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High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25‐dihydroxy vitamin D3 (1,25(OH)2D3) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2D3 could be associated with the expression and activity of Na+/H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration. [ABSTRACT FROM AUTHOR]

A series of indazole derivatives were designed and synthesized by molecular hybridization strategy, and these compounds were evaluated the inhibitory activities against human cancer cell lines of lung (A549), chronic myeloid leukemia (K562), prostate (PC-3), and hepatoma (Hep-G2) by methyl thiazolyl tetrazolium (MTT) colorimetric assay. Among these, compound 6o exhibited a promising inhibitory effect against the K562 cell line with the IC50 (50% inhibition concentration) value of 5.15 µM, and this compound showed great selectivity for normal cell (HEK-293, IC50 = 33.2 µM). Moreover, compound 6o was confirmed to affect apoptosis and cell cycle possibly by inhibiting Bcl2 family members and the p53/MDM2 pathway in a concentration-dependent manner. Overall, this study indicates that compound 6o could be a promising scaffold to develop an effective and low-toxic anticancer agent. [ABSTRACT FROM AUTHOR]

The innate immune system has developed sophisticated strategies to defense against infections. Host cells utilize the recognition machineries such as toll-like receptors and nucleotide binding and oligomerization domain-like receptors to identify the pathogens and alert immune system. However, some pathogens have developed tactics to evade host defenses, including manipulation of host inflammatory response, interference with cell death pathway, and highjack of phagocytosis signaling for a better survival and colonization in host. Enterohemorrhagic Escherichia coli (EHEC) is a notorious foodborne pathogen that causes severe tissue damages and gastrointestinal diseases, which has been reported to disturb host immune responses. Diverse bioactive compounds such as flavonoids, phenolic acids, alkaloids, saccharides, and terpenoids derived from food varieties and probiotics have been discovered and investigated for their capability of combating bacterial infections. Some of them serve as novel antimicrobial agents and act as immune boosters that harness host immune system. In this review, we will discuss how EHEC, specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathway; and highlight the promising role of food-derived bioactive compounds and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies. [ABSTRACT FROM AUTHOR]

Three types of radical–3d/3d–4f heterotrispin complexes [(Cu(hfac)2)4(NIT-4-OMe-4PyPh)2] (1), {[(Cu(hfac)2)3(NIT-4-OMe-4PyPh)2]}n (2) and {[Cu(hfac)2][(NIT-4-OMe-4PyPh)]2[Ln(hfac)3]}n (Ln = Gd 3; Tb 4; Dy 5; Ho 6) (NIT-4-OMe-4PyPh = 2-[4-methoxy-3-(4-pyridinylmethoxy)phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; hfac = hexafluoroacetylacetonate) have been successfully synthesized by adjusting various experimental conditions. Compound 1 is a six-spin cyclic structure including a cyclic molecular structure with two Cu(hfac)2 units linked by free NO groups, while complex 2 possesses a one-dimensional topological structure consisting of cyclic [Cu–radical]2 dimers bridged by CuII ions. Compounds 3–6 display a series of 2p–3d–4f heterotrispin chains in which NIT-4-OMe-4PyPh radical ligands linked LnIII and CuII ions in "head-to-head" mode through pyridine-N atoms and NO moieties. The magnetic behavior for complex 1 revealed a dominant antiferromagnetic exchange interaction between the radical and five coordinated CuII ions while for 2, just a ferromagnetic Cu–ON interaction was obviously observed. Furthermore, Tb and Dy heterotrispin chains showed field-induced slow magnetic relaxation behaviors. In particular, Tb derivative shows the characteristic emission peaks of TbIII ion and can be developed as a prospective recyclable luminescent probe for detecting Fe3+ ion. [ABSTRACT FROM AUTHOR]

Here we report a simple and efficient method for the preparation of CF2H‐substituted pyrido[4,3,2‐gh]phenanthridines under photoredox conditions. The reactions are triggered by addition of a CF2H radical to a carbon–carbon double bond to form three different types of bonds via a cascade radical difluoromethylation/cyano insertion/cyclization. This difluoromethylated transformation exhibits good functional group compatibility, leading to the construction of the desired ring‐fused phenanthridine derivatives in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

In this work, a simple one-step hydrothermal method was employed to prepare the Ce-doped Fe2O3 ordered nanorod arrays (CFT). The Ce doping successfully narrowed the band gap of Fe2O3, which improved the visible light absorption performance. In addition, with the help of Ce doping, the recombination of electron/hole pairs was significantly inhibited. The external voltage will make the performance of the Ce-doped sample better. Therefore, the Ce-doped Fe2O3 has reached superior photoelectrochemical (PEC) performance with a high photocurrent density of 1.47 mA/cm2 at 1.6 V vs. RHE (Reversible Hydrogen Electrode), which is 7.3 times higher than that of pristine Fe2O3 nanorod arrays (FT). The Hydrogen (H2) production from PEC water splitting of Fe2O3 was highly improved by Ce doping to achieve an evolution rate of 21 μmol/cm2/h. [ABSTRACT FROM AUTHOR]

The cyclic adenosine monophosphate‐protein kinase A (cAMP‐PKA) signalling pathway is evolutionarily conserved in eukaryotes and plays a crucial role in defending against external environmental challenges, which can modulate the cellular response to external stimuli. Arthrobotrys oligospora is a typical nematode‐trapping fungus that specializes in adhesive networks to kill nematodes. To elucidate the biological roles of the cAMP‐PKA signalling pathway, we characterized the orthologous adenylate cyclase AoAcy, a regulatory subunit (AoPkaR), and two catalytic subunits (AoPkaC1 and AoPkaC2) of PKA in A. oligospora by gene disruption, transcriptome, and metabolome analyses. Deletion of Aoacy significantly reduced the levels of cAMP and arthrobotrisins. Results revealed that Aoacy, AopkaR, and AopkaC1 were involved in hyphal growth, trap morphogenesis, sporulation, stress resistance, and autophagy. In addition, Aoacy and AopkaC1 were involved in the regulation of mitochondrial morphology, thereby affecting energy metabolism, whereas AopkaC2 affected sporulation, nuclei, and autophagy. Multi‐omics results showed that the cAMP‐PKA signalling pathway regulated multiple metabolic and cellular processes. Collectively, these data highlight the indispensable role of cAMP‐PKA signalling pathway in the growth, development, and pathogenicity of A. oligospora, and provide insights into the regulatory mechanisms of signalling pathways in sporulation, trap formation, and lifestyle transition. [ABSTRACT FROM AUTHOR]

The quality of fresh products through cross-regional sales has been uncertain to consumers. To improve the quality of fresh products, some fresh product supply chains have implemented blockchain technology to provide traceable information for their products, and some regional governments have subsidized their local firms to incentivize them to implement blockchain-driven traceability systems. However, with regional government subsidy heterogeneity, cross-regional fresh product supply chain firms lack theoretical guidance on their operation decisions. Based on the research gap, we investigate optimal operation policies in a fresh product supply chain consisting of a manufacturer and a retailer located in different regions. The local governments may subsidize the manufacturer or the retailer located in their own regions, which construct four subsidy strategies (SS, SN, NS, and NN) along the supply chain. We find that the optimal operation policies under four subsidy strategies can be affected by the sensitivity to traceability level, cost-sharing rate of the manufacturer, rate of products left after corrosion, and subsidy rate to the manufacturer. Moreover, the government subsidy to the retailer is always beneficial to the retailer and the supply chain but does not affect the manufacturer's operation policies and profits. The government subsidy to the manufacturer is always beneficial to the manufacturer but not always beneficial to the retailer and the supply chain. Hence the desired subsidy strategy for the manufacturer is SS and SN, and the one for the retailer and the supply chain is either NS or SS with different conditions. [ABSTRACT FROM AUTHOR]

Salmonella has been implicated in multiple foodborne outbreaks and recalls associated with low water activity foods (LawF). To verify the effectiveness of a process against Salmonella in LawF, validation using a nonpathogenic surrogate strain is essential. Enterococcus faecium NRRL B-2354 strain has been used as a potential surrogate of Salmonella in different processing of LawF. However, the survival of Salmonella and E. faecium in LawF during food processing is a dynamic function of aw, food composition and structure, processing techniques, and other factors. This review assessed pertinent literature on the thermal and non-thermal inactivation of Salmonella and its presumable surrogate E. faecium in various LawF and provided an overview of its suitibility in different LawF. Overall, based on the D-values, survival/reduction, temperature/time to obtain 4 or 5-log reductions, most studies concluded that E. faecium is a suitable surrogate of Salmonella during LawF processing as its magnitude of resistance was slightly greater or equal (i.e., statistical similar) as compared to Salmonella. Studies also showed its unsuitability which either does not provide a proper margin of safety or being overly resistant and may compromise the quality and organoleptic properties of food. This review provides useful information and guidance for future validation studies of LawF. [ABSTRACT FROM AUTHOR]

Herein, we report a DMAP-catalysed Curtius rearrangement and intramolecular cyclisation cascade reaction of 2-substituted aryl carboxylic acids with organic azides for the first time. This protocol features simple operation, broad scope and metal-free conditions, furnishing a broad spectrum of biologically attractive heterocycles. The synthetic virtue of this reaction was demonstrated by gram-scale synthesis and applicability toward drug-like molecules. [ABSTRACT FROM AUTHOR]

Plant polysaccharides are widely found in nature and have a variety of biological activities, including immunomodulatory, antioxidative, and antitumoral. Due to their low toxicity and easy absorption, they are widely used in the health food and pharmaceutical industries. However, low activity hinders the wide application. Chemical modification is an important method to improve plant polysaccharides' physical and chemical properties. Through chemical modification, the antioxidant and immunomodulatory abilities of polysaccharides were significantly improved. Some polysaccharides with poor water solubility also significantly improved their water solubility after modification. Chemical modification of plant polysaccharides has become an important research direction. Research on the modification of plant polysaccharides is currently increasing, but a review of the various modification studies is absent. This paper reviews the research progress of chemical modification (sulfation, phosphorylation, acetylation, selenization, and carboxymethylation modification) of land plant polysaccharides (excluding marine plant polysaccharides and fungi plant polysaccharides) during the period of January 2012–June 2022, including the preparation, characterization, and biological activity of modified polysaccharides. This study will provide a basis for the deep application of land plant polysaccharides in food, nutraceuticals, and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Xanthomonas axonopodis pv. citri (Xac) belongs to the Gram-negative species, causing citrus canker that seriously affects the fruit yield and quality of many rutaceae plants. Herein, we found that compound 2-(butyldisulfanyl) quinazolin-4(3H)-one exhibited remarkable anti-Xac activity in vitro with a half effective concentration (EC50) of 2.6 μg/mL, while the positive controls thiodiazole-copper with 57 μg/mL and bismerthiazol with 68 μg/mL and this compound showed great anti-citrus canker activity in vivo. This active compound also was confirmed to reduce biofilm formation, increase the level of reactive oxygen species, damage the morphological structure of the bacteria, and cause bacterial death. Proteomics and RT-qPCR analysis results indicated that this compound down-regulated the expression of enzymes in the MEP (2-methyl-D-erythritol 4-phosphate) pathway and might achieve destructive ability of Xac. Overall, this study indicates that such derivatives could be a promising scaffold to develop novel bactericides to control citrus canker. [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease (AD), synaptic dysfunction is thought to occur many years before the onset of cognitive decline.Objective: Detecting synaptic dysfunctions at the earliest stage of AD would be desirable in both clinic and research settings.Methods: Population voltage imaging allows monitoring of synaptic depolarizations, to which calcium imaging is relatively blind. We developed an AD mouse model (APPswe/PS1dE9 background) expressing a genetically-encoded voltage indicator (GEVI) in the neocortex. GEVI was restricted to the excitatory pyramidal neurons (unlike the voltage-sensitive dyes).Results: Expression of GEVI did not disrupt AD model formation of amyloid plaques. GEVI expression was stable in both AD model mice and Control (healthy) littermates (CTRL) over 247 days postnatal. Brain slices were stimulated in layer 2/3. From the evoked voltage waveforms, we extracted several parameters for comparison AD versus CTRL. Some parameters (e.g., temporal summation, refractoriness, and peak latency) were weak predictors, while other parameters (e.g., signal amplitude, attenuation with distance, and duration (half-width) of the evoked transients) were stronger predictors of the AD condition. Around postnatal age 150 days (P150) and especially at P200, synaptically-evoked voltage signals in brain slices were weaker in the AD groups versus the age- and sex-matched CTRL groups, suggesting an AD-mediated synaptic weakening that coincides with the accumulation of plaques. However, at the youngest ages examined, P40 and P80, the AD groups showed differentially stronger signals, suggesting "hyperexcitability" prior to the formation of plaques.Conclusion: Our results indicate bidirectional alterations in cortical physiology in AD model mice; occurring both prior (P40-80), and after (P150-200) the amyloid deposition. [ABSTRACT FROM AUTHOR]

• Low-dose radiation upregulates T cell chemokines and iRGD receptors. • Low-dose radiation improves infiltration and antitumor potency of transferred T cells. • Combining low-dose radiation with adoptive cell therapy is beneficial in solid tumors. Poor penetration of transferred T cells represents a critical factor impeding the development of adoptive cell therapy in solid tumors. We demonstrated that iRGD-antiCD3 modification promoted both T cell infiltration and activation in our previous work. Interest in low-dose radiotherapy has recently been renewed due to its immuno-stimulatory effects including T cell recruitment. This study aims to explore the synergistic effects between low-dose radiotherapy and iRGD-antiCD3-modified T cells. Flow cytometry was performed to assess the expression of iRGD receptors and chemokines. T cell infiltration was evaluated by immunohistofluorescence and in vivo real-time fluorescence imaging and antitumor effects were investigated by in vivo bioluminescence imaging in the gastric cancer peritoneal metastasis mouse model. We found that 2 Gy irradiation upregulated the expression of all three iRGD receptors and T-cell chemokines. The addition of 2 Gy low-dose irradiation boosted the accumulation and penetration of iRGD-antiCD3-modified T cells in peritoneal tumor nodules. Combining 2 Gy low-dose irradiation with iRGD-antiCD3-modified T cells significantly inhibited tumor growth and prolonged survival in the peritoneal metastasis mouse model with a favorable safety profile. Altogether, we demonstrated that low-dose radiotherapy could improve the antitumor potency of iRGD-antiCD3-modified T cells by promoting T cell infiltration, providing a rationale for exploring low-dose radiotherapy in combination of other adoptive T cell therapies in solid tumors. [ABSTRACT FROM AUTHOR]

Enhancing the detection power of control charts for detecting small to moderate process changes is always the focus of attention in academia. To improve the detection ability of conventional X ¯ and R control charts, an improved joint X ¯ and R chart, which combines the ordinary X ¯ and R charts with runs rules of the type ' r out of m ', is proposed to monitor the process location and dispersion simultaneously. A finite Markov chain imbedding approach is employed to develop the resulting control scheme. A comparative study is conducted to investigate the performance of the proposed chart in terms of the out-of-control average run length. The statistical performance of the suggested chart when the process parameters are estimated is also evaluated. The numerical results indicate that (1) the proposed chart improves the detection ability of traditional X ¯ and R charts in detecting small to moderate process shifts; (2) the suggested scheme performs better than the EWMA and CUSUM schemes in detecting large process fluctuations. Furthermore, when specific values of r and m are selected, the statistical performance of the proposed chart for detecting small shifts is close to or even better than that of its competitors; (3) the run length performance of the proposed chart is greatly affected by parameter estimation, especially for small process shifts. [ABSTRACT FROM AUTHOR]

Nematode-trapping (NT) fungi play a significant role in the biological control of plant- parasitic nematodes. NT fungi, as a predator, can differentiate into specialized structures called "traps" to capture, kill, and consume nematodes at a nutrient-deprived condition. Therefore, trap formation is also an important indicator that NT fungi transition from a saprophytic to a predacious lifestyle. With the development of gene knockout and multiple omics such as genomics, transcriptomics, and metabolomics, increasing studies have tried to investigate the regulation mechanism of trap formation in NT fungi. This review summarizes the potential regulatory mechanism of trap formation in NT fungi based on the latest findings in this field. Signaling pathways have been confirmed to play an especially vital role in trap formation based on phenotypes of various mutants and multi-omics analysis, and the involvement of small molecule compounds, woronin body, peroxisome, autophagy, and pH-sensing receptors in the formation of traps are also discussed. In addition, we also highlight the research focus for elucidating the mechanism underlying trap formation of NT fungi in the future. [ABSTRACT FROM AUTHOR]

Dauricine (DA) is a natural plant-derived alkaloid extracted from Menispermum dauricum. Menispermum dauricum has been used in traditional Chinese medicine as a classic remedy for rheumatoid arthropathy and is believed to be effective in alleviating swelling and pain in the limbs. Osteoarthritis (OA) is a classic degenerative disease involving chondrocyte death, and there is still a lack of effective therapeutic agents that can reverse the progression of the disease. Here we explored the therapeutic effects of DA against OA and further explored the mechanism. The effect of DA on cell viability was assessed by CCK-8. IL-1β-treated mouse chondrocytes were used as an in vitro model of OA, and apoptosis was detected by flow cytometry. QRT-PCR, western blotting, cell staining, and immunofluorescence were used to detect relevant inflammatory factors and cartilage-specific expression. RNA sequencing was used to identify pertinent signaling pathways. The therapeutic effect of DA was verified by micro-CT, histological analysis and immunohistochemical analysis in a mouse OA model. DA demonstrated a high safety profile on chondrocytes, significantly reversing the inflammatory response induced by IL-1β, and promoting factors associated with cartilage regeneration. Moreover, DA exhibited a significant protective effect on the knee joints of mice undergoing ACLT-DMM, effectively preventing cartilage degeneration and subchondral bone tissue destruction. These positive therapeutic effects were achieved through the modulation of the NF-κB pathway and the Ca2+ signaling pathway by DA. Being derived from a traditional herb, DA exhibits remarkable therapeutic potential and safety in OA treatment, presenting a promising option for patients dealing with osteoarthritis. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the combination of myoelectric characteristics of tensor palatini muscle (TP) and collapsibility of upper airway in obstructive sleep apnea (OSA) patients with different external phenotypes of collapse pattern at velum level under drug-induced sleep endoscopy (DISE). Study design: Case series with planned data collection. Setting: Operation room. Subjects and methods: 36 mainly collapse pattern at velum level OSA subjects underwent DISE with synchronous tensor palatini electromyograms (TP EMG), and polysomnography (ALICE 6). According to the phenotype of collapse pattern at velum level in DISE, the subjects were divided into group 1 (concentric collapse), group 2 (anteroposterior collapse), and group 3 (lateral collapse). Each group consisted of 13, 14, and 9 subjects, respectively, and was observed the electromyographic indexes at awake, sleep onset, during apnea and the third respiratory cycle after apnea. The active and passive upper airway critical closing pressure (Pcrit) of each group were measured at the same time, and the difference of neuromuscular response between different groups was evaluated. Results: In tonic TPEMG, group 1 showed the highest value during awake and sleep onset, while group 2 was the highest during apnea and after apnea. In peak TPEMG, group 1 showed the highest value during awake. Group 2 showed the highest value during other states. In passive Pcrit and D value (difference between passive Pcrit and active Pcrit), group 2 was the highest, while group 1 was the highest in active Pcrit. Difference was statistically significant. Conclusions: Under different states of awake, sleep onset, apnea and after apnea, the response force of tensor palatini muscle of OSA subjects with different phenotypes under DISE was different. Group 1 showed the highest EMG values only when awake and sleep onset, and it was most prone to collapse. Group 2 had the highest anatomical load (passive Pcrit) and the highest neuromuscular compensatory effect (D value). [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux‐en‐Y reconstruction after total gastrectomy is difficult to be performed using routine tools. The aim of this study was to evaluate the feasibility and safety of cap‐assisted routine adult colonoscope (CARAC) for ERCP in these patients. Methods: Sixteen consecutive patients with indications of ERCP who had previously undergone total gastrectomy with Roux‐en‐Y reconstruction at two tertiary care endoscopy centers were identified. All ERCP procedures were carried out by using CARAC. The success rate of reaching the papilla, biliary cannulation and procedure‐related adverse events were analyzed. Results: The papilla was successful reached in 11 (68.8%) of the 16 cases, and biliary cannulation was subsequently reached in eight (72.7%) of the 11 cases. The procedures succeeded in three patients by using a percutaneous–endoscopic rendezvous procedure after failed cannulation. Overall clinical success was achieved in 11 (68.8%) of 16 patients. Procedure‐related mild acute pancreatitis was observed in 25.0% (4/16) of the cases and mild cholangitis in 18.8% (3/16). No serious adverse events were reported. Conclusions: CARAC for therapeutic ERCP is safe and effective in treating patients with Roux‐en‐Y reconstruction after total gastrectomy. [ABSTRACT FROM AUTHOR]

A spatially segregative coacervate-in-proteinosome hybrid microcompartment is constructed by co-encapsulation of either positively or negatively charged polyelectrolytes within proteinosomes with enhanced cascade enzymatic reactions, providing a step towards the development of artificial eukaryotic cell like microcompartments. [ABSTRACT FROM AUTHOR]

Recently, a MIX S2 control chart using both attribute and variable inspections is proposed by Ho and Quinino (2016) to monitor the process variability. This paper considers the variable sampling interval (VSI) MIX S2 control chart in which the sampling interval between two successive sampling points is varied based on the value of the preceding complementary sample variance to improve the performance of the original MIX S2 control chart. Additionally, a unified economical design model for the process is established with the cost function derived. The performance of the VSI chart is compared to that of the original static chart. The numerical results show that comparing to original MIX S2 control chart, the VSI chart yields better performance in terms of less expected cost per unit of time. [ABSTRACT FROM AUTHOR]

Foodborne pathogen contamination in low water activity (a w) foods is a critical problem for both the food industry and public health. Low-moisture foods and food ingredients have been implicated in numerous Salmonella outbreaks and are increasingly involved in the recall of products with possible contamination by Listeria monocytogenes. L. monocytogenes is singled out as a true environmental species and a pathogenic bacterium of concern in ready-to-eat foods including low-moisture foods. L. monocytogenes can survive in a dry environment or in low-moisture foods for an extended period with increased stability at lower storage temperatures. Adaptation to low-moisture foods enables L. monocytogenes to exhibit enhanced thermal resistance. However, compared with Salmonella in low-moisture foods, less information is available about the fate of L. monocytogenes in low-moisture foods during thermal inactivation and the factors influencing its thermotolerance. This review summarizes pertinent literature on the desiccation and thermal resistance of L. monocytogenes in low-moisture foods, discusses factors impacting the desiccation and thermal stability, and compares desiccation and thermal stability of L. monocytogenes with Salmonella in respective low-moisture foods. The possible mechanisms underlying the stability of L. monocytogenes in low-moisture foods are also discussed. L. monocytogenes can survive in low-moisture foods for an extended duration and is highly thermoresistant. Thermal resistance of L. monocytogenes has an inverse relationship with a w , and is dependent on the food matrix, and other factors. • L. monocytogenes is increasingly implicated in low-moisture food (La w F) recall. • L. monocytogenes is highly stable in La w F especially stored at a cooler temperature. • Thermotolerance of L. monocytogenes in La w F highlight its significance in La w F. • Factors influencing its thermotolerance and desiccation stability were discussed. • Thermal- and desiccation-stability of L. monocytogenes was compared with Salmonella. [ABSTRACT FROM AUTHOR]

Objective: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). Methods: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. Results: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. Conclusion: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to explore a novel intraoperative trajectory‐determined strategy of grouped patient‐specific drill templates (PDTs) for transoral C2 pedicle screw insertion (C2TOPI) for atlantoaxial dislocation (AAD) with incomplete reduction and to evaluate its efficiency and accuracy. Methods: Ten cadaveric C2 specimens were scanned by computed tomography (CT) and randomly divided into two groups (the PDT and freehand groups). A novel intraoperative trajectory‐determined strategy of grouped PDTs was created for AAD with incomplete reduction. C2TOPI was performed by use of the PDT technique and the fluoroscopy‐guided freehand technique. After surgery, the screw deviations from the centroid of the cross‐section at the midpoint of the pedicle and screw position grades were assessed in both groups. Results: Compared to the freehand group, the PDT group had a significantly shorter surgery time than the freehand group (47.7 vs 61.9 min, P < 0.001). The absolute deviations from the centroids between the preoperative designs and postoperative measurements on the axial plane of the pedicle were 1.19 ± 0.25 mm in the PDT group and 1.82 ± 0.51 mm in the freehand group. On the sagittal plane of the pedicle, the corresponding values were 1.10 ± 0.33 mm in the PDT group and 1.70 ± 0.49 mm in the freehand group. The absolute deviations of the free‐hand group on both the axial and sagittal planes were higher than that of the freehand group (P < 0.05 and P < 0.05, respectively). For the grade of screw insertion position, nine (90%) were observed in type I and one (10%) in type II in the PDT group, whereas five (50%) were in type I, three (30%) were in type II, and two (20%) in type III in the freehand group. Statistical differences could not be found between the groups in terms of the screw positions (P > 0.05). Conclusion: The novel intraoperative trajectory‐determined strategy of grouped PDTs can be used as an accurate and feasible method for C2TOPI for AAD with incomplete reduction. [ABSTRACT FROM AUTHOR]

Little is known about the migration of the Gray-headed Lapwing (Vanellus cinereus). During the fall migration season of 2018, we tracked 3 birds from Guiyang Airport, China, a stopover site of Gray-headed Lapwing, in order to analyze their migratory and wintering movements by means of GPS-GSM satellite telemetry. We obtained 3 partial fall migration routes and 2 complete spring migration routes from September 2018 to July 2019. We identified E India and Bangladesh as their wintering ground and NE and E China as their breeding area. The spring migration covered 3,380 km and took 12 d on average (n = 2). Gray-headed Lapwings migrated at night, flying at speeds of 29.11–91.12 km/h. In winter, the mean home range area (95% utilization distribution) was 18.56 km2 (SD = 21.74, 3 birds) and the mean core area (50% utilization distribution) was 1.28 km2 (SD = 1.49, 3 birds). [ABSTRACT FROM AUTHOR]

Nutrition-related noncommunicable diseases (NR-NCDs) such as cardiovascular disease and type 2 diabetes both negatively impact the quality of life of many individuals and generate a substantial burden on society, demonstrating a need for intervention. Phytochemicals are investigated as a potential approach for combating NR-NCDs, and those found in hops have gained increased attention in recent decades. Hops, the strobile of the plant Humulus lupulus, are grown primarily for the brewing industry as they confer taste and increased shelf-life. The bitter acids represent the main compounds of interest for improving beer quality. Additionally, bitter acids as well as the prenylated chalcone xanthohumol, exhibit a wide range of health beneficial properties. This review summarizes those beneficial effects of bitter acids and xanthohumol on NR-NCDs, including inflammatory and immune diseases, obesity and metabolic disorders, as well as cancer prevention. [ABSTRACT FROM AUTHOR]

This paper proposes a variable sampling interval npx−X¯ control chart for monitoring the process mean using combined attribute‐variable inspection. An economic design of the proposed chart using Taguchi's quadratic loss function is presented. The proposed model minimizes the total expected cost per unit time while minimizing out‐of‐control average time‐to‐signal and maintaining reasonable in‐control average time‐to‐signal. The numerical results indicate that, compared with the corresponding fixed sampling interval control chart scheme, the proposed control chart yields better performance in terms of both shorter time to signal a process shift and less total expected cost per unit time. Sensitivity analyses of the cost model are also carried out by using a fractional factorial experimental design. [ABSTRACT FROM AUTHOR]

Genetically-encoded calcium indicators (GECIs) are essential for studying brain function, while voltage indicators (GEVIs) are slowly permeating neuroscience. Fundamentally, GECI and GEVI measure different things, but both are advertised as reporters of "neuronal activity". We quantified the similarities and differences between calcium and voltage imaging modalities, in the context of population activity (without single-cell resolution) in brain slices. GECI optical signals showed 8–20 times better SNR than GEVI signals, but GECI signals attenuated more with distance from the stimulation site. We show the exact temporal discrepancy between calcium and voltage imaging modalities, and discuss the misleading aspects of GECI imaging. For example, population voltage signals already repolarized to the baseline (~ disappeared), while the GECI signals were still near maximum. The region-to-region propagation latencies, easily captured by GEVI imaging, are blurred in GECI imaging. Temporal summation of GECI signals is highly exaggerated, causing uniform voltage events produced by neuronal populations to appear with highly variable amplitudes in GECI population traces. Relative signal amplitudes in GECI recordings are thus misleading. In simultaneous recordings from multiple sites, the compound EPSP signals in cortical neuropil (population signals) are less distorted by GEVIs than by GECIs. [ABSTRACT FROM AUTHOR]

Background: Outcomes of surgical management of obstructive sleep apnea–hypopnea syndrome (OSAHS) can be difficult to predict preoperatively. Aims/objectives: To study the effect of applying traction to the velum during drug-induced sleep endoscopy (DISE) in OSAHS patients, and to describe the use of traction velum in predicting surgical success. Materials and methods: 41 adult surgical patients with OSA (Friedman tongue position II and III) were evaluated by DISE. All patients subsequently underwent velopharyngeal surgery in the form of uvulopalatopharyngoplasty with tonsillectomy plus barbed reposition pharyngoplasty. Results: Surgical responders (n = 26, 63.4%) and nonresponders (n = 15, 36.6%) demonstrated no significant differences with regard to preoperative AHI, age, sex, body mass index, and mean/lowest O2 saturation. Responders had a marked decrease in desaturation events (2.96 vs 0.03, p < 0.001) and percentage change in number of desaturation events before/after traction velum (56.7 vs 4.5, p < 0.001). Regression analysis revealed that reduction in mean desaturation events, with traction velum, by a percentage > 26.8% (odds ratio [OR] 1.046; 95% confidence interval [CI] 1.018–1.075; p = 0.001) was the only independent predictor of surgery success. Conclusions and significance: OSAHS patients' velopharyngeal surgical outcome can be predicted by measuring the percentage change in the number of oxygen desaturation events before and after traction velum in DISE. [ABSTRACT FROM AUTHOR]

Background: T cell-redirecting bispecific antibodies (BsAbs) are emerging as a potent cancer therapy that crosslinks tumor cells and T cells by simultaneously binding to tumor-associated antigen and CD3ϵ. However, immune inhibitory molecules can be remarkably upregulated after BsAbs treatment, leading to a suppressive tumor microenvironment and treatment resistance. This can be partially reversed by combination with immune checkpoint inhibitors. In our previous work, we successfully constructed the recombinant protein iRGD-antiCD3 and demonstrated that it promoted antitumor efficacy of transferred T cells by promoting T cell activation and infiltration. Methods: We detected the levels of both PD-1 and PD-L1 as resistance to iRGD-antiCD3 treatment. Using cord blood-derived T cells, we assessed the activation and effects of iRGD-antiCD3 combined with PD-1 as evidenced by activation markers, Th1/Th2-cytokines, and killing capability against tumor cells in vitro. Moreover, to better mimic the physiological characteristics of in vivo solid tumors, we generated 3D spheroids from target cell lines. Spheroids were stained with a Viability/Cytotoxicity Assay Kit and examined by confocal microscopy to study the in vitro antitumor effect of T cells co-administered with combination iRGD-antiCD3 and PD-1 blockade. The mouse peritoneal metastatic gastric tumor model was employed. The synergistic antitumor effect and safety profiles in vivo were evaluated by tumor and body weight of tumor-bearing mice. Results: We found that expression of both PD-1 and PD-L1 were increased as resistance to iRGD-antiCD3 treatment. We found that PD-1 blockade partially restored T cell activation as evidenced by elevated activation markers, Th1-cytokines, and killing capability against tumor cells in vitro. The combination of PD-1 blockade consistently and significantly increased cord blood-derived T cell cytotoxicity against 3D tumor spheroids. In vivo, we observed synergistic antitumor activity without obvious side effects. Conclusion: These results demonstrated that combining iRGD-antiCD3 with PD-1 blockade could further improve antitumor efficacy of T cells, and this strategy holds great potential for the treatment of solid malignancies. [ABSTRACT FROM AUTHOR]

Peracetic acid (PAA) is a commonly used antimicrobial in brush-bed spray bar interventions during apple packing. Prior to sanitizer application on the brush-bed, specific fruit cleaners, such as Acidex Duo (AD), EpiClean (EC), Nature's Shield 220-ACL (NS 220), or Nature's Shield 330-ALK (NS 330), are used to remove of soil, debris, and natural wax from the surfaces of apples. This study evaluated the effectiveness of commonly used cleaners in the apple industry to improve the antimicrobial efficacy of PAA against Listeria monocytogenes on apple surfaces during brush-bed spray bar interventions. Granny Smith apples, 48 h post-inoculation, underwent submersion treatment with different cleaners, as well as PAA alone or in combination with the cleaners. A 30-sec treatment of 5.0% AD, 4.2% EC, 10.0% NS 220, and 10.0% NS 330 resulted in 0.65, 0.50, 0.68, and 0.51 log 10 CFU/apple reduction of L. monocytogenes on apples, respectively. Incorporating AD, NS 220, and EC significantly enhanced the antimicrobial efficacy of an 80 ppm PAA intervention. The enhancing effects were not impacted whether the cleaner was applied consecutively with PAA (sequentially) or in combination with PAA (simultaneously), nor were they impacted by a post-treatment water rinse. A 30–120 s wash of 80 ppm PAA with AD, EC, and NS 220 at their suggested concentration resulted in 2.46–2.55, 1.87–2.03, and 2.34–2.48 log 10 CFU/apple reduction of L. monocytogenes , respectively, compared to 1.39–1.64 log 10 CFU/apple in PAA treatment alone. The inclusion of AD or NS 220 in 80 ppm PAA solution resulted in a reduction of 1.51–1.63 log 10 CFU/apple of Listeria after 30–60 s brush-bed spray wash. This enhancement in efficacy was significant compared to the treatment with 80 ppm PAA alone, which resulted in a reduction of 0.94–1.03 log 10 CFU/apple. This study demonstrated that using certain commercially available cleaners along with PAA can enhance the effectiveness of PAA in reducing L. monocytogenes on fresh apples. • 30-sec submersion treatment of cleaners led to 0.5–0.7 log reduction of L. monocytogenes on apples. • Cleaners applied before or with PAA submersion wash enhanced PAA's anti -listerial efficacy. • The addition of AD/NS220 to the PAA intervention enhanced PAA's efficacy. • 30-sec 80ppm PAA spray wash with cleaners caused 1.6-log reduction of Listeria on apples. • Data present strategies to enhance sanitizer efficacy against Listeria on apples. [ABSTRACT FROM AUTHOR]

Many studies have focused on the significant role of biofilm formation by Bacillus in the biocontrol process. Bacillus pumilus HR10 is a plant growth-promoting rhizobacterium with multiple biocontrol functions, including promoting growth, controlling pathogens, and assisting in the formation of mycorrhizae. Currently, there is no relevant report on the biofilm formation of B. pumilus HR10 and its influencing factors. B. pumilus HR10 was found to easily form a stable biofilm structure on the surface of media, with awesome swarming ability. The optimum temperature for biofilm formation was 37 °C. B. pumilus HR10 formed most obviously at pH 7.0 and was not extremely sensitive to acidic or alkaline conditions. Most of the polysaccharide components of plant root exudates promoted the biofilm formation by B. pumilus HR10, with glucose having the greatest promoting effect. Low concentrations of Fe2+, Mg2+, Ca2+, K+, and Na+ enhanced biofilm formation. In summary, biofilm formation can improve the tolerance of B. pumilus HR10 to salt and certain heavy metal ion stresses and contribute to its application in different plants and soils with high salinity or heavy metals in the field. [ABSTRACT FROM AUTHOR]

A series of potent HIV-1 protease inhibitors, containing diverse piperidine analogues as the P2-ligands, 4-substituted phenylsulfonamides as the P2'-ligands and a hydrophobic cyclopropyl group as the P1'-ligand, were designed, synthesized and evaluated in this work. Among these twenty-four target compounds, many of them exhibited excellent activity against HIV-1 protease with half maximal inhibitory concentration (IC50) values below 20 nM. Particularly, compound 22a containing a (R)-piperidine-3-carboxamide as the P2-ligand and a 4-methoxylphenylsulfonamide as the P2'-ligand exhibited the most effective inhibitory activity with an IC50 value of 3.61 nM. More importantly, 22a exhibited activity with inhibition of 42% and 26% against wild-type and Darunavir (DRV)-resistant HIV-1 variants, respectively. Additionally, the molecular docking of 22a with HIV-1 protease provided insight into the ligand-binding properties, which was of great value for further study. [ABSTRACT FROM AUTHOR]

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by 1H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)−4-chloro-5-((5-((2-ethylphenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5 ± 0.4% and 95.7 ± 1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)−4-chloro-5-((5-((3-fluorophenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3 ± 2.2% and 92.3 ± 0.6% at a concentration of 10 μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)−4-chloro-5-((5-((2,3-dimethylphenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5 m (2-(Tert-butyl)−4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells. [ABSTRACT FROM AUTHOR]

The traditional fixed sampling interval (FSI) synthetic X ¯ control chart is sensitive to large and moderate process shifts, but insensitive to small process shifts. This paper proposes an improved variable sampling interval (VSI) synthetic X ¯ control chart with two sampling interval lengths for monitoring the process mean. A Markov chain method is used to compute the adjusted average time to signal (AATS) of the proposed chart. The statistical design of the VSI chart is then formulated and solved with a specific genetic algorithm. Comparisons are made to show the capability of the VSI chart in yielding average performance boost of 16.4%, in the AATS of the VSI chart scheme compared to the situation in which the corresponding FSI chart is used. [ABSTRACT FROM AUTHOR]

This paper aims to examine the situation of joint families in rural Korean society between the late seventeenth and late nineteenth century, considering changes over time and differences in social status. Also, it hopes to provide some clues for understanding the characteristics of the pre-modern Korean family system by comparing it with China and Europe. We used two different approaches in this paper. First, we reconstructed the family structure in Korea based on the composition of the household and compared the results generally with China, Japan and Europe. We found that joint families were less common in pre-modern southeastern Korea than in the northeastern region of China. Around half of all families belonged to a simple family form. A reasonably high share was also found for extended families and joint families. The share of joint families was lower than that of northeastern China, but was similar to that of Japanese Nishinomiya, higher than that of Britain and France in Western Europe and that of Serbia in Eastern Europe. Second, we analyzed multi-generational living arrangements for elderly people. As a result, we discovered that in pre-modern southeastern Korea the share of elderly people living in joint families was higher than in Western Europe. Compared with Eastern Europe, however, the numbers were on a similar level. In the example of Korea, the living arrangements for elderly people were heavily influenced by the social status of their families. Based on Confucian family ethics, families with a relatively high social status showed a stronger percentage of stem families and joint families. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence indicates that micro-RNAs play a key role in tumor progression and prognosis. However, the overall biological role and clinical significance of microRNA-552 (miR-552) in the pathogenesis of gastric cancer (GC) remain unclear. Methods: miR-552 expression was measured in 122 pairs of cancerous and noncancerous tissues and cell lines by quantitative real-time polymerase chain reaction. The relationship between miR-552 and the clinical parameters of patients was analyzed by the χ2 test; Kaplan-Meier analysis and multivariate Cox regression analysis were used to predict the overall survival time and prognosis of patients with different expression of miR-552. Finally, CCK-8 and Transwell were used to detect the changes in cell proliferation, migration, and invasion ability. Results: miR-552 was expressed at markedly high levels in GC tissues compared to normal tissues and in some GC cell lines (p < 0.001). The upregulation of miR-552 was significantly associated with tumors with advanced TNM stage (p = 0.026), lymph node metastasis (p = 0.018), intestinal metaplasia (p = 0.044), and genomically stable subtype (p = 0.035). Moreover, GC patients with high miR-552 expression showed shorter overall survival (log-rank test, p = 0.011) than those with low expression. Meanwhile, miR-552 was an independent prognostic factor for GC patients (HR 5.657, 95% CI 1.619–19.761, p = 0.007). Finally, miR-552 overexpression promoted the proliferation, migration, and invasion of GC cells (p < 0.01). Conclusion: Taken together, our results indicate that miR-552, as an oncogene of GC, can promote cell proliferation, migration, and invasion, and miR-552 may be a novel prognostic biomarker for GC. [ABSTRACT FROM AUTHOR]

Background: It is a crucial task of brain science researches to explore functional connective maps of Biological Neural Networks (BNN). The maps help to deeply study the dominant relationship between the structures of the BNNs and their network functions.Results: In this study, the ideas of linear Granger causality modeling and causality identification are extended to those of nonlinear Granger causality modeling and network structure identification. We employed Radial Basis Functions to fit the nonlinear multivariate dynamical responses of BNNs with neuronal pulse firing. By introducing the contributions from presynaptic neurons and detecting whether the predictions for postsynaptic neurons' pulse firing signals are improved or not, we can reveal the information flows distribution of BNNs. Thus, the functional connections from presynaptic neurons can be identified from the obtained network information flows. To verify the effectiveness of the proposed method, the Nonlinear Granger Causality Identification Method (NGCIM) is applied to the network structure discovery processes of Spiking Neural Networks (SNN). SNN is a simulation model based on an Integrate-and-Fire mechanism. By network simulations, the multi-channel neuronal pulse sequence data of the SNNs can be used to reversely identify the synaptic connections and strengths of the SNNs.Conclusions: The identification results show: for 2-6 nodes small-scale neural networks, 20 nodes medium-scale neural networks, and 100 nodes large-scale neural networks, the identification accuracy of NGCIM with the Gaussian kernel function was 100%, 99.64%, 98.64%, 98.37%, 98.31%, 84.87% and 80.56%, respectively. The identification accuracies were significantly higher than those of a traditional Linear Granger Causality Identification Method with the same network sizes. Thus, with an accumulation of the data obtained by the existing measurement methods, such as Electroencephalography, functional Magnetic Resonance Imaging, and Multi-Electrode Array, the NGCIM can be a promising network modeling method to infer the functional connective maps of BNNs. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) who have an EGFR mutation. However, little has been reported about the association between EGFR exon 19 deletions or an exon 21 mutation (specifically the L858R point mutation) and survival rates following first-line EGFR-TKI treatment in patients with NSCLC. As a retrospective study, 72 patients with stage IIIB/IV NSCLC carrying EGFR mutations (exon 19 deletions or an exon 21 mutation) were enrolled between 1 January 2008 and 31 December 2013, and all of the patients received first-line EGFR-TKI treatment. The associations between EGFR mutation status or clinical characteristics and response rate (ORR), progression-free survival (PFS) or overall survival (OS) were analyzed. Patients with exon 19 deletions (37 cases) had a higher ORR (75.7 vs. 51.4%; P=0.032), disease control rate (DCR; 89.2 vs. 68.6%; P=0.031), modified median PFS (13.2 vs. 10.8 months; P=0.030) and OS (30.2 vs. 25.6 months; P=0.030) compared with those with an exon 21 mutation (35 cases). Cox multivariate analysis indicated that sex, histological type and smoking history were key factors that affected PFS and OS. Mutations status was associated with PFS, but not OS. Following EGFR-TKI therapy, a better ORR, DCR, PFS and OS was observed in patients with EGFR deletions in exon 19 compared with those with an exon 21 mutation. The EGFR mutation status of patients with non-small cell lung cancer may therefore predict the efficacy and prognosis of EGFR-TKI. [ABSTRACT FROM AUTHOR]

Eupatorium lindleyanum DC. has been used as a functional food in China for a long time. However, the antifibrotic activity of total sesquiterpenoids from Eupatorium lindleyanum DC. (TS-EL) is still unknown. In this study, we discovered that TS-EL reduced the increase in α-smooth muscle actin (α-SMA), type I collagen and fibronectin content, the formation of cell filaments and collagen gel contraction in transforming growth factor-β1-stimulated human lung fibroblasts. Intriguingly, TS-EL did not change the phosphorylation of Smad2/3 and Erk1/2. TS-EL decreased the levels of serum response factor (SRF), a critical transcription factor of α-SMA, and SRF knockdown alleviated the transition of lung myofibroblasts. Furthermore, TS-EL significantly attenuated bleomycin (BLM)-induced lung pathology and collagen deposition and reduced the levels of two profibrotic markers, total lung hydroxyproline and α-SMA. TS-EL also decreased the levels of SRF protein expression in BLM-induced mice. These results suggested that TS-EL attenuates pulmonary fibrosis by inhibiting myofibroblast transition via the downregulation of SRF. [Display omitted] • Antifibrotic activity of TS-EL was demonstrated for the first time. • TS-EL repressed lung fibroblast-to-myofibroblast transition. • TS-EL ameliorated bleomycin-induced fibrosis in mice. • The downregulation of SRF was involved in TS-EL-repressive effect. [ABSTRACT FROM AUTHOR]

In this study, a novel rhodamine-based probe for the detection of Cu2+ which is conjugated with a 2-(1,3,3-trimethylindolin-2-ylidene) acetaldehyde moiety has been designed and synthesized. The detection is based on the fluorescence resonance energy transfer (FRET) mechanism. The probe exhibits colorimetric and ratiometric responses to Cu2+ with a large Stokes shift (237 nm) and is not disturbed by other coexisting metal ions. The probe can achieve the nanomolar detection of Cu2+ with a detection limit of 1.168 × 10−8 mol L−1. The 1 : 1 stoichiometry of the RhF–Cu2+ complex is supported by the Job's plot, ESI-MS analysis, IR spectral data and density functional theoretical (DFT) studies. More importantly, potential applications of the probe can also be achieved by using test paper strips. Furthermore, the probe can be used for the detection of Cu2+ in actual water samples. [ABSTRACT FROM AUTHOR]

IC 50 = 43 nM, 42 nM and 68 nM (in vitro). Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a , 16f and 16j containing N -2-(6-substituted-9 H -purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2′-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC 50 43 nM, 42 nM and 68 nM in vitro , respectively. [ABSTRACT FROM AUTHOR]

The visible‐light‐promoted difluoromethylation and trifluoromethylation/cyclization of β, γ‐unsaturated oximes has been successfully accomplished with fluorinated sulfones as the difluoromethylation and trifluoromethylation reagents. The reaction was proposed to proceed through a sequence comprising CF2X‐radical generation, fluoromethyl radical addition, single electron oxidation, and intramolecular cyclization to afford the corresponding di and trifluoromethylated isoxazoline derivatives in an overall redox‐neutral process. Visible‐light‐promoted difluoromethylation and trifluoromethylation/cyclization of β, γ‐unsaturated oximes has been successfully accomplished. The reaction was proposed to proceed via a sequence comprising CF2X‐radical generation, fluoromethyl radical addition, single electron oxidation, and intramolecular cyclization to afford the corresponding di and trifluoromethylated isoxazoline derivatives in an overall redox‐neutral process. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The design, synthesis and SAR study of a new series of HIV-1 protease inhibitors with pentacyclic triterpenoids as P2 ligands and phenylsulfonamide as P2′ ligands were discussed. These compounds exhibited micromolar inhibitory potency, among which compound T1c displayed HIV-1 protease inhibition with IC 50 values of 0.12 μM, which was 67 times the inhibitory activity of its raw material Ursolic acid (8.0 μM). [ABSTRACT FROM AUTHOR]

Abstract Continuous and high catalytic performance TS-1 zeolite membranes were rapidly prepared on the porous mullite support by dilute precursor synthesis solution. Influences of synthesis conditions (such as molar composition of precursor synthesis solution, crystallization time, and titanium source) on the growth and catalytic activity of TS-1 zeolite membrane for iso-propanol oxidation were systematically studied in this work. When H 2 O/TPAOH and H 2 O/SiO 2 ratios of the precursor synthesis solutions were 1200 and 300, the inter-growth TS-1 zeolite membrane layer could be formed on the support surface. The TS-1 zeolite membrane was coupled with the oxidation of iso-propanol and hydrogen peroxide by pervaporation, when the reaction temperature and initial ratio of the iso-propanol and hydrogen peroxide were 343 K and 1:2, the iso-propanol conversion and flux of the TS-1 zeolite membrane were 97.62% and 2.45 kg/m2·h, respectively. Graphical abstract Continuous and high catalytic activity TS-1 zeolite membranes were rapidly prepared on the porous mullite support by dilute precursor synthesis solution. Image 1 Highlights • Continuous TS-1 zeolite membrane was prepared by dilute precursor synthesis solution. • H 2 O/TPAOH and H 2 O/SiO 2 ratios of the precursor synthesis solution were 1200 and 300. • TS-1 zeolite membrane was a good catalyst for the oxidation of IPA and H 2 O 2. • IPA conversion and flux of the TS-1 zeolite membrane were 97.62% and 2.45 kg/m2·h. • Acetone selectivity of the oxidation was 100% by TS-1 zeolite membrane. [ABSTRACT FROM AUTHOR]

Abstract Objectives To explore the impacts of perioperative blood transfusion on specific pattern of inflammatory gene expression and nosocomial infections in gastrointestinal cancer patients. Methods A total of 60 gastrointestinal cancer patients aged over 27 years were recruited, blood transfusion was administered to 30 patients. The peripheral venous blood was drawn from the 30 patients undergoing transfusions and messenger RNA (mRNA) was extracted from PAXGene tubes collected before surgery and at 48 h following the operation. T-helper cell subtype transcription factors were quantified using quantitative real-time polymerase chain reaction. These genes were selected based on their ability to represent specific immune pathways and their expression level of Th1, Th2 and Th17 and the major Treg-specific TFs T-bet, GATA-3, RORγt and FOXP3 were measured. Postoperative infections were documented using predefined criteria. Results There were significantly lower in Th1-specific TF T-bet (P < 0.001) mRNA levels and significantly higher in Th2-specifc TF, GATA-3 (P < 0.001) mRNA levels assayed at 48 h. There was significantly lower in T-bet mRNA/GATA-3 (P < 0.001) mRNA ratio assayed at 48 h. There were significantly higher in Th17-specific TF RORγt (P < 0.001) and Treg-specific TF Foxp3 (P < 0.001) mRNA levels assayed at 48 h. Patients receiving a blood transfusion were more likely to develop postoperative infections (P = 0.02). Conclusion There is an association between an immunosuppressive pattern of gene expressions and blood transfusion. This gene expression profile includes a reduction in the activity of T helper cell type 1 (Th1) pathways in those patients receiving a blood transfusion. Furthermore, blood transfusion was associated with an increased susceptibility to nosocomial infections. [ABSTRACT FROM AUTHOR]

Background: Parkinson’s disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons. Results: We find that expression of these point mutants in cultured hippocampal neurons from Parkin-deficient and Parkin-null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels and prevents the induction of long-term depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor trafficking through its ubiquitination of GluN1, and that all four mutants are impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic AMPA receptor trafficking via its binding and retention of the postsynaptic scaffold Homer1, and all mutants are similarly impaired in this capacity. Conclusion: Our findings demonstrate that pathogenic Parkin mutations disrupt glutamatergic synaptic transmission in hippocampal neurons by impeding NMDA and AMPA receptor trafficking. Such effects may contribute to the pathophysiology of PD in PARK2 patients. [ABSTRACT FROM AUTHOR]

[Display omitted] A novel benzene sulfonamide compound named IMB16-4 exhibits excellent anti-hepatic fibrosis activity in a recent study. To develop potential anti-hepatic fibrosis agents, a series of benzene sulfonamide derivatives were designed and synthesized based on the scaffold of the lead compound IMB16-4. As it turned out, most of the derivatives displayed potential anti-hepatic fibrosis activity, among which, compounds 11a, 11b, 11d, 13a , 36b , and 47b exhibited inhibition rates of 42.3%, 48.7%, 42.4%, 40.0%, 39.4%, and 49.3%, respectively, which were equivalent to the control IMB16-4 with an inhibition rate of 35.9%, Costunolide with an inhibition rate of 45.4%, and much more potent than that of Epigallocatechin gallate (EGCG) with an inhibition rate of 25.3%. Especially, compounds 46a , 46b , and 46c exhibited excellent anti-hepatic fibrosis activity with inhibition rates of 61.7%, 54.8%, and 60.7%, which were almost 1.5-fold inhibition rates of IMB16-4. In addition, compounds 46a , 46b , and 46c exhibited remarkable inhibitory activity in the gene expression of COL1A1, MMP-2, and the protein expression of COL1A1, FN, α-SMA, and TIMP-1 by inhibiting the JAK1-STAT1/3 pathway. These findings furnished valuable inspiration for the further development of anti-hepatic fibrosis agents. [ABSTRACT FROM AUTHOR]