 0.037). As for the length of the hospital stay and the total treatment cost, the two groups have no difference. CONCLUSION: For Simple stone cases, URSL had a better SFR and higher surgical efficacy, whereas complicated stone cases had a high complication rate and long operation time. Thus, we suggest that URSL is the preferred choice for Simple stone cases rather than complicated stone cases.

Structural stability design of an optical mirror mount adjustment mechanism.

The stability of beam pointing in a laser system depends on the consistency of the optical mirror mount. Typically, a locking mechanism is used to secure the adjustment mechanism after beam alignment, ensuring the mount's stability. However, this process can introduce errors, causing a drift in the optical path. To mitigate this issue, in this study, an interference fit adjustment screw was designed. This development enables the mechanism to self-lock after beam alignment, thereby preventing optical path drift and enhancing overall stability. Specifically, 14 long-term thermal shock stability tests, each lasting 2500 min, were conducted to validate the proposed design. The experimental results showed that the thermal drift of the interference fit adjustment screw was reduced by 47.16%, thermal shift was reduced by 79.59%, and the long-term stability improved by at least 48.67%.

Maximizing Heterogeneous Server Utilization with Limited Availability Times for Divisible Loads Scheduling on Networked Systems.

Most of the available divisible-load scheduling models assume that all servers in networked systems are idle before workloads arrive and that they can remain available online during workload computation. In fact, this assumption is not always valid. Different servers on networked systems may have heterogenous available times. If we ignore the availability constraints when dividing and distributing workloads among servers, some servers may not be able to start processing their assigned load fractions or deliver them on time. In view of this, we propose a new multi-installment scheduling model based on server availability time constraints. To solve this problem, we design an efficient heuristic algorithm consisting of a repair strategy and a local search strategy, by which an optimal load partitioning scheme is derived. The repair strategy guarantees time constraints, while the local search strategy achieves optimality. We evaluate the performance via rigorous simulation experiments and our results show that the proposed algorithm is suitable for solving large-scale scheduling problems employing heterogeneous servers with arbitrary available times. The proposed algorithm is shown to be superior to the existing algorithm in terms of achieving a shorter makespan of workloads.

Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility.

The dynein adaptor Drosophila Bicaudal D (BicD) is auto-inhibited and activates dynein motility only after cargo is bound, but the underlying mechanism is elusive. In contrast, we show that the full-length BicD/F684I mutant activates dynein processivity even in the absence of cargo. Our X-ray structure of the C-terminal domain of the BicD/F684I mutant reveals a coiled-coil registry shift; in the N-terminal region, the two helices of the homodimer are aligned, whereas they are vertically shifted in the wild-type. One chain is partially disordered and this structural flexibility is confirmed by computations, which reveal that the mutant transitions back and forth between the two registries. We propose that a coiled-coil registry shift upon cargo-binding activates BicD for dynein recruitment. Moreover, the human homolog BicD2/F743I exhibits diminished binding of cargo adaptor Nup358, implying that a coiled-coil registry shift may be a mechanism to modulate cargo selection for BicD2-dependent transport pathways.

StomataScorer: a portable and high-throughput leaf stomata trait scorer combined with deep learning and an improved CV model.

To measure stomatal traits automatically and nondestructively, a new method for detecting stomata and extracting stomatal traits was proposed. Two portable microscopes with different resolutions (TipScope with a 40× lens attached to a smartphone and ProScope HR2 with a 400× lens) are used to acquire images of living stomata in maize leaves. FPN model was used to detect stomata in the TipScope images and measure the stomata number and stomatal density. Faster RCNN model was used to detect opening and closing stomata in the ProScope HR2 images, and the number of opening and closing stomata was measured. An improved CV model was used to segment pores of opening stomata, and a total of 6 pore traits were measured. Compared to manual measurements, the square of the correlation coefficient (R2 ) of the 6 pore traits was higher than 0.85, and the mean absolute percentage error (MAPE) of these traits was 0.02%-6.34%. The dynamic stomata changes between wild-type B73 and mutant Zmfab1a were explored under drought and re-watering condition. The results showed that Zmfab1a had a higher resilience than B73 on leaf stomata. In addition, the proposed method was tested to measure the leaf stomatal traits of other nine species. In conclusion, a portable and low-cost stomata phenotyping method that could accurately and dynamically measure the characteristic parameters of living stomata was developed. An open-access and user-friendly web portal was also developed which has the potential to be used in the stomata phenotyping of large populations in the future.

High range resolution wideband terahertz FMCW radar with a large depth of field.

Terahertz frequency modulation continuous wave (THz FMCW) imaging technology has been widely used in non-destructive testing (NDT) applications of non-metallic materials. However, THz FMCW real-aperture radar usually has a narrow bandwidth and small depth of field, thus restricting the application of THz FMCW NDT. In this paper, a wideband THz signal (220-500 GHz) generation method is proposed by time-division multiplexing. Moreover, a dual-band quasi-optical design with a large depth of field is proposed based on the THz Bessel beam, and a high-quality range profile is obtained. Especially, a signal fusion extended Fourier analysis algorithm without prior knowledge is proposed to further enhance the range profile accuracy, which improves the range resolution to 0.28 mm (λ/3, center frequency 360 GHz). The effectiveness and advantages of the proposed system are verified by artificially constructing composite materials.

Evaporation and crystallization process for sessile saline droplets during depressurization.

The evaporation and crystallization process for sessile saline droplets during depressurization is experimentally studied. The relationship between ambient pressure and the crystallization pattern is primarily discussed. When the ambient pressure is low, salt particles are easily formed at the droplet contact line. In contrast, when the ambient pressure is similar to atmospheric pressure, it is more likely for cubic crystals to be formed inside the droplet. By analysing the contact angle fluctuation during crystallization, the experimental results show that the growth of a cubic salt crystal under high ambient pressure or low salt concentration leads to a greater deformation of the liquid-gas interface and a larger contact angle fluctuation. Finally, the Peclet number Pe is introduced to reflect the ratio of the rate of ion advection to the rate of diffusion. The Pe number is larger at lower ambient pressure, which means that the external mass transfer and convection effect is more significant under low pressure, with salt particles easily formed at the droplet contact line. The effect of concentration diffusion inside the droplet increases at higher ambient pressure, thereby, making it easy for cubic crystals to be formed inside the droplet.

Sub-wavelength-pitch silicon-photonic optical phased array for large field-of-regard coherent optical beam steering.

This paper reports on large field-of-regard, high-efficiency, and large aperture active optical phased arrays (OPAs) for optical beam steering in LIDAR systems. The fabricated 5 mm-long silicon photonic OPA with a 1.3 µm waveguide pitch achieved adjacent waveguide crosstalk below -12dB. A relatively large and uniform emission aperture has been achieved with a low-contrast silicon nitride assisted grating (~20 dB/cm) whose emission profile can be further optimized using an apodized design. The fabricated silicon-photonic OPA demonstrated > 40° lateral beam steering with no sidelobes in a ± 33° field-of-regard and 3.3° longitudinal beam steering via wavelength tuning by 20 nm centered at 1550 nm. We have fully integrated the silicon photonic OPA device with electronic controls and successfully demonstrated 2-dimensional coherent optical beam steering of pre-planned far-field patterns. Future improvements include placement of a distributed Bragg reflector (DBR) underneath the grating emitter in order to achieve nearly a factor of two improvement in emission efficiency.

Co-delivery of gambogenic acid and VEGF-siRNA with anionic liposome and polyethylenimine complexes to HepG2 cells.

Background and objective: The combination of two or more different mechanisms of drugs in the treatment of cancer has become one of the effective methods. The purpose of this study was to successfully prepare a non-viral delivery system that could efficiently co-delivery siRNA and gambogenic acid (GNA) to improve the anti-cancer efficiency in HepG2 cells. Methods: The delivery system was prepared by a two-step method. First, the GNA-anionic liposome took shape by a solvent evaporation method, and then the liposome was bound to the PEI/siRNA complex by electrostatic interaction to form the final carrier system (lipopolyplexes). Agarose gel electrophoresis, MTT, particle size and zeta potential were detected to analyse the lipopolyplexes formation. The transfection efficiency of siRNA was determined by confocal laser scanning microscopy and flow cytometry. Western blotting was used to assess the VEGF protein expression levels of HepG2 cells. The cell apoptosis assay was used to assess the anti-tumour superiority of lipopolyplexes. Results: GNA-PEI/siRNA-liposome (lipopolyplexes) are significantly less cytotoxicity compared to PEI mediated carriers. Simultaneously, the results of flow cytometry and confocal laser scanning microscopy indicated that the lipopolyplexes could successfully carry siRNA into the cytoplasm, and the western-blot result evidence that the delivery system has a potential for VEGF to express down. Also compared with the control group, the results of apoptosis test suggest that the lipopolyplexes can significantly promote cell apoptosis. Conclusion: The delivery system has a potential in the combination of various drugs for cancer therapy in future.

Preparation and antioxidant properties of crayfish (Procambarus clarkii) By-products protein hydrolysates and ultra filtration fractions.

Protein isolate from crayfish by-products (CBPI) were hydrolyzed using Alcalase, neutrase, pancreatin and bromelain. Hydrolysis by Alcalase had more remarkable digesting efficiency on crayfish by-products protein than that by the other enzymes. Therefore, protein hydrolysate from Alcalase digestion (CBPHa) was selected to be fractionated by ultrafiltration according to molecular weight into three fractions F1 (MW <1kDa), F2 (MW 1-3kDa) and F3 (MW 3-10kDa). The amino acid determination revealed that CBPI had essential amino acid (EAA) close to that required for human protein synthesis. In vitro activity experiments showed that CBPHa and its fractions possessed considerable antioxidant activity. F1 exhibited the highest DPPH, superoxide radicals scavenging activities and Fe2+ chelating ability, whereas F2 showed the best hydroxyl radicals scavenging capacity and reducing power. In addition, all the fractions showed higher super oxide radical scavenging activity than the crude hydrolysates. Our findings suggest that CBPHa and their ultra filtration fractions have the potential for use in nutraceutical and functional food industries to maximize the use of crayfish processing by-products.

Demonstration of a carrier frequency offset estimator for 16-/32-QAM coherent receivers: a hardware perspective.

We propose and implement a hardware-efficient frequency offset estimator (FOE) optimized for 16- and 32-QAM coherent optical receivers with low hardware cost and high estimation accuracy. The proposed FOE combines a wide-range coarse estimator and a narrow-range highly accurate estimator in a feedforward architecture. We numerically and experimentally investigate the performance of the proposed estimator by using a field-programmable-logic-array (FPGA) based real-time coherent receiver. Compared with other state-of-the-art estimators in literature, the proposed method reduces over 40% of hardware utilizations while maintaining the same level of estimation accuracy in terms of mean-squared-error (MSE) and optical signal-to-noise ratio (OSNR) sensitivity. These results enable the development of next generation DSP circuit capable of supporting high capacity coherent optical communication link with advanced modulation formats.

A narrow open tubular column for high efficiency liquid chromatographic separation.

We report a great feature of open tubular liquid chromatography when it is run using an extremely narrow (e.g., 2 µm inner diameter) open tubular column: more than 10 million plates per meter can be achieved in less than 10 min and under an elution pressure of ca. 20 bar. The column is coated with octadecylsilane and both isocratic and gradient separations are performed. We reveal a focusing effect that may be used to interpret the efficiency enhancement. We also demonstrate the feasibility of using this technique for separating complex peptide samples. This high-resolution and fast separation technique is promising and can lead to a powerful tool for trace sample analysis.

Blind modulation format identification using nonlinear power transformation.

This paper proposes and experimentally demonstrates a blind modulation format identification (MFI) method delivering high accuracy (> 99%) even in a low OSNR regime (< 10 dB). By using nonlinear power transformation and peak detection, the proposed MFI can recognize whether the signal modulation format is BPSK, QPSK, 8-PSK or 16-QAM. Experimental results demonstrate that the proposed MFI can achieve a successful identification rate as high as 99% when the incoming signal OSNR is 7 dB. Key parameters, such as FFT length and laser phase noise tolerance of the proposed method, have been characterized.

Aquaporin-3 is down-regulated in jejunum villi epithelial cells during enterotoxigenic Escherichia coli-induced diarrhea in mice.

Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea is a complex pathological process, involving ion channel regulation and water efflux. While the mechanism underlying water efflux in ETEC-induced diarrhea is still largely unknown, aquaporins (AQPs) play important roles in transcellular water movement, but their expression profile has not been demonstrated in the murine small intestine. We identified AQP3 expression in the jejunum, but not the duodenum or ileum, using reverse transcription PCR and western blotting. Immunohistochemistry showed that AQP3 localized to the jejunum villi epithelial cells. Using an ETEC-induced murine diarrhea model, we demonstrated that both AQP3 mRNA expression and protein concentration in the jejunum were gradually but significantly decreased over 7 d compared with controls. These results suggested impaired water influx also plays an important role in ETEC-induced diarrhea.

[Study on Si-PIN and CdTe Detectors Used in Energy Dispersive X-Ray Fluorescence Measurements].

Semiconductor detector is widely used in energy dispersive X-ray fluorescence measurements due to its excellent performance. In this paper, Si-PIN and CdTe semiconductor detectors were studied, performances of the two detectors were compared in material properties, detection efficiency, energy resolution and other aspects. Focused on the performance of the detectors influenced by the thickness of detector sensitive area, energy of incident X-ray, shaping time of post-stage circuit, and analyzed the differences of energy spectrum caused by escape peaks and hole trailing. Aiming at the problem of incomplete hole collection in detector, a digital multi-channel analyzer (DMCA) based on FPGA with rise-time discriminator was designed, it could reduce the influence of hole trailing effectively and improve energy resolution. The experimentation results indicate that the detection efficiency of Si-PIN and CdTe is roughly equal when energy is below 15 keV while CdTe has much higher detection efficiency than Si-PIN when energy is above 15 keV. The optimum forming time of the Si-PIN detector is about 10 µs, and the CdTe detector is about 2.6 µs, so the CdTe detector is more suitable for the high count rate condition. Si-PIN detector has better energy resolution than CdTe detector for different energy incident X-ray. CdTe detector has obvious hole tailing effect and the energy resolution of CdTe detector is significantly improved by using DMCA with rise-time discrimination.

Microfluidic-Assisted 3D Printing Zinc Powder Anode with 2D Conductive MOF/MXene Heterostructures for High-Stable Zinc-Organic Battery.

Zinc powder (Zn-P) anodes have significant advantages in terms of universality and machinability compared with Zn foil anodes. However, their rough surface, which has a high surface area, intensifies the uncontrollable growth of Zn dendrites and parasitic side reactions. In this study, an anti-corrosive Zn-P-based anode with a functional layer formed from a MXene and Cu-THBQ (MXene/Cu-THBQ) heterostructure is successfully fabricated via microfluidic-assisted 3D printing. The unusual anti-corrosive and strong adsorption of Zn ions using the MXene/Cu-THBQ functional layer can effectively homogenize the Zn ion flux and inhibit the hydrogen evolution reaction (HER) during the repeated process of Zn plating/stripping, thus achieving stable Zn cycling. Consequently, a symmetric cell based on Zn-P with the MXene/Cu-THBQ anode exhibits a highly reversible cycling of 1800 h at 2 mA cm-2 /1 mAh cm-2 . Furthermore, a Zn-organic full battery matched with a 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl organic cathode riveted on graphene delivers a high reversible capacity and maintains a long cycle life.