Establishment of the HPLC fluorescence detection method for plasma trace ivermectin and its pharmacokinetics in Bactrian camel.

BACKGROUND AND OBJECTIVE: Ivermectin (IVM), a widely used veterinary anthelmintic, lacks recommended doses for Bactrian camels. This study aims to establish its pharmacokinetics in Bactrian camels, comparing with other livestock. METHODS: A method for high-performance liquid chromatography fluorescence detection of IVM in plasma was developed. RESULTS: IVM exhibited linear scaling (y = 0.6946x + 0.0088, R2 = 0.9988) within 0.025-5 ng/mL, with a lower limit of quantification of 25.00 pg/mL, high recovery (>70%) and low RSD (<7%). In Bactrian camels, IVM injection showed a low Cmax, extended Tmax and apparent secondary absorption compared to cattle and sheep. CONCLUSIONS: Slow absorption and widespread distribution were observed, with peak concentration and area under the curve correlating positively with the dose. This study provides insights into IVM pharmacokinetics in Bactrian camels, informing dose determination and highlighting potential metabolic differences compared to other livestock.

Mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells based on network pharmacology and experimental validation.

Ageing is becoming an increasingly serious problem; therefore, there is an urgent need to find safe and effective anti-ageing drugs. Aims: To investigate the effects of Bazi Bushen capsule (BZBS) on the senescence of mesenchymal stem cells (MSCs) and explore its mechanism of action. Methods: Network pharmacology was used to predict the targets of BZBS in delaying senescence in MSCs. For in vitro studies, MSCs were treated with D-gal, BZBS, and NMN, and cell viability, cell senescence, stemness-related genes, and cell cycle were studied using cell counting kit-8 (CCK-8) assay, SA-ß-galactosidase (SA-ß-gal) staining, Quantitative Real-Time PCR (qPCR) and flow cytometry (FCM), respectively. Alkaline phosphatase (ALP), alizarin red, and oil red staining were used to determine the osteogenic and lipid differentiation abilities of MSCs. Finally, the expression of senescence-related genes and cyclin-related factors was detected by qPCR and western blotting. Results: Network pharmacological analysis suggested that BZBS delayed cell senescence by interfering in the cell cycle. Our in vitro studies suggested that BZBS could significantly increase cell viability (P < 0.01), decrease the quantity of ß-galactosidase+ cells (P < 0.01), downregulate p16 and p21 (P < 0.05, P < 0.01), improve adipogenic and osteogenic differentiation, and upregulate Nanog, OCT4 and SOX2 genes (P < 0.05, P < 0.01) in senescent MSCs. Moreover, BZBS significantly reduced the proportion of senescent MSCs in the G0/G1 phase (P < 0.01) and enhanced the expression of CDK4, Cyclin D1, and E2F1 (P < 0.05, P < 0.01, respectively). Upon treatment with HY-50767A, a CDK4 inhibitor, the upregulation of E2F1 was no longer observed in the BZBS group. Conclusions: BZBS can protect MSCs against D-gal-induced senescence, which may be associated with cell cycle regulation via the Cyclin D1/CDK4/E2F1 signalling pathway.

An active controllable wide-angle and ultra-wideband terahertz absorber/reflector based on VO2 metamaterial.

The use of metamaterials in the design of optics is an important strategy for controlling light fields. Numerous terahertz metamaterial devices have been recently designed; however, their performance is relatively limited. Here, the thermally induced phase change characteristics of vanadium dioxide (VO2) were harnessed to design a perfect wide-angle and ultra-wideband switchable terahertz absorber/reflector with a simple structure and three layers from top to bottom (VO2, SiO2, and Au). The absorption mechanism based on the impedance matching theory and electric field distribution was investigated, and the influence of structural parameters on the absorption rate and performance of the absorber in a wide wave vector range were analyzed. The study findings showed that the device perfectly absorbed a bandwidth of over 6.0 THz (absorption >90%). The absorption (reflection) was modulated from 0.01 to 0.999 with the change of the background temperature. More importantly, the device could switch between complete ultra-wideband reflection and perfect absorption over a wide angle range. This study provides important insights into the design of terahertz functional devices.

Tumor-derived exosomal hyaluronidase 1 induced M2 macrophage polarization and promoted esophageal cancer progression.

The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.

Angelica keiskei water extract Mitigates Age-Associated Physiological Decline in Mice.

OBJECTIVE: Angelica keiskei is a medicinal and edible plant that has been reported to possess potent antioxidant properties in several in vitro models, but its effectiveness on naturally aging organisms is still lacking. This study explores the antioxidant and health-promoting effects of Angelica keiskei in naturally aging mice. METHODS: We treated 48-week-old mice with Angelica keiskei water extract (AKWE) 30 days, and measured indicators related to aging and antioxidants. In addition, we conducted network pharmacology analysis, component-target molecular docking, real-time PCR, and MTS assays to investigate relevant factors. RESULTS: The results indicated that administration of AKWE to mice led to decrease blood glucose levels, improve muscle fiber structure, muscle strength, gait stability, and increase levels of glutathione and superoxide dismutase in serum. Additionally, it decreased pigmentation of the heart tissues. Angelica keiskei combats oxidative stress by regulating multiple redox signaling pathways, and its ingredients Coumarin and Flavonoids have the potential to bind to SIRT3 and SIRT5. CONCLUSIONS: Our findings indicated the potential of Angelica keiskei as a safe and effective dietary supplement to combat aging and revealed the broad prospects of medicinal and edible plants for addressing aging and age-related chronic diseases.

Identification of freshwater snail species and survey of their trematode infections in Ordos, China.

In order to investigate and study the species and distribution of freshwater snails in Ordos area of Inner Mongolia, as well as the trematode infection in different periods, and to provide a scientific basis for the effective prevention and control of livestock trematodiasis. In this paper, freshwater snails distributed in Ordos were widely collected for morphological identification, and PCR amplification of freshwater snails COI gene and ITS2 gene was carried out with the help of molecular biology. At the same time, microscopic examination was used to observe the trematode infection of freshwater snails in two different periods from May to July and July to September, and the molecular biology of the trematodes was identified. The results showed that the 1796 freshwater snails collected belonged to two orders, three families and four genera, i.e. Bellamya, Radix, Galba, and Gyraulus. Microscopic examination of snails showed that the infection rate of trematode larvae from July to September was significantly higher than that from May to July. The collected trematodes were identified as five species, namely Cotylurus marcogliesei, Fasciola hepatica, Fasciola gigantica, Paramphistomum cervi, and Parastrigea robusta. The combination of freshwater snail species in Ordos and the infection of trematode in snails showed that a large number of freshwater snails were infected with trematodes, especially from July to September, when there is more rain and suitable climate, which causes serious harm to local livestock.

Positive lymph node ratio is an important index to predict long-term survival for advanced esophageal squamous carcinoma patients (II∼III) with R0 resection--a SEER-based analysis.

Background: Esophageal squamous carcinoma (ESCC) is one of the most malignant cancers in the world due to nodal metastasis. Therefore, a reasonable nodal staging system is extremely important for further treatment strategies. Recently the positive lymph node ratio (PLNR) is an important prognostic factor in various solid tumors. Method: In this study, we investigated the clinical significance of the PLNR in stage II∼III ESCC patients. We collected the pathological characteristics of 272 stage II∼III ESCC patients from the SEER database from 2004-2016. ROC curves were used to calculate the best cutoff value of the PLNR; Pearson's Chi-square (χ2) and Fisher's exact probability tests were used to compare the clinical baseline and characteristics of patients. For continuous variables, Student's t-test and ANOVA were performed to evaluate statistical significance. Clinical outcomes were estimated by using the Kaplan‒Meier method and log-rank test. Furthermore, univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors of ESCC patients. Results: Consequently, advanced ESCC patients were effectively stratified into two groups by prognosis using a PLNR cutoff value of 0.15 (P value = 0.04). The median survival time of patients with PLNR <0.15 (n = 145) was much higher than that of patients (n = 127) in the PLNR ≥0.15 group (20.0 vs. 13.0 months, P value < 0.0001). Notably, the PLNR significantly predicted the prognosis of ESCC patients with stage N1 (P value 0.01) and stage III (P value < 0.001) disease. The multivariate Cox proportional hazard model showed that T stage (HR 1.33, 95 % CI 0.97-1.82), tumor size >45 mm (HR 1.32, 95 % CI 1.02-1.70), N stage (HR 1.41, 95 % CI 0.98-2.01) and PLNR ≥0.15 (HR 1.35, 95 % CI 0.87-1.74) were independent risk factors for prognostic prediction in ESCC patients. Meanwhile, 117 II∼III ESCC patients from Shaanxi Provincial People's Hospital shown that the overall survival with a PLNR <0.15 (n = 96) was significantly longer than that with a PLNR ≥0.15 (n = 21) . Conclusions: The PLNR is useful for accurately predicting clinical outcomes and determining postoperative strategies.

Qili Qiangxin (QLQX) capsule as a multi-functional traditional Chinese medicine in treating chronic heart failure (CHF): A review of ingredients, molecular, cellular, and pharmacological mechanisms.

Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.

Comprehensive Comparison of MOCVD- and LPCVD-SiNx Surface Passivation for AlGaN/GaN HEMTs for 5G RF Applications.

Passivation is commonly used to suppress current collapse in AlGaN/GaN HEMTs. However, the conventional PECV-fabricated SiNx passivation layer is incompatible with the latest process, like the "passivation-prior-to-ohmic" method. Research attention has therefore turned to high-temperature passivation schemes. In this paper, we systematically investigated the differences between the SiNx/GaN interface of two high-temperature passivation schemes, MOCVD-SiNx and LPCVD-SiNx, and investigated their effects on the ohmic contact mechanism. By characterizing the device interface using TEM, we reveal that during the process of MOCVD-SiNx, etching damage and Si diffuses into the semiconductor to form a leakage path and reduce the breakdown voltage of the AlGaN/GaN HEMTs. Moreover, N enrichment at the edge of the ohmic region of the LPCVD-SiNx device indicates that the device is more favorable for TiN formation, thus reducing the ohmic contact resistance, which is beneficial to improving the PAE of the device. Through the CW load-pull test with drain voltage VDS = 20V, LPCVD-SiNx devices obtain a high PAE of 66.35%, which is about 6% higher than MOCVD-SiNx devices. This excellent result indicates that the prospect of LPCVD-SiNx passivation devices used in 5G small terminals will be attractive.

Pioglitazone protects PC12 cells against oxidative stress injury: An in vitro study of its antiapoptotic effects via the PPARγ pathway.

To the best of our knowledge, the role of peroxisome proliferator-activated receptor γ (PPARγ) in oxidative stress-induced PC12 cell damage is unknown. Using a PC12 cell model with H2O2 treatment, the present study investigated the expression levels of apoptosis-related genes and neuronal apoptosis after oxidative stress injury. The present study further investigated the protective effect and mechanism of pioglitazone, a PPARγ agonist. PC12 cells treated with H2O2 were used as a model of oxidative stress injury. An MTT assay and flow cytometry were used to detect the effect of H2O2 on PC12 cell viability and the protective effect of pioglitazone. A TUNEL assay was used to detect neuronal apoptosis. The expression levels of PPARγ, Bax, Bcl-2 and caspase-3 were examined by reverse transcription-quantitative PCR and western blotting. H2O2 reduced PC12 cell viability in a dose- and time-dependent manner. H2O2 significantly upregulated the protein expression levels of Bax and the cleaved caspase-3/caspase-3 ratio (P<0.01), decreased the protein expression levels of Bcl-2 (P<0.01), and increased the apoptosis rate of PC12 cells. Pioglitazone significantly reduced the protein expression levels of Bax and the cleaved caspase-3/caspase-3 ratio (P<0.01), increased the expression levels of Bcl-2 (P<0.01), decreased the Bax/Bcl-2 expression ratio (P<0.01) and increased the viability of H2O2-damaged PC12 cells in a dose-dependent manner. Treatment with the PPARγ antagonist GW9662 or PPARγ small interfering RNA counteracted the protective effect of pioglitazone on PC12 cells to different extents (P<0.01). Therefore, the present study reported the role of PPARγ in protecting PC12 cells against oxidative stress injury, which may lead to novel therapeutic approaches for neurodegenerative diseases.

Prognostic value of serum cystatin C in patients with sepsis.

Background: Early identification and diagnosis of sepsis are very important because timely and appropriate treatment can improve the survival outcomes. Aim: The aim of this study was to explore the clinical significance of serum cystatin C level in sepsis. Materials and Methods: The levels of serum cystatin C, C-reactive protein (CRP), and procalcitonin (PCT) were measured via enzyme-linked immunosorbent assay (ELISA). The patients with sepsis were followed up for 30 days to record their survival conditions. Results: The expression level of cystatin C was remarkably elevated in patients with sepsis compared with that in healthy controls. The serum cystatin C level was significantly correlated with the SOFA score and CRP, PCT, and creatinine levels in patients with sepsis. The patients in death group had a markedly higher level of serum cystatin C than those in survival group. The area under curve (AUC) of cystatin C for assessing the 30-day mortality rate of sepsis patients was 0.765. Conclusion: The serum cystatin C level is elevated in patients with sepsis and it may serve as a biomarker for early diagnosis of sepsis and possess promising effects in assessing the severity of sepsis and the prognosis of patients.

In vitro promotion of SDF-1α on the migration and proliferation of C-kit+ cardiac stem cells in neonatal mice.

The aim of this study was to explore the In Vitro effects of stromal-derived factor-1α (SDF-1α) on the migration and proliferation of c-kit+ cardiac stem cells. The lentivirus containing SDF-1α (LV-SDF-1α) was constructed. Primary myocardial fibroblasts were transfected by LV-SDF-1α, followed by primary culture of cardiac tissue cells and separation of c-kit+ cardiac stem cells with a flow cytometer, in order to investigate the effects of SDF-1α on the migration and proliferation of c-kit+ cardiac stem cells using cell co-culture, immunofluorescence and EdU tracing technologies. The results showed that myocardial fibroblasts could secrete SDF-1α after the transfection with LV-SDF-1α. High-purity c-kit+ cardiac stem cells were obtained through flow cytometry sorting and the positive rate was about 40%. The c-kit+ cardiac stem cells cultured In Vitro could be differentiated into cTnT positive cardiomyocyte-like cells. After co-culture of myocardial fibroblasts and c-kit+ cardiac stem cells transfected with lentivirus, SDF-1α might increase the migration of c-kit+ cardiac stem cells, but SDF-1α did not promote the proliferation of c-kit+ cardiac stem cells. In conclusion, the myocardial fibroblasts transfected with lentivirus can highly express SDF-1α, c-kit+ cardiac stem cells can be differentiated into cTnT positive cardiomyocyte-like cells and SDF-1α can effectively enhance the migration of c-kit+ cardiac stem cells but fails to stimulate the proliferation.

Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report.

BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.

Influence of Gate Geometry on the Characteristics of AlGaN/GaN Nanochannel HEMTs for High-Linearity Applications.

In this study, AlGaN/GaN nanochannel high-electron-mobility transistors (HEMTs) with tri-gate (TGN-devices) and dual-gate (DGN-devices) structures were fabricated and investigated. It was found that the peak value of the transconductance (Gm), current gain cut-off frequency (fT) and power gain cut-off frequency (fmax) of the TGN-devices were larger than that of the DGN-devices because of the enhanced gate control from the top gate. Although the TGN-devices and DGN-devices demonstrated flattened transconductance, fT and fmax profiles, the first and second transconductance derivatives of the DGN-devices were lower than those of the TGN-devices, implying an improvement in linearity. With the nanochannel width decreased, the peak value of the transconductance and the first and second transconductance derivatives increased, implying the predominant influence of sidewall gate capacitance on the transconductance and linearity. The comparison of gate capacitance for the TGN-devices and DGN-devices revealed that the gate capacitance of the tri-gate structure was not simply a linear superposition of the top planar gate capacitance and sidewall gate capacitance of the dual-gate structure, which could be attributed to the difference in the depletion region shape for tri-gate and dual-gate structures.

Genome and Transcriptome Analyses Facilitate Genetic Control of Wohlfahrtia magnifica, a Myiasis-Causing Flesh Fly.

Myiasis caused by Wohlfahrtia magnifica is a widespread parasitic infestation in mammals. The infested host suffers from damage as the developing larvae feed on its tissues. For the control of myiasis infestation, genetic methods have been shown to be effective and promising as an alternative to insecticides. Combining genome, isoform sequencing (Iso-Seq), and RNA sequencing (RNA-seq) data, we isolated and characterized two sex-determination genes, W. magnifica transformer (Wmtra) and W. magnifica transformer2 (Wmtra2), whose orthologs in a number of insect pests have been utilized to develop genetic control approaches. Wmtra transcripts are sex-specifically spliced; only the female transcript encodes a full-length functional protein, while the male transcript encodes a truncated and non-functional polypeptide due to the presence of the male-specific exon containing multiple in-frame stop codons. The existence of five predicted TRA/TRA2 binding sites in the male-specific exon and the surrounding intron of Wmtra, as well as the presence of an RNA-recognition motif in WmTRA2 may suggest the auto-regulation of Wmtra by its own protein interacting with WmTRA2. This results in the skipping of the male-specific exon and translation of the full-length functional protein only in females. Our comparative study in dipteran species showed that both the WmTRA and WmTRA2 proteins exhibit a high degree of similarity to their orthologs in the myiasis-causing blow flies. Additionally, transcriptome profiling performed between adult females and adult males reported 657 upregulated and 365 downregulated genes. Functional analysis showed that among upregulated genes those related to meiosis and mitosis Gene Ontology (GO) terms were enriched, while, among downregulated genes, those related to muscle cell development and aerobic metabolic processes were enriched. Among the female-biased gene set, we detected five candidate genes, vasa (vas), nanos (nanos), bicoid (bcd), Bicaudal C (BicC), and innexin5 (inx5). The promoters of these genes may be able to upregulate Cas9 expression in the germline in Cas9-based homing gene drive systems as established in some flies and mosquitoes. The isolation and characterization of these genes is an important step toward the development of genetic control programs against W. magnifica infestation.

Repositioning of clinically approved drug Bazi Bushen capsule for treatment of Aizheimer's disease using network pharmacology approach and in vitro experimental validation.

Aims: To explore the new indications and key mechanism of Bazi Bushen capsule (BZBS) by network pharmacology and in vitro experiment. Methods: The ingredients library of BZBS was constructed by retrieving multiple TCM databases. The potential target profiles of the components were predicted by target prediction algorithms based on different principles, and validated by using known activity data. The target spectrum of BZBS with high reliability was screened by considering the source of the targets and the node degree in compound-target (C-T) network. Subsequently, new indications for BZBS were predicted by disease ontology (DO) enrichment analysis and initially validated by GO and KEGG pathway enrichment analysis. Furthermore, the target sets of BZBS acting on AD signaling pathway were identified by intersection analysis. Based on STRING database, the PPI network of target was constructed and their node degree was calculated. Two Alzheimer's disease (AD) cell models, BV-2 and SH-SY5Y, were used to preliminarily verify the anti-AD efficacy and mechanism of BZBS in vitro. Results: In total, 1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula, and 1320 BZBS targets with high confidence were predicted. Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treatment of AD. GO and KEGG enrichment results provide a preliminary verification of this point. Among them, 113 functional targets of BZBS belong to AD pathway. A PPI network containing 113 functional targets and 1051 edges for the treatment of AD was constructed. In vitro experiments showed that BZBS could significantly reduce the release of TNF-α and IL-6 and the expression of COX-2 and PSEN1 in Aß25-35-induced BV-2 cells, which may be related to the regulation of ERK1/2/NF-κB signaling pathway. BZBS reduced the apoptosis rate of Aß25-35 induced SH-SY5Y cells, significantly increased mitochondrial membrane potential, reduced the expression of Caspase3 active fragment and PSEN1, and increased the expression of IDE. This may be related to the regulation of GSK-3ß/ß-catenin signaling pathway. Conclusions: BZBS formula has a potential use in the treatment of AD, which is achieved through regulation of ERK1/2, NF-κB signaling pathways, and GSK-3ß/ß-catenin signaling pathway. Furthermore, the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action. The study lays a foundation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Involvement of CBF in the fine-tuning of litchi flowering time and cold and drought stresses.

Litchi (Litchi chinensis) is an economically important fruit tree in southern China and is widely cultivated in subtropical regions. However, irregular flowering attributed to inadequate floral induction leads to a seriously fluctuating bearing. Litchi floral initiation is largely determined by cold temperatures, whereas the underlying molecular mechanisms have yet to be identified. In this study, we identified four CRT/DRE BINDING FACTORS (CBF) homologs in litchi, of which LcCBF1, LcCBF2 and LcCBF3 showed a decrease in response to the floral inductive cold. A similar expression pattern was observed for the MOTHER OF FT AND TFL1 homolog (LcMFT) in litchi. Furthermore, both LcCBF2 and LcCBF3 were found to bind to the promoter of LcMFT to activate its expression, as indicated by the analysis of yeast-one-hybrid (Y1H), electrophoretic mobility shift assays (EMSA), and dual luciferase complementation assays. Ectopic overexpression of LcCBF2 and LcCBF3 in Arabidopsis caused delayed flowering and increased freezing and drought tolerance, whereas overexpression of LcMFT in Arabidopsis had no significant effect on flowering time. Taken together, we identified LcCBF2 and LcCBF3 as upstream activators of LcMFT and proposed the contribution of the cold-responsive CBF to the fine-tuning of flowering time.

A cooling-driven self-adaptive and removable hydrogel coupled with combined chemo-photothermal sterilization for promoting infected wound healing.

Hydrogel dressings that can fit irregular wounds, promote wound healing, and detach from wounds without damage represent the development trend of modern medical dressings. Herein, a novel composite hydrogel with excellent wound shape matching and painless removability via a gel-sol phase transition is constructed through dynamic borate ester bonds between phenylboronic acid-grafted F127 (PF127) and polydopamine-coated reduced graphene oxide/silver nanoparticles (rGO@PDA/Ag NPs). After contact with the skin tissues, the administered liquid-like sols gradually transform into solid-like gels, robustly adhering to the wound. The hydrogel dressings containing near-infrared (NIR)-responsive rGO@PDA and in situ formed Ag NPs can generate localized heat and gradually release Ag+ to realize safe, effective, and durable photothermal-chemical combined sterilization. In addition, catechol-rich PDA endows the hydrogel dressings with good antioxidant activity and adhesiveness. In vivo study results indicate that the hydrogel dressings can significantly accelerate full-thickness skin infected wound healing by eliminating bacteria, promoting collagen deposition and angiogenesis, as well as reducing inflammation. Collectively, the thermoreversible rGO@PDA/Ag-PF127 hydrogel dressings with an improved self-adapting ability, superior antimicrobial activity, and tunable adhesion appear to be a promising candidate for the treatment of infected wounds.

Development and validation of machine learning models to predict survival of patients with resected stage-III NSCLC.

Objective: To compare the performance of three machine learning algorithms with the tumor, node, and metastasis (TNM) staging system in survival prediction and validate the individual adjuvant treatment recommendations plan based on the optimal model. Methods: In this study, we trained three machine learning madel and validated 3 machine learning survival models-deep learning neural network, random forest and cox proportional hazard model- using the data of patients with stage-al3 NSCLC patients who received resection surgery from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database from 2012 to 2017,the performance of survival predication from all machine learning models were assessed using a concordance index (c-index) and the averaged c-index is utilized for cross-validation. The optimal model was externally validated in an independent cohort from Shaanxi Provincial People's Hospital. Then we compare the performance of the optimal model and TNM staging system. Finally, we developed a Cloud-based recommendation system for adjuvant therapy to visualize survival curve of each treatment plan and deployed on the internet. Results: A total of 4617 patients were included in this study. The deep learning network performed more stably and accurately in predicting stage-iii NSCLC resected patients survival than the random survival forest and Cox proportional hazard model on the internal test dataset (C-index=0.834 vs. 0.678 vs. 0.640) and better than TNM staging system (C-index=0.820 vs. 0.650) in the external validation. The individual patient who follow the reference from recommendation system had superior survival compared to those who did not. The predicted 5-year-survival curve for each adjuvant treatment plan could be accessed in the recommender system via the browser. Conclusion: Deep learning model has several advantages over linear model and random forest model in prognostic predication and treatment recommendations. This novel analytical approach may provide accurate predication on individual survival and treatment recommendations for resected Stage-iii NSCLC patients.

Research progress and limitation analysis of RNA interference in Haemonchus contortus in China.

Haemonchus contortus is a highly pathogenic and economically important parasitic nematode that affects small ruminants worldwide. While omics studies hold great promise, there are fewer research tools available for analyzing subsequent gene function studies. RNA interference (RNAi) technology offers a solution to this problem, as it especially allows for the knockout or shutting off of the expression of specific genes. As a result, RNAi technology has been widely used to explore gene function and disease treatment research. In this study, we reviewed the latest advancements in RNAi research on Haemonchus contortus in China, with the aim of providing a reference for the identification of key genes involved in growth and development, anthelmintic resistance, diagnostic markers, and diagnostic drug targets for the treatment of Haemonchus contortus.