Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Platycodin D ameliorates polycystic ovary syndrome-induced ovarian damage by upregulating CD44 to attenuate ferroptosis.

Recently, the potential association between polycystic ovary syndrome (PCOS) development and progression and ferroptosis has garnered attention. Increasing evidence suggests that targeting ferroptosis may be an effective strategy for treating PCOS. First, we observed that the expression of the ferroptosis regulatory molecules SLC7A11, GPX4, and FTH1 was decreased in the granulosa cells (GCs) of patients with PCOS and ovarian tissues of rats with PCOS; in contrast, TFR1 expression was increased. This suggests that GC ferroptosis is involved in PCOS pathogenesis. Furthermore, bioinformatics analysis of GC datasets from patients with PCOS and PCOS clinical samples and animal model analysis revealed CD44 as a key molecule regulating ferroptosis in PCOS, which was down-regulated in GCs of PCOS patients and rats. Subsequently, molecular docking was performed to screen existing natural compounds for inhibiting ferroptosis. Dynamic simulation and cellular thermal shift assay identified platycodin D as a natural plant extract for inhibiting ferroptosis by targeting CD44 in GCs. Subsequently, a series of functional experiments revealed that platycodin D ameliorated ovarian damage in rats with PCOS. This was primarily owing to the protective effects achieved by promoting glutathione production, attenuating lipid accumulation and lipid peroxidation in GCs, inhibiting iron overload, and scavenging reactive oxygen species. In addition, western blotting and immunofluorescence staining revealed that platycodin D upregulated the expression of CD44 and SLC7A11 in GCs. Furthermore, by knocking down CD44 and SLC7A11 in vivo and in vitro, respectively, the ameliorative effect of platycodin D on ferroptosis in the GCs of rats with PCOS was reversed. Collectively, these findings suggest that platycodin D attenuates ferroptosis in GCs by activating CD44/SLC7A11 axis, thereby upregulating system Xc-. In conclusion, platycodin D can attenuate ferroptosis in GCs by activating CD44, potentially ameliorating ovarian damage in PCOS.

[Simultaneous determination of 102 synthetic cannabinoids in electronic cigarette oil by liquid chromatography-tandem mass spectrometry].

Synthetic cannabinoids (SCs), which are among the most widely abused new psychoactive substances, are much more potent and have greater efficacy than natural cannabis. SCs can be disguised in various ways and are commonly sold in the form of electronic cigarette oil. SCs belong to a large family with structures consisting of a core with substituents, linker, ring with substituents, and tail. New SCs can be developed by adding substituents, such as halogen, alkyl, and alkoxy groups, to the aromatic ring system or by changing the alkyl chain length. Since the emergence of so-called first-generation SCs, subsequent developments have led to eighth-generation indole/indazole amide-based SCs. As of July 1, 2021, the entire category of SCs was added to the list of controlled substances, but implementation requires urgent improvements in detection technologies. Typically, each method is limited to a few SCs. Owing to the vast number of chemically diverse SCs and their fast update speed, the determination and identification of various types of SCs using a single method is challenging. Therefore, rapid, sensitive, and accurate quantitative methods that includes various types of SCs must be developed to meet the demand for the qualitative and quantitative analysis of new SCs in seized electronic cigarette oil. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of 102 SCs in electronic cigarette oil. The mass spectrometry and liquid-phase conditions influencing SC separation and determination were optimized. Using the external standard method, 102 SCs were successfully identified in electronic cigarette oil. The samples were extracted using methanol. Target analytes were separated on a Shimadzu Shim-pack GIST-HP C18 AQ column (100 mm×2.1 mm, 1.9 µm) at a column temperature of 40 ℃. The mobile phases consisted of (A) 0.1% formic acid aqueous solution and (B) methanol-acetonitrile (1∶1, v/v). The gradient elution conditions were as follows: 0-8 min, 55%A-15%A; 8-15 min, 15%A; 15-16 min, 15%A-55%A; 16-18 min, 55%A. The flow rate was 0.4 mL/min and the injection volume was 1 µL. Operating in the multiple reaction monitoring mode, the 102 SCs were identified within 18 min. Each SC exhibited a good linear relationship in the range of 1-100.0 µg/L with a correlation coefficient (r)≥0.9915. The limits of detection were 0.01-0.30 µg/L and the limits of quantification were 0.04-0.99 µg/L, which meet the requirements for analyzing SCs in actual samples. Precision was determined using standard solutions with 2, 10, and 50 µg/L of the SCs. The precisions (n=6) were 0.3%-6.0%. The recoveries of the 102 SCs, as evaluated by spiking electronic cigarette oil at low (2 µg/mL), medium (10 µg/mL), and high (50 µg/mL) levels, were 80.1%-119.8%. Good performance was observed for the analysis of real samples. The developed method is accurate, rapid, sensitive, and effective for the determination of the 102 SCs in electronic cigarette oil, satisfying the requirements for practical qualitative and quantitative analysis.

Iron Nanoparticles-Confined Graphene Oxide Membranes Coupled with Sulfite-Based Advanced Reduction Processes for Highly Efficient and Stable Removal of Bromate.

Advanced reduction processes (ARPs) are promising for pollutant removal in drinking water treatment. In this study, we demonstrated highly efficient reduction of bromate, a harmful disinfection byproduct, by coupling ARPs with an iron nanoparticles-intercalated graphene oxide (GO@FeNPs) catalytic membrane. In the presence of 1.0 mM sulfite (S(IV)), the GO@FeNPs membrane/S(IV) system achieved nearly complete removal of 80 µg/L bromate in 3 min. The first-order reaction rate constant for bromate removal in this system was 420 ± 42 min-1, up to 5 orders of magnitude faster than previously reported ARPs. The GO@FeNPs catalytic membrane may offer potential advantages of nanoconfinement and facilitated electron shuttling in addition to the high surface area of the fine FeNPs, leading to the remarkable ARP performance. The GO@FeNPs membrane showed excellent stability, maintaining >97.0% bromate removal over 20 cycles of repeated runs. The membrane can also be applied for fast catalytic reduction of other oxyanions, showing >98.0% removal of nitrate and chlorate. This work may present a viable option for utilizing high-performance reductive catalytic membranes for water decontamination.

SimpleTrackV2: Rethinking the Timing Characteristics for Multi-Object Tracking.

Multi-object tracking tasks aim to assign unique trajectory codes to targets in video frames. Most detection-based tracking methods use Kalman filtering algorithms for trajectory prediction, directly utilizing associated target features for trajectory updates. However, this approach often fails, with camera jitter and transient target loss in real-world scenarios. This paper rethinks state prediction and fusion based on target temporal features to address these issues and proposes the SimpleTrackV2 algorithm, building on the previously designed SimpleTrack. Firstly, to address the poor prediction performance of linear motion models in complex scenes, we designed a target state prediction algorithm called LSTM-MP, based on long short-term memory (LSTM). This algorithm encodes the target's historical motion information using LSTM and decodes it with a multilayer perceptron (MLP) to achieve target state prediction. Secondly, to mitigate the effect of occlusion on target state saliency, we designed a spatiotemporal attention-based target appearance feature fusion (TSA-FF) target state fusion algorithm based on the attention mechanism. TSA-FF calculates adaptive fusion coefficients to enhance target state fusion, thereby improving the accuracy of subsequent data association. To demonstrate the effectiveness of the proposed method, we compared SimpleTrackV2 with the baseline model SimpleTrack on the MOT17 dataset. We also conducted ablation experiments on TSA-FF and LSTM-MP for SimpleTrackV2, exploring the optimal number of fusion frames and the impact of different loss functions on model performance. The experimental results show that SimpleTrackV2 handles camera jitter and target occlusion better, achieving improvements of 1.6%, 3.2%, and 6.1% in MOTA, IDF1, and HOTA, respectively, compared to the SimpleTrack algorithm.

Overexpression of dehydroascorbate reductase gene IbDHAR1 improves the tolerance to abiotic stress in sweet potato.

Dehydroascorbate reductase (DHAR), an indispensable enzyme in the production of ascorbic acid (AsA) in plants, is vital for plant tolerance to various stresses. However, there is limited research on the stress tolerance functions of DHAR genes in sweet potato (Ipomoea batatas [L.] Lam). In this study, the full-length IbDHAR1 gene was cloned from the leaves of sweet potato cultivar Xu 18. The IbDHAR1 protein is speculated to be located in both the cytoplasm and the nucleus. As revealed by qRT-PCR, the relative expression level of IbDHAR1 in the proximal storage roots was much greater than in the other tissues, and could be upregulated by high-temperature, salinity, drought, and abscisic acid (ABA) stress. The results of pot experiments indicated that under high salinity and drought stress conditions, transgenic Arabidopsis and sweet potato plants exhibited decreases in H2O2 and MDA levels. Conversely, the levels of antioxidant enzymes APX, SOD, POD, and ACT, and the content of DHAR increased. Additionally, the ratio of AsA/DHA was greater in transgenic lines than in the wild type. The results showed that overexpression of IbDHAR1 intensified the ascorbic acid-glutathione cycle (AsA-GSH) and promoted the activity of the related antioxidant enzyme systems to improve plant stress tolerance and productivity.

SLL-1A-16 suppresses proliferation and induces autophagy in non-small-cell lung cancer cells via the AKT/mTOR signaling pathway.

Non-small-cell lung cancer (NSCLC), which accounts for approximately eighty-five percent of lung cancer diagnoses worldwide, is a malignancy with high incidence and mortality rates. Among the various antitumor compounds, organic selenium-containing compounds have emerged as a promising class of therapeutic agents for cancer treatment. In the present study, SLL-1A-16, a new organoselenium small molecule, was discovered to exhibit antiproliferative activity against NSCLC both in vitro and in vivo. Treatment with SLL-1A-16 significantly inhibited NSCLC cell proliferation and induced apoptosis and autophagy. Mechanistically, SLL-1A-16 inhibited cell proliferation through G1-S phase arrest by reducing cyclin D1 and CDK4 expression. Additionally, SLL-1A-16 significantly induced apoptosis by upregulating cleaved caspase 3 and Bax expression, while downregulating Bcl-2 levels. Our study also demonstrated that SLL-1A-16 induced autophagy in NSCLC cells by inhibiting the Akt/mTOR pathway. Overall, our findings suggest that SLL-1A-16 could induce cell cycle arrest, apoptosis and autophagy in NSCLC cells by inhibiting the Akt/mTOR signaling pathways, providing a theoretical basis for the potential clinical application of SLL-1A-16 as a chemotherapeutic agent in NSCLC treatment.

Extending The Calendar Life of Fiber Lithium-Ion Batteries to 200 Days with Ultra-High Barrier Polymer Tubes.

Scalable fiber lithium-ion batteries (FLIBs) have garnered significant attention due to huge potential applications in wearable technology. However, their widespread applications have been limited by inadequate cycle and calendar life, primarily due to the high permeability of the encapsulation layer to water vapor in ambient air. To address this challenge, an ultra-high barrier composite tube is developed by blending polytrifluorochloroethylene (PCTFE) with organically modified montmorillonite (OMMT) for the continuous packaging of FLIBs. Due to the high crystallinity (≈40.21%) and small free volume (103.443 Å3), the PCTFE tube exhibited a low water vapor transmission rate (WVTR) of 0.123 mg day-1 pkg-1. Furthermore, through the melt extrusion, OMMT with its plate-like morphology are fully exfoliated and dispersed within the PCTFE matrix. This created more complex pathways for water, increasing the diffusion path length and thereby reducing WVTR to 0.006 mg day-1 pkg-1. This innovation enabled an ultra-long calendar life of 200 days and cycle life of 870 cycles for FLIBs, with over 80% capacity retention in ambient air. Additionally, 2%OMMT-PCTFE-FLIBs exhibited excellent flexibility, retaining an impressive 85.31% capacity after 10 000 bending cycles. This research presents a simple yet effective approach to enhance the lifetime and practicality of FLIBs through building a high-performance polymer-based encapsulation layer.

Predictive performance of Metagenomic Next Generation Sequencing in early detection of post-liver transplantation infections.

Objective: To evaluate the predictive performance of metagenomic next-generation sequencing (mNGS) in identifying and predicting pulmonary infections following liver transplantation and to investigate its association with patient outcomes within the initial four-week post-transplantation period. Methods: We retrospectively analyzed 41 liver transplant patients with suspected pulmonary infections from August 2022 to May 2023. Bronchoalveolar lavage fluid (BALF) samples were collected on the first postoperative day for metagenomic next generation sequencing (mNGS) and culture. The predictive capability of mNGS for subsequent infections was assessed by monitoring inflammatory biomarkers and comparing the detection rates with culture methods. Real-time Polymerase Chain Reaction (Rt-PCR) was used to monitor Human betaherpesvirus 5 (CMV) and Human parvovirus B19 (B19) weekly during a four-week postoperative period. Inflammatory biomarkers and blood coagulation function were evaluated on specific days throughout the first, third, fifth, and during four weeks following surgery. The study was conducted until August 2023 to evaluate the patients' prognostic survival outcome, classifying them into groups based on the mortality and survival. Results: The analysis included a total of 41 patients, comprising 32 males and 9 females, with an average age of 52 (47, 63) years. Within one week after liver transplantation, there were 7 cases of bacterial infections, 5 cases of fungal infections, 19 cases of mixed infections, 8 cases without any infection, and 2 cases with unidentified pathogen-associated infections. mNGS successfully predicted 39 (72 %) strains of pathogens, while culture-based methods only detected 28 (52 %) strains. Among the 8 patients diagnosed as non-infected, culture methods identified positive results in 4 cases (50 %), whereas mNGS yielded positive results in 7 cases (87.5 %). The detection rates of CMV and B19 by Rt-PCR within 4 weeks after liver transplantation were 61 % and 17 %, respectively (25/41, 7/41) among the patients. During the study period, a total of 9 patients succumbed while 32 patients survived. The death group and the survival group exhibited significant differences in CRP, HGB, and INR levels at specific monitoring time points. The proportion of CMV detection in blood was significantly higher in the death group compared to the surviving group. Elevated CRP level was identified as a prognostic risk factor. Conclusions: Despite the presence of false positives, mNGS still presents a potential advantage in predicting pulmonary infection pathogens following liver transplantation. Furthermore, the levels of CRP and CMV carrier status within four weeks post-surgery exhibit significant associations with patient survival and prognosis.

Maggot extract accelerates skin wound healing of diabetic rats via enhancing STAT3 signaling.

BACKGROUND: Diabetic skin wound is a complex problem due to the disruption of normal repairing program and lack of effective remedy. Lucilia sericata larvae (maggot) is a folk method to treat chronic skin wound, while its therapeutic effects on that caused by diabetic remains unknown. OBJECTIVE: This study aims to investigate the therapeutic effects of maggot extract (M.E.) on diabetic skin wound and its molecular mechanism by establishing the skin wound model of diabetic Sprague Dawley (SD) rats. METHODS: Diabetic model was established by injecting intraperitoneally streptozotocin in SD rats under specific pathogen-free (SPF) conditions. The rat fasting blood glucose values were ≧16.7 mmol/L 72 hours after intraperitoneal streptozotocin (60mg/kg body weight) injection. The rats were divided into five groups (n = 10/group): normal group: normal SD rats without any treatment, diabetic blank group: the diabetic rats without any treatment, Vaseline group: the diabetic rats dressed with Vaseline, recombinant human epidermal-growth-factor (rhEGF) group: the diabetic rats dressed with a mixture of Vaseline and 200 µg/g rhEGF, M.E. group: the diabetic rats dressed with a mixture of Vaseline and 150 µg/ml maggot extract. The round open wounds (1.0 cm in diameter) down to the muscle fascia were made on both sides of rat dorsa by removing the skin layer (epidermis and dermis) and were daily photographed for calculating their healing rates. Hematoxylin-eosin (HE) and Masson's trichrome staining were performed on skin wound sections to analyze re-epithelialization and granulation tissue formation. Immunohistochemical (IHC), immunofluorescent (IF) stainings and Western blotting were conducted to analyze the statuses of STAT3 signaling. RESULTS: The average wound healing rates on the 14th day were 91.7% in the normal, 79.6% in M.E., 71% in rhEGF, 55.1% in vaseline and 43.3% in the diabetes blank group. Morphological staining showed more active granulation tissue formation, re-epithelialization and neovascularization in M.E.-group than those in the blank and the vaseline-treated groups. Decreased p-STAT3 nuclear tranlocation and down-regulated Bcl-2, CyclinD1 and vascular endothelial growth factor (VEGF) expression were evidenced in the diabetic rats, which could be improved by rhEGF and especially M.E. CONCLUSION: Maggot extract would be an alternative and/or adjuvant candidate for the better management of diabetic skin wounds because of its activity in enhancing STAT3 activation.

Identification of novel PHGDH inhibitors based on computational investigation: an all-in-one combination strategy to develop potential anti-cancer candidates.

Objective: Biological studies have elucidated that phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the serine synthesis pathway in humans that is abnormally expressed in numerous cancers. Inhibition of the PHGDH activity is thought to be an attractive approach for novel anti-cancer therapy. The development of structurally diverse novel PHGDH inhibitors with high efficiency and low toxicity is a promising drug discovery strategy. Methods: A ligand-based 3D-QSAR pharmacophore model was developed using the HypoGen algorithm methodology of Discovery Studio. The selected pharmacophore model was further validated by test set validation, cost analysis, and Fischer randomization validation and was then used as a 3D query to screen compound libraries with various chemical scaffolds. The estimated activity, drug-likeness, molecular docking, growing scaffold, and molecular dynamics simulation processes were applied in combination to reduce the number of virtual hits. Results: The potential candidates against PHGDH were screened based on estimated activity, docking scores, predictive absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties, and molecular dynamics simulation. Conclusion: Finally, an all-in-one combination was employed successfully to design and develop three potential anti-cancer candidates.

Innovative lipid nanoparticles: A cutting-edge approach for potential renal cell carcinoma therapeutics.

The kidney plays a crucial role in regulating homeostasis within the human body. Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for nearly 90 % of all renal malignancies. Despite the availability of various therapeutic strategies, RCC remains a challenging disease due to its resistance to conventional treatments. Nanotechnology has emerged as a promising field, offering new opportunities in cancer therapeutics. It presents several advantages over traditional methods, enabling diverse biomedical applications, including drug delivery, prevention, diagnosis, and treatment. Lipid nanoparticles (LNPs), approximately 100 nm in size, are derived from a range of lipids and other biochemical compounds. these particulates are designed to overcome biological barriers, allowing them to selectively accumulate at diseased target sites for effective therapeutic action. Many pharmaceutically important compounds face challenges such as poor solubility in aqueous solutions, chemical and physiological instability, or toxicity. LNP technology stands out as a promising drug delivery system for bioactive organic compounds. This article reviews the applications of LNPs in RCC treatment and explores their potential clinical translation, identifying the most viable LNPs for medical use. With ongoing advancement in LNP-based anticancer strategies, there is a growing potential to improve the management and treatment of renal cancer.

Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.

BACKGROUND: AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/ß tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo. METHODS: Immunohistochemistry was used to examine the expression of AGTPBP1 in PC and non-cancerous tissues. Additionally, we assessed the malignant behaviors of PC cells following siRNA-mediated AGTPBP1 knockdown both in vitro and in vivo. RNA sequencing and bioinformatics analysis were performed to identify the differentially expressed genes regulated by AGTPBP1. RESULTS: We determined that AGTPBP1 was overexpressed in PC tissues and the higher expression of AGTPBP1 was closely related to the location of tumors. AGTPBP1 inhibition can significantly decrease cell progression in vivo and in vitro. Moreover, the knockdown of AGTPBP1 inhibited the expression of ERK1/2, P-ERK1/2, MYLK, and TUBB4B proteins via the ERK signaling pathway. CONCLUSION: Our research indicates that AGTPBP1 may be a putative therapeutic target for PC.

Research on the application of radiomics in breast cancer: A bibliometrics and visualization analysis.

Breast cancer is the most prevalent form of cancer worldwide. Therefore, improved disease detection has emerged as a focal point in clinical studies. At the forefront of innovation, radiomics has the capability to extract comprehensive insights from medical images, ultimately enhancing the accuracy of diagnostic procedures. There has been rapid growth in the field of radiomics research on breast cancer in the past few years. We explored pertinent research articles in the Web of Science Core Collection database to gain a thorough understanding of breast cancer radiomics. We used CiteSpace to conduct a bibliometric analysis of the annual distribution of different nations, institutions, journals, authors, keywords, and references in the field of breast cancer radiomics. GraphPad Prism software was used to examine and graph yearly and country-specific trends and the proportions of publications. The tools utilized for the visualization of science mapping included CiteSpace and VOSviewer. Of the 891 publications, most were original articles (731, 91.09%) and a few were reviews (160, 8.91%). Most academic research has been published in China and the United States. The study centers predominantly consisted of major academic institutions, such as Fudan University and the Chinese Academy of Sciences, with some of their members being prominent figures in the field. Pinker, Katja has published the largest number of research papers. The majority of these studies have been published in medical journals focusing on radiology and oncology in recent years. In the realm of cutting-edge medical research, the top two keywords, magnetic resonance imaging and machine learning stand at the forefront as current areas of intense focus. Breast cancer radiomics is advancing rapidly, presenting numerous opportunities and obstacles. Our study of the literature in this academic area aimed to pinpoint the primary themes addressed in the studies and anticipate prospective avenues for research.

Optical scattering measurement of highly reflective coatings with the cavity ring-down technique.

Cavity ringdown (CRD) is employed for the first time, to the best of our knowledge, to precisely measure the optical scattering of highly reflective (HR) optics with measurement sensitivity greatly enhanced via power trapping inside the ringdown cavity. The scattering measurement accuracy is significantly improved by calibrating the photo-detector for the scattering measurement with the low transmittance of the cavity mirror or test HR mirror, which is also accurately measured by CRD. The influence of environmental stray light (such as the probe light scattered by optics and mechanical parts outside the ringdown cavity) and other background noises on the scattering measurement is greatly eliminated by the temporal behavior of the scattering CRD signal. A scattering measurement sensitivity of 4.0 × 10-13 is experimentally achieved with a laser with output power of 12 mW.

Horizontal Transport in Ti3C2Tx MXene for Highly Efficient Osmotic Energy Conversion from Saline-Alkali Environments.

Osmotic energy from the ocean has been thoroughly studied, but that from saline-alkali lakes is constrained by the ion-exchange membranes due to the trade-off between permeability and selectivity, stemming from the unfavorable structure of nanoconfined channels, pH tolerance, and chemical stability of the membranes. Inspired by the rapid water transport in xylem conduit structures, we propose a horizontal transport MXene (H-MXene) with ionic sequential transport nanochannels, designed to endure extreme saline-alkali conditions while enhancing ion selectivity and permeability. The H-MXene demonstrates superior ion conductivity of 20.67 S m-1 in 1 M NaCl solution and a diffusion current density of 308 A m-2 at a 10-fold salinity gradient of NaCl solution, significantly outperforming the conventional vertical transport MXene (V-MXene). Both experimental and simulation studies have confirmed that H-MXene represents a novel approach to circumventing the permeability-selectivity trade-off. Moreover, it exhibits efficient ion transport capabilities, addressing the gap in saline-alkali osmotic power generation.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Hospitalized children with COVID-19 infection during large outbreak of SARS-CoV-2 Omicron strain: a retrospective study in Chaozhou, Guangdong, China.

OBJECTIVE: We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022. METHOD: All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively. RESULTS: A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient's condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels. CONCLUSIONS: Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

ZMAT2 condensates regulate the alternative splicing of TRIM28 to reduce cellular ROS accumulation, thereby promoting the proliferation of HCC cells.

Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Hypoxia-related signature to risk stratify patients for the benefit of immune checkpoint inhibitors therapy in head and neck squamous cell carcinoma: An experimental study.

BACKGROUND: Increasing evidence has shown that hypoxia is a biomarker of tumor proliferation and metastasis. This research aimed to identify a hypoxia-associated gene prognostic index (HAGPI) in head and neck squamous cell carcinoma (HNSCC) and based on HAGPI-defined subgroups to predict prognosis and response to immune checkpoint inhibitors therapy. METHODS: RNA-sequencing transcriptomic data for patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA). Protein-protein interaction network analysis was performed to select hypoxia-related hub genes. Univariate and multivariate cox regression analyses were used to identify hub genes to develop the HAGPI. Afterward expression data were imported into CIBERSORT to evaluate the relative proportion of 22 immune cells and compared the relative proportions of immune cells between the 2 HAGPI subgroups. The relationship between immunopheno score (IPS) and HAGPI was validated for immune checkpoint inhibitors (ICIs) response in TCGA cohorts. RESULTS: The HAGPI was constructed based on HS3ST1, HK1, PGK1, STC2, SERPINE1, PKLR genes. In high-HAGPI patients, the primary and secondary endpoint events in TCGA and GEO cohorts were significantly lower than low-HAGPI groups (P < .05). HAGPI-high patients exhibited a poorer prognosis than HAGPI-low patients did. The abundance of M2 macrophages and NK cell were significantly enhanced in the high-HAGPI while T cells regulatory and T cells CD8, were markedly elevated in the low-HAGPI. Meanwhile, patients in the low-HAGPI patients had higher levels of immunosuppressant expression and less aggressive phenotypes. Furthermore, IPS analysis showed that the low-HAGPI group with higher IPS represented a more immunogenic phenotype. CONCLUSION: The current study developed and verified a HAPGI model that can be considered as an independent prognostic biomarker and elucidated the tumor immune microenvironment of HNSCC.