Synthesis of 3,4-Disubstituted Maleimide Derivatives via Phosphine-Catalyzed Isomerization of α-Succinimide-Substituted Allenoates Cascade γ'-Addition with Aryl Imines.

3,4-disubstituted maleimides find wide applications in various pharmacologically active compounds. This study presents a highly effective approach for synthesizing derivatives of 3,4-disubstituted maleimides through the direct isomerization of α-succinimide-substituted allenoates, followed by a cascade γ'-addition and aryl imines using PR3 as a catalyst. The resulting series of 3,4-disubstituted maleimides exhibited excellent stereoselectivities, achieving yields of up to 86%. To our knowledge, the phosphine-mediated γ'-addition reaction of allenoates is seldom reported.

Intravitreal Dexamethasone Implant (Ozurdex) for Ocular Toxocariasis.

This study aimed to evaluate the efficacy and safety of intravitreal dexamethasone implants in the treatment of ocular toxocariasis (OT). A retrospective analysis was performed on 6 cases in which laboratory tests diagnosed OT. All patients were administered with intravitreal dexamethasone implants with or without vitrectomy. The average follow-up time was 19.7 months. All operated eyes achieved anatomic success, and all patients' visual acuity was improved. Five of these six had a visual acuity of 20/100, and three had final acuity of 20/40 or even better. Intravitreal dexamethasone implants can be used to treat different types of OT, which not only effectively control inflammation and improve the patient's vision but also reduce the use of systemic glucocorticoids.

Non-alcoholic fatty liver disease increases the risk of biochemical recurrence in high-grade metastatic prostate cancer patients.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients. METHODS: We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables. RESULTS: NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005). CONCLUSIONS: NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.

Causal role of immune cells in uveitis: Mendelian randomization study.

Background: Uveitis, characterized by inflammation of the iris, ciliary body, and choroid, presents a significant global clinical challenge, contributing substantially to visual impairment. Risk factors include autoimmune diseases and immune cell dysfunctions, yet many remain unidentified. Immune cells, notably T cells, B cells, and monocytes, play pivotal roles in uveitis pathogenesis. While biologic agents show promise, comprehensive studies on immune cell types in ocular diseases are lacking. Genome-wide association studies (GWAS) and Mendelian randomization (MR) present promising avenues to elucidate genetic susceptibilities and causal relationships between immune cell traits and uveitis risk. Methods: Two-sample MR analysis was used to evaluate the causal relationship between 731 immune cells and uveitis, and genome-wide significance analysis was performed for genetic variation in 731 immune cells traits (P < 5 × 10-8). Immune characteristics include median fluorescence intensity (MFI), relative cell counts (RC), absolute cell counts (AC), and morphological parameters (MP), which were determined by published GWAS, and public data from the IEU Open GWAS database. The main analysis method of MR is inverse variance weighting (IVW). Heterogeneity and horizontal pleiotropy were also assessed. Results: 5 immunophenotypes, including CD62L-DC %DC, IgD+ CD38dim %B cell, CD3 on CM CD4+T cell, CD3 on CD45RA-CD4 +T cell, and CD3 on CD39+ CD4+ Treg may increase the risk of uveitis. 5 immunophenotypes, including CD11b on CD33dim HLA DR-Myeloid cell, HLA DR on CD33dim HLA DR+ CD11b-myeloid cell, CD14-CD16 + %monocyte, HLA DR on CD14-CD16 + monocyte and PDL-1 on CD14-CD16 + monocyte was negatively associated with the risk of uveitis. Among them, HLA DR on CD14-CD16 + monocyte (OR=0.921, 95%CI =0.875-0.970, P=0.001) and HLA DR on CD33dim HLA DR+ CD11b- (OR=0.879, 95%CI = 0.833-0.927, P=0.00) were negatively associated with the risk of uveitis in bi-direction. Conclusion: These results indicate that 10 immune cells traits are significantly associated with the risk of developing uveitis and 2 of them were strongly associated with uveitis bi-directionally, after excluding the effects of confounding factors such as some immune diseases, which provided new ideas and therapeutic targets for the study of immune mechanism of uveitis.

KKL-35 inhibits growth of Staphylococcus aureus by systematically changing bacterial phenotypes.

KKL-35 is a new oxadiazole compound with potent broad-spectrum antibacterial activity against a number of gram-positive and gram-negative bacteria. However, its influences on bacterial growth are unclear. This study is to investigate phenotypic changes of Staphylococcus aureus (SA) caused by KKL-35 and evaluate antibacterial activity of combinations of KKL-35 with 7 class of antibiotics available in medical facilities. KKL-35-treated SA showed significantly lower survival under stresses of NaCl and H2O2 than DMSO (21.03 ± 2.60% vs. 68.21 ± 5.31% for NaCl, 4.91 ± 3.14% vs. 74.78 ± 2.88% for H2O2). UV exposure significantly decreased survival of SA treated with KKL-35 than DMSO-treated ones (23.91 ± 0.71% vs. 55.45 ± 4.70% for 4.2 J/m2, 12.80 ± 1.03% vs. 31.99 ± 5.99% for 7.0 J/m2, 1.52 ± 0.63% vs. 6.49 ± 0.51% for 14.0 J/m2). KKL-35 significantly decreased biofilm formation (0.47 ± 0.12 vs. 1.45 ± 0.21) and bacterial survival in the serum resistance assay (42.27 ± 2.77% vs. 78.31 ± 5.64%) than DMSO. KKL-35 significantly decreased ethidium bromide uptake and efflux, as well as the cell membrane integrity. KKL-35 had low cytotoxicity and low propensity for resistance. KKL-35 inhibited SA growth in concentration-independent and time-dependent manners, and showed additivity when combined with the majority class of available antibiotics. Antibiotic combinations of KKL-35 with ciprofloxacin, rifampicin, or linezolid significantly decreased bacterial loads than the most active antibiotic in the corresponding combination. Thus, KKL-35 inhibits growth of SA by decreasing bacterial environmental adaptations, biofilm formation, membrane uptake and efflux, as well as increasing antibiotic sensitivity. Its potent antibacterial activity, low cytotoxicity, low propensity for resistance, and wide choices in antibiotic combinations make KKL-35 a promising leading compound to design new antibiotics in monotherapies and combination therapies to treat bacterial infections.

Population genetic structure of Culex tritaeniorhynchus in different types of climatic zones in China.

BACKGROUND: Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. RESULTS: In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P < 0.05), indicating many low-frequency mutations in the populations and that the populations might be in the process of expansion. Moreover, Wolbachia infection was detected only in SDJN (Jining) (2.24%), and all Wolbachia genotypes belonged to supergroup B. To understand the influence of environmental factors on mosquito-borne viruses, we examined the prevalence of Culex tritaeniorhynchus infection in three ecological environments in Shandong Province. We discovered that the incidence of JEV infection was notably greater in Culex tritaeniorhynchus from lotus ponds compared to those from irrigation canal regions. In this study, the overall JEV infection rate was 15.27 per 1000, suggesting the current risk of Japanese encephalitis outbreaks in Shandong Province. CONCLUSIONS: Tropical and subtropical populations of Culex tritaeniorhynchus showed higher genetic diversity and those climatic conditions provide great advantages for the establishment and expansion of Culex tritaeniorhynchus. There are differences in JEV infection rates in wild populations of Culex tritaeniorhynchus under different ecological conditions. Our results suggest a complex interplay of genetic differentiation, population structure, and environmental factors in shaping the dynamics of Culex tritaeniorhynchus. The low prevalence of Wolbachia in wild populations may reflect the recent presence of Wolbachia invasion in Culex tritaeniorhynchus.

Acupuncture as adjunctive treatment for linezolid-induced peripheral neuropathy: a case series report.

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

Structural analysis of type 3 resistant starch from Canna edulis during in vitro simulated digestion and its post-digested residue impact on human gut microbiota.

Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

Type 3 resistant starch from Canna edulis reduce lipid levels in patients with mild hyperlipidemia through altering gut microbiome: A double- blind randomized controlled trial.

Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).

Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration.

Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3, which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3-knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3-knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.

Phosphine-Catalyzed γ'-Carbon 1,6-Conjugate Addition of α-Succinimide Substituted Allenoates with Para-Quinone Methides: Synthesis of 4-Diarylmethylated 3,4-Disubstituted Maleimides.

In this paper, an interesting γ'-carbon 1,6-conjugate addition for phosphine-catalyzed α-succinimide substituted allenoates has been disclosed. A wide array of substrates was found to participate in the reaction, resulting in the production of diverse 4-diarylmethylated 3,4-disubstituted maleimides with satisfactory to outstanding yields. Furthermore, a plausible mechanism for the reaction was proposed by the investigators.

Effects of a Complex Environment on Fatigue and Self-Healing Characterization of Asphalt Composites Containing Rock Asphalt.

In recent years, asphalt pavement has been subjected to varied environmental conditions during its service life, conditions that predispose it to deformation and cracking. To enhance the performance of asphalt pavement, rock asphalt has been selected as a modifier due to its good compatibility with virgin asphalt binder and its ability to improve the fatigue cracking resistance of asphalt mixtures. Although scholars have conducted some studies on rock asphalt mixtures, research on the fatigue and self-healing performance of these mixtures under conditions such as ultraviolet (UV) aging and freeze-thaw remains limited. This paper presents findings from a study that employs a combined fatigue-healing test to assess the impact of such complex environmental factors on the fatigue and self-healing properties of fine aggregate matrix (FAM) mixtures containing three types of rock asphalts, i.e., Buton, Qingchuan (QC), and Uintaite Modifier (UM). The analysis of fatigue-healing test results, grounded in viscoelastic continuum damage (VECD) theory, indicates that rock asphalt can extend the fatigue life of FAM mixtures, albeit with a concomitant decrease in their self-healing capabilities. The study further reveals that UV aging, freeze-thaw, and UV aging-freeze-thaw conditions all led to a diminution in the fatigue and self-healing properties of FAM mixtures. However, FAM mixtures containing rock asphalt demonstrated greater resilience against these reductions. Atomic force microscope (AFM) results indicate that UV aging reduced the number of bee-structures and enlarged their area, whereas the incorporation of rock asphalt enhanced the uniformity of these structures' distribution, thereby improving the fatigue cracking resistance of FAM mixtures. Fourier transform infrared spectroscopy (FTIR) analysis reveals that while UV aging increased the carbonyl and sulfoxide indices within the asphalt binder, rock asphalt is effective in mitigating this effect to a certain degree, thereby enhancing the aging resistance of FAM mixtures.

Lacticaseibacillus paracasei JS-3 Isolated from "Jiangshui" Ameliorates Hyperuricemia by Regulating Gut Microbiota and iTS Metabolism.

Background: A diet high in purines can impair the function of the gut microbiota and disrupt purine metabolism, which is closely associated with the onset of hyperuricemia. Dietary regulation and intestinal health maintenance are key approaches for controlling uric acid (UA) levels. Investigating the impacts of fermented foods offers potential dietary interventions for managing hyperuricemia. Methods: In this study, we isolated a strain with potent UA-degrading capabilities from "Jiangshui", a fermented food product from Gansu, China. We performed strain identification and assessed its probiotic potential. Hyperuricemic quails, induced by a high-purine diet, were used to assess the UA degradation capability of strain JS-3 by measuring UA levels in serum and feces. Additionally, the UA degradation pathways were elucidated through analyses of the gut microbiome and fecal metabolomics. Results: JS-3, identified as Lacticaseibacillus paracasei, was capable of eliminating 16.11% of uric acid (UA) within 72 h, rapidly proliferating and producing acid within 12 h, and surviving in the gastrointestinal tract. Using hyperuricemic quail models, we assessed JS-3's UA degradation capacity. Two weeks after the administration of JS-3 (2 × 108 cfu/d per quail), serum uric acid (SUA) levels significantly decreased to normal levels, and renal damage in quails was markedly improved. Concurrently, feces from the JS-3 group demonstrated a significant degradation of UA, achieving up to 49% within 24 h. 16S rRNA sequencing revealed JS-3's role in gut microbiota restoration by augmenting the probiotic community (Bifidobacterium, Bacteroides unclassified_f-Lachnospiraceae, and norank_fynorank_o-Clostridia_UCG-014) and diminishing the pathogenic bacteria (Macrococus and Lactococcus). Corresponding with the rise in short-chain fatty acid (SCFA)-producing bacteria, JS-3 significantly increased SCFA levels (p < 0.05, 0.01). Additionally, JS-3 ameliorated metabolic disturbances in hyperuricemic quails, influencing 26 abnormal metabolites predominantly linked to purine, tryptophan, and bile acid metabolism, thereby enhancing UA degradation and renal protection. Conclusions: For the first time, we isolated and identified an active probiotic strain, JS-3, from the "Jiangshui" in Gansu, used for the treatment of hyperuricemia. It modulates host-microbiome interactions, impacts the metabolome, enhances intestinal UA degradation, reduces levels of SUA and fecal UA, alleviates renal damage, and effectively treats hyperuricemia without causing gastrointestinal damage. In summary, JS-3 can serve as a probiotic with potential therapeutic value for the treatment of hyperuricemia.

Mechanistic Insights into the Excited-State Intramolecular Proton Transfer (ESIPT) Process of 2-(2-Aminophenyl)naphthalene.

The 2-(2-aminophenyl)naphthalene molecule attracted much attention due to excited-state intramolecular proton transfer (ESIPT) from an amino NH2 group to a carbon atom of an adjacent aromatic ring. The ESIPT mechanisms of 2-(2-aminophenyl)naphthalene are still unclear. Herein, the decay pathways of this molecule in vacuum were investigated by combining static electronic structure calculations and nonadiabatic dynamics simulations. The calculations indicated the existence of two stable structures (S0-1 and S0-2) in the S0 and S1 states. For the S0-1 isomer, upon excitation to the Franck-Condon point, the system relaxed to the S1 minimum quickly, and then there exist four decay pathways (two ESIPT ones and two decay channels with C atom pyramidalization). In the ESIPT decay pathways, the system encounters the S1S0-PT-1 or S1S0-PT-2 conical intersection, which funnels the system rapidly to the S0 state. In the other two pathways, the system de-excited from the S1 to the S0 state via the S1S0-1 or S1S0-2 conical intersection. For the S0-2 structure, the decay pathways were similar to those of S0-1. The dynamics simulations showed that 75 and 69% of trajectories experienced the two ESIPT conical intersections for the S0-1 and S0-2 structures, respectively. Our simulations showed that the lifetime of the S1 state of S0-1 (S0-2) is estimated to be 358 (400) fs. Notably, we not only found the detailed reaction mechanism of the system but also found that the different ground-state configurations of this system have little effect on the reaction mechanism in vacuum.

Evaluation of a miniature mass spectrometer based point-of-care-test method for direct analysis of amlodipine and benazepril in whole blood.

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.

Enhanced Lightweight YOLOX for Small Object Wildfire Detection in UAV Imagery.

Target detection technology based on unmanned aerial vehicle (UAV)-derived aerial imagery has been widely applied in the field of forest fire patrol and rescue. However, due to the specificity of UAV platforms, there are still significant issues to be resolved such as severe omission, low detection accuracy, and poor early warning effectiveness. In light of these issues, this paper proposes an improved YOLOX network for the rapid detection of forest fires in images captured by UAVs. Firstly, to enhance the network's feature-extraction capability in complex fire environments, a multi-level-feature-extraction structure, CSP-ML, is designed to improve the algorithm's detection accuracy for small-target fire areas. Additionally, a CBAM attention mechanism is embedded in the neck network to reduce interference caused by background noise and irrelevant information. Secondly, an adaptive-feature-extraction module is introduced in the YOLOX network's feature fusion part to prevent the loss of important feature information during the fusion process, thus enhancing the network's feature-learning capability. Lastly, the CIoU loss function is used to replace the original loss function, to address issues such as excessive optimization of negative samples and poor gradient-descent direction, thereby strengthening the network's effective recognition of positive samples. Experimental results show that the improved YOLOX network has better detection performance, with mAP@50 and mAP@50_95 increasing by 6.4% and 2.17%, respectively, compared to the traditional YOLOX network. In multi-target flame and small-target flame scenarios, the improved YOLO model achieved a mAP of 96.3%, outperforming deep learning algorithms such as FasterRCNN, SSD, and YOLOv5 by 33.5%, 7.7%, and 7%, respectively. It has a lower omission rate and higher detection accuracy, and it is capable of handling small-target detection tasks in complex fire environments. This can provide support for UAV patrol and rescue applications from a high-altitude perspective.

Comparative study on the structure characterization and activity of RS5 made from Canna edulis native starch and high-amylose corn starch.

In this study, the high amylose corn starch and Canna edulis native starch were compounded with lauric acid and fermented by human fecal inoculation in vitro. Changes in beneficial metabolite profile and microbiota composition were evaluated. The structural properties showed that both NS-12C and HAMS-12C formed V-shaped crystals under the same preparation method, but NS-12C had a higher composite index and resistance content than HAMS-12C. At the end of fermentation, the starch-lauric acid complexes prepared from the two types of starch significantly promoted the formation of short-chain fatty acids and the contents of acetic acid, butyric acid and valeric acid produced by NS-12C were higher than those of HAMS-12C(p>0.05). HAMS-12C and NS-12C both increased the relative abundance of Blautia. Notably, NS-12C also increased the relative abundance of beneficial bacteria Bifidobacterium and Meganomas, while HAMS-12C did not. These results suggested that this effect may be related to starch type and provide a basis for designing and producing functional foods to improve intestinal health in Canna edulis native starch.

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters.

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain.

BACKGROUND: The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. METHODS: We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. RESULTS: The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. CONCLUSION: Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). RESULTS: The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = - 0.06 (- 0.12, - 0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = - 55.63 (- 90.73, - 20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. CONCLUSION: The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.