Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer.

BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. METHODS: This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every three weeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. RESULTS: Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 28 (46.7%) patients. CONCLUSIONS: Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. CLINICALTRIALS: gov NCT04169672.

A Dual-Bond Crosslinking Strategy Enabling Resilient and Recyclable Electrolyte Elastomers for Solid-State Lithium Metal Batteries.

Elastomeric solid polymer electrolytes (SPEs) are highly promising to address the solid-solid-interface issues of solid-state lithium metal batteries (LMBs), but compromises have to be made to balance the intrinsic trade-offs among their conductive, resilient and recyclable properties. Here, we propose a dual-bond crosslinking strategy for SPEs to realize simultaneously high ionic conductivity, elastic resilience and recyclability. An elastomeric SPE is therefore designed with hemiaminal dynamic covalent networks and Li+-dissociation co-polymer chains, where the -C-N- bond maintains the load-bearing covalent network under stress but is chemically reversible through a non-spontaneous reaction, the weaker intramolecular hydrogen bond is mechanically reversible to dissipate elastic energy, and the soft chains endow the rapid ion conduction. With this delicate structure, the optimized SPE elastomer achieves high elastic resilience without loading-unloading hysteresis, outstanding ionic conductivity of 0.2 mS cm-1 (25 °C) and chemical recyclability. Then, exceptional room-temperature performances are obtained for repeated Li plating/stripping tests, and stable cycling of LMBs with either LiFePO4 or 4.3 V-class LiFe0.2Mn0.8PO4 cathode. Furthermore, the recycled SPE can be circularly reused in LMBs without significant performance degradation. Our findings provide an inspiring design principle for SPEs to address the solid-solid-interface and sustainability challenges of solid-state LMBs.

Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Alternative splicing plays a nonredundant role in greater amberjack (Seriola dumerili) in acclimation to ambient salinity fluctuations.

Alternative splicing (AS) is an important post-transcriptional mechanism for adaptation of fish to environmental stress. Here, we performed a genome-wide investigation to AS dynamics in greater amberjack (Seriola dumerili), an economical marine teleost, in response to hypo- (10 ppt) and hyper-salinity (40 ppt) stresses. Totally, 2267-2611 differentially spliced events were identified in gills and kidney upon the exposure to undesired salinity regimes. In gills, genes involved in energy metabolism, stimulus response and epithelial cell differentiation were differentially spliced in response to salinity variation, while sodium ion transport and cellular amide metabolism were enhanced in kidney to combat the adverse impacts of salinity changes. Most of these differentially spliced genes were not differentially expressed, and AS was found to regulate different biological processes from differential gene expression, indicative of the functionally nonredundant role of AS in modulating salinity acclimation in greater amberjack. Together, our study highlights the important contribution of post-transcriptional mechanisms to the adaptation of fish to ambient salinity fluctuations and provides theoretical guidance for the conservation of marine fishery resources against increasingly environmental challenges.

Benzaldehyde acts as a behaviorally active component in brewer's yeast protein powder which attracts B. dorsalis through olfaction.

The Oriental fruit fly, Bactrocera dorsalis, is a significant pest that damages a variety of fruit crops. The effectiveness of chemical pesticides against such pests is limited, raising concerns about pesticide residues and resistance. Proteins naturally attract B. dorsalis and have led to the development of a management strategy known as protein bait attractant technology (BAT). Although the attraction of protein sources to B. dorsalis is well-documented, the biologically active components within these sources are not fully understood. This study employed analytical chemistry, behavioral tests, and electrophysiological techniques to investigate the behaviorally active components of beer yeast protein powder (BYPD), aiming to provide a basis for improving and developing protein baits. An olfactory trap assay confirmed the attractiveness of BYPD, and five components with high abundance were identified from its headspace volatiles using GC-MS. These components included ethanol, isoamyl alcohol, ethyl decanoate, benzaldehyde, and phenylethyl alcohol. Mixtures of these five components demonstrated significant attraction to B. dorsalis adults, with benzaldehyde identified as a potential key component. The attractiveness of benzaldehyde required a relatively large dose, and it was most attractive to adults that had been starved from dusk until the following morning. Attraction of adult flies to benzaldehyde appeared mainly mediated by inputs from olfactory receptors. While EAG data supports that ionotropic receptors could influence the detection of benzaldehyde in female adults, they did not affect female behavior towards benzaldehyde. These findings indicate that benzaldehyde is an important behaviorally active component in BYPD and offer insights for developing novel protein lures to control B. dorsalis in an environmentally friendly manner.

Changes in metabolic parameters and serum YKL-40 levels in Chinese rheumatoid arthritis patients during tocilizumab therapy.

OBJECTIVE: To investigate the metabolic changes during therapy of tocilizumab (TCZ) and methotrexate (MTX) in non-diabetic rheumatoid arthritis (RA) patients and for the first time explore the associations between metabolic parameters and serum YKL-40 (sYKL-40) levels. METHODS: We enrolled active non-diabetic RA patients who were refractory to MTX. Patients received intravenous TCZ (8 mg/kg) once every 4 weeks combined with MTX for 24 weeks. Metabolic parameters and sYKL-40 levels were measured before TCZ infusion at baseline, week 4, week 12, and week 24. Correlations were assessed by the Spearman's rank correlation analysis. RESULTS: A total of 91 non-diabetic RA patients were enrolled in this study. At week 24, we observed a significant elevation in body mass index (BMI), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels. In contrast, there was a significant decrease in TC/HDL­C ratio. No apparent changes in insulin resistance were found. Additionally, we detected a significant reduction in sYKL-40 levels during the study. At week 24, changes in sYKL-40 levels showed a significant negative correlation (r = -0.334, p = 0.002) with changes in TC levels. CONCLUSION: The combined therapy of TCZ and MTX resulted in a significant increase in BMI and lipid levels, while an evident decrease in the TC/HDL­C ratio and sYKL-40 levels in RA patients. Additionally, there was a significant correlation between the decrease in sYKL-40 levels and the increase in TC levels during treatment with TCZ and MTX. Key Points • Lipid levels elevated significantly and sYKL-40 levels decreased obviously after therapy of TCZ combined with MTX in Chinese RA patients. • There was a significant correlation between the increase in TC levels and the decrease in sYKL-40 levels during treatment with TCZ and MTX in RA patients.

Construction of cellulose-based hybrid hydrogel beads containing carbon dots and their high performance in the adsorption and detection of mercury ions in water.

Cellulose-based adsorbents have been extensively developed in heavy metal capture and wastewater treatment. However, most of the reported powder adsorbents suffer from the difficulties in recycling due to their small sizes and limitations in detecting the targets for the lack of sensitive sensor moieties in the structure. Accordingly, carbon dots (CDs) were proposed to be encapsulated in cellulosic hydrogel beads to realize the simultaneous detection and adsorption of Hg (II) in water due to their excellent fluorescence sensing performance. Besides, the molding of cellulose was beneficial to its recycling and further reduced the potential environmental risk generated by secondary pollution caused by adsorbent decomposition. In addition, the detection limit of the hydrogel beads towards Hg (II) reached as low as 8.8 × 10-8 M, which was below the mercury effluent standard declared by WHO, exhibiting excellent practicability in Hg (II) detection and water treatment. The maximum adsorption capacity of CB-50 % for Hg (II) was 290.70 mg/g. Moreover, the adsorbent materials also had preeminent stability that the hydrogel beads could maintain sensitive and selective sensing performance towards Hg (II) after 2 months of storage. Additionally, only 3.3% of the CDs leaked out after 2 weeks of immersion in water, ensuring the accuracy of Hg (II) evaluation. Notably, the adsorbent retained over 80% of its original adsorption capacity after five consecutive regeneration cycles, underscoring its robustness and potential for sustainable environmental applications.

Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials.

PURPOSE: CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC). PATIENTS AND METHODS: These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity. RESULTS: The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients. CONCLUSION: In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.

Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN). Cells 2020, 9, 559.

In the original publication [...].

Green and Sustainable Forward Osmosis Process for the Concentration of Apple Juice Using Sodium Lactate as Draw Solution.

China is the world's largest producer and exporter of concentrated apple juice (CAJ). However, traditional concentration methods such as vacuum evaporation (VE) and freeze concentration cause the loss of essential nutrients and heat-sensitive components with high energy consumption. A green and effective technique is thus desired for juice concentration to improve product quality and sustainability. In this study, a hybrid forward osmosis-membrane distillation (FO-MD) process was explored for the concentration of apple juice using sodium lactate (L-NaLa) as a renewable draw solute. As a result, commercial apple juice could be concentrated up to 65 °Brix by the FO process with an average flux of 2.5 L·m-2·h-1. Most of the nutritional and volatile compounds were well retained in this process, while a significant deterioration in product quality was observed in products obtained by VE concentration. It was also found that membrane fouling in the FO concentration process was reversible, and a periodical UP water flush could remove most of the contaminants on the membrane surface to achieve a flux restoration of more than 95%. In addition, the L-NaLa draw solution could be regenerated by a vacuum membrane distillation (VMD) process with an average flux of around 7.87 L∙m-2∙h-1 for multiple reuse, which further enhanced the long-term sustainability of the hybrid process.

Cellulose-based adsorbent using in mercury detection and removal from water via an efficient grafting strategy of fluorometric sensors by click reaction.

Mercury pollution in waters attracts lots of attention due to its serious toxicity and high bioenrichment and many efforts have been devoted in the development of adsorbents for mercury detection and removal. Herein, a cellulose-based adsorbent Cell-TriA-HQ is functionalized with quinoline fluorophore by covalent immobilization through "Click reaction" with high yield. In addition to the admirable adsorptive performance, the prepared adsorbent exhibits excellent selectivity and sensitivity towards Hg (II) in water that the detection limit for Hg (II) is determined to be as low as 1.92 × 10-7 M. The sensitive fluorescence enhancement response is considered to be resulted from the inhibition of photo-induced electron transfer between triazole and quinoline groups and the reinforcement of structural rigidity. The easy manipulation along with excellent performance of adsorption capacity, detective ability and reusability for the multifunctional adsorbent makes it potential in mercury monitoring and removal from aqueous solutions in the field of water treatment.

Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. AIM OF THE STUDY: This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. MATERIALS AND METHODS: GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. RESULTS: Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. CONCLUSIONS: The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.

Peripheral Blood Lymphocyte Subsets and Heterogeneity of B Cell Subsets in Patients of Idiopathic Inflammatory Myositis with Different Myositis-specific Autoantibodies.

Idiopathic inflammatory myopathies (IIM) are a group of myopathies that present with muscle weakness and multiple extra-muscular manifestations, in which lymphocytes play central roles in myositis pathogenesis. This study aimed to explore the clinical characteristics of lymphocyte subsets, especially B cell subsets, in patients with IIM. Our study included 176 patients with active IIM and 210 gender/age-matched healthy controls (HCs). Compared to HCs, patients have reduced counts of T cells, B cells, and natural killer cells. In addition, B cell subsets from 153 patients with IIM and 92 HCs were characterized. Patients had a lower percentage of memory B cells and translational memory B cells, while those patients were with an elevated percentage of CD19+ B cells, plasmablast and naïve B cells compared with HCs. Moreover, to further explore the heterogeneity of B cells in IIM, patients were categorized into three clusters based on clustering analysis. Cluster 1 was dominated by CD19+ B cells, Bregs and naïve B cells, cluster 3 was dominated by memory B cells and plasmablast, and cluster 2 had the highest proportion of translational memory B cells. Notably, patients in cluster 1 presented with higher CK levels, indicating muscle damage, whereas patients in cluster 3 showed a higher incidence of chest tightness. Our study indicated that lymphopenia is a common manifestation in patients with IIM. B cell subsets are abnormally expressed and showed high heterogeneity in patients with IIM. The patients with IIM were divided into three different clusters with different percentages of chest tightness and distinct CK levels.

Enhanced UV protection in silk fibroin based electrospun fabrics realized via orientation induced high efficiency of azobenzene isomerization.

Due to the poor UV protection capability, natural silk fabrics not only suffer from easy damage by sunshine but also induce possible sunburn in the human body. Efficient azobenzene isomerization and enhanced UV shielding are realized by replacing the natural silk with natural protein silk fibroin (SF) and electrospinning together with light-responsive copolymer P(MEO2-co-OEG300-co-AHMA). Compared to a solution cast film, the absorption peak intensity at 355 nm is 60 % higher in UV-Vis spectra of the electropsun SF/P(MEO2-co-OEG300-co-AHMA) fabrics. This improvement is related to the highly oriented chains, inducing more space and higher efficiency for azobenzene isomerization. Only exposure to visible light for 20 min, the absorption peak corresponding to the trans- state at 355 nm recovers to 92.5 % in the electrospun fabrics, which is at least 100 % faster than that in the solution cast film (50 min). It is related to the zip effect of the isomerization in the oriented chain structure. Thus, not only the absorption of UV radiation, but also the isomerization rate is enhanced. Based on these unique absorption and recovery capabilities, the SF based electrospun fabrics can be used to replace the natural silk fabrics for UV shielding in summer, especially for cyclic use.

Dietary inflammatory index is associated with severe depression in older adults with stroke: a cross-sectional study.

Inflammation is involved in the pathogenesis of stroke and depression. We aimed to investigate the association between the dietary inflammatory index (DII) and depression in American adults with stroke. Adults with stroke were enrolled from the National Health and Nutrition Examination Survey between 2005 and 2018 in the United States. The DII was obtained from a 24-h dietary recall interview for each individual. Multivariate regression and restricted cubic spline analyses were conducted to evaluate the association between DII and depression in adults with stroke. The mean age of the 1,239 participants was 63.85 years (50.20% women), and the prevalence of depression was 18.26%. DII showed a linear and positive association with severe depression in adults with stroke (OR, 1.359; 95% CI, 1.021, 1.810; p for non-linearity=0.493). Compared with those in the lowest tertile of the DII, adults with stroke in the third tertile of the DII had a 3.222-fold higher risk of severe depression (OR, 3.222; 95% CI, 1.150, 9.026). In the stratified analyses, the association between DII score and severe depression was more significant in older adults (p for interaction=0.010) but not significant with respect to sex (p for interaction=0.184) or smoking status (p for interaction=0.396). No significant association was found between DII and moderate-to-moderately severe depression in adults with stroke. In conclusion, an increase in DII score was associated with a higher likelihood of severe depression in older adults with stroke.

Genetic and phenotypic profiling of single living circulating tumor cells from patients with microfluidics.

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non-small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction.

Effect of Mixed Probiotics on Ovalbumin-Induced Atopic Dermatitis in Juvenile Mice.

Atopic dermatitis is one of the most common dermatologic problems, especially in children. Given the ability of symbiotic microorganisms in modulating the immune system, probiotics administration has been studied in previous research in the management of atopic dermatitis. However, there are conflicting results between studies. In this study, we aimed to assess the effectiveness of mixed probiotics as a treatment option for atopic dermatitis induced by ovalbumin. BALB/c juvenile mice were classified and divided into the ovalbumin group, mixed probiotic group (ovalbumin + LK), and control group. Except for the control group, all mice were sensitized with ovalbumin to establish a model of atopic dermatitis. The mixed probiotics were given by gavage for 14 days. Mice body weight, skin lesions, skin inflammation, ovalbumin-specific Ig, the number of Treg and CD103+DC, and the expression level of PD-1/PD-L1 were examined. The results showed that mixed probiotics can improve body weight and alleviate skin symptoms. Mixed probiotics reduced serum Th2 inflammatory factors, eosinophils, mast cell degranulation, mast cell count, and the expression of ovalbumin-specific immunoglobulin E/G1 and increased the anti-inflammatory cytokine interleukin-10, Treg cells, CD103+DC cells, and the expression level of PD-1/PD-L1. These findings suggest that mixed probiotics could be a viable treatment option for atopic dermatitis and provide insight into the underlying mechanisms involved.

Structure elucidation and antiviral activity of a cold water-extracted mannogalactofucan Ts1-1A from Trametes sanguinea against human cytomegalovirus in vitro.

In this study, we purified a partially acetylated heteropolysaccharide (Ts1-1A) from the fruit bodies of Trametes sanguinea Lloyd through cold water extraction and serial chromatographic separation. The purified polysaccharide Ts1-1A (12.8 kDa) was characterized as a branched mannogalactofucan with a backbone of alternately connected 1,3-linked α-Fucp and 1,6-linked α-Galp, which was partially substituted by non-reducing end units of ß-Manp at O-2 and O-3 positions of 1,6-linked α-Galp. Ts1-1A showed pronounced anti-human cytomegalovirus activity at the concentration of 200 and 500 µg/mL in systematical assessments including morphological changes, western blotting, qPCR, indirect immunofluorescence and tissue culture infective dose assays. Moreover, Ts1-1A exerted its antiviral activity at two distinct stages of viral proliferation manifesting as significantly inhibiting viral protein (IE1/2 and p52) expression and reducing viral gene (UL123, UL44 and UL32) replication in the HCMV-infected WI-38 cells. At viral attachment stage, Ts1-1A interacted with HCMV and prevented HCMV from attaching to its host cells. While at early phase of viral replication stage, Ts1-1A suppressed HCMV replication by downregulating NQO1 and HO-1 proteins related to oxidative stress as an antioxidant. To sum up, Ts1-1A is a promising anti-HCMV agent which could be developed for HCMV infection prevention and therapy.

Design, Synthesis, and Biological Evaluation of 2-Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect.

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 µg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 µg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect.

Odorant Receptor BdorOR49b Mediates Oviposition and Attraction Behavior of Bactrocera dorsalis to Benzothiazole.

The ability to recognize a host plant is crucial for insects to meet their nutritional needs and locate suitable sites for laying eggs. Bactrocera dorsalis is a highly destructive pest in fruit crops. Benzothiazole has been found to induce oviposition behavior in the gravid B. dorsalis. However, the ecological roles and the olfactory receptor responsible for benzothiazole are not yet fully understood. In this study, we found that adults were attracted to benzothiazole, which was an effective oviposition stimulant. In vitro experiments showed that BdorOR49b was narrowly tuned to benzothiazole. The electroantennogram results showed that knocking out BdorOR49b significantly reduced the antennal electrophysiological response to benzothiazole. Compared with wild-type flies, the attractiveness of benzothiazole to BdorOR49b knockout adult was significantly attenuated, and mutant females exhibited a severe decrease in oviposition behavior. Altogether, our work provides valuable insights into chemical communications and potential strategies for the control of this pest.