Lactoferrin/CD133 antibody conjugated nanostructured lipid carriers for dual targeting of blood-brain-barrier and glioblastoma stem cells.

The main reasons for the difficulty in curing and high recurrence rate of glioblastoma multiforme (GBM) include: 1. The difficulty of chemotherapy drugs in penetrating the blood-brain barrier (BBB) to target tumor cells; 2. The presence of glioma stem cells (GSCs) leading to chemotherapy resistance. Therefore, breaking through the limitations of the BBB and overcoming the drug resistance caused by GSCs are the main strategies to address this problem. This study presents our results on the development of lactoferrin/CD133 antibody conjugated nanostructured lipid carriers (Lf/CD133-NLCS) for simultaneously targeting BBB and GSCs. Temozolomide (TMZ) loaded Lf/CD133-NLCS (Lf/CD133-NLCS-TMZ) exhibited high-efficiency in vitro anti-tumor effects toward malignant glioma cells (U87-MG) and GSCs, while demonstrating no significant toxicity to human normal macrophages and L929 cells at concentrations lower than 200 µg/mL. The results of the in vitro targeting GBM study revealed a notably higher cellular uptake of Lf/CD133-NLCS-TMZ in U87-MG cells and GSCs in comparison to NLCS-TMZ. This suggests that the active targeting of GBM was enhanced following Lf/CD133 modification. In addition, increased BBB permeability were confirmed for Lf/CD133-NLCS-TMZ compared to NLCS-TMZ both in vitro and in vivo. Taking the results together, Lf/CD133-NLCS-TMZ show great potential for dual targeting of BBB and GSCs, as well as GBM therapy based on this strategy. .

Estimation of irrigated crop artificial irrigation evapotranspiration in China.

Agriculture water use accounts for 70% of the total water withdrawal worldwide. The evapotranspiration during crop growth is one of the important hydrological processes in the agricultural water cycle. This study proposed the concept of artificial irrigation evapotranspiration of irrigated crops to describe that the evapotranspiration caused by irrigation water use. Irrigated crops rely on two kinds of water sources: precipitation and irrigation water. With the construction of irrigation schemes, the artificial irrigation evapotranspiration plays an increasingly important role in the dualistic water cycle system of irrigated cropland. To reveal the amount of artificial irrigation evapotranspiration of 17 categories of irrigated crops in China, this study proposed a new quantitative model system which was established based on traditional evapotranspiration models and soil water balance models. Based on the new model system, we calculated the annual artificial irrigation evapotranspiration of irrigated crops for the period 2013 to 2017 in China. The results showed that the proportion of artificial irrigation evapotranspiration to the total evapotranspiration of irrigated crops was 41.3%, whose value was 228.1 km3 a-1. The artificial irrigation evapotranspiration in different agricultural water management regions were 90.0 km3 a-1 in the northeast region, 86.0 km3 a-1 in the southeast region, and relatively low 52.2 km3a-1 in the west region. The results of this study can provide methods for water management and policy-making in agricultural irrigated areas, and it can also provide a preliminary understanding of the influence of human activities on the dualistic water cycle in cropland.

Transient Chiral Dynamics in the Fenna-Matthews-Olson Complex Revealed by Two-Dimensional Circular Dichroism Spectroscopy.

Chirality plays a pivotal role across scientific disciplines with profound implications spanning light-matter interactions, molecular recognition, and natural evolutionary processes. This study delves into the active influence of molecular chirality on exciton energy transfer within photosynthetic protein complexes, focusing on the Fenna-Matthews-Olson (FMO) complex. Employing two-dimensional circular dichroism (2DCD) spectroscopy, we investigate the transient chiral dynamics of excitons during energy transfer processes within the FMO complex. Our approach, incorporating pulse information into population dynamics based on the third-order response function, facilitates the calculation of 2DCD spectra and dynamics. This enables the extraction of chiral contributions to excitonic energy transfer and the examination of electronic wave functions. We demonstrate that 2DCD spectra offer excitation energies that are better resolved than those from conventional two-dimensional electronic spectroscopy. These findings deepen our understanding of exciton energy transfer mechanisms in natural photosynthesis, emphasizing the potential of 2DCD spectroscopy as a powerful tool for unraveling the chiral contribution to exciton dynamics.

Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study.

BACKGROUND: Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer. METHODS: This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations. RESULTS: The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism. CONCLUSION: This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

Mapping of a Major-Effect Quantitative Trait Locus for Seed Dormancy in Wheat.

The excavation and utilization of dormancy loci in breeding are effective endeavors for enhancing the resistance to pre-harvest sprouting (PHS) of wheat varieties. CH1539 is a wheat breeding line with high-level seed dormancy. To clarify the dormant loci carried by CH1539 and obtain linked molecular markers, in this study, a recombinant inbred line (RIL) population derived from the cross of weak dormant SY95-71 and strong dormant CH1539 was genotyped using the Wheat17K single-nucleotide polymorphism (SNP) array, and a high-density genetic map covering 21 chromosomes and consisting of 2437 SNP markers was constructed. Then, the germination percentage (GP) and germination index (GI) of the seeds from each RIL were estimated. Two QTLs for GP on chromosomes 5A and 6B, and four QTLs for GI on chromosomes 5A, 6B, 6D and 7A were identified. Among them, the QTL on chromosomes 6B controlling both GP and GI, temporarily named QGp/Gi.sxau-6B, is a major QTL for seed dormancy with the maximum phenotypic variance explained of 17.66~34.11%. One PCR-based diagnostic marker Ger6B-3 for QGp/Gi.sxau-6B was developed, and the genetic effect of QGp/Gi.sxau-6B on the RIL population and a set of wheat germplasm comprising 97 accessions was successfully confirmed. QGp/Gi.sxau-6B located in the 28.7~30.9 Mbp physical position is different from all the known dormancy loci on chromosomes 6B, and within the interval, there are 30 high-confidence annotated genes. Our results revealed a novel QTL QGp/Gi.sxau-6B whose CH1539 allele had a strong and broad effect on seed dormancy, which will be useful in further PHS-resistant wheat breeding.

Role and targeting of the AGC kinase family in pulmonary fibrosis (Review).

Pulmonary fibrosis (PF) is a progressive and irreversible pulmonary disease with a high mortality rate and limited treatment options. The cAMP-dependent protein kinase A, cGMP-dependent protein kinase G and phospholipid-dependent protein kinase C, collectively known as AGC kinases, are evolutionarily conserved protein kinases that are widely distributed among eukaryotes. AGC kinases serve a crucial role in a variety of cellular functions and pathological processes, including cancer, diabetes, inflammation and viral infections, where they have been implicated the pathogenesis of PF. The present review summarizes the evidence for the involvement of specific AGC kinases in the pathogenesis of PF, and provides a theoretical basis for the development of targeted AGC kinase small molecule inhibitors or targeted drugs, offering more effective treatment options and strategies for patients with PF.

Application and progress of nanozymes in antitumor therapy.

Tumors remain one of the major threats to public health and there is an urgent need to design new pharmaceutical agents for their diagnosis and treatment. In recent years, due to the rapid development of nanotechnology, biotechnology, catalytic science, and theoretical computing, subtlety has gradually made great progress in research related to tumor diagnosis and treatment. Compared to conventional drugs, enzymes can improve drug distribution and enhance drug enrichment at the tumor site, thereby reducing drug side effects and enhancing drug efficacy. Nanozymes can also be used as tumor tracking imaging agents to reshape the tumor microenvironment, providing a versatile platform for the diagnosis and treatment of malignancies. In this paper, we review the current status of research on enzymes in oncology and analyze novel oncology therapeutic approaches and related mechanisms. To date, a large number of nanomaterials, such as noble metal nanomaterials, nonmetallic nanomaterials, and carbon-based nanomaterials, have been shown to be able to function like natural enzymes, particularly with significant advantages in tumor therapy. In light of this, the authors in this review have systematically summarized and evaluated the construction, enzymatic activity, and their characteristics of nanozymes with respect to current modalities of tumor treatment. In addition, the application and research progress of different types of nicknames and their features in recent years are summarized in detail. We conclude with a summary and outlook on the study of nanozymes in tumor diagnosis and treatment. It is hoped that this review will inspire researchers in the fields of nanotechnology, chemistry, biology, materials science and theoretical computing, and contribute to the development of nano-enzymology.

Lipid-based nanoparticles to address the limitations of GBM therapy by overcoming the blood-brain barrier, targeting glioblastoma stem cells, and counteracting the immunosuppressive tumor microenvironment.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, characterized by high heterogeneity, strong invasiveness, poor prognosis, and a low survival rate. A broad range of nanoparticles have been recently developed as drug delivery systems for GBM therapy owing to their inherent size effect and ability to cross the blood-brain barrier (BBB). Lipid-based nanoparticles (LBNPs), such as liposomes, solid lipid NPs (SLNs), and nano-structured lipid carriers (NLCs), have emerged as the most promising drug delivery system for the treatment of GBM because of their unique size, surface modification possibilities, and proven bio-safety. In this review, the main challenges of the current clinical treatment of GBM and the strategies on how novel LBNPs overcome them were explored. The application and progress of LBNP-based drug delivery systems in GBM chemotherapy, immunotherapy, and gene therapy in recent years were systematically reviewed, and the prospect of LBNPs for GBM treatment was discussed.

Pure testicular choriocarcinoma, a rare and highly malignant subtype with challenging treatment: A case report and review of the literature.

Testicular choriocarcinoma (CC) is the rarest subtype of germ cell tumours (GCTs) of the testis, with a high malignant potential and early haematogenous metastasis. Radical surgical resection should be performed primarily for histological diagnosis, while chemotherapy remains the mainstay of therapy for advanced disease. In the present study, the case of a 65-year-old male patient diagnosed with metastatic testicular CC, who did not fully respond to chemotherapy is reported. This patient underwent surgical removal of the testicular tumour, chemotherapy with etoposide and cisplatin, and radiotherapy of the intracranial lesions. Although the serum human chorionic gonadotropin (HCG) levels of the patient and most of the metastases continued decreasing during chemotherapy, complete response was not achieved after six cycles of chemotherapy. The patient refused high-dose chemotherapy and autologous stem cell transplantation due to severe side effects, and eventually developed respiratory failure on maintenance therapy with oral etoposide. A literature review was then performed, aiming to summarize the characteristics and therapeutic principles of testicular CC. In addition, the emerging therapeutic agents that could be used in maintenance therapy for GCTs, particularly for testicular CC, were also discussed. The limited clinical trials of targeted treatments showed potential benefit for long survival of patients with selected GCTs with fewer side effects. In particular, immunotherapy showed unique potential for testicular CC in preclinical studies, offering new approaches of maintenance therapy for advanced disease. Further studies should shed light on the identification of prognostic factors that predict the response to immune-based therapy in GCTs.

E3 ligase TRIM65 alleviates intestinal ischemia/reperfusion injury through inhibition of TOX4-mediated apoptosis.

Intestinal ischemia-reperfusion (II/R) injury is an urgent clinical disease with high incidence and mortality, and impaired intestinal barrier function caused by excessive apoptosis of intestinal cells is an important cause of its serious consequences. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase that is recently reported to suppress the inflammatory response and apoptosis. However, the biological function and regulation of TRIM65 in II/R injury are totally unknown. We found that TRIM65 was significantly decreased in hypoxia-reoxygenation (H/R) induced intestinal epithelial cells and II/R-induced intestine tissue. TRIM65 knockout mice markedly aggravated intestinal apoptosis and II/R injury. To explore the molecular mechanism of TRIM65 in exacerbating II/R-induced intestinal apoptosis and damage, thymocyte selection-associated high mobility group box factor 4 (TOX4) was screened out as a novel substrate of TRIM65 using the yeast two-hybrid system. TRIM65 binds directly to the N-terminal of TOX4 through its coiled-coil and SPRY structural domains. Immunofluorescence confocal microscopy showed that they can co-localize both in the cytoplasm and nucleus. Furthermore, TRIM65 mediated the K48 ubiquitination and degradation of TOX4 depending on its E3 ubiquitin ligase activity. In addition, TRIM65 inhibits H/R-induced intestinal epithelial apoptosis via TOX4. In summary, our results indicated that TRIM65 promotes ubiquitination and degradation of TOX4 to inhibit apoptosis in II/R. These findings provide a promising target for the clinical treatment of II/R injury.

Generation of a vector conventional soliton via a graphene oxide saturable absorber.

We have experimentally observed an ultrashort conventional vector soliton in an erbium-doped fiber laser. The few-layered graphene oxide (GO) is used as a saturable absorber (SA). It is found that the saturable absorption characteristic of GO is polarization independent. Therefore, vector solitons can be obtained without polarization control by using such SA. By using a polarization beam splitter to split the mode-locked pulse obtained in the oscillator, two orthogonal polarization vector solitons with equal intensity and consistent characteristics can be obtained. It demonstrates that the initial soliton consists of two orthogonal polarization components. It is worth noting that these two orthogonal polarization component solitons improve the signal-to-noise ratio (SNR) of 3 dB compared with the initial soliton. The improvement in SNR is very significant and cannot be neglected. This phenomenon has not been reported before, to our knowledge. In addition, the conventional soliton generated by this mode-locked laser has a central wavelength of 1559 nm with 1.1 ps pulse duration. The mode-locking state of this laser can be self-started. After mode locking, the environmental stability is excellent. The experimental results indicate that GO as a broadband SA has great potential and application prospects in the field of vector soliton generation.

Green infrastructure optimization considering spatial functional zoning in urban stormwater management.

Green infrastructure (GI) is used as an alternative and complement to traditional urban drainage system for mitigating urban stormwater issues mainly caused by climate change and urbanization. The combination of hydrological model and optimization algorithm can automatically find the optimal solution under multiple objectives. Given the multi-functional characteristics of GI, choosing the optimization objectives of GI are critical for multiple stakeholders. This study proposes a GI optimization method considering spatial functional zoning. Based on the basic conditions, the study area is divided into the flood risk control zone (FRCZ) and the total runoff control zone (TRCZ). The integrated model coupling hydrological model and optimization algorithm is applied to obtain the Pareto fronts and corresponding non-dominated solutions. The Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is used to support the decision-making process. The optimal solution obtained for the FRCZ achieves a flood risk reduction rate of 60.49% with an average life cycle cost per year of 0.20 × 108 Chinese Yuan (CNY); The optimal solution obtained for the TRCZ achieves a total runoff reduction rate of 22.83% with an average life cycle cost per year of 0.17 × 108 CNY. This study provides a reference for stakeholders in GI planning and design.

Skin infectome of patients with a tick bite history.

Introduction: Ticks are the most important obligate blood-feeding vectors of human pathogens. With the advance of high-throughput sequencing, more and more bacterial community and virome in tick has been reported, which seems to pose a great threat to people. Methods: A total of 14 skin specimens collected from tick-bite patients with mild to severe symptoms were analyzed through meta-transcriptomic sequencings. Results: Four bacteria genera were both detected in the skins and ticks, including Pseudomonas, Acinetobacter, Corynebacterium and Propionibacterium, and three tick-associated viruses, Jingmen tick virus (JMTV), Bole tick virus 4 (BLTV4) and Deer tick mononegavirales-like virus (DTMV) were identified in the skin samples. Except of known pathogens such as pathogenic rickettsia, Coxiella burnetii and JMTV, we suggest Roseomonas cervicalis and BLTV4 as potential new agents amplified in the skins and then disseminated into the blood. As early as 1 day after a tick-bite, these pathogens can transmit to skins and at most four ones can co-infect in skins. Discussion: Advances in sequencing technologies have revealed that the diversity of tick microbiome and virome goes far beyond our previous understanding. This report not only identifies three new potential pathogens in humans but also shows that the skin barrier is vital in preventing horizontal transmissions of tick-associated bacteria or virus communities to the host. It is the first research on patients' skin infectome after a tick bite and demonstrates that more attention should be paid to the cutaneous response to prevent tick-borne illness.

Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine.

Ovarian cancer (OC) remains the most fatal disease of gynecologic malignant tumors. Angiogenesis refers to the development of new vessels from pre-existing ones, which is responsible for supplying nutrients and removing metabolic waste. Although not yet completely understood, tumor vascularization is orchestrated by multiple secreted factors and signaling pathways. The most central proangiogenic signal, vascular endothelial growth factor (VEGF)/VEGFR signaling, is also the primary target of initial clinical anti-angiogenic effort. However, the efficiency of therapy has so far been modest due to the low response rate and rapidly emerging acquiring resistance. This review focused on the current understanding of the in-depth mechanisms of tumor angiogenesis, together with the newest reports of clinical trial outcomes and resistance mechanism of anti-angiogenic agents in OC. We also emphatically summarized and analyzed previously reported biomarkers and predictive models to describe the prospect of precision therapy of anti-angiogenic drugs in OC.

2-µm nonlinear post-compression for generating ∼100-MHz few-cycle laser pulses with watt-level average power.

We firstly report a high pulse repetition rate (101.4 MHz) nonlinear post-compression based on the normal dispersion fiber (NDF) operating in 2-µm wavelength region. With only one-stage NDF-based nonlinear pulse compressor, the 2-µm ultrafast laser pulses are compressed from ∼460 fs down to 70 fs, corresponding to ∼10.4 optical oscillation cycle. With two-stage nonlinear pulse compressor, the input ultrafast laser pulses are further compressed to 28.3 fs (∼4.3 optical oscillation cycle). In each case, the average power of the compressed 2-µm laser pulses exceeds 1 W, which is believed to be the highest average power never achieved at ∼100-MHz pulse repetition rate. The efficiencies of the one-stage and two-stage nonlinear pulse compressors are 64% and 47% respectively.

Factors affecting the medication literacy of older adults and targeted initiatives for improvement: a cross-sectional study in central China.

Introduction: This study explored the state of rational drug use among older adults in central China, aiming to unveil factors influencing their medication literacy and proposing targeted improvement measures. Methods: A cross-sectional study involving 454 participants aged 60 and above was conducted in Hubei province between February 1 and May 30, 2023, with data collected through face-to-face interviews by pharmacists. Multiple logistic regression analysis was conducted to determine factors that affected medication literacy. Results: Of the 412 valid questionnaires, findings revealed inadequate knowledge of rational drug use among older adults in central China. Those who fully understood (105, 25.49%, OR = 9.349, p < 0.001, 95%CI = 3.884-22.502) or partially understood (228, 55.34%, OR = 3.295, p = 0.002, 95%CI = 1.548-7.013) drug instructions exhibited significantly higher medication literacy than those who did not understand (79, 19.17%). Subsequent research revealed a lack of awareness in reading drug instructions or difficulty in understanding them. Most older adults seldom heard of but exhibited high acceptance of medication guidance services. Discussion: In conclusion, the ability to comprehend drug instructions significantly influenced the medication literacy of older adults. Initiatives such as revising age-appropriate drug instructions could effectively enhance rational drug use among this demographic.

Multimedia visual physiological stimulation combined with stereoscopic system training for the treatment of ametropic amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the efficacy of multimedia visual physiological stimulation combined with stereoscopic system training in the treatment of ametropic amblyopia in children.METHODS: A total of 102 patients(102 eyes)with ametropic amblyopia admitted to our hospital from June 2021 to June 2022 were randomly divided into two groups. The control group consisted of 51 patients(51 eyes)who received multimedia visual physiological stimulation on the basis of conventional treatment, while the observation group consisted of 51 patients(51 eyes)who received stereoscopic training on the basis of the control group. The binocular fusion function, binocular stereopsis and binocular disparity of the two groups of children were evaluated at 3mo after treatment, and the clinical efficacy was assessed based on the improvement of vision.RESULTS: After 3mo of treatment, the normal rates of binocular fusion function, binocular stereopsis, and binocular disparity in the observation group were significantly higher than those in the control group(all P&#x003C;0.05). The total effective rate of the observation group was significantly higher than that of the control group(94.1% vs. 60.8%, P&#x003C;0.05), and the total effective rate of treatment in children of different ages in the observation group was higher than that in the control group(P&#x003C;0.05), with children aged 6-8 having the highest effective rate of treatment; The total effective rate of treatment for children with mild to moderate amblyopia in the observation group was higher than that in the control group(94.0% vs. 61.2%, P&#x003C;0.05).CONCLUSION: The combination of multimedia visual physiological stimulation and stereoscopic system training has a good therapeutic effect on ametropic amblyopia, which can promote visual recovery, help reconstruct binocular stereopsis, and has a better effect on children aged 6-8 years or children with mild to moderate amblyopia.

Design of Compact and Broadband Polarization Beam Splitters Based on Surface Plasmonic Resonance in Photonic Crystal Fibers.

In this work, a polarization beam splitter (PBS) based on surface plasmonic resonance is proposed and realized in a designed photonic crystal fiber (PCF). The PCF consists of two kinds of air holes with different diameters. Two solid silica cores near the center of the PCF are established by removing the cladding air holes. A gold film is plated at the external surface of the central air hole of the PCF to excite the surface plasmonic resonance. In order to minimize the length and improve the operation bandwidth of the PBS, the influences of the transversal structural parameters of the PCF are investigated in the context of both X and Y polarization beams. It was found that a 123.6-µm-long PBS with an operation bandwidth of 314 nm could be realized after the global optimization of five structural parameters. The proposed PBS may have potential applications in micro-/nano-optical systems for sensing and communications.

A Surface Plasmon Resonance-Based Photonic Crystal Fiber Sensor for Simultaneously Measuring the Refractive Index and Temperature.

In this paper, a surface plasmon resonance (SPR)-based photonic crystal fiber (PCF) sensor is proposed for simultaneously measuring the refractive index (RI) and temperature. In the design, the central air hole and external surface of the proposed PCF are coated with gold films, and an air hole is filled with the temperature-sensitive material (TSM). By introducing the inner and outer gold films and TSM, the RI and temperature can be measured simultaneously at different wavelength regions. The simulation results show that the average wavelength sensitivities of the proposed SPR-based PCF sensor can reach 4520 nm/RIU and 4.83 nm/°C in the RI range of 1.35~1.40 and a temperature range of 20~60 °C, respectively. Moreover, because of using the different wavelength regions for sensing, the RI and temperature detections of the proposed SPR-based PCF sensor can be achieved independently. It is believed that the proposed SPR-based PCF RI and temperature sensor has important applications in biomedicine and in environmental science.