Improved Liver Intravital Microscopic Imaging Using a Film-Assisted Stabilization Method.

Intravital microscopy (IVM) is a valuable method for biomedical characterization of dynamic processes, which has been applied to many fields such as neuroscience, oncology, and immunology. During IVM, vibration suppression is a major challenge due to the inevitable respiration and heartbeat from live animals. In this study, taking liver IVM as an example, we have unraveled the vibration inhibition effect of liquid bridges by studying the friction characteristics of a moist surface on the mouse liver. We confirmed the presence of liquid bridges on the liver through fluorescence imaging, which can provide microscale and nondestructive liquid connections between adjacent surfaces. Liquid bridges were constructed to sufficiently stabilize the liver after abdominal dissection by covering it with a polymer film, taking advantage of the high adhesion properties of liquid bridges. We further prototyped a microscope-integrated vibration-damping device with adjustable film tension to simplify the sample preparation procedure, which remarkably decreased the liver vibration. In practical application scenarios, we observed the process of liposome phagocytosis by liver Kupffer cells with significantly improved image and video quality. Collectively, our method not only provided a feasible solution to vibration suppression in the field of IVM, but also has the potential to be applied to vibration damping of precision instruments or other fields that require nondestructive ″soft″ vibration damping.

Momentum-space spin texture induced by strain gradient in nominally centrosymmetric SrIrO3 films.

Spin texture in k-space is a consequence of spin splitting due to strong spin-orbit coupling and inversion symmetry breaking. It underlies fertile spin transport phenomena and is of crucial importance for spintronics. Here, we observe the spin texture in k-space of nominally centrosymmetric SrIrO3 grown on NdGaO3 (110) substrates, using non-linear magnetotransport measurements. We demonstrate that the spin texture is not only induced by the interface, which inherently breaks the inversion symmetry in strong spin-orbit coupled SrIrO3 films, but also originates from the film bulk. Structural analysis reveals that thicker SrIrO3 films exhibit a strain gradient, which could be considered as a continuous change in the lattice constant across different layers and breaks the inversion symmetry throughout the entire SrIrO3 films, giving rise to the spin texture in k-space. First-principles calculations reveal that the strain gradient creates large spin-splitting bands, inducing the spin texture with anisotropy, which is consistent with our experimental observations. Our results offer an efficient method for inducing the spin textures in k-space.

A dynamic regulome of shoot-apical-meristem-related homeobox transcription factors modulates plant architecture in maize.

BACKGROUND: The shoot apical meristem (SAM), from which all above-ground tissues of plants are derived, is critical to plant morphology and development. In maize (Zea mays), loss-of-function mutant studies have identified several SAM-related genes, most encoding homeobox transcription factors (TFs), located upstream of hierarchical networks of hundreds of genes. RESULTS: Here, we collect 46 transcriptome and 16 translatome datasets across 62 different tissues or stages from the maize inbred line B73. We construct a dynamic regulome for 27 members of three SAM-related homeobox subfamilies (KNOX, WOX, and ZF-HD) through machine-learning models for the detection of TF targets across different tissues and stages by combining tsCUT&Tag, ATAC-seq, and expression profiling. This dynamic regulome demonstrates the distinct binding specificity and co-factors for these homeobox subfamilies, indicative of functional divergence between and within them. Furthermore, we assemble a SAM dynamic regulome, illustrating potential functional mechanisms associated with plant architecture. Lastly, we generate a wox13a mutant that provides evidence that WOX13A directly regulates Gn1 expression to modulate plant height, validating the regulome of SAM-related homeobox genes. CONCLUSIONS: The SAM-related homeobox transcription-factor regulome presents an unprecedented opportunity to dissect the molecular mechanisms governing SAM maintenance and development, thereby advancing our understanding of maize growth and shoot architecture.

A CD25×TIGIT bispecific antibody induces anti-tumor activity through selective intratumoral Treg cell depletion.

Intratumoral regulatory T cells (Tregs) express high levels of CD25 and TIGIT, which are also recognized as markers of effector T cell (Teff) activation. Targeting these molecules each alone with monoclonal antibodies (mAbs) poses a risk of concurrently depleting both Teffs and peripheral Tregs, thereby compromising the effectiveness and selectivity of intratumoral Treg depletion. Here, leveraging the increased abundance of CD25+ TIGIT+ double-positive Tregs in the solid tumor microenvironment (but not in peripheral tissues), we explore the feasibility of using a CD25×TIGIT bispecific antibody (bsAb) to selectively deplete intratumoral Tregs. We initially constructed a bsAb co-targeting mouse CD25 and TIGIT, NSWm7210, and found that NSWm7210 conferred enhanced intratumoral Treg depletion, Teff activation, and tumor suppression as compared to the parental monotherapies in mouse models. We subsequently constructed a bsAb co-targeting human CD25 and TIGIT (NSWh7216), which preferentially eliminated CD25+ TIGIT+ double-positive cells over single-positive cells in vitro. NSWh7216 exhibited enhanced anti-tumor activity without toxicity of peripheral Tregs in CD25 humanized mice compared to the parental monotherapies. Our study illustrates the use of CD25×TIGIT bsAbs as effective agents against solid tumors based on selective depletion of intratumoral Tregs.

Metabolomics ravels flavor compound formation and metabolite transformation in rapid fermentation of salt-free fish sauce from catfish frames induced by mixed microbial cultures.

This study demonstrates that the co-inoculation with Lactiplantibacillus plantarum, Pichia fermentans and Staphylococcus saprophyticus accelerates catfish frame fish sauce fermentation. Over a 3-day period, significant changes occurred in physicochemical properties, microbial profiles, flavor compounds, and metabolomic spectra. Notable increases in acidity coupled with decreases in glucose underscored the robust environmental adaptability of the employed microorganisms. A reduction in total amino acids, alongside a rise in umami amino acids, suggested flavor enhancement. GC-MS analysis identified 40 key volatile compounds, with esters and aldehydes crucial for aroma development. UPLC-QTOF-MS-based untargeted analysis identified 934 metabolites, with 377 differential metabolites being vital (VIP > 1.5, P < 0.05), including amino acids, peptides, organic acids, nucleic acids, and fatty acids. Metabolites linked to amino acid metabolism, particularly phenylalanine and arginine, were associated with fermentation duration. These findings offer a theoretical basis for optimizing flavor and quality in fish sauces from fish by-products through accelerated fermentation.

A sex-oriented analysis concerning skeletal muscle quantity and quality and associations to quality of life in hospitalized patients with cirrhosis.

BACKGROUND: There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities. METHODS: Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity. RESULTS: The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm2/m2, P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index. CONCLUSIONS: Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL.

Adult attachment, social anxiety, and problematic social media use: A meta-analysis and meta-analytic structural equation model.

The relationship between adult attachment (anxious attachment and avoidant attachment) and problematic social media use is controversial and contradictory. Hence, the present study clarified the relationship between adult attachment dimensions and problematic social media use through meta-analysis. To better explain the relationship, this study also established meta-analytic structural equation modeling to examine the mediating role of social anxiety in the relationship. This study used CMA and R software for data analysis. Forty-five effect sizes were included in the study, including 11,746 individuals. Results showed that anxious attachment was strongly correlated with problematic social media use (r = 0.319, 95 %CI[0.271, 0.366]), whereas avoidant attachment was weakly correlated with problematic social media use (r = 0.091, 95 %CI[0.011,0.170]). Moderating effects showed that the relationship between anxious attachment and problematic social media use was moderated by the measurement instrument. Meta-analytic structural equation modeling showed that anxious attachment had a significant positive effect on PSMU through social anxiety, anxious attachment had a significant positive effect on PSMU through social anxiety. This study clarifies inconsistencies in the existing literature through meta-analysis, providing reliable conclusions and novel perspectives. It assists clinical practitioners in developing tailored treatment programs for practical interventions. It is suggested that treatment for problematic social media use requires attention to individuals with insecure adult attachment and social anxiety. For individuals with high anxious attachment and social anxiety, it is essential to help them manage their social media use effectively and reduce their dependence on it. Concurrently, interventions for attachment avoidant individuals should focus on enhancing their social self-confidence to reduce the influence of social anxiety on their social media use.

Local mRNA Delivery from Nanocomposites Made of Gelatin and Hydroxyapatite Nanoparticles.

Local delivery of messenger ribonucleic acid (mRNA) is increasingly being advocated as a promising new strategy to enhance the performance of biomaterials. While extensive research has been dedicated to the complexation of these oligonucleotides into nanoparticles to facilitate systemic delivery, research on developing suitable biomaterial carriers for the local delivery of mRNA is still scarce. So far, mRNA-nanoparticles (mRNA-NPs) are mainly loaded into traditional polymeric hydrogels. Here, we show that calcium phosphate nanoparticles can be used for both reinforcement of nanoparticle-based hydrogels and the complexation of mRNA. mRNA was incorporated into lipid-coated calcium phosphate nanoparticles (LCPs) formulated with a fusogenic ionizable lipid in the outer layer of the lipid coat. Nanocomposites of gelatin and hydroxyapatite nanoparticles were prepared at various ratios. Higher hydroxyapatite nanoparticle content increased the viscoelastic properties of the nanocomposite but did not affect its self-healing ability. Combination of these nanocomposites with peptide, lipid, and the LCP mRNA formulations achieved local mRNA release as demonstrated by protein expression in cells in contact with the biomaterials. The LCP-based formulation was superior to the other formulations by showing less sensitivity to hydroxyapatite and the highest cytocompatibility.

Divergent Reactions of α-Diazo 1,3-Dicarbonyl Compounds with Allylic Carbonates Involving Ketene versus Carbene Intermediates Enabled by Cooperative Rh(II)/Pd(0) Dual Catalysis.

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that enabled divergent reactions of α-diazo 1,3-dicarbonyl compounds with allylic carbonates involving ketene versus carbene intermediates is described. The efficient synthesis of α-quaternary allylated ß-keto-esters was accomplished by the Rh(II)/Pd(0) dual-catalysis allylic alkylation of α-diazo 1,3-dicarbonyl compounds. Alternatively, an unprecedented (1+4) annulation of α-diazo 1,3-dicarbonyl compounds with 2-(hydroxymethyl)allyl carbonates via Rh(II)/Pd(0) dual catalysis was also successfully developed, affording a wide variety of α-quaternary tetrahydrofurans in good to high yields.

Mechanical performance study of PVA fiber-reinforced seawater and sea sand cement-based composite materials.

Due to the swift progress in the construction sector, there is a global concern about the potential scarcity of river sand and freshwater resources. The development of new construction materials is considered an inevitable trend for industry growth. PVA fibers, known for their strong corrosion resistance, cost-effectiveness, and high toughness, have the potential to enhance the corrosion resistance and seismic performance of structures in marine environments. However, their mechanical properties and durability in the seawater and sea sand environment are not well understood. Therefore, the investigation of the impact of seawater and sea sand on the mechanical properties and durability of PVA fiber-reinforced cement composites is considered crucial. A mechanical performance analysis of PVA fiber-reinforced seawater and sea sand fiber cement composites was conducted in this study. PVA fiber volume fractions of 0%, 0.75%, and 1.5%, cement composite matrix strength grades of C30 and C50, and curing periods of 28 days, 90 days, and 180 days were examined, investigating their influence on the bending toughness of PVA fiber-reinforced seawater and sea sand cement composites. Specific conclusions include the addition of fibers increased the peak bending load, had a less corrosive effect in seawater, and improved the flexural toughness of the material. The most significant improvement was observed at 1.5% fiber content, where the load-deflection curve was fuller and the energy absorption capacity of the material increased by 33-109%, maintaining good bending toughness. Furthermore, higher fiber contents are required for high-strength cementitious composites to improve flexural toughness and durability. The formulation of calculation formulas for predicting bending strength and corresponding deflection, which fit well with the experimental results; and the development of a calculation model for the bending toughness index of PVA fiber-reinforced seawater and sea sand cement composites, providing an effective prediction of material bending toughness.

METTL16 participates in haemoglobin H disease through m6A modification.

BACKGROUND: Haemoglobin H (HbH) disease is caused by a disorder of α-globin synthesis, and it results in a wide range of clinical symptoms. M6A methylation modification may be one of the mechanisms of heterogeneity. Therefore, this article explored the role of methyltransferase like 16 (METTL16) in HbH disease. METHOD: The results of epigenetic transcriptome microarray were analysed and verified through bioinformatic methods and qRT-PCR, respectively. The overexpression or knock down of METTL16 in K562 cells was examined to determine its role in reactive oxygen species (ROS), cell cycle processes or iron overload. YTH domain family protein 3 (YTHDF3) was knocked down in K562 cells and K562 cells overexpressing METTL16 via siRNA to investigate its function. In addition, haemoglobin expression was detected through benzidine staining. qRT-PCR, WB, methylated RNA Immunoprecipitation (MeRIP) and (RNA Immunoprecipitation) RIP experiments were conducted to explore the mechanism of intermolecular interaction. RESULTS: METTL16, YTHDF3 and solute carrier family 5 member 3 (SLC5A3) mRNA and the methylation level of SLC5A3 mRNA were downregulated in HbH patients. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA expression was negatively correlated with HGB content among patients with HbH-CS disease. Overexpression of METTL16 increased ROS and intracellular iron contents in K562 cells, changed the K562 cell cycle, reduced hemin-induced haemoglobin synthesis, increased the expressions of SLC5A3 and HBG and increased SLC5A3 mRNA methylation levels. Knockdown of METTL16 reduced ROS and intracellular iron contents in K562 cells. Hemin treatment of K562 cells for more than 14 days reduced the protein expressions of METTL16 and SLC5A3 and SLC5A3 mRNA methylation levels. Knockdown of YTHDF3 rescued the intracellular iron content changes induced by the overexpression of METTL16. The RIP experiment revealed that SLC5A3 mRNA can be enriched by METTL16 antibody. CONCLUSION: METTL16 may affect the expression of SLC5A3 by changing its m6A modification level and regulating ROS synthesis, intracellular iron and cycle of red blood cells. Moreover, METTL16 possibly affects the expression of haemoglobin through IGF2BP3, which regulates the clinical phenotype of HbH disease.

Clinical effects of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy on complications and recurrence in patients with advanced gastric cancer.

Objective: To compare the clinical effects of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT) on complications and recurrence in patients with advanced gastric cancer (AGC). Method: This was a retrospective study. A total of 83 patients with AGC admitted to Chengde Central Hospital between Jan. 2019 and Jun. 2021 were selected and divided into the observation group(n=41) and the control group(n=42) using a random number table. Patients in the control group received XELOX chemotherapy, and those in the observation group received intensity-modulated radiotherapy (IMRT) with concurrent XELOX chemotherapy. Compared efficacy, pathological complete response rate (pCR), R0 resection rate, adverse reactions, and quality of life (QOL) before and after treatment between the two groups. Results: The efficacy, pCR, and R0 resection rate of the observation group were significantly increased compared with those of the control group. Comparison of complications showed the number of patients experiencing gastrointestinal (GI) reactions, increased BUN, increased GPT, alopecia, and pigmentation in the observation group was decreased compared with that in the control group, with no statistically significant differences(p>0.05), and the number of patients experiencing myelosuppression was statistically significant between the two groups(p<0.05). There were no significant differences in sub-scores of physical, role, emotional, cognitive, and social functions and the overall score of QOL between the two groups(p>0.05) before treatment. Conclusion: NCRT is safer and more effective in patients with AGC compared with NCT, and can significantly improve the QOL of patients. It can be widely used in clinical practice.

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OBJECTIVES: To investigate the amplitude-integrated electroencephalography (aEEG) monitoring results of hospitalized neonates in plateau areas. METHODS: A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology, Kunming Children's Hospital, and received aEEG monitoring from January 2020 to December 2022. According to the aEEG monitoring results, they were divided into a normal aEEG group and an abnormal aEEG group. The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases, as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities. RESULTS: Among the 5 945 neonates, the aEEG abnormality rate was 19.28% (1 146/5 945), with an abnormality rate of 29.58% (906/3 063) in critically ill neonates and 8.33% (240/2 882) in non-critically ill neonates (P<0.05). The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77% (79/130), followed by those with central nervous system disorders [42.22% (76/180)] and preterm infants [35.53% (108/304)]. Compared with the normal aEEG group, the abnormal aEEG group had significantly lower age and gestational age, as well as a significantly lower birth weight of preterm infants (P<0.05). Among the 1 146 neonates with aEEG abnormalities, the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates (52.09%), background activity abnormalities in 294 neonates (25.65%), and epileptiform activity in 255 neonates (22.25%), and there were 902 neonates (78.71%) with abnormal clinical manifestations. The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51% and 92.50%, respectively. CONCLUSIONS: In plateau areas, there is a relatively high rate of aEEG abnormalities among hospitalized neonates, particularly in critically ill neonates and those with smaller gestational ages and younger ages, suggesting a high risk of brain injury. Therefore, routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities, the decision-making in treatment, and the formulation of brain protection strategies.

New insight into the CNC-bZIP member, NFE2L3, in human diseases.

Nuclear factor erythroid 2 (NF-E2)-related factor 3 (NFE2L3), a member of the CNC-bZIP subfamily and widely found in a variety of tissues, is an endoplasmic reticulum (ER) membrane-anchored transcription factor that can be released from the ER and moved into the nucleus to bind the promoter region to regulate a series of target genes involved in antioxidant, inflammatory responses, and cell cycle regulation in response to extracellular or intracellular stress. Recent research, particularly in the past 5 years, has shed light on NFE2L3's participation in diverse biological processes, including cell differentiation, inflammatory responses, lipid homeostasis, immune responses, and tumor growth. Notably, NFE2L3 has been identified as a key player in the development and prognosis of multiple cancers including colorectal cancer, thyroid cancer, breast cancer, hepatocellular carcinoma, gastric cancer, renal cancer, bladder cancer, esophageal squamous cell carcinoma, T cell lymphoblastic lymphoma, pancreatic cancer, and squamous cell carcinoma. Furthermore, research has linked NFE2L3 to other cancers such as lung adenocarcinoma, malignant pleural mesothelioma, ovarian cancer, glioblastoma multiforme, and laryngeal carcinoma, indicating its potential as a target for innovative cancer treatment approaches. Therefore, to gain a better understanding of the role of NFE2L3 in disease, this review offers insights into the discovery, structure, function, and recent advancements in the study of NFE2L3 to lay the groundwork for the development of NFE2L3-targeted cancer therapies.

Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8+ T cells and inhibited tumor growth.

BACKGROUND: Tumor necrosis factor receptor superfamily 25 (TNFRSF25) is a T-cell co-stimulatory receptor. Expression of its ligand, TNF-like cytokine 1A (TL1A), on mouse tumor cells has been shown to promote tumor regression. This study aimed to develop TNFRSF25 agonists (both antibodies (Abs) and TL1A proteins) and to investigate their potential antitumor effects. METHODS: Anti-mouse TNFRSF25 (mTNFRSF25) Abs and multimeric TL1A proteins were generated as TNFRSF25 agonists. Their agonism was assessed in luciferase reporter and T-cell co-stimulation assays, and their antitumor effects were evaluated in syngeneic mouse tumor models. TNFRSF25 expression within the tumor microenvironment and the effects of an anti-mTNFRSF25 agonistic Ab on tumor-infiltrating T cells were evaluated by flow cytometry. Cell depletion assays were used to identify the immune cell types that contribute to the antitumor effect of the anti-mTNFRSF25 Ab. The Fc gamma receptor (FcγR) dependence of TNFRSF25 agonists was assessed in an in vivo T-cell expansion model and a mouse tumor model using Fc variants and FcγR-deficient mice. RESULTS: TNFRSF25 agonists exhibited antitumor effects in syngeneic mouse tumor models without causing observed side effects. We identified an anti-mTNFRSF25 agonistic Ab, 1A6-m1, which exhibited greater antitumor activity than a higher affinity anti-TNFRSF25 Ab which engages an overlapping epitope with 1A6-m1. 1A6-m1 activated CD8+ T cells and antigen-specific T cells, leading to tumor regression; it also induced long-term antitumor immune memory. Although activating TNFRSF25 by 1A6-m1 expanded splenic regulatory T (Treg) cells, it did not influence intratumoral Treg cells. Moreover, 1A6-m1's antitumor effects required the engagement of both inhibitory FcγRIIB and activating FcγRIII. Replacing 1A6-m1's CH1-hinge region with that of human IgG2 (h2) conferred enhanced antitumor effects. Finally, we also generated multimeric human and mouse TL1A fusion proteins as TNFRSF25 agonists, and they co-stimulated CD8+ T cells and reduced tumor growth, even in the absence of Fc-FcγR interactions. CONCLUSION: Our data demonstrates the potential of activating TNFRSF25 by Abs and multimeric TL1A proteins for cancer immunotherapy and provides insights into their development astherapeutics.

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Nanyang Cattle.

The objective of this study was to determine the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, in Nanyang cattle after a single intravenous (IV), and intramuscular (IM) administration of enrofloxacin at 2.5 mg/kg body weight (BW). Blood samples were collected at predetermined time points. Enrofloxacin and ciprofloxacin concentrations in plasma were simultaneously determined using a high-performance liquid chromatography (HPLC) assay method and subjected to a non-compartmental analysis. After IV administration, enrofloxacin had a mean (±SD) volume of distribution at steady state (VSS) of 1.394 ± 0.349 L/kg, a terminal half-life (t1/2λz) of 3.592 ± 1.205 h, and a total body clearance (Cl) of 0.675 ± 0.16 L/h/kg. After IM administration, enrofloxacin was absorbed relatively slowly but completely, with a mean absorption time (MAT) of 6.051 ± 1.107 h and a bioavailability of 99.225 ± 7.389%. Both compounds were detected simultaneously in most plasma samples following both routes of administration, indicating efficient biotransformation of enrofloxacin to ciprofloxacin. After IV injection, the peak concentration (Cmax) of ciprofloxacin was 0.315 ± 0.017 µg/mL, observed at 0.958 ± 0.102 h. Following IM injection, the corresponding values were 0.071 ± 0.006 µg/mL and 3 ± 1.095 h, respectively. Following IV and IM administration, the conversion ratio of enrofloxacin to ciprofloxacin was calculated as 59.2 ± 9.6% and 31.2 ± 7.7%, respectively. The present results demonstrated favorable pharmacokinetic profiles for enrofloxacin, characterized by complete absorption with relatively slow kinetics, extensive distribution, efficient biotransformation to ciprofloxacin, and prolonged elimination in Nanyang cattle.

Photodynamic therapy with NIR-II probes: review on state-of-the-art tools and strategies.

In 2022 10% of the world's population was aged 65+, and by 2100 this segment is expected to hit 25%. These demographic changes place considerable pressure over healthcare systems worldwide, which results in an urgent need for accurate, inexpensive and non-invasive ways to treat cancers, a family of diseases correlated with age. Among the therapeutic tools that gained important attention in this context, photodynamic therapies (PDT), which use photosensitizers to produce cytotoxic substances for selectively destroying tumor cells and tissues under light irradiation, profile as important players for next-generation nanomedicine. However, the development of clinical applications is progressing at slow pace, due to still pending bottlenecks, such as the limited tissue penetration of the excitation light, and insufficient targeting performance of the therapeutic probes to fully avoid damage to normal cells and tissues. The penetration depth of long-wavelength near infrared (NIR) light is significantly higher than that of short-wavelength UV and visible light, and thus NIR light in the second window (NIR-II) is acknowledged as the preferred phototherapeutic means for eliminating deep-seated tumors, given the higher maximum permissible exposure, reduced phototoxicity and low autofluorescence, among others. Upon collective multidisciplinary efforts of experts in materials science, medicine and biology, multifunctional NIR-II inorganic or organic photosensitizers have been widely developed. This review overviews the current state-of-the art on NIR-II-activated photosensitizers and their applications for the treatment of deep tumors. We also place focus on recent efforts that combine NIR-II activated PDT with other complementary therapeutic routes such as photothermal therapy, chemotherapy, immunotherapy, starvation, and gas therapies. Finally, we discuss still pending challenges and problems of PDT and provide a series of perspectives that we find useful for further extending the state-of-the art on NIR-II-triggered PDT.

Wheat Stripe Rust Inoculum from the Southwest Dispersed to the East Huang-Huai-Hai Region through Southern Anhui in China.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a continuous threat to global wheat production. In 2021, the epidemic of wheat stripe rust in China affected approximately 4.5 million hectares, resulting in severe yield losses. When confronted with the epidemic, tracing the sources of the pathogen can offer valuable insights for disease prevention and control. This study was conducted to analyze the genetic structure, aerodynamics, geographical features, and cultivation practices of the pathogen population in various wheat-producing regions, and to further reveal the spread patterns of the stripe rust pathogens in China. The findings indicated an overall trend of the pathogen dissemination from the west to the east. The pathogen was primarily spread from the northwestern region to the Huang-Huai-Hai region through the Guanzhong Plain and the NanXiang Plain. Meanwhile, the pathogen was also spread eastward from the southwestern region to the lower reaches of the Yangtze River, utilizing the Jianghan Plain as a bridge and the Yangtze River Valley in southwestern Anhui as the main pathway. Furthermore, the pathogen spread northward into Shandong under the driving force of the southeast winds. The findings of this study may provide valuable insights for the integrated management of wheat stripe rust in China.