A review of dose escalation for FDA-approved products treating solid tumors and hematological malignancies in first-in-human trials.

First-in-human (FIH) dose-escalation trials on oncology should prioritize safety and emphasize efficacy. We reviewed the FIH trials of 67 anti-tumor products approved by the Food and Drug Administration between 2018 and 2023 and found that the "3 + 3" design remains the predominant dose-escalation method (66.2%). The number of patients receiving sub-therapeutic doses is positively correlated with the maximum tolerated dose (MTD) or maximum dose (MD) to starting dose ratio (P = 0.056) and the number of dose levels in trials (P < 0.001). In addition, the proportion of products with a high ratio in antibody drugs is higher than that in small molecules (P < 0.001). The MTD or MD exceeded the label dose by three or more doses in 22.03% of the products. In conclusion, optimizing the starting dose selection method, refining the way of determining doses, and finding alternative indicators to replace toxicity as the endpoints will increase the effectiveness and broaden the beneficiary scope.

The Structure of Hypersexuality and Its Relation to Impulsivity.

Among the multiple controversies surrounding hypersexuality is the important issue of whether it constitutes a univocal construct. Although an initial study supported its homogeneity, more resent research has identified two separate subcomponents-problematic sexuality and sexual drive. The present survey study addressed this issue in a sample that included both in-person tested college students (n = 69) and online respondents (n = 339). A factor analysis of scales attempting to capture the indicators of each subcomponent of hypersexuality yielded two correlated, but separate factors. Whereas Problematic Sexuality (PS) comprised scales measuring sexual compulsivity, using sex as a coping mechanism, and the negative consequences of sexual behavior, Sexual Drive (SD) was defined by frequent sexual activity, preoccupation with sexual fantasies, a predilection for impersonal sexual behavior, and facile sexual arousal. These two subcomponents of hypersexuality were found to covary with different types of impulsivity, further supporting their discrimination and providing external validation for their differentiation. Contrary to a priori hypotheses, however, PS correlated highly with Callous/Manipulative/Risk-Taking as well as with a predicted Affective Instability/Behavioral Disinhibition factor, suggesting that PS may constitute an equifinality of separate developmental trajectories for those high on both subtypes of hypersexuality.

The risk factors for postoperative temporary vocal cord paralysis after thyroid cancer surgery: an observational retrospective cohort study.

OBJECTIVE: To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. METHODS: Case information of 8,340 thyroid cancer patients hospitalized at XX from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a chi-square test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by ROC, calibration curves, and DCA. RESULTS: The STROCSS guideline was followed to conduct a retrospective cohort study. A total of 8,340 patients, including 1,817 (21.8%) men and 6,523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8,340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland (P = 0.042), ultrasound showing a maximum nodal diameter > 1 cm (P = 0.002), multifocal carcinoma (P < 0.001), invasion of surrounding tissue (P = 0.005), lymph node metastases in the central compartment (P = 0.034), lateral cervical lymph node metastasis (P < 0.001), and prolonged operation (P < 0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR = 1.411, P = 0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR = 1.532, P = 0.013, 95% CI: 1.095-2.144), and duration of surgery (OR = 1.009, P < 0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. CONCLUSION: High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

Palmatine improves cognitive dysfunction in Alzheimer's disease model rats through autophagy pathway and regulation of gut microbiota.

Alzheimer's disease (AD) is a primary degenerative encephalopathy that first appeared as a decline in memory and learning skills. Over time, the condition's severity grew. Palmatine (Pal) alleviates Alzheimer's disease symptoms, which has neuroprotective benefits. Numerous investigations have demonstrated a close relationship among AD and gut structure changes. The aim of the research was investigating whether the improvement of Pal on AD is linked to regulating gut flora and autophagy. First, we used Aß1-40 to induce apoptosis in HT22 cells. After Pal treatment, apoptosis can be improved. Then, We used bilateral intracranial hippocampal injection of Aß1-40 for establishing the AD model, after treatment with Pal, the morris water maze experiment and eight-arm maze test demonstrated that Pal enhanced the AD rats' capacity for learning and memory, HE staining illustrated that Pal improved the morphological abnormalities of brain cells and gut tissue damage. Pal reduced the death of hippocampus neurons, as shown by Nissl staining. Pal substantially reduced Tau hyperphosphorylation and Aß accumulation in the brain, according to immunohistochemical labelling. Pal improved the expression of LC3, Beclin 1, AMPK, and suppressed the expression of mTOR and P62, as validated by RT-qPCR and immunofluorescence labelling. This suggests that Pal's treatment of AD may be associated with the control of the AMPK/mTOR autophagy signalling system. 16S rRNA sequencing and short-chain fatty acids (SCFAs) content detection analysis illustrated that Pal has the potential to enhance the content of SCFAs, reverse the alterations in gut microorganisms. It has been showed by the study that Pal could improve AD by activating autophagy signaling pathway and improving gut barrier changes.

[Effectiveness of vertical compression of locking plate combined with hollow screws in treatment of Sanders type â ¡ and â ¢ calcaneal fractures].

Objective: To probe into the effectiveness of vertical compression of locking plate combined with hollow screws in the treatment of Sanders type Ⅱ and Ⅲ calcaneal fractures. Methods: The clinical data of 128 patients with Sanders type Ⅱ and Ⅲ calcaneal fractures who were admitted between March 2019 and April 2022 and met the selection criteria were retrospectively analyzed. Among them, 65 patients were treated with locking plate combined with hollow screw vertical compression (study group), and 63 patients were treated with simple locking plate (control group). There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, fracture side and Sanders classification, cause of injury, time from injury to operation. The operation time, intraoperative blood loss, hospital stay, and fracture healing time were recorded and compared between the two groups. Before operation and at 12 months after operation, the American Orthopaedic Foot and Ankle Association (AOFAS) score (including total score, pain score, functional score, and alignment score) was used to evaluate the recovery of foot function, and imaging indicators such as calcaneal width, calcaneal height, calcaneal length, Böhler angle, and Gissane angle were measured on X-ray films. Results: All patients were followed up 12 months after operation. There was no significant difference in operation time, intraoperative blood loss, hospital stay, and fracture healing time between the two groups ( P>0.05). Poor wound healing occurred in 1 case in the study group and 2 cases in the control group. At 12 months after operation, there was no significant difference between the two groups in the pre- and post-operative difference of calcaneal length, calcaneal height, Gissane angle, and Böhler angle ( P>0.05). However, the pre- and post-operative difference in calcaneal width in the study group was significantly higher than that in the control group ( P<0.05). The pre- and post-operative difference of AOFAS total score in the study group was significantly higher than that in the control group ( P<0.05), and further analysis showed that the pre- and post-operative difference of pain and function scores in the study group were significantly higher than those in the control group ( P<0.05), while there was no significant difference in the pre- and post-operative difference of force score between the two groups ( P>0.05). Conclusion: Compared with simple locking plate treatment, the treatment of Sanders type Ⅱ and Ⅲ calcaneal fractures with vertical compression of locking plate combined with hollow screws can more effectively improve the width of the subtalar calcaneal articular surface, avoid peroneal longus and brevis impingement, reduce pain, and increase the range of motion of the subtalar joint, and the effectiveness is better.

Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.

Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high-energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two-pore-domain K+ channel (K2P) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin-mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.

Review of yeast culture concerning the interactions between gut microbiota and young ruminant animals.

Microorganisms inhabit the gastrointestinal tract of ruminants and regulate body metabolism by maintaining intestinal health. The state of gastrointestinal health is influenced not only by the macro-level factors of optimal development and the physiological structure integrity but also by the delicate equilibrium between the intestinal flora and immune status at the micro-level. Abrupt weaning in young ruminants causes incomplete development of the intestinal tract resulting in an unstable and unformed microbiota. Abrupt weaning also induced damages to the microecological homeostasis of the intestinal tract, resulting in the intestinal infections and diseases, such as diarrhea. Recently, nutritional and functional yeast culture has been researched to tackle these problems. Herein, we summarized current known interactions between intestinal microorganisms and the body of young ruminants, then we discussed the regulatory effects of using yeast culture as a feed supplement. Yeast culture is a microecological preparation that contains yeast, enriched with yeast metabolites and other nutrient-active components, including ß-glucan, mannan, digestive enzymes, amino acids, minerals, vitamins, and some other unknown growth factors. It stimulates the proliferation of intestinal mucosal epithelial cells and the reproduction of intestinal microorganisms by providing special nutrient substrates to support the intestinal function. Additionally, the ß-glucan and mannan effectively stimulate intestinal mucosal immunity, promote immune response, activate macrophages, and increase acid phosphatase levels, thereby improving the body's resistance to several disease. The incorporation of yeast culture into young ruminants' diet significantly alleviated the damage caused by weaning stress to the gastrointestinal tract which also acts an effective strategy to promote the balance of intestinal flora, development of intestinal tissue, and establishment of mucosal immune system. Our review provides a theoretical basis for the application of yeast culture in the diet of young ruminants.

Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 -/- mice.

Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.

Total paeony glycoside relieves neuroinflammation to exert antidepressant effect via the interplay between NLRP3 inflammasome, pyroptosis and autophagy.

BACKGROUND: Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE: To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN: A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS: The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS: TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1ß, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION: These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.

In Vivo Fluorescent Labeling of Foam Cell-Derived Extracellular Vesicles as Circulating Biomarkers for In Vitro Detection of Atherosclerosis.

Real-time monitoring of the development of atherosclerosis (AS) is key to the management of cardiovascular disease (CVD). However, existing laboratory approaches lack sensitivity and specificity, mostly due to the dearth of reliable AS biomarkers. Herein, we developed an in vivo fluorescent labeling strategy that allows specific staining of the foam cell-derived extracellular vesicles (EVs) in atherosclerotic plaques, which are released into the blood as circulating biomarkers for in vitro detection of AS. This strategy relies on a self-assembled nanoprobe that could recognize foam cells specifically, where the probe is degraded by the intracellular HClO to produce a trifluoromethyl-bearing boron-dipyrromethene fluorophore (termed B-CF3), a lipophilic dye that can be transferred to the exosomal membranes. These circulating B-CF3-stained EVs can be detected directly on a fluorescence spectrometer or microplate reader without resorting to any sophisticated analytical method. This liquid-biopsy format enables early detection and real-time differentiation of lesion vulnerability during AS progression, facilitating effective CVD management.

M1 intestinal macrophages-derived exosomes promote colitis progression and mucosal barrier injury.

AIM: This work aimed to investigate the role of M1 intestinal macrophages-derived exosomes (M1-Exo) in colitis and its mechanism. METHODS: M1 polarization of intestinal macrophages was induced in vitro, and their exosomes were extracted and identified. Thereafter, the DSS-induced colitis mouse model was built. Each mouse was given intraperitoneal injection of exosomes, and then mouse weight and DAI were dynamically monitored. In addition, the levels of cytokines were detected by ELISA. After treatment with the TLR4 inhibitor Resatorvid, the effects of M1 macrophages-derived exosomes were observed. Besides, the mouse intestinal epithelial cells were cultured in vitro for observing function of M1-Exo. RESULTS: M1-exo aggravated the colitis and tissue inflammation in mice, activated the TLR4 signal, and destroyed the mucosal barrier. But M0 macrophages-derived exosomes (M0-Exo) did not have the above effects. Resatorvid treatment antagonized the roles of M1-exo. Moreover, as confirmed by cellular experiments in vitro, M1-exo destroyed mucosal barrier. CONCLUSION: M1-exo serve as the pro-inflammatory mediator, which can promote mouse colitis progression by activating TLR4 signal.

Stable continuous flow CANDAN process transitioning from anammox UASB reactor by facilitating indigenous nitrite-producing denitrification community.

The emerging nitrogen removal process known as CANDAN (Complete Ammonium and Nitrate removal via Denitratation-Anammox over Nitrite) has been developed in Sequencing Batch Reactors (SBRs). Yet, starting up and maintaining stability in continuous-flow reactors remain challenging. This study explores the feasibility of transitioning the CANDAN process from an anammox-dominated process by introducing appropriate external organics to facilitate indigenous nitrite-producing denitrification community in an Upflow Anaerobic Sludge Blanket (UASB) reactor. 150-day operation results indicate that under feeding rates of domestic wastewater at 0.54 L/h and nitrate-containing wastewater at 1.08 L/h, excellent N removal was achieved, with effluent TN below 10.0 mg N/L. Adding external sodium acetate at a COD/NO3--N = 2.0 triggered denitratation, ex-situ denitrification activity tests showed increased nitrite production rates, maintaining the nitrate-to-nitrite transformation ratio (NTR) above 90 %. Consequently, anammox activity was consistently maintained, dominating Total Nitrogen (TN) removal with a contribution as high as 78.3 ± 8.0 %. Anammox functional bacteria, Brocadia and Kuenenia were identified and showed no decrease throughout the operation, indicating the robustness of the anammox process. Notably, the troublesome of sludge flotation, did not occur, also contributing to sustained outstanding performance. In conclusion, this study advances our understanding of the synergistic interplay between anammox and denitrifying bacteria in the Anammox-UASB system, offering technical insights for establishing a stable continuous-flow CANDAN process for simultaneous ammonium and nitrate removal.

Selective genes expression and metabolites transformation drive a robust nitrite accumulation during nitrate reduction under alternating feast-famine condition.

Nitrite production via denitrification has been regarded as a key approach for survival of anaerobic ammonium oxidation (anammox) bacteria. Despite the important carbon substrate, little is known about the role of differential genes expression and extracellular metabolite regulation among diverse microbial communities. In this study, a novel alternating feast-famine strategy was proposed and demonstrated to efficiently accumulate nitrite in a low-nitrogen loading rate (NLR) (0.2∼0.8 kg N/m3/d) denitrification system. Highly selective expression of denitrifying genes was revealed as key regulators. Interestingly, in absence of carbon source (ACS) condition, the expression of narG and narI/V genes responsible for reduction of nitrate to nitrite jumped to 2.5 and 5.1 times higher than that in presence of carbon source (PCS) condition with carbon to nitrate ratio of 3.0. This fortunately facilitated a rapid nitrite accumulation once acetate was added, despite a significantly down-regulated narG and narI/narV and up-regulated nirS/nirK. This strategy selected Thauera as the most dominant denitrifier (50.2 %) with the highest contribution to narG and narI/narV genes, responsible for the high nitrite accumulation. Additionally, extracellular xylose, pyruvate, and glucose jointly promoted carbon-central metabolic pathway of key denitrifiers in ACS stage, playing an important role in the process of self-growth and selective enrichment of functional bacteria. The relatively rapid establishment and robust performance obtained in this study shows an engineering-feasible and economically-favorable solution for the regulation of partial denitrification in practical application.

Modulating charge oriented accumulation via interfacial chemical-bond on In2O3/Bi2MoO6 heterostructures for photocatalytic nitrogen fixation.

Photocatalytic nitrogen fixation presents an eco-friendly approach to converting atmospheric nitrogen into ammonia (NH3), but the process faces challenges due to rapid interface charge recombination. Here, we report an innovative charge transfer and oriented accumulation strategy using an In-O-Mo bond-modulated S-scheme heterostructure composed of In2O3/Bi2MoO6 (In/BMO) synthesized using a simple electrostatic assembly. The unique interfacial arrangement with optimal photocatalyst configuration (3 % In/BMO) enabled enhanced photogenerated electron separation and transfer, leading to a remarkable nitrogen fixation rate of approximately 150.9 µmol·gcat-1·h-1 under visible light irradiation. The performance of the photocatalyst was 9-fold and 27-fold higher than that of its pristine components, Bi2MoO6 and In2O3, respectively. The experimental and theoretical evaluation deemed interfacial In-O-Mo bonds crucial for rapid transfer and charge-oriented accumulation. Whereas the generated internal electric field drove the spatial separation and transfer of photo-generated electrons and holes, significantly enhancing the photocatalytic N2-to-NH3 conversion efficiency. The proposed work lays the foundation for designing S-scheme heterostructures with highly efficient interfacial bonds, offering a promising avenue for substantial improvements in photocatalytic nitrogen fixation.

Prevalence of Mycobacterium bovis in deer in mainland China: a systematic review and meta-analysis.

Background: Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis. Methodology: This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses. Results: In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). Elaphurus davidianus was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis. Conclusion: Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.

Regulating Triplet Excitons of Organic Luminophores for Promoted Bioimaging.

Afterglow materials with organic room temperature phosphorescence (RTP) or thermally activated delayed fluorescence (TADF) exhibit significant potential in biological imaging due to their long lifetime. By utilizing time-resolved technology, interference from biological tissue fluorescence can be mitigated, enabling high signal-- to-background ratio imaging. Despite the continued emergence of individual reports on RTP or TADF in recent years, comprehensive reviews addressing these two materials are rare. Therefore, this review aims to provide a comprehensive overview of several typical molecular designs for organic RTP and TADF materials. It also explores the primary methods through which triplet excitons resist quenching by water and oxygen. Furthermore, we analyze the principal challenges faced by afterglow materials and discuss key directions for future research with the hope of inspiring developments in afterglow imaging.

ARHGEF18 can promote BVDV NS5B activation of the host NF-κB signaling pathway by combining with the NS5B-palm domain.

Rho guanine nucleotide exchange factor 18 (ARHGEF18) is a member of the Rho guanine nucleotide exchange factor (RhoGEF) family. RhoGEF plays an important role in the occurrence of tumors and neurological diseases; however, its involvement in host cell resistance against pathogenic microorganisms is mostly unknown. Herein, we report that bovine viral diarrhea virus (BVDV) nonstructural protein 5B (NS5B) can activate the nuclear factor kappa B (NF-κB) signaling pathway to induce an immune response. To clarify the functional domains of NS5B that activate NF-κB signaling, the six structural domains of NS5B were expressed separately: NS5B-core, NS5B-finger, NS5B-palm, NS5B-thumb, NS5B-N and NS5B-c domain. We preliminarily determined that the functional domains of NS5B that activate NF-κB signaling are the finger and palm domains. We used a bovine kidney cell cDNA library and yeast two-hybrid technology to identify that the host protein ARHGEF18 interacts with NS5B. Co-immunoprecipitation assays showed that ARHGEF18 interacts strongly with NS5B-palm. Interestingly ARHGEF18 could promote NF-κB signaling activation by BVDV NS5B. In addition silencing ARHGEF18 significantly inhibited NS5B-palm activation of NF-κB signaling. We concluded that ARHGEF18 can bind to BVDV NS5B through the palm domain to activate the NF-κB pathway. These findings provide direct evidence that BVDV NS5B induces immune responses by activating NF-κB signaling.

Worldwide Swine Tuberculosis-Positive Rate and Associated Risk Factors, 1966-2020: A Systematic Review and Meta-Analysis.

Background: Tuberculosis (TB) is a chronic, zoonotic infectious disease caused by Mycobacterium tuberculosis that infects not only humans but also animals such as pigs, cows, buffaloes, sheep, and goats. Among them, pigs are one of the main food animals in the world. If pigs are infected with M. tuberculosis, meat products will be negatively affected, causing economic losses to the livestock industry. There is currently no systematic epidemiological assessment of swine TB in the world, so it is important to know the prevalence of swine, and these data are currently lacking, so we performed a statistical analysis. Results: We searched 6791 articles and finally included data from 35,303 pigs from 15 countries or territories, showing a combined prevalence of TB in pigs of 12.1% (95% confidence interval [CI]: 9.2 to 15.9). Among them, the prevalence rate of swine TB in Europe was 15.2% (95% CI: 11.1 to 20.7, 2491/25,050), which was higher compared with other continents, and the difference was significant; the positive rate of PCR method was higher in the detection method subgroup, which was 15.7% (95% CI: 8.0 to 31.0, 376/2261); Mycobacterium bovis was detected in pigs in the M. tuberculosis typing group (9.5%, 95% CI: 6.7 to 13.5, 1364/21,430). The positive rate is higher compared with Mycobacterium capris. Conclusion: This systematic review and meta-analysis is the first to determine the global prevalence of TB in swine herds. Although the seroprevalence of swine TB in this article is very low, the harm of TB cannot be ignored. It is important to take effective control and preventive measures to stop the spread of TB to reduce the impact of diseased pigs on animal husbandry and human health.

Endophytic Streptomyces sp. NEAU-DD186 from Moss with Broad-Spectrum Antimicrobial Activity: Biocontrol Potential Against Soilborne Diseases and Bioactive Components.

Soilborne diseases cause significant economic losses in agricultural production around the world. They are difficult to control because a host plant is invaded by multiple pathogens, and chemical control often does not work well. In this study, we isolated and identified an endophytic Streptomyces sp. NEAU-DD186 from moss, which showed broad-spectrum antifungal activity against 17 soilborne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. The strain also exhibited strong antibacterial activity against soilborne phytopathogenic bacteria Ralstonia solanacearum. To evaluate its biocontrol potential, the strain was prepared into biofertilizer by solid-state fermentation. Response surface methodology was employed to optimize the fermentation conditions for maximizing spore production and revealed that the 1:1 ratio of vermicompost to wheat bran, a temperature of 28°C, and 50% water content with an inoculation amount of 15% represented the optimal parameters. Pot experiments showed that the application of biofertilizer with a spore concentration of 108 CFU/g soil could effectively suppress the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana, and the biocontrol efficacy was 81.2 and 72.2%, respectively. Chemical analysis of strain NEAU-DD186 extracts using nuclear magnetic resonance spectrometry and mass analysis indicated that 25-O-malonylguanidylfungin A and 23-O-malonylguanidylfungin A were the main active constituents, which showed high activity against R. solanacearum (EC50 of 2.46 and 2.58 µg ml-1) and B. sorokiniana (EC50 of 3.92 and 3.95 µg ml-1). In conclusion, this study demonstrates that Streptomyces sp. NEAU-DD186 can be developed as biofertilizer to control soilborne diseases.

Effects of Dietary Alfalfa Meal Supplementation on the Growth Performance, Nutrient Apparent Digestibility, Serum Parameters, and Intestinal Microbiota of Raccoon Dogs (Nyctereutes procyonoides).

The raccoon dog (Nyctereutes procyonoides) is a typical omnivore possessing wide dietary adaptability and tolerance to rough feeding, which may be attributed to its intestinal microbiota. The study aimed to investigate the effect of dietary alfalfa meal levels on the growth performance, nutrient apparent digestibility, serum parameters, and intestinal microbiota of raccoon dogs. Sixty raccoon dogs were randomly divided into four dietary treatments containing 0% (AM0), 5% (AM5), 10% (AM10), and 15% (AM15) alfalfa meal for a 60-day experiment. The results showed that compared to raccoon dogs fed the AM0 diet, those fed the AM5 and AM10 diets had no significant difference in growth performance, while those fed the AM15 diet experienced a significant decrease. Raccoon dogs fed the AM5 diet had no significant effect on the nutrient apparent digestibility. Dietary supplementation with alfalfa meal significantly decreased serum urea levels and increased the antioxidant capacity of raccoon dogs. The intestinal microbiome analysis showed that the richness and diversity of colonic microbiota significantly increased in the AM15 group. With the increase in dietary alfalfa meal levels, the relative abundance of fiber-degrading bacteria in the colon of raccoon dogs, such as Treponema, Phascolarctobacterium, and Christensenellaceae R-7 group, increased. However, the relative abundance of pathogenic bacteria, including Anaerobiospirillum, decreased. In conclusion, the inclusion of 5% alfalfa meal in the raccoon dogs' diet had no effect on growth performance, but it exhibited the potential to improve serum antioxidant capacity and intestinal microbiota. This indicates that raccoon dogs have a certain tolerance to the addition of alfalfa meal in their diet.