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The non‐destructive inspection of Printed Circuit Boards (PCBs) through r‐ray Computer Tomography (CT) is a recently developed method that offers several advantages over traditional inspection techniques. This method is non‐invasive, quick, and offers high resolution, leading to significant improvements in inspection and repair efficiency. Post‐image analysis is an important step in PCB inspection and has important practical significance for automatic positioning and determining the location of faults. Usually, the results of image segmentation are an important basis for PCB defect detection, and accurate segmentation results can effectively improve the efficiency and accuracy of PCB inspection and increase the level of automation. This paper discusses two innovative improvements for the automatic segmentation process: firstly determining which slices of an x‐ray CT 3D PCB stack belong to which layer on a physical PCB in an automatic, generic and completely unsupervised way, which is verified on a 4‐layer PCB; secondly proposing a level set‐based image segmentation algorithm for the problem of gray scale inhomogeneity present in PCB CT. Experimental results on real PCB CT images with high aliasing and artifacts show that the proposed model can obtain better performance than the popular active contour models. [ABSTRACT FROM AUTHOR]

With the development of photon counting detectors (PCDs), spectral CT achieves higher performance than in the past, thus has better application prospects. In this paper, an adaptive dual effect decomposition (ADED) algorithm is proposed to perform the quantitative estimation of effective atomic number and electron density. The algorithm is an empirical material identification algorithm that achieves calibration by combining polynomials on the projection data and constraining in the image domain. In addition, we also propose an innovative effective atomic number estimation model with an accurate physical model that adaptively adjusts the parameters according to the x‐ray energy and material type. The performance of the algorithm was verified by experiment and simulation in this paper. Compared to the conventional basis material decomposition algorithm, the proposed ADED algorithm reduces the relative error in the quantification of the effective atomic number from 4.5%–12.0% to 0.3%–4.5%. Overall, the results demonstrate that the proposed algorithm significantly improves the accuracy of quantifying the effective atomic number. [ABSTRACT FROM AUTHOR]

Two different skeletons have been constructed by cyclization of α‐(3‐isoindolinonyl) propargylic alcohols with 5‐aminoisoxazoles bearing different N‐substituents under the relay catalysis of Brønsted acid and Lewis acid. This method provided spiro‐isoindolinone‐dihydropyridines with moderate to high yields (up to 99 %) as well as isoxazolo[4,5‐b]pyridines in moderate to good yields (up to 86 %). The structures of two products were determined by X‐ray crystal structural analyses. Moreover, fluorescence testing proved that one of the isoxazolo[4,5‐b]pyridines exhibited aggregation induced emission (AIE) effect. Finally, the control experiments revealed the possible reaction mechanism. [ABSTRACT FROM AUTHOR]

Aim: The seagrass Zostera japonica is a dramatically declined endemic species in the Northwestern Pacific from the (sub)tropical to temperate areas, however, it is also an introduced species along the Pacific coast of North America from British Columbia to northern California. Understanding the population's genetic patterns can inform the conservation and management of this species. Location: North Pacific. Methods: We used sequences of the nuclear rDNA internal transcribed spacer (ITS) and chloroplast trnK intron maturase (matK), and 24 microsatellite loci to survey 34 native and nonnative populations (>1000 individuals) of Z. japonica throughout the entire biogeographic range. We analysed the phylogeographic relationship, population genetic structure and genetic diversity of all populations and inferred possible origins and invasion pathways of the nonnative ones. Results: All markers revealed a surprising and significant deep divergence between northern and southern populations of Z. japonica in the native region separated by a well‐established biogeographical boundary. A secondary contact zone was found along the coasts of South Korea and Japan. Nonnative populations were found to originate from the central Pacific coast of Japan with multiple introductions from at least two different source populations, and secondary spread was likely aided by waterfowl. Main Conclusions: The divergence of the two distinct clades was likely due to the combined effects of historical isolation, adaptation to distinct environments and a contemporary physical barrier created by the Yangtze River, and the warm northward Kuroshio Current led to secondary contact after glacial separation. Existing exchanges among the nonnative populations indicate the potential for persistence and further expansion. This study not only helps to understand the underlying evolutionary potential of a widespread seagrass species following global climate change but also provides valuable insights for conservation and restoration. [ABSTRACT FROM AUTHOR]

Background: A novel regimen with high‐dose dual therapy (HDDT) has emerged, but its impact on the gut microbiota is not well understood. This study aimed to evaluate the impact of HDDT on the gut microbiota and compare it with that of bismuth quadruple therapy (BQT). Methods: We enrolled outpatients (18–70 years) diagnosed with Helicobacter pylori infection by either histology or a positive 13C‐urea breath test (13C‐UBT) and randomly assigned to either the BQT or HDDT group. Subjects consented to provide fecal samples which were collected at baseline, Week 2, and Week 14. Amplification of the V1 and V9 regions of the 16S rRNA was conducted followed by high‐throughput sequencing. Results: Ultimately, 78 patients (41 patients in the HDDT group and 37 in the BQT group) were enrolled in this study. Eradication therapy significantly altered the diversity of the gut microbiota. However, the alpha diversity rebounded only in the HDDT group at 12 weeks post‐eradication. Immediately following eradication, the predominance of Proteobacteria, replacing commensal Firmicutes and Bacteroidetes, did not recover after 12 weeks. Species‐level analysis showed that the relative abundances of Klebsiella pneumoniae and Escherichia fergusonii significantly increased in both groups at Week 2. Enterococcus faecium and Enterococcus faecalis significantly increased in the BQT group, with no significant difference observed in the HDDT group. After 12 weeks of treatment, the relative abundance of more species in the HDDT group returned to baseline levels. Conclusion: Eradication of H. pylori can lead to an imbalance in gut microbiota. Compared to BQT, the HDDT is a regimen with milder impact on gut microbiota. [ABSTRACT FROM AUTHOR]

Isoxazolopyridines are highly significant for the development of pharmaceuticals and new materials. In continuation of our ongoing research on transformations of 5‐aminoisoxazoles, we report herein a divergent synthesis of two kinds of novel isoxazolo[5,4‐b] pyridines through condensation of 5‐aminoisoxazoles with β,γ‐alkynyl‐α‐imino esters. By using two different silver salts and a phosphoric acid as catalysts, isoxazolo[5,4‐b] pyridine‐α‐carboxylates and isoxazolo[5,4‐b] pyridine‐γ‐carboxylates were constructed as major isomers in moderate to good yields, respectively. The structures of the two kinds of the isoxazolo[5,4‐b] pyridines were confirmed by X‐ray crystal structural analysis. Furthermore, control experiments were conducted to elucidate the reaction mechanism. [ABSTRACT FROM AUTHOR]

The issue of bacterial resistance has become a matter of significant concern globally, prompting extensive research into the development and clinical application of aminoglycoside antibiotics (AGAs) as a crucial antibacterial therapy. One of the primary mechanisms contributing to aminoglycoside antibiotic resistance is the action of aminoglycoside modifying enzymes (AMEs), which modify aminoglycoside antibiotics and consequently confer drug resistance. Chemical modification of the AME action site can eliminate functional groups vulnerable to AMEs, thus improving drug resistance. This study involves the introduction of α‐hydroxy‐γ‐aminobutyric acid and amidine to the 1 and 6′ positions of sisomicin, respectively, to produce a range of 6′‐amidine modified sisomicin derivatives of AGAs. The research evaluates the antibacterial activity, absorption, distribution, metabolism, and excretion (ADME) properties, pharmacokinetic properties, cytotoxicity, nephrotoxicity, and drug resistance of AGAs. The outcomes of this study are significant in terms of enriching the structural understanding of aminoglycosides, providing insight into their structure–activity relationship, and producing new AGAs with high antibacterial activity, low ototoxicity, and nephrotoxicity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of metabolic associated fatty liver disease (MAFLD) on chronic kidney disease (CKD) and abnormal albuminuria and the interaction between MAFLD and diabetes on abnormal albuminuria. Methods: Data of participants in the American 2017–2018 National Health and Nutrition Examination Survey were analyzed. Hepatic steatosis was defined as median controlled attenuation parameter ≥248 dB/m, which was measured by ultrasound transient elastography. MAFLD was defined by evidence of hepatic steatosis on ultrasound in addition to any metabolic dysregulation. Hepatic fibrosis was detected by FibroScan and quantified by parameter of stiffness (E). Hepatic fibrosis was defined as E ≥ 9.7 kPa. As component of CKD, reduced estimated glomerular filtration rate (eGFR) was defined as<60 mL/min/1.73 m2 and abnormal albuminuria was defined as urinary albumin‐to‐creatinine ratio ≥ 30 mg/g. Results: Data pertaining to 5119 participants were included in the analysis, with 40.6% hepatic normal, 52.1% MAFLD, and 7.2% hepatic fibrosis. Multivariable regression analyses showed that for abnormal albuminuria, the odds ratio (OR) was 0.82 (0.65–1.04) for MAFLD group and 1.73 (1.14.–,2.63) for hepatic fibrosis group, both taking the hepatic healthy group as reference. As for reduced eGFR, the OR was 0.68 (0.51–0.92) for MAFLD group and 0.93 (0.56–1.53) for hepatic fibrosis group. Diabetes was significantly related to greater risk of abnormal albuminuria (3.04 [2.70–3.42]) and reduced eGFR (1.53 [1.33–1.77]). With regard to the prevalence of abnormal albuminuria, the OR was 1.64 (1.03–2.60) for those with hepatic fibrosis only, 3.30 (2.80–3.89) for those with diabetes only, and 5.05 (3.30–7.72) for those with both two conditions. But there were neither additive interaction (relative excess risk due to interaction 0.56 [−1.41–.53], p =.577) nor multiplicative interaction (OR 0.81 [0.45–1.47], p =.492) between hepatic fibrosis and diabetes on the prevalence of abnormal albuminuria. Conclusion: MAFLD with hepatic fibrosis is an independent risk factor for abnormal albuminuria, but it does not have interaction with diabetes on abnormal albuminuria. [ABSTRACT FROM AUTHOR]

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti‐receptor binding domain of spike protein (anti‐S‐RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti‐S‐RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID‐19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75–12.00, p = 0.002), clinical course of COVID‐19 ≤ 7 days (OR = 2.86, 95% CI: 1.31–6.25, p = 0.008) and severe B‐cell reduction (0–10/μL) (OR = 3.22, 95% CI: 1.32–7.88, p = 0.010). Risk factors associated with low anti‐S‐RBD IgG titer were clinical course of COVID‐19 ≤ 7 days (OR = 2.58, 95% CI: 1.59–4.18, p < 0.001) and severe B‐cell reduction (0–10/μL) (OR = 2.87, 95% CI: 1.57–5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS‐CoV‐2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830. [ABSTRACT FROM AUTHOR]

The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS‐CoV‐2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID‐19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S‐82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10‐3), were closely associated with the presence of SARS‐CoV‐2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID‐19 cases in 2020, S82‐IgG titers were higher in NAbs‐positive samples (p = 0.002) than in NAbs‐negative samples using enzyme‐linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82‐IgG titers, NAb titers were significantly higher in the samples with higher S82‐IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay‐associated signatures of SARS‐CoV‐2 NAbs. [ABSTRACT FROM AUTHOR]

Studying the evolution history of the southwest summer monsoon (SSM) throughout geological time, particularly during its strongest period in the Holocene, can improve our understanding of its variation and driving mechanisms, and even help predict future climate changes, due to its significant social and economic implications. Here, we reconstructed the history of chemical weathering intensity since the Last Glacial Maximum (LGM) based on clay mineral proxies [(illite/smectite)/(illite + chlorite) and illite crystallinity] obtained from Qionghai Lake sediments and examined its response to paleoclimate and SSM. Our findings indicate that the intensity of chemical weathering generally aligned with changes in paleoclimate, exhibiting strong chemical weathering intensity during warm and humid climate conditions. In addition, the intensity of chemical weathering basically tracks the evolution of the SSM since the LGM. Our results support the view that the highest SSM intensity occurred during the early‐middle Holocene, followed by gradual weakening during the late Holocene, with Northern Hemisphere summer insolation being the primary driver of the SSM evolution. The variations of the SSM and the corresponding intensity of chemical weathering were also influenced by the cumulative effects of glacier boundary conditions, North Atlantic climate fluctuations, and Intertropical Convergence Zone migrations. Key Points: Clay minerals can effectively reflect regional chemical weathering intensityChemical weathering intensity was following the monsoon variabilityThe strongest southwest summer monsoon occurred in the early‐middle Holocene [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to elucidate the pathogenesis and heterogeneity of Behçet's disease (BD) involving different organs using in‐depth proteomics to identify the biomarkers for clinical assessment and treatment of patients with BD. Methods: We measured the expression levels of proteins in plasma samples from 98 patients with BD and from 31 healthy controls using our in‐depth proteomics platform with a data‐independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the BD group and constructed a proteomics landscape of organ‐resolved BD pathogenesis. We then validated the biomarkers of disease severity and the vascular subset in an independent cohort of 108 BD patients and 29 healthy controls using an enzyme‐linked immunosorbent assay. Results: The BD group had 220 differentially expressed proteins, which discriminated between BD patients (88.6%) and healthy controls (95.5%). The bioinformatics analyses revealed different biologic processes associated with BD pathogeneses, including complement activation, wound healing, angiogenesis, and leukocyte‐mediated immunity. Furthermore, the constructed proteomics landscape of organ‐resolved BD identified proteomics features of BD associated with different organs and protein targets that could be used for the development of therapeutic treatment. Hyaluronic binding protein 2, tenascin, and serpin A3 were validated as potential biomarkers for the clinical assessment of vascular BD and treatment targets. Conclusion: Our results provide valuable insight into the pathogenesis of organ‐resolved BD in terms of proteomics characteristics and potential biomarkers for clinical assessment and potential therapies for vascular BD. [ABSTRACT FROM AUTHOR]

Isothiazole units exist in many natural products and pharmaceutics. Up to now, construction of isothiazole‐containing axially chiral biaryls has not been reported yet. Herein we disclose a chiral phosphoric acid catalyzed atropoenantioselective arylation of 5‐amino‐isothiazoles with methyl p‐quinone carboxylate. Various novel isothiazole‐containing axially chiral biaryls were achieved in moderate to good yields (up to 95%) with generally moderate to good enantioselectivities (up to 90% ee). In addition, the structure of one product was determined by an X‐ray crystal structural analysis and a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

As seagrass bed restoration by seeding becomes more common, it is necessary to develop a simple and reliable method to improve the efficiency of seed‐based restoration. In this study, we describe a novel method using seed ball burial for eelgrass restoration. Using this method, seeds were wrapped in a wet mud ball, which represented a transplant unit, and the balls were then buried in the sediment. Three experiments (proof of concept study, main study, and large‐scale restoration) were conducted to test this method at three degraded sites (Rizhao, Qingdao, and Tangshan) with different environmental conditions. The density of seedlings and seedling shoots was 54 and 110 per m2, respectively, in Rizhao, a site with coarser sediment and higher temperatures. Seedling survival in Qingdao reached 46.67 ± 9.46%. Relatively low seedling survival (26.67 ± 7.03%) in Tangshan was induced by local waves and currents. Seedling survival was also low (ca. 15% in April and 2% in July) at the large‐scale restoration site , reflecting a mismatch between the environment at this site and the seed ball restoration method. In conclusion, our study provides evidence of the effectiveness of a novel seagrass seed planting method referred to as seed balls. [ABSTRACT FROM AUTHOR]

Cordyceps sensu lato is a complex fungus‐larva symbiote, and its distribution is affected by the geography, climate, soil environment, and cohabitating microorganisms. However, despite the fact Cordyceps militaris and Ophiocordyceps highlandensis are different species, they coexist in the Pinus armandi forest of Dashao in Songming County, Yunnan, China. We explored the microbial compositions and soil metabolism inhabited by C. militaris and O. highlandensis using high‐throughput sequencing and nontargeted metabonomics. The results indicated that the bacterial and fungal compositions in the soil microhabitat communities of C. militaris, O. highlandensis, and null Cordyceps group were similar. However, the community compositions in the fruiting bodies of C. militaris and O. highlandensis were different. The dominant phylum Ascomycota and dominant genus Cordyceps were detected in the fruiting body of C. militaris. Except for Ascomycota, the dominant phylum Chytridiomycota and dominant genera Ophiocordyceps, Unclassified_k__Hypocreales, Circinotrichum, Cladosporium, and Unclassified_k__chytridiomycetesg were detected in the fruiting body of O. highlandensis. The plant probiotic bacteria Phyllobacterium was detected in the fruiting body of C. militaris. The growth‐promoting bacteria Pseudomonas was detected in the fruiting body of O. highlandensis. Soil metabolism analysis revealed that pathways associated with amino acid metabolism was significantly enriched in O. highlandensis. Correlation analysis of bacterial diversity and soil metabolites revealed that the relative abundances of bacterial operational taxonomic units and the relative contents of metabolites were consistent. Our results provide insights into the microbial diversity and soil metabolism of naturally coexisting C. militaris and O. highlandensis. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from the gastrointestinal epithelium. Although the pathogenesis of GIC has not been fully elucidated, angiogenesis is recognized as the key pathological basis for the growth, invasion and metastasis of cancer cells, and GIC angiogenesis is closely related to vascular endothelial growth factor family, hypoxia‐inducible factor family, fibroblast growth factor family and matrix metalloproteinase family. Recently, many natural products have shown a wide range of pharmacological biological activities against GIC. In this review, the effects and mechanisms of natural compounds on the angiogenesis of gastric and colorectal cancer were summarized. The results show that some natural compounds, especially gallic catechin gallate, astragaloside and curcumin, can effectively inhibit angiogenesis; the HIF‐1α/VEGF, COX‐2/PGE2, HGF/c‐Met and PI3K/Akt/mTOR are involved in these inhibition effects. This review examines the anti‐angiogenesis potential of natural products in the GIC treatment and provides clues to the development of vascular targeted agents. [ABSTRACT FROM AUTHOR]

3‐Methyleneisoindolin‐1‐one units exist in many natural products and pharmaceutics. Up to now, synthesis of axially chiral 3‐methyleneisoindolin‐1‐ones has been rarely reported. Herein we disclose a chiral phosphoric acid catalyzed enantioselective condensation of 2‐acetylbenzoic acid derivatives with 2‐substituted aniline derivatives, leading to the construction of a series of novel C−N axially chiral N‐aryl‐3‐methylene‐isoindolin‐1‐ones in moderate to good yields (up to 97%) with generally moderate enantioselectivities (up to 87% ee). In addition, the absolute configuration of one product was determined by an X‐ray crystal structural analysis. Furthermore, one product was subjected to oxidative cleavage to generate an axially chiral phthalimide. [ABSTRACT FROM AUTHOR]

In recent years, constructing van der Waals (vdW) heterostructures based on different 2D materials has been a highly effective way to obtain desired electronic and optical properties. Herein, on the basis of first‐principles calculations, a 2D vdW heterostructure is constructed by vertically stacking the indirect‐bandgap gallium nitride (GaN) and silicane (SiH) monolayers. For the formed heterostructure, the structural, electronic, and optical properties are all computed. The obtained results show that the heterostructure is a direct‐bandgap semiconductor with typical type‐II band alignment. Furthermore, the linearly tunable bandgap, together with the robust type‐II band alignment, can be realized by applying vertical strains or external electric fields. It is also found that both monolayers exhibit the same UV absorption range and the notably enhanced UV absorption is obtained after forming the heterostructure. In particular, the maximum absorptivity can reach to 21.6%. These results are expected to provide useful references for the design of ultraviolet optoelectronic devices based on the 2D GaN/SiH vdW heterostructure. [ABSTRACT FROM AUTHOR]

Summary GPS traces collected by IoT‐enabled vehicle sensors are highly informative and exploitable in the area of human mobility analysis and traffic control. In this work, we focus on generating effective bus routes and networks by analyzing and exploiting the Taxi GPS trajectories. Specifically, we develop a novel framework for yielding potential bus stations by analyzing passenger boarding and getting spots collected by IoT‐enabled vehicle sensors, a novel ant‐colony‐based heuristic for generating serving routes and further for yielding the bus network. For the model validation purpose, we perform extensive simulations upon a dataset of metropolitan traveling traces and illustrate that our approach definitely beats state‐of‐the‐art ones in terms of the number of people served. [ABSTRACT FROM AUTHOR]

Isoxazolines are highly significant for the development of new synthetic methodology and pharmaceutics. Indolines and 2,3‐dihydrobenzofurans are also privileged structures in natural products and pharmaceuticals. In continuation of our ongoing research on transformations of 5‐aminoisoxazoles and quinone derivaties, herein we report Sc(OTf)3‐catalyzed dearomative [3+2] annulations of 5‐aminoisoxazoles with quinone imine ketals (QIKs) and quinone monoacetals (QMAs). A variety of indoline‐ and 2,3‐dihydrobenzofuran‐fused isoxazolines were afforded in moderate to good yields with excellent diastereoselectivities (all cases >20 : 1 dr). This method featured mild reaction conditions, wide substrate scope, and gram‐scale synthesis. [ABSTRACT FROM AUTHOR]

The present report uncovers the Fenton‐like and solar‐Fenton activity of nickel‐coordinated phthalocyanines and their potential as antibacterial agents. In particular, two NiPcs, one achiral and the other chiral, with both having similar molecular structures, are designed. Both compounds aggregate to form crystals with large diversity in molecular stacking. The crystal grown from the achiral NiPc demonstrates superior Fenton‐like activity especially under NIR‐light illumination, and also exhibits efficient antibacterial activity in vitro toward both E. coli and S. aureus. On the contrary, the crystal formed from stacked chiral molecules demonstrates weak Fenton‐like reactivity and is inefficient for bacterial disinfection. By examining the differences between the two crystals, we have disclosed the mechanism of the Fenton‐like reactivity of the NiPcs associated with molecular aggregation. Moreover, the chiral NiPc and its crystal provide a good platform to inspect the correlation between the functions, for instance the antibacterial activity between the chiral selections. This work indicates that controlling small differences in molecular structure can provide an effective way to achieve specific functions, such as Fenton‐like activity, of organic semiconductors. [ABSTRACT FROM AUTHOR]

This study aimed to determine the bioavailability and pharmacokinetic parameters of sulfadiazine (SDZ) in channel catfish (Ictalurus punctatus) following oral gavage and intravenous injection. The healthy channel catfish were orally and intravenously administrated with SDZ solution at doses of 50 and 5 mg/kg, respectively. Plasma samples were determined by ultra‐performance liquid chromatography with an ultraviolet detector. The results demonstrated that the concentration‐time profile of SDZ after oral dosing was best described by a one‐compartmental open model with first‐order absorption. The absorption half‐life (t1/2Kα), the elimination half‐life (t1/2Ke), and the area under concentration‐time profile (AUC0‐∞) were estimated to be 0.87 h, 29.04 h, and 1311.72 mg.h/L, respectively. After intravenous administration, the concentration‐time curve of SDZ conformed to a two‐compartmental open model without absorption. The distribution half‐life (t1/2α), the elimination half‐life (t1/2β), the apparent distribution volume (Vss), the total clearance (CL), and AUC0‐∞ were calculated to be 0.19 h, 14.24 h, 0.36 L/kg, 0.018 L/h/kg, and 277.12 mg.h/L, respectively. Finally, the bioavailability was estimated to be 47.33%. This study will provide some useful information for the modification of the dosage form of SDZ in aquaculture, and is partly beneficial for appropriate use of SDZ in the future. [ABSTRACT FROM AUTHOR]

Copper plays pivotal roles in metabolic homoeostasis, but its potential role in human tumorigenesis is not well defined. Here, it is revealed that copper activates the phosphoinositide 3‐kinase (PI3K)‐protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, copper binds 3‐phosphoinositide dependent protein kinase 1 (PDK1), in turn promotes PDK1 binding and subsequently activates its downstream substrate AKT to facilitate tumorigenesis. Blocking the copper transporter 1 (CTR1)‐copper axis by either depleting CTR1 or through the use of copper chelators diminishes the AKT signaling and reduces tumorigenesis. In support of an oncogenic role for CTR1, the authors find that CTR1 is abnormally elevated in breast cancer, and is subjected by NEDD4 like E3 ubiquitin protein ligase (Nedd4l)‐mediated negative regulation through ubiquitination and subsequent degradation. Accordingly, Nedd4l displays a tumor suppressive function by suppressing the CTR1‐AKT signaling. Thus, the findings identify a novel regulatory crosstalk between the Nedd4l‐CTR1‐copper axis and the PDK1‐AKT oncogenic signaling, and highlight the therapeutic relevance of targeting the CTR1‐copper node for the treatment of hyperactive AKT‐driven cancers. [ABSTRACT FROM AUTHOR]

A diastereo‐ and enantioselective aza‐Mannich addition of oxazolones to α‐amino sulfones catalyzed by tertiary amine‐1‐phenylethyl thiourea based on cinchona structure has been developed. The reaction afforded the azlactone adducts bearing quaternary and tertiary stereogenic centers with high yields (up to 98 %) and moderate to excellent diastereo‐ and enantioselectivities (up to >99 : 1 dr and 96 % ee). The absolute configuration of a product was assigned by X‐ray crystal structural analyses and a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Maternal nutrition can influence the composition of human breastmilk by altering the components that are sensitive to maternal diet pattern. Traditional Tibetan maternal diet pattern among native rural lactating women possesses distinct characteristics due to its unique geographical environment and dietary habits. This study investigated maternal diet pattern and human breastmilk composition of Tibetan lactating women through different lactation stages during the first month postpartum in Shigatse. The results indicated that Tibetan maternal diet profile was apparently monotonous, mainly sufficient in Zanba, buttered tea, red meat, and fatty soup, yet insufficient in white meat, eggs, leafy vegetables, and fruits, leading to imperfect maternal nutritional intakes with high‐level carbohydrates and deficient proteins. Distinctions of maternal diet profiles in various degrees can be discovered upon different lactation stages, which brings multiple influences to the composition of human milk. There was significantly weak‐to‐medium correlation of protein contents between maternal diet intakes and human milk, while other macronutrients correlated insignificantly. Micronutrient constituents in human milk, involving functional unsaturated fatty acids and free essential amino acids, were also impacted by maternal diet intakes through different lactation stages. These results show that more systematic and profound research is requisite for the clarification and development of Tibetan maternal diet to offer more enhanced and individualized nutritional recommendations for Tibetan lactating women and infants. [ABSTRACT FROM AUTHOR]

Chiral indolines represent important structural motifs in a large number of natural products and pharmaceutics. Chiral succinimideunits are also found in a wide range of natural products and pharmaceutical substances. Herein we report an enantioselective dearomative [3+2] annulation of 3‐hydroxymaleimides with azonaphthalenes using a chiral squaramide‐tertiary amine as catalyst. The reactions afforded a large variety of novel succinimide fused indolines in moderate to good yields (up to 99 %) with generally good enantioselectivities (up to 98 % ee). The absolute configuration of one product was assigned by an X‐ray crystal structural analysis and a plausible reaction mechanism was proposed accordingly. Afterwards, under different conditions, one product was treated with triethylsilane and provided two kinds of reductive products in moderate to good yields with good enantioselectivities. [ABSTRACT FROM AUTHOR]

As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC‐derived extracellular vesicles (MSC‐EVs) are newly uncovered messengers for intercellular communication. Herein, it is reported that umbilical cord‐derived MSCs (UC‐MSCs) improve liver IRI in mice through their secreted EVs. It is also visualized that UC‐MSC‐EVs mainly concentrate in liver after 6 h of reperfusion. Furthermore, UC‐MSC‐EVs are found to significantly modulate the membranous expression of CD154 of intrahepatic CD4+ T cells, which is an initiation of inflammatory response in liver and can aggravate liver IRI. Mechanistically, protein mass spectrum analysis is performed and it is revealed that Chaperonin containing TCP1 subunit 2 (CCT2) enriches in UC‐MSC‐EVs, which regulates the calcium channels to affect Ca2+ influx and suppress CD154 synthesis in CD4+ T cells. In conclusion, these results highlight the therapeutic potential of UC‐MSC‐EVs in attenuating liver IRI. This finding suggests that CCT2 from UC‐MSC‐EVs can modulate CD154 expression of intrahepatic CD4+ T cells during liver IRI through the Ca2+‐calcineurin‐NFAT1 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Chinese guidelines for the treatment of type 2 diabetes (T2D) recommend basal or premixed insulins as insulin starters after failed oral antihyperglycaemic medication (OAM). This pragmatic study compared effectiveness and safety of add‐on basal insulin analog (BI) and mid‐mixture insulin analog (MMI; 50:50 premixed insulin) as starter insulin regimens in Chinese patients with T2D in a real‐world setting. Materials and Methods: This was a multicentre, open‐label, randomized, parallel, pragmatic trial. Patients receiving OAMs were randomized 1:1 to BI (n = 410) or MMI (n = 404) for 24 weeks. Insulin titration and OAM adjustment were determined by investigators following usual standard‐of‐care. The primary outcome was change in glycated haemoglobin (HbA1c) from baseline. Results: Least‐squares mean changes in HbA1c from baseline to week 24 were −2.00% and −2.15% for BI and MMI groups, respectively (P =.13). The MMI group demonstrated a greater reduction in concomitant OAM therapies used than BI group (53.8% vs. 35.3%, respectively; P <.001). Very limited daily insulin dose increments were observed from baseline to week 24 in both BI and MMI groups (2.5 U/day and 1.8 U/day, respectively). Although both insulin analogs were well‐tolerated without severe hypoglycaemia, small weight gains were seen with both treatments. Higher total hypoglycaemia rates were noticed with the MMI group, while nocturnal hypoglycaemia events were comparable. Conclusions: In real‐world settings, BI and MMI provided similar improvement in glucose control without conceding hypoglycaemia. The BI group received a greater number of OAMs in real‐world settings. Limited insulin dose titration was observed, while more adjustments occurred with OAM usage. [ABSTRACT FROM AUTHOR]

The corona virus disease 2019 (COVID‐19) is a highly contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). More than 18 million people were infected with a total of 0.7 million deaths in ∼188 countries. Controlling the spread of SARS‐CoV‐2 is therefore inherently dependent on identifying and isolating infected individuals, especially since COVID‐19 can result in little to no symptoms. Here, we provide a comprehensive review of the different primary technologies used to test for COVID‐19 infection, discuss the advantages and disadvantages of each technology, and highlight the studies that have employed them. We also describe technologies that have the potential to accelerate SARS‐CoV‐2 detection in the future, including digital PCR, CRISPR, and microarray. Finally, remaining challenges in COVID‐19 diagnostic testing are discussed, including (a) the lack of universal standards for diagnostic testing; (b) the identification of appropriate sample collection site(s); (c) the difficulty in performing large population screening; and (d) the limited understanding of SARS‐COV‐2 viral invasion, replication, and transmission. [ABSTRACT FROM AUTHOR]

Cutaneous malignant melanoma (hereafter called melanoma) is one of the most aggressive cancers with increasing incidence and mortality rates worldwide. In this study, we performed a systematic investigation of the tumor microenvironmental and genetic factors associated with melanoma to identify prognostic biomarkers for melanoma. We calculated the immune and stromal scores of melanoma patients from the Cancer Genome Atlas (TCGA) using the ESTIMATE algorithm and found that they were closely associated with patients' prognosis. Then the differentially expressed genes were obtained based on the immune and stromal scores, and prognostic immune‐related genes further identified. Functional analysis and the protein–protein interaction network further revealed that these genes enriched in many immune‐related biological processes. In addition, the abundance of six infiltrating immune cells was analyzed using prognostic immune‐related genes by TIMER algorithm. The unsupervised clustering analysis using immune‐cell proportions revealed eight clusters with distinct survival patterns, suggesting that dendritic cells were most abundant in the microenvironment and CD8+ T cells and neutrophils were significantly related to patients' prognosis. Finally, we validated these genes in three independent cohorts from the Gene Expression Omnibus database. In conclusion, this study comprehensively analyzed the tumor microenvironment and identified prognostic immune‐related biomarkers for melanoma. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis B virus (HBV) infection is the most critical factor underlying liver cirrhosis and hepatocellular carcinoma worldwide. IL‐1β and IL‐18, generated by activation of the inflammasome/caspase‐1 signaling pathway, play important roles in the control and clearance of HBV. However, the specific relationship between the inflammasome response and IFN‐α resistance or viral persistence is yet to be established. Methods: Blood samples of patients and supernatant fractions of HBV cell lines were collected for analysis and the effects on inflammasome activation and IL‐1β production evaluated via enzyme‐linked immunosorbent assay (ELISA), western blot, quantitative RT‐PCR and immunofluorescence. Results: IL‐1β and IL‐18 levels produced in sera of IFN‐α non‐responders were significantly lower than those of responders and normal donors. Additionally, expression of IL‐1β and inflammasome components was decreased in peripheral blood mononuclear cells (PBMC) of non‐responders, compared with those of responders. In vitro experiments on HepG2, HepG2.2.15 and HepAD38 cell lines showed that HBV induces a significant decrease in IL‐1β production through inhibiting activation of the NF‐κB signaling and inflammasome/caspase‐1 pathways. And hepatitis B virus polymerase (HBV‐Pol) appeared crucial for these inhibitory effects of HBV. Conclusion: IL‐1β production is suppressed in HBV carriers and IFN‐α non‐responders. HBV induces a significant decrease in IL‐1β production through inhibiting the NF‐κB signaling and inflammasome pathways, for which HBV‐Pol is a crucial requirement. Trial approval number: 20 173 402. [ABSTRACT FROM AUTHOR]

The luminescence mechanism of blue devices is a Direct Chargerecombination mechanism, that is, the electrons is captured by the host and transferred to the dopant, and holes are directly captured by dopant, and the two directly recombine formed excitons on dopant. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) has played the important function in regulation of various biological processes and in diagnostic value has been widely appreciated. In the present study, we have found that LOC101928316 was significantly downregulated in gastric cancer (GC) tissues specimen, GC cell lines, and associated with the GC patients tumor, node, and metastasis (TNM) stage and degree of differentiation (P ＜ 0.05). LOC101928316 overexpression can significantly inhibit SGC‐7901 cell migration, invasion, and proliferation (P＜0.05). LOC101928316 molecular mechanism investigates suggested that LOC101928316 can regulate PI3K‐Akt‐mTOR signaling pathway and change the GC development progression in vivo and in vitro. In vivo experiment also revealed that LOC101928316‐Overexpression can inhibit the tumorigenicity of GC cells in tumor‐burdened experimental nude mice (P ＜ 0.05). LOC101928316 may function as anti‐oncogene and also plays an important role in GC tumorigenesis. Collectively, our data provided the key role of LOC101928316 in the tumorigenesis of GC. In addition, the present study elucidates LOC101928316 potential regulatory network, which may help us to lead a better knowing of the pathogenesis of GC and probe the lncRNA as a novel biomarker to diagnosis and therapy for this malignant tumor. [ABSTRACT FROM AUTHOR]

Canine distemper virus (CDV), bearing a close resemblance to measles virus, represents a promising candidate for oncolytic therapy; however, its application and underlying oncolytic mechanisms in canine mammary carcinoma cells remain to be explored. Here, we found that an attenuated canine distemper vaccine strain, CDV‐L, efficiently infected and inhibited the growth of canine mammary tubular adenocarcinoma CIPp cells but not MDCK cells in vitro. Transcriptomic analysis of CDV‐L‐infected CIPp cells revealed substantially differentially expressed genes in apoptotic and NF‐κB signalling pathways. Subsequent validations confirmed that CDV‐L‐induced apoptosis of CIPp cells through the caspase‐8 and caspase‐3 pathway. Identification of phosphorylated‐IκBα, phosphorylated‐p65 and the nuclear translocation of p65 confirmed the activation of the NF‐κB signalling pathway. Inhibition of the NF‐κB pathway abrogated CDV‐L‐induced cleaved‐caspase‐3 and cleaved‐PARP. In a CIPp subcutaneous xenograft mouse model, intratumoural injections of CDV‐L significantly restricted tumour growth without apparent pathology, and virus remained localized within the tumour. Taken altogether, these findings indicate that CDV‐L exerts an antitumour effect in CIPp cells, and that apoptosis and the NF‐κB pathway play essential roles in this process. [ABSTRACT FROM AUTHOR]

By employing triethylamine as a catalyst, [3 + 2] coupling‐elimination cascade of α,α‐dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Chiral α‐mercapto‐β‐amino acid derivatives are highly significant for the development of new synthetic methodology and pharmaceutics. Until now, only a few catalytic asymmetric transformations for the synthesis of optically active α‐mercapto‐β‐amino acid derivatives have been developed. In continuation of our ongoing research on asymmetric hydrosilylation, herein we report a one‐pot asymmetric hydrosilylation‐transacylation of N‐unprotected α‐acylthio‐β‐enamino esters by employing a chiral picolinamide Lewis base as a catalyst. The reactions afforded a wide variety of α‐mercapto‐β‐acylamido esters with good yields (up to 99%) in good diastereoselectivities (>20 : 1 d.r.) and moderate to good enantioselectivities (up to 86% ee). Furthermore, the absolute configuration of one product was determined and the configurations of other products were assigned by analogy. Finally, based on the absolute configuration of the product, a mechanism was proposed. One cold pot: An asymmetric hydrosilylation−transacylation of α‐acylthio‐β‐enamino esters provided several α‐mercapto‐β‐acylamido esters in good yields and with excellent diastereoselectivities and moderate to good enantioselectivities. [ABSTRACT FROM AUTHOR]