Copper Sulfate Combined with Photodynamic Therapy Enhances Antifungal Effect by Downregulating AIF1.

Candida albicans is a clinically significant opportunistic fungus that is generally treated with antifungal drugs such as itraconazole and fluconazole. However, the recent emergence of fungal resistance has made treatment increasingly difficult. Therefore, novel antifungal treatment methods are urgently required. Hexanol ethosome photodynamic therapy (HE-PDT) is a method that uses photosensitizers (PS), such as hexanol ethosome, to exert antifungal effects, and can be used to treat resistant fungal strains. However, due to the high dose of PS required for antifungal treatment, excess photosensitizers may remain. Furthermore, once exposed to light, normal tissues or cells are damaged after photodynamic therapy, which limits the clinical application of HE-PDT. Therefore, improving the efficacy without increasing the dose is the key to this treatment. In this study, the antifungal effect of copper sulfate combined with HE-PDT was investigated, and its mechanism was explored. The results suggested that exogenous copper sulfate significantly increased the antifungal effect of HE-PDT by enhancing the rate of C. albicans inhibition, increasing reactive oxygen species (ROS) accumulation, increasing the rate of apoptosis, and altering the mitochondrial membrane potential (MMP) and ATP concentration, which is related to the downregulation of apoptosis-inducing factor (AIF1) expression. In conclusion, copper sulfate combined with photodynamic therapy significantly inhibited the activity of C. albicans by inducing apoptosis. The combined approach reported herein provides new insights for future antifungal therapy.

The impact of ischemic vascular stenosis on LIPU hyperthermia efficacy investigated Based on in vivo rabbit limb ischemia model.

Ischemic diseases due to arterial stenosis or occlusion are common and can have serious consequences if untreated. Therapeutic ultrasound like high-intensity focused ultrasound (HIFU) ablates tissues while low-intensity pulsed ultrasound (LIPU) promotes healing at relatively low temperatures. However, blood vessel cooling effect and reduced flow in ischemia impact temperature distribution and ultrasonic treatment efficacy. This work established a rabbit limb ischemia model by ligating the femoral artery, measuring vascular changes and temperature rise during LIPU exposures. Results showed the artery diameter was narrowed by 46.2% and the downstream velocity was reduced by 51.3% after ligation. Finite element simulations verified that the reduced flow velocity impaired heat dissipation, enhancing LIPU-induced heating. Simulation results also suggested the temperature rise was almost related linearly to vessel diameter but decayed exponentially with the increasing flow velocity. Findings indicate that the proposed model could be used as an effectively tool to model the heating effects in ischemic tissues during LIPU treatment. This research on relating varied ischemic flow to LIPU-induced thermal effects is significant for developing safe and efficacious clinical ultrasound hyperthermia treatment protocols for the patients with ischemic diseases.

Effects of dietary Clostridium butyricum and rumen protected fat on meat quality, oxidative stability, and chemical composition of finishing goats.

BACKGROUND: Clostridium butyricum (CB) is a probiotic that can regulate intestinal microbial composition and improve meat quality. Rumen protected fat (RPF) has been shown to increase the dietary energy density and provide essential fatty acids. However, it is still unknown whether dietary supplementation with CB and RPF exerts beneficial effects on growth performance and nutritional value of goat meat. This study aimed to investigate the effects of dietary CB and RPF supplementation on growth performance, meat quality, oxidative stability, and meat nutritional value of finishing goats. Thirty-two goats (initial body weight, 20.5 ± 0.82 kg) were used in a completely randomized block design with a 2 RPF supplementation (0 vs. 30 g/d) × 2 CB supplementation (0 vs. 1.0 g/d) factorial treatment arrangement. The experiment included a 14-d adaptation and 70-d data and sample collection period. The goats were fed a diet consisted of 400 g/kg peanut seedling and 600 g/kg corn-based concentrate (dry matter basis). RESULT: Interaction between CB and RPF was rarely observed on the variables measured, except that shear force was reduced (P < 0.05) by adding CB or RPF alone or their combination; the increased intramuscular fat (IMF) content with adding RPF was more pronounced (P < 0.05) with CB than without CB addition. The pH24h (P = 0.009), a* values (P = 0.007), total antioxidant capacity (P = 0.050), glutathione peroxidase activities (P = 0.006), concentrations of 18:3 (P < 0.001), 20:5 (P = 0.003) and total polyunsaturated fatty acids (P = 0.048) were increased, whereas the L* values (P < 0.001), shear force (P = 0.050) and malondialdehyde content (P = 0.044) were decreased by adding CB. Furthermore, CB supplementation increased essential amino acid (P = 0.027), flavor amino acid (P = 0.010) and total amino acid contents (P = 0.024) as well as upregulated the expression of lipoprotein lipase (P = 0.034) and peroxisome proliferator-activated receptor γ (PPARγ) (P = 0.012), and downregulated the expression of stearoyl-CoA desaturase (SCD) (P = 0.034). The RPF supplementation increased dry matter intake (P = 0.005), averaged daily gain (trend, P = 0.058), hot carcass weight (P = 0.046), backfat thickness (P = 0.006), concentrations of 16:0 (P < 0.001) and c9-18:1 (P = 0.002), and decreased the shear force (P < 0.001), isoleucine (P = 0.049) and lysine content (P = 0.003) of meat. In addition, the expressions of acetyl-CoA carboxylase (P = 0.003), fatty acid synthase (P = 0.038), SCD (P < 0.001) and PPARγ (P = 0.022) were upregulated due to RPF supplementation, resulting in higher (P < 0.001) content of IMF. CONCLUSIONS: CB and RPF could be fed to goats for improving the growth performance, carcass traits and meat quality, and promote fat deposition by upregulating the expression of lipogenic genes of Longissimus thoracis muscle.

Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China.

Sharing of genetic elements among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 Escherichia coli and Salmonella enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using data-mining methods. Most isolates within same hosts possessed the same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Supervised machine learning classifiers revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials, primarily associated with resistance in E. coli and susceptibility in S. enterica. Many were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

Deep neural network with self-attention based automated determination system for treatment zone and peripheral steepened zone in Orthokeratology for adolescent myopia.

PURPOSE: The aim of this study is to develop an automatic model based on deep learning techniques for determining the Treatment Zone (TZ) and Peripheral Steepened Zone (PSZ) following Orthokeratology (OK) treatment. METHODS: A total of 1346 corneal topography maps were included in the study. A deep neural network based on the Segformer architecture was constructed to automatically detect TZ and PSZ. The model was optimized and trained multiple times, and the areas of TZ, PSZ, and TZ decentration were calculated based on the segmentation results. RESULTS: The mean Intersection over Union (mIoU) of the overall segmentation results of the model reached over 97% after multiple training with different optimization methods, and the IoU for the TZ and PSZ segmentation tasks were 98.08% and 94.54% in test set, respectively. Moreover, the model demonstrated high consistency with the expert annotation for the TZ segmentation, while a significant difference was found in the PSZ segmentation and expert annotation due to several interference factors. CONCLUSION: This study presents an efficient and repeatable system for clinical research, based on a deep neural network that accurately determines TZ and PSZ after OK treatment using the Segformer architecture. However, further deployment validation may be necessary.

Establishment of pseudorabies virus latency and reactivation model in mice dorsal root ganglia culture.

Pseudorabies virus (PRV) belongs to the alpha herpesvirus family and is responsible for Aujeszky's disease in pigs. Similar to other alpha herpesviruses, PRV establishes a lifelong latent infection in trigeminal ganglion. These latently infected pigs serve as a reservoir for recurrent infections when reactivation is triggered, making the eradication of PRV a challenging task. However, the molecular mechanism underlying PRV latency and reactivation in neurons is still poorly understood due to limitations in the in vitro model. To establish a pseudorabies virus latency and reactivation model in primary neuron cultures, we isolated dorsal root ganglion (DRG) from newborn Kunming mice using a method named epineurium-pulling for DRG collection (EPDC) and cultured primary neurons in vitro. A dual-colour recombinant PRV BAC mRuby-VP16 was constructed and 0.5 multiplicity of infection (MOI) was found as an appropriate dose in the presence of aciclovir to establish latency. Reactivation was induced using UV-inactivated herpesviruses or a series of chemical inhibitors. Interestingly, we found that not only UV-PRV, but also UV-HSV-1 and UV-BHoV-5 were able to induce rapid PRV reactivation. The efficiency of reactivation for LY294002, forskolin, etoposide, dexamethasone, and acetylcholine was found to be dependent on their concentration. In conclusion, we developed a valuable model of PRV latency and reactivation, which provides a basis for future mechanism research.

KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations.

BACKGROUND: Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based "one-two punch" therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations. RESULTS: We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the "one-two punch' therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin. CONCLUSIONS: This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescence in gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel 'one-two punch' therapeutic strategy for the more malignant gastric cancer subtypes.

[Research progress on oxaliplatin-induced neurotoxicity in traditional Chinese medicine (TCM) and western medical cognition and prevention and treatment by TCM].

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

Single-Cell RNA-Seq Reveals Changes in Cell Subsets in the Cortical Microenvironment during Acute Phase of Ischemic Stroke Rats.

BACKGROUND: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. METHODS: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. RESULTS: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0-3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. CONCLUSIONS: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.

Machine learning and metagenomics reveal shared antimicrobial resistance profiles across multiple chicken farms and abattoirs in China.

China is the largest global consumer of antimicrobials and improving surveillance methods could help to reduce antimicrobial resistance (AMR) spread. Here we report the surveillance of ten large-scale chicken farms and four connected abattoirs in three Chinese provinces over 2.5 years. Using a data mining approach based on machine learning, we analysed 461 microbiomes from birds, carcasses and environments, identifying 145 potentially mobile antibiotic resistance genes (ARGs) shared between chickens and environments across all farms. A core set of 233 ARGs and 186 microbial species extracted from the chicken gut microbiome correlated with the AMR profiles of Escherichia coli colonizing the same gut, including Arcobacter, Acinetobacter and Sphingobacterium, clinically relevant for humans, and 38 clinically relevant ARGs. Temperature and humidity in the barns were also correlated with ARG presence. We reveal an intricate network of correlations between environments, microbial communities and AMR, suggesting multiple routes to improving AMR surveillance in livestock production.

Brain-Targeting Emodin Mitigates Ischemic Stroke via Inhibiting AQP4-Mediated Swelling and Neuroinflammation.

Failure to achieve target-specific delivery to ischemic brain sites has hampered the clinical efficacy of newly developed therapies for ischemic stroke. Emodin, an active ingredient isolated from traditional Chinese medicine, has been indicated to alleviate ischemic stroke; however, the underlying mechanism remains unclear. In this study, we aimed to achieve brain-targeted delivery of emodin to maximize its therapeutic efficacy and elucidate the mechanisms by which emodin alleviates ischemic stroke. A polyethylene glycol (PEG)/cyclic Arg-Gly-Asp (cRGD)-modified liposome was used to encapsulate emodin. TTC, HE, Nissl staining, and immunofluorescence staining were employed to evaluate the therapeutic efficacy of brain-targeting emodin in MCAO and OGD/R models. Inflammatory cytokine levels were determined using ELISA. Immunoprecipitation, immunoblotting, and RT-qPCR were utilized for clarifying the changes in key downstream signaling. Lentivirus-mediated gene restoration was employed to verify the core effector of emodin for relieving ischemic stroke. Encapsulating emodin in a PEG/cRGD-modified liposome enhanced its accumulation in the infarct region and substantially raised its therapeutic efficacy. Furthermore, we demonstrated that AQP4, the most abundant water transporter subunit expressed in astrocytes, plays a crucial role in mediating the mechanisms by which emodin inhibits astrocyte swelling, neuroinflammatory blood-brain barrier (BBB) breakdown in vivo and in vitro, and brain edema in general. Our study unveiled the critical target of emodin responsible for alleviating ischemic stroke and a localizable drug delivery vehicle in the therapeutic strategy for ischemic stroke and other brain injuries.

Development and Application of a Nanobody-Based Competitive ELISA for Detecting Antibodies against Hepatitis E Virus from Humans and Domestic Animals.

Hepatitis E virus (HEV) is a zoonotic pathogen that is widespread worldwide. At present, most enzyme-linked immunosorbent assay (ELISA) kits only detect antibodies against human HEV. In this study, a nanobody-horseradish peroxidase (HRP) fusion protein-based competitive ELISA (cELISA) with more convenience and spectral characteristics for HEV antibody detection was developed and used to detect HEV IgG in various species. First, 6 anti-swine HEV capsid protein nanobodies were screened using phage display technology from an immunized Bactrian camel. Then, HEV-Nb67-HRP fusions were expressed and used as a probe for developing a cELISA. The cutoff value of the cELISA was 17.8%, and there was no cross-reaction with other anti-swine virus antibodies, suggesting that the cELISA had good specificity. The intra-assay and interassay coefficients of variation (CVs) were 1.33 to 5.06% and 1.52 to 6.84%, respectively. The cELISA and Western blot showed a higher coincidence rate (97.14%, kappa value = 0.927) than cELISA and indirect ELISA (95.00%, kappa value = 0.876) in clinical swine serum samples. Finally, the seroprevalence of HEV IgG in humans, pigs, rabbits, cows, and goats was 30.67%, 19.26%, 8.75%, 27.59%, and 18.08%, respectively, suggesting that cELISA may have a broader scale for mammalian HEV antibody detection. These results suggest that the newly developed cELISA was rapid, low-cost, reliable, and useful for the serological evaluation of current HEV. IMPORTANCE HEV is thought to be a zoonotic infection and is widespread worldwide; it is beneficial to establish a more convenient and spectral method for HEV antibody detection. In this study, a convenient, time-saving, reproducible, highly sensitive, specific, and novel nanobody-based cELISA was developed and can be used to detect IgG antibodies against mammalian HEV. It provides a new technique for serological evaluation and ELISA-based diagnosis of HEV infection.

Enabling Highly Efficient and Thermal-Stable Polymer Solar Cells through Semi-Alloy Acceptors Composed of a Hinge-Like Dimer: A Versatile Doping Protocol.

The simultaneous improvement of power conversion efficiency (PCE) and thermal stability is a critical scientific challenge in advancing the commercial applications of polymer solar cells. To address this challenge, a dumbbell-shaped dimeric acceptor, DT19, is successfully designed and synthesized. It is incorporated as a third component into the PM1:BTP-eC9 system. This ternary strategy demonstrates a synergistic enhancement of the PCE and thermal stability of the host binary system. In particular, the PM1:BTP-eC9:DT19 system maintains a PCE of over 90% even after heating at 120 °C for 200 h. Additionally, the dimer-doping ternary strategy exhibits excellent generality for the other four Y-series systems and outperforms ternary systems containing alloy-like acceptors in terms of thermal stability. It is because DT19, with its hinge-like structure, can form a semi-alloy acceptor with the host acceptor, leading to strong interchain entanglement with the polymer donor, thus overcoming phase separation and excessive aggregation under thermal stress. This new type of dimeric material, which can synergistically enhance the device efficiency and thermal stability of active layers, presents promising application prospects.

Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins.

ETHNOPHARMACOLOGICAL RELEVANCE: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. AIM OF THE STUDY: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). MATERIALS AND METHODS: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. RESULTS: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. CONCLUSION: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

High-Performance Small Molecule Organic Solar Cells Enabled by a Symmetric-Asymmetric Alloy Acceptor with a Broad Composition Tolerance.

Using a combinatory blending strategy is demonstrated as a promising path for designing efficient organic solar cells (OSCs) by boosting the short-circuit current density and fill factor. Herein, a high-performance ternary all-small molecule OSC (all-SMOSCs) using a narrow-bandgap alloy acceptor containing symmetric and asymmetric molecules (BTP-eC9 and SSe-NIC) and a wide-bandgap small molecule donor MPhS-C2 is reported. Introducing the synthesized SSe-NIC into the MPhS-C2:BTP-eC9 host system can broaden the absorption spectrum, modulate energy offsets, and optimize the molecular packing of the host materials. After systematically optimizing the weight ratio of MPhS-C2:BTP-eC9:SSe-NIC, a champion efficiency of 18.02% is achieved. Impressively, the ternary system not only delivered a broad composition tolerance with device efficiencies over 17% throughout the whole blend ratios, but also exhibited less non-geminate recombination and energy loss, and better-light-soaking stability than the corresponding binary systems. This work promotes the development of high-performance ternary all-SMOSCs and heralds their brighter application prospects.

Altering the ratio of palmitic, stearic, and oleic acids in dietary fat affects nutrient digestibility, plasma metabolites, growth performance, carcass, meat quality, and lipid metabolism gene expression of Angus bulls.

This study evaluated the effects of changing the ratio of palmitic, stearic, and oleic acids in dietary fat on nutritional metabolism, growth performance, and meat quality of finishing Angus bulls. Bulls received the following three treatments: (1) a control diet without fat supplement (CON), (2) CON + mixed fatty acid supplement (58% C16:0 + 28% cis-9 C18:1; MIX), (3) CON + saturated fatty acid supplement (87% C16:0 + 10% C18:0; SFA). In summary, both fat treatment diets simultaneously increased saturated fatty acids C16:0 (P = 0.025), C18:0 (P < 0.001) and total monounsaturated fatty acids (P = 0.008) in muscle, thus balancing the ratio of unsaturated to saturated fatty acids in muscle. MIX diet increased the digestibility of dry matter (P = 0.014), crude protein (P = 0.038), and ether extract (P = 0.036). SFA diet increased the daily gain (P = 0.032) and intramuscular fat content (P = 0.043). The high content of C16:0 and C18:0 in the SFA diet promoted weight gain and fat deposition of beef cattle by increasing feed intake, up-regulating the expression of lipid uptake genes and increasing deposition of total fatty acids, resulting in better growth performance and meat quality.

Injectable Supramolecular Hybrid Hydrogel Delivers IL-1ß-Stimulated Exosomes to Target Neuroinflammation.

Long-term neuroinflammation is a major barrier to neurological recovery after cerebral ischemia-reperfusion injury (CIRI). Here, a thermosensitive injectable supramolecular hybrid hydrogel is developed to sustainably deliver exosomes derived from interleukin-1ß-stimulated bone marrow stromal cells (BMSCs) (ßExos) with improved exosome production and anti-inflammatory capacity for neuroinflammation inhibition and neurological recovery. The supramolecular hydrogel displays self-healing and injectable features, along with high biocompatibility and tissue-like softness. The ßExos effectively reduce the lipopolysaccharide-induced inflammatory responses in the immortalized mouse microglia (BV2) cell line, and the in situ formed hydrogel improves the exosome retention in the ischemic core area. More remarkably, in the middle cerebral artery occlusion in vivo model, glial scar formation and neuronal loss are significantly reduced by regulating neuroinflammation using the released ßExos. Therefore, the combination of interleukin-1ß-stimulated exosomes with injectable supramolecular hydrogel provides an appealing strategy for treating central nervous system diseases.

A Versatile and Low-Cost Polymer Donor Based on 4-Chlorothiazole for Highly Efficient Polymer Solar Cells.

Benefiting from the emergence of narrow-band-gap small-molecule acceptors (SMAs), especially "Y" series, the power conversion efficiency (PCE) of polymer solar cells (PSCs) is rapidly improved. However, polymer donors with high efficiency, easy synthesis, and good universality are relatively scarce except PBDB-TF and D18. Herein, two polymer donors are designed and synthesized based on 4-chlorothiazole derivatives with simple structures, namely PTz3Cl and PBTTz3Cl. The OSCs based on PBTTz3Cl with slightly weaker intermolecular forces in comparison to PTz3Cl exhibits a decent PCE of 18.38% in blending with SMA L8-BO, owing to its strong donor/acceptor interaction with L8-BO, which shapes suitable phase separation morphology. Further research finds that PBTTz3Cl can exhibit excellent photovoltaic performances with various SMA materials, highlighting its universality. Based on this, ternary PSCs are designed where BTP-eC9 is introduced as a guest into the PBTTz3Cl:L8-BO host system. Thanks to further optimal blend morphology and more balanced charge transport, the PCE is improved up to 19.12%, which is among the highest values for PSCs. This work provides a new design of low-cost electron-deficient units for constructing highly versatile, high-performance polymer donors.

Development of a novel competitive ELISA based on nanobody-horseradish peroxidase fusion protein for rapid detection of antibodies against avian hepatitis E virus.

Avian hepatitis E virus (avian HEV) increases poultry mortality and decreases egg production, leading to huge economic losses worldwide. However, there is no effective serological test for avian HEV. Researchers previously created a testing platform using the nanobody (Nb)-horseradish peroxidase (HRP) fusion protein as an ultrasensitive probe to develop competitive ELISA (cELISA) to detect antibodies against different animal viruses. In this study, a rapid and reliable cELISA was developed to test for antibodies against avian HEV using the same platform. Six anti-avian HEV capsid protein nanobodies were selected from an immunized Bactrian camel using phage display technology. The avian HEV-Nb49-HRP fusion protein was expressed and used as a probe for developing a cELISA assay to test for avian HEV antibodies. The cut-off value of the developed cELISA was 22.0%. There was no cross-reaction with other anti-avian virus antibodies, suggesting that the cELISA had good specificity. The coefficients of variation were 0.91% to 4.21% (intra-assay) and 1.52% to 6.35% (inter-assay). Both cELISA and indirect ELISA showed a consistency of 86.7% (kappa = 0.738) for clinical chicken serum samples, and coincidence between cELISA and Western blot was 96.0% (kappa = 0.919). The epitope recognized by Nb49 was located in aa 593-604 of the avian HEV capsid protein, and the peptide (TFPS) in aa 601-604 was essential for binding. The novel cELISA is a saving cost, rapid, useful, and reliable assay for the serological investigation of avian HEV. More importantly, the peptide TFPS may be crucial to immunodominant antigen composition and protection.

Analysis and Validation of TMED3 correlates with poor prognosis and tumor immune infiltration of glioma.

BACKGROUND: Glioma is the most common primary intracranial tumor. It is notorious for its high degree of malignancy, strong invasion, and poor prognosis. The transmembrane emp24 trafficking protein 3 (TMED3) belongs to the TMED family, which is responsible for intracellular protein transport and innate immune signal transmission. More and more evidence shows that TMED3 plays a key role in the tumor progression of human cancer. However, the role and potential molecular mechanism of TMED3 in glioma have not been clarified. METHODS: TMED3 expression levels, clinical data, survival prognosis, prediction of upstream miRNA, and immune-related analyses were all analyzed utilizing relevant databases. Finally, a molecular cell experiment confirmed TMED3 expression in glioma. RESULTS: We discovered that TMED3 is overexpressed in most tumors, including gliomas, and is associated with tumor staging and prognosis. Subsequently, a combination of a series of bioinformatics analyses, including correlation and survival analyses, identified miR-1296-5p as the most potent upstream miRNA of TMED3 in gliomas.Additionally, we analyzed the relationship between TMED3 level and tumor immune cell infiltration and immune checkpoint expression. CONCLUSION: TMED3 is highly expressed in gliomas and is associated with tumor staging and affects the prognosis of patients. Therefore, the TMED3 gene may be a potential immunotherapy target and prognostic marker for gliomas.