Search

Abstract Purpose In the Zhejiang region, research on Helicobacter pylori is lacking. The purpose of this study was to assess the extent of antibiotic resistance in H. pylori in this region, explore alternative methods for predicting the resistance patterns of H. pylori, and investigate the colonization of native gastric mucosa by other clades of H. pylori in the structure population of this bacterium. Methods Strains were cultured under microaerobic conditions, and antimicrobial susceptibility testing (AST) was performed via agar dilution. Whole-genome sequencing (WGS) was performed via next-generation sequencing (NGS) technology. Epidemiological data including data from this study and reported articles from Zhejiang, China, were included. Further analyses based on AST, WGS, and epidemiological date include virulence genes, antibiotic resistance-related mutations, and phylogenetic trees based on 7 housekeeping genes and core-genome single nucleotide polymorphisms (SNPs). Results The bacterial isolates in this study presented higher antibiotic resistance rates than previously reported, especially against levofloxacin and clarithromycin. The point mutation A2147G in 23 S rRNA is specific to clarithromycin resistance. Mutations at position/s 87 and/or 91 of the gyrA gene amino acid sequence are highly consistent with levofloxacin resistance highly. The point mutations C1707T in 23 S rRNA and E463K in the gyrB gene have not been previously documented in China. All the bacterial isolates belong to Asian branches in the structure population. The resistance rate to clarithromycin of isolates from hosts born after January 1, 1977 is statistically higher than that of hosts born before 1977. Conclusion Eradication therapy based on AST results is urgently needed in Zhejiang. The point mutation A2147G in 23 S rRNA and point mutations in the gyrA gene at amino acid/s 87 and/or 91 are sufficient for predicting resistance to clarithromycin and levofloxacin, respectively. The isolate with the mutation E463K in the gyrB gene represents a significant contribution to the field. Mutations in 23 S rRNA may offer valuable insights into the dynamics of H. pylori transmission among hosts.

Abstract This study employed Environmental DNA (eDNA) barcoding technology to delve into the influence of the tributaries and mainstem on fish diversity and spatiotemporal distribution in a hotspot fish conservation area in the upper Yangtze River. A total of 123 fish species were detected, belonging to 7 orders, 19 families, and 77 genera. The composition of fish species in tributaries is similar to that in mainstem, with higher fish community diversity in tributaries during the spring and summer. Exploration of fish ecotypes revealed significant differences between mainstem and tributaries. The fish community is mainly influenced by key environmental factors such as water temperature, dissolved oxygen, electrical conductivity, and ammonia nitrogen, with a higher impact of these factors on tributaries than on mainstem. In conclusion, while tributaries and mainstem in the Jiangjin section exhibit similarities in fish community composition, there are notable differences in community structure and diversity. Therefore, the protection of not only mainstem but also tributaries and their associated fish habitats is crucial for promoting the overall health and sustainability.

Abstract Background KIAA1429, a regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of KIAA1429 in gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate the role of KIAA1429 in GC and to elucidate the underlying mechanisms. Methods The expression patterns and clinical relevance of KIAA1429 in GC were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and bioinformatic analysis. In vitro and in vivo loss- and gain-of-function assays, m6A dot blot assays, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter assays, RNA stability assays, RNA immunoprecipitation (RIP) assays, and RNA pull-down assays were performed to investigate the biological functions and underlying molecular mechanisms of KIAA1429 in GC. Results Both the mRNA and protein expression of KIAA1429 were greater in GC tissues than in normal gastric tissues. High KIAA1429 expression correlated positively with poor prognosis in GC patients. KIAA1429 not only promoted GC cell proliferation, colony formation, G2/M cell cycle transition, migration, and invasion in vitro but also enhanced GC tumor growth and metastasis in vivo. Mechanistically, KIAA1429 increased the m6A level of RASD1 mRNA and enhanced its stability in an m6A-YTHDF2-dependent manner, thereby upregulating its expression. RASD1 knockdown partially rescued the KIAA1429 knockdown-induced impairment of pro‑oncogenic ability in GC cells. The expression levels of KIAA1429 and RASD1 were negatively correlated in GC tissues. Conclusions KIAA1429 plays a pro‑oncogenic role in GC by downregulating RASD1 expression through destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. KIAA1429 may serve as a prognostic biomarker and therapeutic target for GC.

Despite providing significant assistance to human society, cascade dams can also have negative impacts on river ecosystems. As the crucial components of river ecosystem, the responses of phytoplankton and zooplankton to cascade dams have rarely been studied simultaneously, and thus, lacking the understanding of the difference in succession between them. Here, we investigated the phytoplankton and zooplankton communities in a river-way with cascade dams using an environmental DNA metabarcoding technology. Along the reservoir areas separated by dams, we found an obvious downward trend in diversity of plankton communities with significant variations in their compositions. The relative abundances of Bacillariophyta and Chlorophyta continued to decrease while Intramacronucleata increased along the river-way. Results of association analyses recognized temperature and flow rate as potential factors resiling the impacts of cascade dams. Beta diversity decomposition indicated species replacement as the main mechanism for variations in plankton communities with higher contribution for phytoplankton. Additionally, we detected wider environmental adaptation (broader environmental breadth, phylogenetic single, and niche breadth) and stronger dispersal ability in phytoplankton than in zooplankton. Environmental variables showed a stronger effect for variations in phytoplankton than zooplankton. Furthermore, we observed that community assembly of phytoplankton and zooplankton was, based on the null model, by heterogeneous selection and drift, respectively. These results suggested differences in phytoplankton and zooplankton response to cascade dams and highlighted the stronger environmental filtering in phytoplankton.

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is associated with altered gut microbiota; however, there has been a focus on fecal samples, which are not representative of the entire digestive tract. Mucosal biopsies of the descending duodenum were collected. Five regions of the 16S rRNA gene were amplified and sequenced. Other assessments conducted on the study subjects included body mass index, transient elastography, liver enzymes, and lipid profile. Fifty-one subjects (36 with MASLD and 15 controls) were evaluated. There was no significant difference between the two groups regarding alpha- or beta-diversity of the duodenal mucosal microbiota. Linear discriminant analysis effect size (LEfSe) analysis showed that the genera Serratia and Aggregatibacter were more abundant in the duodenal mucosa of patients with MASLD, whereas the duodenal mucosal microbiota of the healthy controls was enriched with the genus Petrobacter. PICRUSt2 analysis revealed that genes associated with amino acid degradation and carboxylate degradation were significantly enriched in the duodenal mucosal microbiota of patients with MASLD. Our findings reveal the duodenal mucosal microbiota in patients with MASLD, which could contribute to future studies investigating the causal relationship between duodenal microbiota and MASLD.

Abstract Background Culex pipiens pallens and Culex pipiens quinquefasciatus are the dominant species of Culex mosquitoes in China and important disease vectors. Long-term use of insecticides can cause mutations in the voltage-gated sodium channel (vgsc) gene of mosquitoes, but little is known about the current status and evolutionary origins of vgsc gene in different geographic populations. Therefore, this study aimed to determine the current status of vgsc genes in Cx. p. pallens and Cx. p. quinquefasciatus in China and to investigate the evolutionary inheritance of neighboring downstream introns of the vgsc gene to determine the impact of insecticides on long-term evolution. Methods Sampling was conducted from July to September 2021 in representative habitats of 22 provincial-level administrative divisions in China. Genomic DNA was extracted from 1308 mosquitoes, the IIS6 fragment of the vgsc gene on the nerve cell membrane was amplified using polymerase chain reaction, and the sequence was used to evaluate allele frequency and knockdown resistance (kdr) frequency. MEGA 11 was used to construct neighbor-joining (NJ) tree. PopART was used to build a TCS network. Results There were 6 alleles and 6 genotypes at the L1014 locus, which included the wild-type alleles TTA/L and CTA/L and the mutant alleles TTT/F, TTC/F, TCT/S and TCA/S. The geographic populations with a kdr frequency less than 20.00% were mainly concentrated in the regions north of 38° N, and the geographic populations with a kdr frequency greater than 80.00% were concentrated in the regions south of 30° N. kdr frequency increased with decreasing latitude. And within the same latitude, the frequency of kdr in large cities is relatively high. Mutations were correlated with the number of introns. The mutant allele TCA/S has only one intron, the mutant allele TTT/F has three introns, and the wild-type allele TTA/L has 17 introns. Conclusions Cx. p. pallens and Cx. p. quinquefasciatus have developed resistance to insecticides in most regions of China. The neighboring downstream introns of the vgsc gene gradually decreased to one intron with the mutation of the vgsc gene. Mutations may originate from multiple mutation events rather than from a single origin, and populations lacking mutations may be genetically isolated. Graphical Abstract

Abstract 21st century has witnessed a profound metamorphosis in human civilization, primarily driven by the confluence of advanced network technologies and industrial modernization. This transformative period has expanded our understanding of the world, paving the way for innovative concepts such as the “smart city”. At its essence, a smart city harnesses the power of artificial intelligence (AI) to revolutionize urban living, presenting a paradigm shift towards more efficient service models and an elevated standard of living for its inhabitants. Integrating AI into the fabric of urban infrastructure marks a monumental leap in societal evolution, underscoring the imperative to cultivate and advance AI technologies. This paper endeavors to elucidate the multifaceted applications of AI within the domains of smart cities, illuminating its pivotal role in shaping and advancing our contemporary era. From intelligent transportation systems and energy management to public safety and healthcare, AI permeates various aspects of urban life, ushering in unprecedented efficiencies and novel solutions to age-old challenges. The symbiotic relationship between AI and smart cities is explored in detail, showcasing how AI technologies are instrumental in optimizing resource allocation, improving decision-making processes, and ultimately enhancing the overall quality of life. Furthermore, this paper delves into the imperative of fostering the development and advancement of AI technologies within the context of smart cities. It underscores the interconnectedness of technological progress and urban development, emphasizing how a concerted effort to cultivate AI capabilities can propel cities into a future marked by sustainable growth, resilience, and innovation. The exploration of challenges and opportunities in deploying AI within urban environments adds a critical dimension to the discourse, encouraging a balanced consideration of ethical, regulatory, and societal implications. In conclusion, this paper seeks to contribute to the ongoing dialogue surrounding smart cities and the transformative impact of AI. By shedding light on the diverse applications of AI within urban landscapes and emphasizing its pivotal role in shaping the trajectory of our era, it underscores the critical importance of advancing AI technology development for the continued progress of smart cities and, by extension, the broader global community.

Abstract Currently, the clinical treatment of critical bone defects attributed to various causes remains a great challenge, and repairing these defects with synthetic bone substitutes is the most common strategy. In general, tissue engineering materials that mimic the structural, mechanical and biological properties of natural bone have been extensively applied to fill bone defects and promote in situ bone regeneration. Hydrogels with extracellular matrix (ECM)-like properties are common tissue engineering materials, among which methacrylate-based gelatin (GelMA) hydrogels are widely used because of their tunable mechanical properties, excellent photocrosslinking capability and good biocompatibility. Owing to their lack of osteogenic activity, however, GelMA hydrogels are combined with other types of materials with osteogenic activities to improve the osteogenic capability of the current composites. There are three main aspects to consider when enhancing the bone regenerative performance of composite materials: osteoconductivity, vascularization and osteoinduction. Bioceramics, bioglass, biomimetic scaffolds, inorganic ions, bionic periosteum, growth factors and two-dimensional (2D) nanomaterials have been applied in various combinations to achieve enhanced osteogenic and bone regeneration activities. Three-dimensional (3D)-bioprinted scaffolds are a popular research topic in bone tissue engineering (BTE), and printed and customized scaffolds are suitable for restoring large irregular bone defects due to their shape and structural tunability, enhanced mechanical properties, and good biocompatibility. Herein, the recent progress in research on GelMA-based composite hydrogel scaffolds as multifunctional platforms for restoring critical bone defects in plastic or orthopedic clinics is systematically reviewed and summarized. These strategies pave the way for the design of biomimetic bone substitutes for effective bone reconstruction with good biosafety. Graphical Abstract This review provides novel insights into the development and current trends of research on GelMA-based hydrogels as effective bone tissue engineering (BTE) scaffolds for correcting bone defects, and these contents are summarized and emphasized from various perspectives (osteoconductivity, vascularization, osteoinduction and 3D-bioprinting). In addition, advantages and deficiencies of GelMA-based bone substitutes used for bone regeneration are put forward, and corresponding improvement measures are presented prior to their clinical application in near future (created with BioRender.com).

Abstract The physics principle of pulse flight positioning is the main theoretical bottleneck that restricts the spatial resolution of the existing Raman distributed optical fiber sensing scheme. Owing to the pulse width of tens of nanoseconds, the spatial resolution of the existing Raman distributed optical fiber sensing scheme with kilometer-level sensing distance is limited to the meter level, which seriously restricts the development of the optical time-domain reflection system. In this paper, a chaos laser is proposed in the context of the physical principle of the Raman scattering effect, and a novel theory of chaos Raman distributed optical fiber sensing scheme is presented. The scheme reveals the characteristics of chaos Raman scattering light excited by a chaotic signal on the sensing fiber. Further, the chaos time-domain compression demodulation mechanism between the temperature variation information and chaos correlation peak is demonstrated. Then, the position of the temperature variation signal is precisely located using the delay time of the chaos correlation peak combined with the chaos pulse flight time. Based on this novel optical sensing mechanism, an experiment with 10 cm spatial resolution and 1.4 km sensing distance was conducted, and the spatial resolution was found to be independent of the sensing distance. Within the limit of the existing spatial resolution theory, the spatial resolution of the proposed scheme is 50 times higher than that of the traditional scheme. The scheme also provides a new research direction for optical chaos and optical fiber sensing.

Abstract Background The current prevention and control strategy for Aedes albopictus heavily relies on comprehensive management, such as environmental management and chemical control. However, the wide application of pyrethroids has facilitated the development of insecticide resistance, primarily via mutations in the voltage-gated sodium channel (VGSC) gene. This study aims to develop a novel strategy for detecting mutations in the VGSC gene in Ae. albopictus using multiplex PCR-mass spectrometry (MPCR-MS) minisequencing technology. Methods We established a new strategy for detecting mutations in the VGSC gene in Ae. albopictus using MPCR-MS minisequencing technology. MPCR amplification and mass probe extension (MPE) were first used, followed by single nucleotide polymorphism (SNP) typing mass spectrometry, which allows the simultaneous detection of multiple mutation sites of the VGSC gene in 96 samples of Ae. albopictus. A total of 70 wild-collected Ae. albopictus were used to evaluate the performance of the method by comparing it with other methods. Results Three target sites (1016, 1532, 1534) in the VGSC gene can be detected simultaneously by double PCR amplification combined with matrix-assisted laser desorption ionization–time-of-flight mass spectrometry, achieving a detection limit of 20 fg/μl. We applied this method to 70 wild-collected Ae. albopictus, and the obtained genotypes were consistent with the routine sequencing results, suggesting the accuracy of our method. Conclusions MPCR-MS minisequencing technology provides a sensitive and high-throughput approach to Ae. albopictus VGSC gene mutation screening. Compared with conventional sequencing, this method is economical and time-saving. It is of great value for insecticide resistance surveillance in areas with a high risk of vector-borne disease. Graphical Abstract

Abstract Background Intestinal inflammation has become a threatening concern in chicken production worldwide and is closely associated with Th17/Treg cell imbalance. Several studies described that gut microbiota is significantly implicated in chicken growth by modulating intestinal immune homeostasis and immune cell differentiation. Whether reshaping gut microbiota by fecal microbiota transplantation (FMT) could improve chicken growth by balancing Th17/Treg cells is an interesting question. Results Here, the chickens with significantly different body weight from three different breeds (Turpan cockfighting × White Leghorn chickens, white feather chickens, and yellow feather chickens) were used to compare Th17 and Treg cells. qPCR and IHC staining results indicated that Th17 cell-associated transcriptional factors Stat3 and rorγt and cytokines IL-6, IL-17A, and IL-21 were significantly (P

Abstract Background Anthracosis is a disease generally considered to be in the lungs resulting from exposure to industrial dust in the workplace. Esophageal anthracosis is a fairly rare phenomenon and shows a strong correlation with tuberculosis. Moreover, esophageal involvement in tuberculosis is also rare. We here present an extremely rare case in which follow-up gastroesophageal endoscopy revealed a mass with a sunken, black area in the center and raised ring-like pattern in the surrounding mucosa resembling malignant melanoma. Uncovering the patient’s tuberculosis history finally avoided a misdiagnosis or overtreatment. Case presentation A 67-year-old male patient was admitted to the hospital due to “repeated chest pain for 1 month”. Endoscopic ultrasonography and contrast-enhanced CT scans revealed a mass adjacent to the esophageal wall with unclear boundaries. Aspiration biopsy confirmed that esophageal tuberculosis was caused by nearby mediastinal tuberculous lymphadenitis. After a standard anti-tuberculosis treatment regimen, the patient achieved a favorable prognosis. The follow-up gastroesophageal endoscopy showed a sunken black lesion with elevated peripheral mucosa replacing the original tuberculous mass, which was thought to be anthracosis, a disease that rarely occurs in the esophagus. Conclusion The diagnosis of tuberculosis should be taken into consideration when a submucosal mass appears in the middle part of the esophagus. Endoscopic ultrasonography can effectively contribute to a definite diagnosis. Moreover, this is the first case of esophageal anthracosis observed only 1 year after the treatment of tuberculosis, indicating esophageal anthracosis can be a short-term disease. The traction of the reduction of tubercular mediastinal lymph nodes after anti-tuberculosis treatment may create a circumstance for pigmentation or dust deposition.

IntroductionThe recently established Linderniaceae, separated from the traditionally defined Scrophulariaceae, is a taxonomically complicated family. Although previous phylogenetic studies based on a few short DNA markers have made great contributions to the taxonomy of Linderniaceae, limited sampling and low resolution of the phylogenetic tree have failed to resolve controversies between some generic circumscriptions. The plastid genome exhibits a powerful ability to solve phylogenetic relationships ranging from shallow to deep taxonomic levels. To date, no plastid phylogenomic studies have been carried out in Linderniaceae.MethodsIn this study, we newly sequenced 26 plastid genomes of Linderniaceae, including eight genera and 25 species, to explore the phylogenetic relationships and genome evolution of the family through plastid phylogenomic and comparative genomic analyses.ResultsThe plastid genome size of Linderniaceae ranged from 152,386 bp to 154,402 bp, exhibiting a typical quartile structure. All plastomes encoded 114 unique genes, comprising 80 protein-coding genes, 30 tRNA genes, and four rRNA genes. The inverted repeat regions were more conserved compared with the single-copy regions. A total of 1803 microsatellites and 1909 long sequence repeats were identified, and five hypervariable regions (petN-psbM, rps16-trnQ, rpl32-trnL, rpl32, and ycf1) were screened out. Most protein-coding genes were relatively conserved, with only the ycf2 gene found under positive selection in a few species. Phylogenomic analyses confirmed that Linderniaceae was a distinctive lineage and revealed that the presently circumscribed Vandellia and Torenia were non-monophyletic.DiscussionComparative analyses showed the Linderniaceae plastomes were highly conservative in terms of structure, gene order, and gene content. Combining morphological and molecular evidence, we supported the newly established Yamazakia separating from Vandellia and the monotypic Picria as a separate genus. These findings provide further evidence to recognize the phylogenetic relationships among Linderniaceae and new insights into the evolution of the plastid genomes.

Accurate tropical cyclone (TC) intensity and size estimation are key in disaster management and prevention. While great breakthroughs have been made in TC intensity estimation research, there is currently a lack of research on TC size reflecting TC influence radius. Therefore, we propose a lightweight multi-task learning model (TC-MTLNet) with adaptive loss balance to simultaneously estimate TC intensity and size. Adaptive loss balance is utilized to solve the problem of inconsistent convergence speed of TC intensity and size estimation tasks. The model based on four 2-D convolutions, four 3-D convolutions and three fully connected layers takes up less computational and storage space and improves the accuracy of TC intensity and size estimation by sharing knowledge among multiple tasks. In addition, due to the imbalanced distribution of TC samples, with significantly few low-intensity and high-intensity TC satellite data, this phenomenon poses a great challenge to TC intensity and size estimation. So, we utilize the influence of nearby samples to calibrate the sample density to weight the loss function to enable the model to be generalized to all samples. The result shows that the root-mean-square error (RMSE) of TC intensity estimation is $\text{8.40}\,\text{kts}$, which is 33.5% lower than that of the Advanced Dvorak Technique (ADT) and 11.4% lower than that of the deep learning method (3DAttentionTCNet). The mean absolute error (MAE) of the TC size estimation is $\text{20.89}\,\text{nmi}$, which is a 16% reduction compared to the Multi-Platform Tropical Cyclone Surface Winds Analysis (MTCSWA).

Pandemic influenza virus and SARS-CoV-2 vaiants have posed major global threats to public health. Broad-spectrum antivirals blocking viral entry can be an effective strategy for combating these viruses. Here, we demonstrate a frog-defensin-derived basic peptide (FBP), which broadly inhibits the influenza virus by binding to haemagglutinin so as to block low pH-induced HA-mediated fusion and antagonizes endosomal acidification to inhibit the influenza virus. Moreover, FBP can bind to the SARS-CoV-2 spike to block spike-mediated cell–cell fusion in 293T/ACE2 cells endocytosis. Omicron spike shows a weak cell–cell fusion mediated by TMPRSS2 in Calu3 cells, making the Omicron variant sensitive to endosomal inhibitors. In vivo studies show that FBP broadly inhibits the A(H1N1)pdm09 virus in mice and SARS-CoV-2 (HKU001a and Delta)in hamsters. Notably, FBP shows significant inhibition of Omicron variant replication even though it has a high number of mutations in spike. In conclusion, these results suggest that virus-targeting FBP with a high barrier to drug resistance can be an effective entry-fusion inhibitor against influenza virus and SARS-CoV-2 in vivo.

Raman distributed optical fiber temperature sensors possess the unique capability of measuring spatial environmental temperatures, which can be of great interest in several fields of application. The key physics barrier to spatial resolution for most optical time-domain reflection (OTDR) systems is the positioning principle of pulse-time-flight. It obtains the spatial resolution of the existing Raman distributed optical fiber temperature sensor, with the kilometer-level sensing distance being limited to the meter-level. Here, we propose a chaotic laser Raman distributed optical fiber temperature sensing scheme that replaces the traditional OTDR positioning principle used for more than 40 years with the chaotic correlation positioning principle. The proposed scheme possesses the characteristics of the chaos Raman scattering light excited by the chaos signal along the sensing fiber. A novel measurement mechanism based on chaotic time-domain differential reconstruction and chaotic correlation demodulation is developed, and a relationship between the temperature variation information and the chaotic correlation peak is experimentally demonstrated. Importantly, the proposed optics mechanism scheme overcomes the physics limitation of the effect of a wide pulse width on sensing spatial resolution; its spatial resolution is optimized from 50 to 0.3 m under the modulation of a 500 ns pulse width. This scheme provides a new concept for chaos optics and fiber sensing research.

The Belian (Eusideroxylon zwageri Teijsm. & Binn.) is a commercially important timber species in Southeast Asia that was listed on the IUCN Red List of threatened species in 1998. Six years ago, we published an article in Genome Biology Ecology entitled “Evolutionary Comparisons of the Chloroplast Genome in Lauraceae and Insights into Loss Events in the Magnoliids” in which one complete plastid genome of Belian was assembled for comparative analyses of the plastomes in Lauraceae. However, a recent study concluded that our sequenced Belian individual can be located in the clade of Myristicaceae instead of that of Lauraceae. Here, we performed reanalyses of an additional two Belian plastomes, along with 42 plastomes from plants spanning 10 families of the Magnoliids. The three Belian plastomes are 39% CG and vary in length from 157,535 to 157,577 bp. A total of 37 tRNA genes, 8 rRNA genes, and 85 protein-coding genes were among the 130 annotated genes. There were 95–101 repeat sequences and 56–61 simple repeat sequences (SSRs). Comparative genomic analysis revealed 170 mutation sites in their plastomes, which include 111 substitutions, 53 indels, and 6 microinversions. Phylogeny was reconstructed using maximum-likelihood and Bayesian approaches for 44 magnoliids species, indicating that the 3 Belian individuals were nested among the species in the Lauraceae family rather than Myristicaceae.

Abstract Breakdown of blood-brain barrier (BBB) is recognized as serious pathological marker of Alzheimer’s disease development. Studies confirmed that β-amyloid (Aβ) deposition induced high BBB permeability by disrupting tight junction (TJ) proteins formed from endothelial cells (ECs). Here, we found TARBP2, SNHG7 and NFATC3 in expressions were increased and miR-17-5p expression was decreased in Aβ(1-42)-incubated ECs. Overexpression of TARBP2, SNHG7 and NFATC3 elevated BBB permeability and knockdown of them had converse results. Agomir-17-5p decreased BBB permeability and antagomir-17-5p increased BBB permeability. TARBP2 as a RNA-binding protein (RBP) bound to SNHG7 and resulted in longer half-life of SNHG7. The decreased expression of miR-17-5p had a negative post-transcriptional regulation to NFATC3, leading to the increased expression of NFATC3. In addition, SNHG7 regulated NFATC3 expression by acting as a molecule sponge targeting to miR-17-5p. NFATC3 inhibited TJ proteins expression by functioning as a transcription factor. TARBP2/SNHG7/miR-17-5p/NFATC3 pathway implied a potential mechanism in studies of BBB changes in AD pathological progression.

BackgroundAedes albopictus, commonly known as the tiger mosquito, has attracted global attention because its bite can transmit several viruses, such as dengue virus. With the absence of an effective therapy and vaccine, mosquito control is the sole method for dengue fever control. However, Ae. albopictus has developed resistance to most insecticides, especially pyrethroids. Many scholars have conducted thorough research for the target-site of pyrethroids. The main target-site is the voltage-gated sodium channel gene (VGSC) whose mutation causes knockdown resistance (kdr). The spatial distribution of three locus kdr mutations in Ae. albopictus has not been comprehensively analyzed nationwide in China. In addition, the relationship between the frequency of kdr mutations and dengue fever has not yet been explored.MethodsA total of 2,241 Ae. albopictus samples from 49 populations from 11 provinces of mainland China were collected in 2020 and analyzed for mutations in the VGSC gene. DNAstar 7.1. Seqman and Mega-X were used to compare the sequences and read the peak map to confirm the genotypes and alleles of each mutation. ArcGIS 10.6 software was used to make interpolation and extract meteorological data of collection sites and to conduct spatial autocorrelation analysis. R 4.1.2 software was used to conduct a chi-square test for kdr mutations and dengue area and to analyze the correlation between meteorological factors and kdr mutations.ResultsThe overall frequencies of mutant alleles at 1016G, 1532T, and 1534S/C/L were 13.19%, 4.89%, and 46.90%, respectively. Mutations at the three loci were found at 89.80% (44/49), 44.90% (22/49), and 97.96% (48/49) of the field populations. At each of the loci V1016 and I1532, only one allele was detected, which was GGA(G) and ACC(T), respectively. Five mutant alleles were found at codon 1534: TCC/S (33.49%), TGC/C (11.96%), TTG/L (0.60%), CTC/L (0.49%), and TTA/L (0.58%). In total, 31 triple-locus genotype combinations were found, and the single locus mutation was the most common. We also found firstly triple-locus mutant individuals, whose genotypes were V/G+I/T+F/S and V/G+I/T+S/S. The 1016 and 1532 mutation rates were significantly negatively related to the annual average temperature (AAT), but the 1534 mutation rate was significantly positively related to AAT. The 1532 mutation rate was significantly positively related to the 1016 mutation rate but negatively related to the 1534 mutation rate. A relationship was observed between the 1534 codon mutation rate and dengue epidemic areas in this study. Furthermore, spatial autocorrelation analysis results showed that the mutation rates of different codons in different geographical areas had spatial aggregation and positive spatial correlation.ConclusionThis study showed that the multiple kdr mutations at codon 1016, 1532 and 1534 of Ae. albopictus were found in most areas of China. Two novel triple-locus genotype combinations, V/G+I/T+F/S and V/G+I/T+S/S, were detected in this study. In addition, the relationship between mosquito resistance and dengue fever outbreak should be further explored, especially considering the insecticide-usage history in different areas. The characteristic of spatial aggregation of VGSC gene mutation rates reminds us to notice the gene exchange and similarity of insecticide usage in the adjacent areas. The use of pyrethroids should be restricted to delay resistance development. New-type insecticides should be developed to adjust the changes in the resistance spectrum. Our study provides abundant data on the Ae. albopictus kdr gene mutation in China; these findings will be useful for the correlation analysis of molecular mechanism of insecticide resistance.

Objectives: To evaluate the effectiveness and safety of a newly designed self-assembling gel in treating ESD-induced gastric ulcers in patients.Methods: This open-label, multicenter, randomized controlled trial enrolled patients who underwent ESD between September 2020 and May 2021. Patients were randomized (1:1) to receive the gel (applied to cover the entire ulcer bed under endoscopic guidance immediately after ESD; gel group) or not (control group). The primary outcome was the ulcer healing rate at 28 days. And the secondary outcomes were the delayed bleeding, changes in the ulcer stage, and adverse events.Results: Finally, 125 patients (mean age, 63.7 years; 70 [56.0%] males) were enrolled. The ulcer healing rate was higher in the gel group than in the control group at 28 days (96.9 ± 4.1% vs. 94.7 ± 5.0%; p = 0.001). The ulcer reduction rate at 28 days differed significantly (p < 0.001) between ulcers with majority gel coverage (99.8%), ulcers with minority gel coverage (96.2%), and ulcers with no gel coverage (98.0%). Delayed bleeding was found in 1/63 gel-treated patients (1.6%) versus 5/62 controls (8.1%). A1-stage ulcers were found in 16/63 patients in the gel group versus 44/62 patients in the control group (25.4% vs. 71.0%, p < 0.001) at 3–5 days.Conclusion: The newly developed self-assembling gel was safe and effective in accelerating gastric ulcer healing in patients after ESD.Clinical Trial Registration: UMIN Clinical Trials Registry System (registration number, ChiCTR2100052935).

With the rapid development of science and technology, the problem of energy load monitoring and decomposition of electrical equipment has been receiving widespread attention from academia and industry. For the purpose of improving the performance of non-intrusive load decomposition, a non-intrusive load decomposition method based on a hybrid deep learning model is proposed. In this method, first of all, the data set is normalized and preprocessed. Secondly, a hybrid deep learning model integrating convolutional neural network (CNN) with long short-term memory network (LSTM) is constructed to fully excavate the spatial and temporal characteristics of load data. Finally, different evaluation indicators are used to analyze the mixture. The model is fully evaluated, and contrasted with the traditional single deep learning model. Experimental results on the open dataset UK-DALE show that the proposed algorithm improves the performance of the whole network system. In this paper, the proposed decomposition method is compared with the existing traditional deep learning load decomposition method. At the same time, compared with the obtained methods: spectral decomposition, EMS, LSTM–RNN, and other algorithms, the accuracy of load decomposition is significantly improved, and the test accuracy reaches 98%.

ObjectiveThe primary goals of this study were to investigate the potential roles of ZNF22 and HDAC3 as a histone deacetylase in regulating an increases in blood-tumor barrier (BTB) permeability and some of the possible molecular mechanisms associated with this effect.MethodsThe expression of ZNF22 and HDAC3 in glioma-exposed endothelial cells (GECs) of BTB were detected transcription real-time PCR or western blot. The interaction of ZNF22 and HDAC3 in GECs associated with transcript effect was analyzed by means of Co-Immunoprecipitation and luciferase reporter assay.ResultsIn the present investigation, GECs expressed higher levels of ZNF22 as a zinc finger transcription factor and HDAC3 than endothelial cells. We then affirmed that silencing HDAC3 or ZNF22 led to a reduction in BTB permeability. By bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and luciferase assay, we found that ZNF22 had a target binding relationship with the promoter regions of ZO-1, Occludin, and Claudin-5 and negatively regulated the expression of ZO-1, Occludin, and Claudin-5. Furthermore, we revealed that HDAC3, as a co-transcript repressor with histone deacetylase activity, could interact with ZNF22 to hinder the expression of TJ-associated proteins, thereby further facilitating the permeability of BTB.ConclusionZNF22 acted as a transcription factor in conjunction with HDAC3 to modulate the expression of TJ-associated proteins, which was correlated with an increase in BTB permeability. These results may provide new strategies and targets for the chemotherapy of gliomas as well as intracranial infections.

BackgroundAlcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD.Materials and methodsA total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse.ResultsThe sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan–Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05).ConclusionThis study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

Non-alcoholic fatty liver disease (NAFLD) is currently related to a heavy socioeconomic burden and increased incidence. Since obesity is the most prevalent risk factor for NAFLD, weight loss is an effective therapeutic solution. Bariatric surgery (BS), which can achieve long-term weight loss, improves the overall health of patients with NAFLD. The two most common surgeries are the Roux-en-Y gastric bypass and sleeve gastrectomy. The gut-liver axis is the complex network of cross-talking between the gut, its microbiome, and the liver. The gut microbiome, involved in the homeostasis of the gut-liver axis, is believed to play a significant role in the pathogenesis of NAFLD and the metabolic improvement after BS. Alterations in the gut microbiome in NAFLD have been confirmed compared to that in healthy individuals. The mechanisms linking the gut microbiome to NAFLD have been proposed, including increased intestinal permeability, higher energy intake, and other pathophysiological alterations. Interestingly, several correlation studies suggested that the gut microbial signatures after BS become more similar to those of lean, healthy controls than that of patients with NAFLD. The resolution of NAFLD after BS is related to changes in the gut microbiome and its metabolites. However, confirming a causal link remains challenging. This review summarizes characteristics of the gut microbiome in patients with NAFLD before and after BS and accumulates existing evidence about the underlying mechanisms of the gut microbiome.

Traditional Chinese medicine (TCM) includes over ten thousand herbal medicines, some of which were introduced from outside countries and territories. The Silk Road enabled the exchange of merchandise such as teas, silks, carpets, and medicines between the East and West of the Eurasia continent. During this time, the ‘Compendium of Materia Medica’ (CMM) was composed by a traditional medicine practitioner, Shizhen Li (1,518–1,593) of the Ming Dynasty. This epoch-making masterpiece collected knowledge of traditional medical materials and treatments in China from the 16th century and before in utmost detail, including the origin where a material was obtained. Of 1892 medical materials from the CMM, 46 came from Persia (now Iran). In this study, the basic information of these 46 materials, including the time of introduction, the medicinal value in TCM theory, together with the current status of these medicines in China and Iran, are summarized. It is found that 20 herbs and four stones out of the 46 materials are registered as medicinal materials in the latest China Pharmacopoeia. Now most of these herbs and stones are distributed in China or replacements are available but saffron, ferula, myrrh, and olibanum are still highly dependent on imports. This study may contribute to the further development, exchange, and internationalization of traditional medicine of various backgrounds in the world, given the barriers of transportation and language are largely eased in nowadays.

Green and low carbon automated production has become a research hotspot. In this paper, the AGV transport resource constraint, machine layout and job setup time have been integrated into the background of a flexible job shop. From a whole life-cycle perspective, the AGV allocation strategy has been formulated by simulating multiple scenarios within the production system. Aimed at makespan, carbon footprint, and machine load, a green low-carbon flexible job shop scheduling model with multiple transport equipment (GFJSP-MT) has been constructed. To address this problem, a relevant case dataset was formed, and a heuristic strategy NSGA-II using a real number encoded embedded cycle to replace repeated individuals was proposed. Through longitudinal and horizontal comparisons, the effectiveness of the AGV allocation strategy has been verified and the optimum number of AGVs in the case determined. Finally the quality and diversity of the Pareto frontier solutions are compared and the scheduling scheme for each sub-objective are discussed. The results show that the model and algorithm constructed in this paper can effectively achieve the optimal scheduling of green flexible shop production.

The cuttage rooting method for Acer species is difficult to achieve a good efficacy as trees maintain good characteristics at the rejuvenation stage, thus improving the rooting of Acer species. The addition of exogenous hormones and rejuvenation can improve the rooting effect of cuttings; however, the specific regulatory mechanism is still unclear. Here, Acer mono Maxim rejuvenation and non-rejuvenation cuttings were used as test subjects, to investigate the effects of exogenous hormones on the activities of endogenous hormones and antioxidant enzymes in the rooting process of young cuttings. The results showed that exogenous growth-regulating substances significantly improved the rooting rate of A. mono. Exogenous hormones naphthylacetic acid (NAA) + indolebutyric acid (IBA) increased the initial levels of the endogenous hormones, indoleacetic acid (IAA) and abscisic acid (ABA), and the enzyme activities of peroxidase (POD) and polyphenol oxidase (PPO). Rejuvenation treatment prolonged the time of increase in ABA content and indoleacetic acid oxidase (IAAO) activity at the root primordium induction stage, while increasing trans-zeatin riboside (ZR) content and decreasing POD enzyme activity in cuttings. These results demonstrate that A. mono cuttings can achieve the purpose of improving the rooting rate by adding the exogenous hormone (NAA + IBA), which is closely related to the changes of endogenous hormone content and enzyme activity, and these changes of A. mono rejuvenation cuttings are different from non-rejuvenation cuttings.

As a kind of first aid healthcare service, emergency medical services (EMSs) present high spatiotemporal sensitivity due to significant changes in the time-dependent urban environment. Taking full advantage of big spatiotemporal data to realize multiperiod relocation optimization of EMSs can reduce idle resources and improve service utilization efficiency and fairness. First, we established the dynamic time-dependent accessibility and equality model to formulate the multiperiod maximization objective of global equality. Second, we proposed a capacitated integer evolution algorithm that relocates emergency medical vehicles to optimize the scheduling scheme. Based on multiperiod mobile phone records and multiperiod online route planner data, the equality of EMSs in the research metropolis, Nanjing, China, rose by 41.5% on average, which has an incentivizing effect on alleviating the tension of prehospital service and minimizes accessibility disparities without constructing more infrastructure. We also created maps to visualize the changes in equality patterns over time. This relocation optimization approach can be regarded as a trade-off approach to dispatch time-dependent sensitive services and provide a practical tool for healthcare decision-makers to evaluate public healthcare systems and improve strategic urban service planning.

Load forecasting is very essential in the analysis and grid planning of power systems. For this reason, we first propose a household load forecasting method based on federated deep learning and non-intrusive load monitoring (NILM). As far as we know, this is the first research on federated learning (FL) in household load forecasting based on NILM. In this method, the integrated power is decomposed into individual device power by non-intrusive load monitoring, and the power of individual appliances is predicted separately using a federated deep learning model. Finally, the predicted power values of individual appliances are aggregated to form the total power prediction. Specifically, by separately predicting the electrical equipment to obtain the predicted power, it avoids the error caused by the strong time dependence in the power signal of a single device. In the federated deep learning prediction model, the household owners with the power data share the parameters of the local model instead of the local power data, guaranteeing the privacy of the household user data. The case results demonstrate that the proposed approach provides a better prediction effect than the traditional methodology that directly predicts the aggregated signal as a whole. In addition, experiments in various federated learning environments are designed and implemented to validate the validity of this methodology.

Background and objectiveEndoscopic bariatric and metabolic therapies (EBMTs) are emerging minimally invasive therapeutic options for obesity and its related complications, including non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the effects of EBMTs on NALFD in patients with obesity.MethodsFour databases were searched until Nov 2021. Randomized controlled trials (RCTs) and observational studies reporting liver-related outcomes following Food and Drug Administration (FDA)-approved and non-FDA-approved EBMTs were included. Liver parameters, metabolic parameters, and weight loss were evaluated. Risk of bias was assessed using the “risk of bias” tool in the Cochrane Collaboration for RCTs and the Methodological Index for Non-Randomized Studies criteria for observational studies.ResultsThirty-three studies with 1710 individuals were included. Regarding the effects of EBMTs on liver fibrosis, a significant decline of NAFLD Fibrosis Score, but not transient elastography-detected liver stiffness or Fibrosis-4 Index, was observed. EBMTs significantly improved liver steatosis (control attenuation parameter and Hepatic Steatosis Index), NAFLD Activity Score, and Homeostasis Model Assessment of Insulin Resistance. EBMTs reduced serum levels of alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transpeptidase considerably. Moreover, EBMTs had reducing effects on the serum levels of triglycerides and total cholesterol as well as body weight.ConclusionsOur meta-analysis suggested that EBMTs could ameliorate NAFLD based on the evidence of improved liver steatosis, liver function, and insulin resistance. Large-scale, prospective, long-term studies are warranted to clarify the role of EBMTs in patients with different stages of NAFLD.

Until today effective antivirals for COVID-19 treatment are not widely available. Here, Zhao et al. characterize a dual-functional cross-linking peptide, 8P9R, that can inhibit SARS-CoV-2 virus entry in vitro and suppresses viral replication in vivo in golden Syrian hamster.

Accurate tropical cyclone (TC) intensity estimation is crucial for prediction and disaster prevention. Currently, significant progress has been achieved for the application of convolutional neural networks (CNNs) in TC intensity estimation. However, many studies have overlooked the fact that the local convolution used by CNNs does not consider the global spatial relationships between pixels. Hence, they can only capture limited spatial contextual information. In addition, the special rotation invariance and symmetry structure of TC cannot be fully expressed by convolutional kernels alone. Therefore, this study proposes a new deep learning-based model for TC intensity estimation, which uses a combination of rotation equivariant convolution and Transformer to address the rotation invariance and symmetry structure of TC. Combining the two can allow capturing both local and global spatial contextual information, thereby achieving more accurate intensity estimation. Furthermore, we fused multi-platform satellite remote sensing data into the model to provide more information about the TC structure. At the same time, we integrate the physical environmental field information into the model, which can help capture the impact of these external factors on TC intensity and further improve the estimation accuracy. Finally, we use TCs from 2003 to 2015 to train our model and use 2016 and 2017 data as independent validation sets to verify our model. The overall root mean square error (RMSE) is 8.19 kt. For a subset of 482 samples (from the East Pacific and Atlantic) observed by aircraft reconnaissance, the root mean square error is 7.88 kt.

Context Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. Objective To examine hypouricaemic action of Poria coco. Materials and methods Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. Results P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 μmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 μmol/L (p

Background. Gastrointestinal stromal tumors (GISTs) are prevalent in elderly patients. Endoscopic resection has become popular for treating small (≤5 cm) gastric GISTs. However, little is known about the outcomes of endoscopic resection in elderly patients. Aim. To assess the efficacy and safety of endoscopic resection for small (≤5 cm) gastric GISTs in elderly patients (≥65 years old). Methods. A total of 260 patients (265 lesions) with gastric GISTs treated via endoscopic resection from January 2011 to May 2020 were retrospectively analyzed. Among them, 65 patients were ≥65 years old (elderly group), and 195 patients were

In this study, to discover how the growth of digital agriculture has impacted agricultural green total factor productivity (AGTFP), we take panel data from 2011 to 2019 for 30 Chinese provinces as the research object, measure the growth of AGTFP and digital agriculture development using the SBM-ML and entropy method, and use a fixed effect model to analyze the effects of digital agriculture development on AGTFP. The results demonstrate that (1) from the time-series characteristics, digital agriculture presented a steady growth state from 2011 to 2019; (2) during the study period, the technical efficiency index was slightly lower than the technological progress index in the AGTFP index, meaning that there is room for further development; (3) the relationship between the growth of digital agriculture and AGTFP presents an inverted U-shaped curve, with human capital playing a moderating role. Finally, corresponding countermeasures are proposed in four aspects: strengthening the construction of organizational mechanisms, building a standardized base for digital agriculture output, enhancing the traceability and certification of agricultural products, and improving social services in the agricultural industry.

Novel high light transmittance material was synthesized by dimethyl itaconic acid and diethyl itaconic acid via piecewise bulk polymerization, using benzoyl peroxide (BPO) as catalyst. Its chemical structure was characterized by gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR) and fourier transform infrared spectroscopy (FTIR). The thermal performance of polymer was characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), showing its glass transition temperature (Tg) was between 52 °C and 72 °C, thermal decomposition temperature above 230 °C, suitable for processing. The transmittance of the polymer is as high as 92% and a density of 1.1 g/cm3, which has the optical device application potential. We also tested the hydrophilicity of the material surface by the contact angle test, combined with the data of simulated calculation to explore the influence factors of hydrophilic change on the material surface.

A novel optical mechanism and scheme of Raman optical time domain reflection (ROTDR) for improving achievable spatial resolution is proposed. Herein, the Raman backscattering characteristic of the optical fiber based on the amplified spontaneous emission (ASE) detection is first theoretically analyzed. Then, the propagation model of the ASE Raman anti‐Stokes trace is established. Based on the propagation model, the time domain difference reconstruction is applied to the whole collected Raman anti‐Stokes trace. The reconstructed Raman anti‐Stokes signal and ASE signal, which are first proposed here, show a distinct correlation characteristic. For this characteristic, a higher signal‐to‐noise ratio (SNR) demodulation scheme, named compression correlation demodulation, is used to detect the temperature change along the optical fiber. The positive correlation peak generated by the proposed mechanism produces a multiplied amplification effect through compressing the whole intensity points of Raman anti‐Stokes in the fiber under test (FUT) region. Furthermore, the proposed scheme reduces the crosstalk of the non‐FUT in the demodulation process. Benefiting from this new optical sensing mechanism and scheme, a simulation experiment with 7.5 mm spatial resolution and 0.1 °C temperature sensitivity is demonstrated, and the spatial resolution is independent of sensing distance. These advances greatly facilitate the practicability of ROTDR.

It’s of great significance to develop insulin-loaded dissolving microneedles (MNs) which are fabricated with various methods and materials for transdermal delivery of insulin to effectively and efficiently treat diabetes. In this work, we present a kind of FITC-insulin tip-loaded dissolving MNs fabricated with the mixture of polyvinyl alcohol (PVA) and sucrose using homemade PDMS MNs mold under vacuum conditions. The uniform appearance of MN arrays contributes to controlling the drug dosage well as required. Sufficient mechanical strength for penetrating tough stratum corneum can be obtained by vacuum frozen-drying for at least 6 h after peeling MNs off the mold. About 90% of the FITC-insulin is localized in the conical MN tips and can be released into the skin within 2 min after insertion. The in vivo insulin absorption study and hypoglycemic effect in diabetic mice demonstrate that the proposed insulin-loaded MNs can efficiently deliver the insulin to the systemic circulation and exhibit a similar effect to hypodermic injection on hypoglycemic administration. Together these results suggested that the efficient MN fabrication process proposed in this work shows great potential for mass production and practical application of drug-loaded dissolving MNs in the future.

In recent years, deep learning has become the mainstream development direction in the change-detection field, and its accuracy and speed have also reached a high level. However, the change-detection method based on deep learning cannot predict all the change areas accurately, and its application is limited due to local prediction defects. For this reason, we propose an interactive change-detection network (ICD) for very high resolution (VHR) based on a deep convolution neural network. The network integrates positive- and negative-click information in the distance layer of the change-detection network, and users can correct the prediction defects by adding clicks. We carried out experiments on the open source dataset WHU and LEVIR-CD. By adding clicks, their F1-scores can reach 0.920 and 0.912, respectively, which are 4.3% and 4.2% higher than the original network. To better evaluate the correction ability of clicks, we propose a set of evaluation indices—click-correction ranges, which is suitable for evaluating clicks, and we carry out experiments on the above models. The results show that the method of adding clicks can effectively correct the prediction defects and improve the result accuracy.

Abstract Background HIV-associated neurocognitive disorders (HANDs) afflict more than half of HIV-1-positive individuals. The transactivator of transcription (Tat) produced by HIV virus elicits inflammatory process and is a major neurotoxic mediator that induce neuron damage during HAND pathogenesis. Activated astrocytes are important cells involved in neuroinflammation and neuronal damage. Purinergic receptors expressed in astrocytes participate in a positive feedback loop in virus-induced neurotoxicity. Here, we investigated that whether P2Y4R, a P2Y receptor subtype, that expressed in astrocyte participates in Tat-induced neuronal death in vitro and in vivo. Methods Soluble Tat protein was performed to determine the expression of P2Y4R and proinflammatory cytokines in astrocytes using siRNA technique via real-time PCR, Western blot, and immunofluorescence assays. Cytometric bead array was used to measure proinflammatory cytokine release. The TUNEL staining and MTT cell viability assay were analyzed for HT22 cell apoptosis and viability, and the ApopTag® peroxidase in situ apoptosis detection kit and cresyl violet staining for apoptosis and death of hippocampal neuron in vivo. Results We found that Tat challenge increased the expression of P2Y4R in astrocytes. P2Y4R signaling in astrocytes was involved in Tat-induced inflammatory cytokine production via PI3K/Akt- and ERK1/2-dependent pathways. Knockdown of P2Y4R expression significantly reduced inflammatory cytokine production and relieved Tat-mediated neuronal apoptosis in vitro. Furthermore, in vivo challenged with Tat, P2Y4R knockdown mice showed decreased inflammation and neuronal damage, especially in hippocampal CA1 region. Conclusions Our data provide novel insights into astrocyte-mediated neuron damage during HIV-1 infection and suggest a potential therapeutic target for HANDs.

In crop fields, resistance to acetolactate synthase (ALS)-inhibiting herbicides found in many troublesome weed species, including Bromus japonicus Thunb, is a worldwide problem. In particular, the development of herbicide resistance in B. japonicus is a severe threat to wheat production in China. The purpose of this research was to investigate the physiological and molecular basis of B. japonicus resistance to flucarbazone-sodium. Dose-response analysis demonstrated that, compared with the susceptible B. japonicus (S) population, the resistant (R) population exhibited a 120-fold increase in flucarbazone-sodium resistance. Nucleotide sequence alignment of the ALS gene indicated that the Pro-197-Ser mutation in ALS was associated with resistance to flucarbazone-sodium in the R population. The results of a malathion pretreatment study showed that B. japonicus might also have remarkable cytochrome P450 monooxygenase (P450)-mediated metabolic resistance. This is the first report of a Pro-197-Ser mutation and P450-mediated metabolism conferring resistance to flucarbazone-sodium in B. japonicus.

The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori, which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori-associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non-H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC.

The functions of non-coding RNA, including microRNA (miRNA), have attracted considerable attention in the field of oncology, In this report, we examined the roles and molecular mechanisms of miR-128-3p, as related to the biological behaviors of malignant melanoma (MM). We found that miR-128-3p was expressed in low levels in these MM cells and may serve as a tumor suppressor by inhibiting proliferation, migration, and invasion, as well as inducing apoptosis in these MM cells. Moreover, neurotrophin receptor 3 (NTRK3), which serves as an oncogene that can enhance malignant behaviors of MM cells, was up-regulated in MM cells. Our current survey disclosed a complementary binding between miR-128-3p and the NTRK3 3′ untranslated regions (3′-UTR), while luciferase activities of NTRK3 3′-UTR were restrained by miR-128-3p in 293T cells. The effects of pre-miR-128-3p and sh-NTRK3 as well as anti-miR-128-3p and NTRK3(+) appeared to function synergistically in producing malignant progression. Moreover, there were possible to have counteracted effects for pre-miR-128-3p and NTRK3(+) in malignant progression. These findings established that miR-128-3p can function as a tumor suppressor by inhibiting carcinogenesis of the oncogene, NTRK3. Collectively, miR-128-3p and NTRK3 genes participate in modulating the malignant behavior of MM, and may represent new therapeutic targets for MM.

Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis.

OBJECTIVES: Anemia and changes in platelets (PLT) are common in inflammatory bowel disease (IBD). In our study, we aimed to verify whether PLT count can independently reflect the severity of IBD. METHODS: In our hospital, 137 Crohn’s Disease (CD), 69 Ulcerative colitis (UC) patients, and 412 healthy controls were included to compare the differences in PLT count. In addition, the effect of anemia, C-reactive protein (CRP), age, CD activity index (CDAI) or Mayo on PLTs was also analyzed. If PLTs independently affected CD or UC, we used the receiver operating characteristic (ROC) curve to verify the diagnostic value and obtain the cut-off value of PLT. RESULTS: CD and UC patients had higher PLT than controls (p

In Traditional Chinese Medicine (TCM), the prescription Baihe - Zhimu Tang has been using to treat depression for hundreds of years. However, its underlying mechanism is still unclear. Saponin compounds extracted from TCM have been reported to exert antidepressant-like effect. In present study, we investigated the efficacy and mechanism of Saponin extract from Baihe - Zhimu Tang (SBZT) in treating depression. Results confirmed that SBZT can act as an anti-depressant agent in a murine model of depression-like abnormality. SBZT demonstrated significant efficacy in ameliorating depression-like behaviors and the abnormal levels of pathological markers associated with depression. While, based on microarray analysis, we found the mechanisms were related to its inhibition activity on hypothalamic-pituitaryadrenal axis hyperactivation, improvement ability in synthesis and transport processes of neurotransmitters and neuroprotection upon inflammation-related neuronal apoptosis. In conclusion, SBZT demonstrated significant efficacy in treating depression, suggesting its clinical potential as an anti-depressant TCM agent.

In intercity expressway traffic, the multiplicity of available routes leads to randomness in exit selection. Random exit selection by drivers is hard to observe, and thus it is a challenge to model intercity expressway traffic sufficiently. In this paper, we developed a Random Quantum Traffic Model (RQTM), which modeled the stochastic traffic fluctuation caused by random exit selection and the residual regularity fluctuation with the quantum walk and autoregressive moving average model (ARMA), respectively. The RQTM considered the random exit selection of a driver as a quantum stochastic process with a dynamic probability function. A quantum walk was applied to update the probability function, which simulated when and where a driver will leave the expressway. We validated our model with hourly traffic data from seven exits from the Nanjing–Changzhou expressway in eastern China. For the seven exits, the coefficients of determination of the RQTM ranged from 0.5 to 0.85. Compared with the classical random walk and the ARMA model, the coefficients of determination were increased by 21.28% to 104.98%, and the relative mean square error decreased by 11.61% to 32.92%. We conclude that the RQTM provides new potential for modeling traffic dynamics with consideration of unobservable random driver decision making.

Abstract Heightened experience of disgust is a feature of obsessive-compulsive disorder (OCD), particularly contamination-related OCD (C-OCD). Previous studies of the rubber hand illusion (RHI) reported that the sense of body ownership is related to the interaction between vision, touch, and proprioception. One recent study demonstrated a link between the RHI and disgust, suggesting that there is an interaction between these three perceptual modalities and disgust (Jalal et al., PLOS ONE 10:e0139159, 2015). However, there have been no direct replications of this initial study. We therefore performed a direct replication of Jalal et al.’s (PLOS ONE 10:e0139159, 2015) study. We examined 133 participants (based on a power analysis) to determine whether placing contamination-related stimuli on a rubber hand causes OCD-like disgust among healthy participants experiencing the RHI. That is, we tested whether Japanese participants experience more intense disgust when the rubber hand and the participant’s hidden hand are stroked synchronously than when stroked asynchronously, in order to replicate and examine the cross-cultural validity of this effect. The main finding of the original study by Jalal and colleagues was successfully replicated in a large sample. Some inconsistencies in one of the control procedures exploring coldness sensations during the RHI were found, which could possibly be due to cross-cultural differences or the improved statistical power of the present study. Based on the present replication study, we conclude that an intervention using the RHI as proposed by Jalal et al. (PLOS ONE 10:e0139159, 2015) might potentially be useful for the treatment of OCD following replications in clinical OCD populations. Preregistration details: This study was preregistered with Cognitive Research: Principles and Implications. The Authors’ protocol received in-principle acceptance on 31 March 2017. The preregistered protocol is available here: https://doi.org/10.6084/m9.figshare.6217295.

Promoting the ability of anti-bursting of the confining rock of a coal roadway is of significant importance to the safe production of a coal mine. In particular, in deep-buried coal mines, highly frequent rock burst occurs due to large earth pressure and complex geological conditions, which needs serious improvement. This paper investigated a type of confining rock modified method, which can modify the physical properties of the surrounding rock and form a crack region and a reinforced region by blasting and grouting reinforcement. Based on a set of physical model experiments and numerical modeling, the results of a comparative analysis between a normal roadway and the modified roadway in the static stress redistribution, dynamic stress, damage evolution, and energy dissipation suggest that the modified confining rock is capable of protecting the coal roadway against rock burst from roof stratum, obviously reducing and transferring the concentered static–dynamic stress out of the cracked region, dissipating the dynamic energy by plastic damage in the cracked region, and keeping the integrity of the reinforced region. In addition, the velocity of the dynamic stress vibration wave at the surface of the modified coal roadway is obviously reduced, which is beneficial for decreasing the movement of cracked rock blocks and protecting the lives and goods in the coal roadway.

In order to prevent the multi-dynamic disasters induced by rock burst and roof water inrush in strong rock burst coal seams under multi-aquifers, such as is the case with the 207 working face in the Tingnan coal mine considered in this study, the exhibited characteristics of two types of dynamic disasters, namely rock burst and water inrush, were analyzed. Based on the lithology and predicted caving height of the roof, the contradiction between rock burst and water inrush was analyzed. In light of these analyses, an integrated method, roof pre-splitting at a high position and shattering at a low position, was proposed. According to the results of numerical modelling, pre-crack blasting at higher rock layers enables a cantilever roof cave in time, thereby reducing the risk of rock burst, and pre-crack blasting at underlying rock layers helps increase the crushing degree of the rock, which is beneficial for decreasing the caving height of rock layers above goaf, thereby preventing the occurrence of water inrush. Finally, the proposed method was applied in an engineering case, and the effectiveness of this method for prevention and control of multi-dynamics disasters was evaluated by field observations of the caving height of rock layers and micro-seismic monitoring. As a result, the proposed method works well integrally to prevent and control rock burst and water inrush.