Potential Therapeutic Targets in Myeloid Cell Therapy for Overcoming Chemoresistance and Immune Suppression in Gastrointestinal Tumors.

In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells. However, an excessive M1 response may lead to pro-tumoral inflammation. As a result, myeloid cells have emerged as crucial targets in cancer therapy. This review concentrates on gastrointestinal tumors, detailing methods for targeting macrophages to enhance tumor radiotherapy and immunotherapy sensitivity. We specifically delve into monocytes and tumor-associated macrophages' various functions, establishing an immunosuppressive microenvironment, promoting tumorigenic inflammation, and fostering neovascularization and stromal remodeling. Additionally, we examine combination therapeutic strategies.

Earthquake supercycles and fault interaction over the past 32 ka in the Lake Ebinur area, Xinjiang, China.

Earthquake prediction and disaster assessment in tectonically active regions require a continuous and complete regional seismic archive, which is commonly difficult to obtain, especially for prehistoric records. Here, high-resolution analysis of the sedimentary sequence from Lake Ebinur in Xinjiang revealed a detailed history of environment evolution since 32 ka ago. Both the Cl content and ultrafine proportion revealed the changing climate: the climate was relatively dry with low lake-water volumes from 32 to 12 ka, while the climate became warmer and wetter since 12 ka. In addition, eight earthquakes were identified by comprehensive analysis of grain size and geochemical element proxies, showing more than two seismic supercycles, with gaps of ∼10.4 ka; these gaps are much larger than those inferred previously (∼4-7 ka). Notably, these seismic events exhibited a pattern of mutual transmittance between the BoA and Jinghenan faults. Such fault interaction can occur in the Lake Ebinur area because it is dominated by weak lithosphere in which strain is easily accumulated and released; the interaction can also be attributed to the unique spatial distribution and immature nature of both faults. Combined with trenching investigations, our high-resolution analysis of lacustrine sediments can reveal a complete history of tectonic activity, which can efficiently serve regional earthquake prediction and disaster assessment.

Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting.

Helicobacter pylori (H. pylori) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori, underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections.

Isolation of Fluorescent 2π-Aromatic 1,3-Disiladiboretenes.

Herein, we reported the isolation of 2π-aromatic disiladiboretenes (L2Si2B2Ph2) [L = ArC(NtBu)2, Ar = Ph (1), Mes (2)], which have been synthesized from the straightforward reduction of silylene-borane adducts (LSiX → BX2Ph) [X = Cl, Br] with potassium graphite (KC8). X-ray diffraction analysis of 1 and 2 revealed that the Si2B2 units are completely planar, and DFT calculations suggested delocalization of 2π-electrons over the Si2B2 rings. Moreover, their photophysical properties and reactivity toward sulfur were also investigated in detail.

Development of a Wideband Precision Electric Field Measuring Sensor.

High-voltage electric field measurement technology has certain applications in electric field measurement of power systems, but due to the limitation of its measurement accuracy and bandwidth, it cannot be used for the measurement of lightning-impulse voltage. In order to calibrate the nonlinearity of the MV-level lightning-impulse voltage measurement system, this paper proposes the design and implementation of a high-precision inductive wideband electric field measuring sensor (EFMS). The influence of the metal shell on the electric field distribution was simulated, and the influence of the electric field non-uniformity coefficient was studied. The characteristics of the EFMS were tested, and the results showed that the EFMS can accurately reproduce the waveform of lightning-impulse voltage and power-frequency voltage, with a proportionality coefficient of 0.05664 V/(kV/m). In mostly uniform and extremely non-uniform fields, the nonlinearity of the EFMS for impulse voltage is less than ±0.25%, and the nonlinearity of the EFMS for power-frequency voltage is less than 0.1%. It is shown that the EFMS can be used for the nonlinearity calibration of ultra-high voltage impulse measurement devices.

Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine.

Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases.

Macrophages are a heterogeneous cell type with high plasticity, exhibiting unique activation characteristics that modulate the progression and resolution of diseases, serving as a key mediator in maintaining tissue homeostasis. Macrophages display a variety of activation states in response to stimuli in the local environment, with their subpopulations and biological functions being dependent on the local microenvironment. Resident tissue macrophages exhibit distinct transcriptional profiles and functions, all of which are essential for maintaining internal homeostasis. Dysfunctional macrophage subpopulations, or an imbalance in the M1/M2 subpopulation ratio, contribute to the pathogenesis of diseases. In skeletal muscle disorders, immune and inflammatory damage, as well as fibrosis induced by macrophages, are prominent pathological features. Therefore, targeting macrophages is of great significance for maintaining tissue homeostasis and treating skeletal muscle disorders. In this review, we discuss the receptor-ligand interactions regulating macrophages and identify potential targets for inhibiting collateral damage and fibrosis in skeletal muscle disorders. Furthermore, we explore strategies for modulating macrophages to maintain tissue homeostasis.

GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer.

BACKGROUND: The receptor tyrosine kinases TAM family (TYRO3, AXL, and MERTK) are highly expressed in multiple forms of cancer cells and tumor-associated macrophages and promote the development of cancers including pancreatic tumor. Targeting TAM receptors could be a promising therapeutic option. METHODS: We designed a novel CAR based on the extracellular domain of growth arrest-specific protein 6 (GAS6), a natural ligand for all TAM members. The ability of CAR-T to kill pancreatic cancer cells is tested in vitro and in vivo, and the safety is evaluated in mice and nonhuman primate. RESULTS: GAS6-CAR-T cells efficiently kill TAM-positive pancreatic cancer cell lines, gemcitabine-resistant cancer cells, and cancer stem-like cells in vitro. GAS6-CAR-T cells also significantly suppressed the growth of PANC1 xenografts and patient-derived xenografts in mice. Furthermore, these CAR-T cells did not induce obvious side effects in nonhuman primate or mice although the CAR was demonstrated to recognize mouse TAM. CONCLUSIONS: Our findings indicate that GAS6-CAR-T-cell therapy may be effective for pancreatic cancers with low toxicity.

Automated Drone-Delivery Solar-Driven Onsite Wastewater Smart Monitoring and Treatment System.

Treating potential polluted water sources is urgent and challenging, especially for natural water sources. Numerous research groups focus on either smart water monitoring or new adsorbent. However, either aspect alone is insufficient for complex nature water source treatment. Here, integrating the state-of-art machine learning technique, a sustainable silk-based bioadsorbent, and wireless Internet of Things, an integrated automated drone-delivery solar driven onsite water monitoring & treatment system (WMTS) for the contaminated nature water sources is developed. In short, the embedded sensors and microprogrammed control unit capture and upload the real-time monitoring data to the cloud server for data analysis and optimized treatment strategy. Meanwhile, a grid map system based on the satellite remote sensing images directs the minimum number of WMTS units to cover the entire polluted region. Finally, unmanned aerial vehicles provide autonomous dispatch, operation, and maintenance, especially in hard-to-reach sites. Overall, this work offers a general, sustainable, energy-efficient, and closed-loop solution toward efficiently alerting and on-site treating nature water source contamination.

Physician-Modified Endovascular Graft for Left Subclavian Artery Fenestration during Thoracic Endovascular Aortic Repair.

BACKGROUND: This study aimed to evaluate the safety and efficacy of physician-modified endovascular graft for preservation of left subclavian artery during thoracic endovascular aortic repair. METHODS: From June 2019 to October 2022, 66 patients with a variety of thoracic aortic pathologies were treated with thoracic endovascular aortic repair using physician-modified endovascular graft left subclavian artery fenestration to achieve adequate proximal landing zone. The details of surgical techniques were described. The perioperative morbidity, mortality, and the outcomes of mid-term follow-up were analyzed. RESULTS: Of the 66 patients (men: women, 53:13; age, 55.18 [55.18 ± 10.62] years), 53 (80.30%) presented with type B aortic dissection, 10 (15.15%) with thoracic penetrating aortic ulcer, 2 (3.03%) with thoracic aortic aneurysm, and 1 (1.52%) with left subclavian artery aneurysm. All of them underwent thoracic endovascular aortic repair using physician-modified endovascular graft left subclavian artery fenestration on the sterile back table. The technique success rate was 96.97% (n = 64). Total operation time was 92 min (interquartile range, 86-118), graft modification time was 19 min (interquartile range, 17-21), fluoroscopy time was 49 min (interquartile range, 41-62), and contrast agent dosage was 165 mL (interquartile range, 155-185). 30-day perioperative morbidities were 3 (4.55%) strokes, 1 (1.52%) retrograde type A aortic dissection, 1 (1.52%) aortic intimal intussusception, 1 (1.52%) left arm ischemia, and 3 (4.55%) type Ia endoleaks. Postoperative 30-day mortality and reintervention rates were 1.52% and 4.55%, respectively. Among the 63 patients included in the follow-up of 17 months (interquartile range, 7.75-18.25), the primary patency of left subclavian artery fenestration stents was 100%. Late complications were 1 (1.59%) distal stent graft-induced new entry and 1 (1.59%) death due to retrograde type A aortic dissection during the follow-up. The stent graft-induced new entry patient was observed with stable false lumen. CONCLUSIONS: Thoracic endovascular aortic repair with physician-modified endovascular graft for left subclavian artery revascularization is a safe, feasible, and efficacious technique associated with high success rate. Further study is needed for long-term outcome investigation.

Standardization of Panax ginseng: Current Status of Global Trade, Demands, and Development.

Panax ginseng, as a kind of rare and valuable Chinese materia medica with the largest global trade volume, has been widely applied in many fields, such as medicine, food, health care, and production of daily chemical products. It is widely used in Asia, Europe, and America. However, its global trade and standardization present different features and an uneven development in different countries or regions. As the main country for its production and consumption, Panax ginseng in China is characterized by its large cultivation area and high total yield and is mainly sold as a raw material or primary processed product. By contrast, Panax ginseng produced in South Korea is mainly sold in manufactured products. Besides, European countries, as another consumption market of Panax ginseng, pay more attention to the research and development of its products. Although Panax ginseng has been widely recorded in various national pharmacopoeias and regional standards, the current standards of Panax ginseng differ in quantity, composition, and distribution, and the existing standards cannot be enough to meet the demands of its global trade. Based on the above issues, we systemically summarized and analyzed the status and features of Panax ginseng standardization and put forward suggestions on the development needs of international standardization of Panax ginseng to guarantee its quality and safety, regulate the order of its global trade, and resolve trade disputes, thereby promoting the high-quality development of the Panax ginseng industry.

Combined effect of konjac glucomannan addition and ultrasound treatment on the physical and physicochemical properties of frozen dough.

The effects of dual sequential modification using konjac glucomannan and ultrasound treatments at power densities of 15-37.5 W/L on the hydration, rheology and structural characteristics of frozen dough were investigated in this study. The results revealed that the konjac glucomannan and ultrasound treatments improved the textural properties of frozen dough, but had a negative impact on its viscoelasticity. Furthermore, konjac glucomannan and ultrasound treatments increased the content of free sulfhydryl group and disulfide bond, as well as improved the freeze tolerance of dough. The results exhibited that the enthalpy of frozen dough decreased by 20.42 % compared with the frozen blank control dough under ultrasonic power density of 22.5 W/L. The network structure of frozen dough treated by konjac glucomannan and ultrasound was more ordered and integral than that of frozen blank control dough. These results provide valuable knowledge on the application of konjac glucomannan and ultrasound to frozen wheat-based foods.

Distinct lake sedimentary imprints of earthquakes, floods and human activities in the Xiaojiang Fault zone: Towards a quantitative paleoseismograph in the southeastern Tibetan Plateau.

Lake sediments that widely distributed in the active and complicated fault zones have been recently showing great potential for paleoseismic reconstruction. However, flood events and human activities may make the seismic signal unrecognizable. In this study, high-resolution analyses of sedimentary structure, physical and chemical proxies, as well as absolutely radioactive dating were conducted on seven representative sediment cores from the depocenter, nearshore and inlet areas of Yangzong Lake, a typical fault lake in the Xiaojiang Fault zone, southeastern Tibetan Plateau (TP). These new data were calibrated by historical documents, suggesting that seismically induced mass-transport deposits (MTDs, i.e., turbidites) were massive and/or amalgamated (earthquake doublet), became fining and thickening towards the lake center (without changing lake morphology), and occasionally exhibited soft sediment deformation structures (SSDs, i.e., microfaults). These sediments were relatively poorly sorted and instantaneously deposited from slope failures within the lake. An extremely strong earthquake could cause coseismic subsidence of the lake basin and destruct the local hydrological system, resulting in exceptionally high Mn and total inorganic carbon (TIC) contents in the lake center. In contrast, flood deposits were thinner with horizontal beddings, had higher terrestrial organic matter (higher C/N ratios), and distributed locally in the lake inlet area. Human activities-induced sediments were inversely graded, poorly sorted and gradually deposited, had horizontal beddings and no erosive base, and exhibited high carbon, Pb and Zn contents and low C/N ratios. In addition, macroseismic investigations and statistical results from intensity prediction equations (IPEs) provided a conservative threshold of ∼8 Modified Mercalli Intensities (MMI) for triggering turbidites, and a ∼ 10 MMI for inducing coseismic subsidence and hydrological destruction. This study was among the first attempts to establish a quantitative lacustrine paleoseismograph in the southeastern TP, and the new results would greatly improve the valid assessment of geohazard risks.

Low salinity enhances azo dyes degradation in aerobic granular sludge systems: Performance and mechanism analysis.

The biodegradation performance of azo dyes can be enhanced under low salinity conditions, but the internal biodegradation mechanism is still unclear. Aerobic granular sludge (AGS), a salt-tolerant biological wastewater treatment technology, was used in this study to explore the enhancement mechanism of acid orange 7 (AO7) degradation at low salinity level (1.0 %). Results indicated that the AGS structure and reactor performance were almost unaffected by different AO7 concentrations (5-10 mg/L). Compared with salt-free conditions, the AO7 removal efficiency was elevated by 9.9 %-19.0 % at 1.0 % salinity level, owing to the enrichment of AO7 decolorizing bacteria (e.g. Acinetobacter) and functional enzymes (e.g. FMN-dependent azoreductase). The up-regulated genes involving in the key metabolic functions (e.g. carbon metabolism and oxidative phosphorylation) promoted the electron and energy production, thereby facilitating the AO7 decolorization and degradation. These results aid understanding of the enhancement mechanism of AO7 biodegradation under low salinity conditions from macroscopic and microscopic perspectives.

Ostracods from the Kunming area of SW China, with description of two new species and male records of Cypridopsis vidua (O.F. Mller, 1776).

Previous studies of the Recent non-marine ostracods of Yunnan Province in southwestern China yielded 42 species, among which only 18 species were reported based on living material. Such a low number is likely to underestimate the species diversity of ostracods in Yunnan, considering the geographical disparity among its different parts. In this study, we report 11 nominal species and one species left in open nomenclature from 22 samples collected from the Kunming area in eastern-central part of Yunnan. Among these species, seven are new to the province, including Notodromas semiovata n. sp., Chrissia acuminata n. sp., and the first records of the male of Cypridopsis vidua (O.F. Mller, 1776) outside the USA. A review of previous literature indicates that, with the exception of the two new species, all the other 23 species have Palaearctic (PA) distributions, while only 14 have Oriental (OL) distributions. Such a composition contradicts previous vertebrate-based zoogeographical subdivisions of China in which Yunnan was included in the OL region, and adds to the argument that the geographical distributions of various invertebrate groups need to be investigated to map the PAOL boundary in China more appropriately.

Potential therapeutic target for polysaccharide inhibition of colon cancer progression.

In recent years, colon cancer has become one of the most common malignant tumors worldwide, posing a great threat to human health. Studies have shown that natural polysaccharides have rich biological activities and medicinal value, such as anti-inflammatory, anti-cancer, anti-oxidation, and immune-enhancing effects, especially with potential anti-colon cancer mechanisms. Natural polysaccharides can not only protect and enhance the homeostasis of the intestinal environment but also exert a direct inhibition effect on cancer cells, making it a promising strategy for treating colon cancer. Preliminary clinical experiments have demonstrated that oral administration of low and high doses of citrus pectin polysaccharides can reduce tumor volume in mice by 38% (p < 0.02) and 70% (p < 0.001), respectively. These results are encouraging. However, there are relatively few clinical studies on the effectiveness of polysaccharide therapy for colon cancer, and ensuring the effective bioavailability of polysaccharides in the body remains a challenge. In this article, we elucidate the impact of the physicochemical factors of polysaccharides on their anticancer effects and then reveal the anti-tumor effects and mechanisms of natural polysaccharides on colon cancer. Finally, we emphasize the challenges of using polysaccharides in the treatment of colon cancer and discuss future applications.

Transcriptomic analysis reveals the formation mechanism of anemone-type flower in chrysanthemum.

BACKGROUND: The ray and disc florets on the chrysanthemum capitulum are morphologically diverse and have remarkably abundant variant types, resulting in a rich variety of flower types. An anemone shape with pigmented and elongated disk florets is an important trait in flower shape breeding of chrysanthemums. The regulatory mechanism of their anemone-type disc floret formation was not clear, thus limiting the directional breeding of chrysanthemum flower types. In this study, we used morphological observation, transcriptomic analysis, and gene expression to investigate the morphogenetic processes and regulatory mechanisms of anemone-type chrysanthemum. RESULT: Scanning electron microscopy (SEM) observation showed that morphological differences between non-anemone-type disc florets and anemone-type disc florets occurred mainly during the petal elongation period. The anemone-type disc florets elongated rapidly in the later stages of development. Longitudinal paraffin section analysis revealed that the anemone-type disc florets were formed by a great number of cells in the middle layer of the petals with vigorous division. We investigated the differentially expressed genes (DEGs) using ray and disc florets of two chrysanthemum cultivars, 082 and 068, for RNA-Seq and their expression patterns of non-anemone-type and anemone-type disc florets. The result suggested that the CYCLOIDEA2 (CYC2s), MADS-box genes, and phytohormone signal-related genes appeared significantly different in both types of disc florets and might have important effects on the formation of anemone-type disc florets. In addition, it is noteworthy that the auxin and jasmonate signaling pathways might play a vital role in developing anemone-type disc florets. CONCLUSIONS: Based on our findings, we propose a regulatory network for forming non-anemone-type and anemone-type disc florets. The results of this study lead the way to further clarify the mechanism of the anemone-type chrysanthemum formation and lay the foundation for the directive breeding of chrysanthemum petal types.

Engineered nanomaterials trigger abscopal effect in immunotherapy of metastatic cancers.

Despite advances in cancer treatment, metastatic cancer is still the main cause of death in cancer patients. At present, the treatment of metastatic cancer is limited to palliative care. The abscopal effect is a rare phenomenon in which shrinkage of metastatic tumors occurs simultaneously with the shrinkage of a tumor receiving localized treatment, such as local radiotherapy or immunotherapy. Immunotherapy shows promise for cancer treatment, but it also leads to consequences such as low responsiveness and immune-related adverse events. As a promising target-based approach, intravenous or intratumoral injection of nanomaterials provides new opportunities for improving cancer immunotherapy. Chemically modified nanomaterials may be able to trigger the abscopal effect by regulating immune cells. This review discusses the use of nanomaterials in killing metastatic tumor cells through the regulation of immune cells and the prospects of such nanomaterials for clinical use.

Nrf2 transcriptional upregulation of IDH2 to tune mitochondrial dynamics and rescue angiogenic function of diabetic EPCs.

Endothelial progenitor cells (EPCs) are reduced in number and impaired in function in diabetic patients. Whether and how Nrf2 regulates the function of diabetic EPCs remains unclear. In this study, we found that the expression of Nrf2 and its downstream genes were decreased in EPCs from both diabetic patients and db/db mice. Survival ability and angiogenic function of EPCs from diabetic patients and db/db mice also were impaired. Gain- and loss-of-function studies, respectively, showed that knockdown of Nrf2 increased apoptosis and impaired tube formation in EPCs from healthy donors and wild-type mice, while Nrf2 overexpression decreased apoptosis and rescued tube formation in EPCs from diabetic patients and db/db mice. Additionally, proangiogenic function of Nrf2-manipulated mouse EPCs was validated in db/db mice with hind limb ischemia. Mechanistic studies demonstrated that diabetes induced mitochondrial fragmentation and dysfunction of EPCs by dysregulating the abundance of proteins controlling mitochondrial dynamics; upregulating Nrf2 expression attenuated diabetes-induced mitochondrial fragmentation and dysfunction and rectified the abundance of proteins controlling mitochondrial dynamics. Further RNA-sequencing analysis demonstrated that Nrf2 specifically upregulated the transcription of isocitrate dehydrogenase 2 (IDH2), a key enzyme regulating tricarboxylic acid cycle and mitochondrial function. Overexpression of IDH2 rectified Nrf2 knockdown- or diabetes-induced mitochondrial fragmentation and EPC dysfunction. In a therapeutic approach, supplementation of an Nrf2 activator sulforaphane enhanced angiogenesis and blood perfusion recovery in db/db mice with hind limb ischemia. Collectively, these findings indicate that Nrf2 is a potential therapeutic target for improving diabetic EPC function. Thus, elevating Nrf2 expression enhances EPC resistance to diabetes-induced oxidative damage and improves therapeutic efficacy of EPCs in treating diabetic limb ischemia likely via transcriptional upregulating IDH2 expression and improving mitochondrial function of diabetic EPCs.