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Organic acids are a key active component of Pinellia ternata (Thunb.) Breit, and their concentration is closely associated with the quality of P. ternata. Developing an efficient and rapid method for detecting organic acids can offer a valuable technology for real-time assessment of P. ternata quality. In this work, a high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QqQ-MS/MS) approach, combining the optimization of extraction conditions using response surface methodology (RSM), was developed for the simultaneous quantitative analysis of six organic acids in P. ternata. The optimal extraction conditions for organic acids in P. ternata were ultrasonic extraction with a solid–liquid ratio of 1:50, ultrasonic time of 60 min, and extraction temperature of 55 °C. Multiple-reaction monitoring (MRM) scanning was employed for quantification using HPLC-QqQ-MS/MS in negative ionization mode through a single run of 10 min, and the limit of detection (LLOD) and limit of quantification (LLOQ) for organic acids were as low as 0.138 ng/mL and 0.614 ng/mL, respectively. The relative standard deviations (RSDs) of reproducibility, precision, and stability were all lower than 5.0%, and recovery rates were 97.75–107.14%, with RSDs < 5.0%. Finally, this method was successfully applied to determine the investigated organic acids in 12 production regions of P. ternata, revealing significant differences between different production areas. This indicates that the optimized method is suitable for further accurate investigations of organic acids of P. ternata.

In order to further explore the forming limits of thin-wall tube necking and thickening, and obtain sufficient thickness of the tube in the thickening area, local electric pulse-assisted forming experiments were carried out to study the effects of current intensity and feed speed on the necking and thickening forming of thin-wall tube. The experimental results show that with the increase in current intensity, the temperature in the forming area of the tube increases, and the forming load for necking and thickening decreases. However, with the increase in feed speed, the overall forming load for necking and thickening increases in general, and the smaller feed speed is more conducive to forming. Taking into account the forming efficiency and electrode loss, the corresponding forming process window is obtained for the manufacturing of good parts. That is, during the necking stage, the current intensity shall not be less than 300 A, and the feed speed shall not exceed 10 mm/min. During the thickening stage, the current intensity should not be less than 1400 A, and the feed speed should not exceed 1 mm/min. The target part is finally formed, with an average wall thickness of 5.984 mm in the thickening zone and a thickening rate of 303.2%.

The safety, inclusivity, accessibility, and green communities emphasized in the United Nations’ Sustainable Development Goals (SDGs) play a vital role in the establishment of child-friendly cities. The governments are actively promoting the development of sustainable, child-friendly cities that prioritize people’s needs and aim to enhance the well-being of residents, from children to families. However, there is limited research utilizing GIS analysis techniques and internet big data to analyze spatial equity in children’s spatial accessibility. Therefore, this study introduces an innovative approach focusing on the community level. Drawing on data from the popular social networking platform mobile application “Xiaohongshu” and employing network analysis methods based on walking and driving modes, this study analyzed and investigated the accessibility of children’s spaces in the city of Hangzhou, China. Regarding spatial characteristics, the distribution of children’s space resources in the main urban area of Hangzhou exhibited a “peripheral low and central high” trend, which was closely linked to the distribution of population space. This pattern indicates potential significant disparities in the allocation of children’s space resources. Notably, the core area of Hangzhou demonstrated the highest level of accessibility to children’s spaces, with Gongshu District exhibiting the best accessibility. Conversely, non-core urban areas generally had relatively poor accessibility. Furthermore, different types of children’s spaces, such as indoor cultural spaces, indoor entertainment spaces, outdoor parks, and outdoor nature areas, all exhibited the highest accessibility in the city center, which gradually decreased towards the periphery. Additionally, this study evaluated the convenience of children’s spaces in various communities by combining population size and accessibility levels. The findings revealed that communities in the core area had higher accessibility levels in the northwest–southeast direction, while accessibility decreased towards the northeast–southwest direction. Consequently, the relative convenience of these communities tended to be lower. By examining spatial equity, this study provides valuable insights into the promotion of sustainable, child-friendly cities that prioritize people’s needs and contribute to the well-being of residents, from children to families.

Spatiotemporal variation in rainfall erosivity resulting from changes in rainfall characteristics due to climate change has implications for soil erosion in developing countries. To promote soil and water conservation planning, it is essential to understand past and future changes in rainfall erosivity and their implications on a national scale. In this study, we present an approach that uses a Bayesian model averaging (BMA) method to merge multiple regional climate models (RCMs), thereby improving the reliability of climate-induced rainfall erosivity projections. Our multi-climate model and multi-emission scenario approach utilize five RCMs and two Representative Concentration Pathways (RCP4.5 and RCP8.5) scenarios for the baseline period (1986–2005) and future periods (2071–2090) to characterize the spatiotemporal projection of rainfall erosivity and assess variations in China. Our results indicate that the two models outperform other models in reproducing the spatial distribution and annual cycle of rainfall erosivity in China. Moreover, we found an increasing trend in the annual rainfall erosivity from the baseline climate up to the RCMs for all models, with an average change in erosivity of approximately 10.9% and 14.6% under RCP4.5 and RCP8.5, respectively. Our BMA results showed an increase in the absolute value of rainfall erosivity by 463.3 and 677.0 MJ·mm·hm ^−2 ·h ^−1 , respectively, in the South China red soil region and the Southwest China karst region under the RCP8.5 scenario. This increase indicates that climate warming will significantly enhance the potential erosion capacity of rainfall in these regions. Additionally, our study revealed that the Southwest China karst region and the Northwest China Loess Plateau region are more sensitive to radiation forcing. To mitigate the risk of soil erosion caused by climate change, it is necessary to consider changes in rainfall erosivity, local soil conditions, vegetation coverage, and other factors in different regions and take appropriate soil and water conservation measures.

High‐performance beam‐steering devices play a crucial role for optical wireless communication (OWC), which can meet the demand for increasing number of wireless mobile devices and emerging high‐speed multimedia applications. Conventional beam‐steering optical components like spatial light modulator and digital micromirror device are limited to realize a small steering angle (typ. several degrees), thus dramatically limits the spatial scope of OWC. Herein, a beam‐steering metadevice utilizing an ultracompact metasurface assisted with a spatial light modulator is presented, which can significantly increase the beam‐steering angle without at the cost of complicated optical setup like conventionally used angle magnifier. Based on the actively tunable beam‐steering metadevice, an intelligent bidirectional optical broadcasting communication system is designed and experimentally demonstrated, which exhibits nine broadcasting areas covering a large field‐of‐view of 20° × 20°, with user‐defined dynamic beam‐steering ability in each area, and each user has a data rate of 10 Gbps for both upstream and downstream transmission. The proposed metadevices can meet the demand of intelligent optical wireless communication which requires both high‐performance and low‐cost for practical purpose, under currently available technical architectures.

Background2’,5’-oligoadenylate synthetase 1 (OAS1), has been reported as a tumor driver gene in breast carcinoma and pancreatic carcinoma. However, the role of OAS1 in most tumors has not been reported.MethodsThe original data of 35 tumor types were down load from the TCGA (The Cancer Genome Atlas) database and Human Protein Atlas (HPA) database. TIMER2, Kmplot, UALCAN, and TISIDB tools were used to investigate the expression and function of OAS1, and the role of OAS1 in prognosis, diagnostic value, and immune characteristics of pan-cancer. LUAD and PRAD cell lines, A549, H1975, PC-3 and C4-2 were utilized to perform cell function tests.ResultsOAS1 expression was up-regulated in 12 tumor types and down-regulated in 2 tumor types. High OAS1 expression was correlated with poor prognosis in 6 tumor types, while high OAS1 expression was correlated with good prognosis in 2 tumor types. OAS1 was correlated with molecular subtypes in 8 tumor types and immune subtypes in 12 tumor types. OAS1 was positively associated with the expression of numerous immune checkpoint genes and tumor mutational burden (TMB). OAS1 had potential diagnostic value in 15 tumor types. Silence of OAS1 significantly inhibited the cell proliferation ability, and promoted G2/M cell cycle arrest of LUAD and PRAD cells. Meanwhile, silence of OAS1 enhanced cisplatin-induced apoptosis of LUAD and PRAD cells, but weakened cell migration.ConclusionThis pan-cancer study suggests that OAS1can be used as a molecular biomarker for prognosis in pan-cancer and may play an important role in tumor immune response.

The deployment of disease resistance genes is currently the most economical and environmentally sustainable method of crop protection. However, disease resistance genes can rapidly break down because of constant pathogen evolution, particularly when they are deployed singularly. Polygenic resistance is, therefore, considered the most durable, but combining and maintaining these genes by breeding is a laborious process as effective genes are usually unlinked. The deployment of polygenic resistance with single-locus inheritance is a promising innovation that overcomes these difficulties while enhancing resistance durability. Because of major advances in genomic technologies, increasing numbers of plant resistance genes have been cloned, enabling the development of resistance transgene stacks (RTGSs) that encode multiple genes all located at a single genetic locus. Gene stacks encoding five stem rust resistance genes have now been developed in transgenic wheat and offer both breeding simplicity and potential resistance durability. The development of similar genomic resources in phytopathogens has advanced effector gene isolation and, in some instances, enabled functional validation of individual resistance genes in RTGS. Here, the wheat stem rust pathosystem is used as an illustrative example of how host and pathogen genomic advances have been instrumental in the development of RTGS, which is a strategy applicable to many other agricultural crop species.

Abstract Turbulent dissipation rate (ɛ) is a crucial parameter in turbulence theory, and an essential component of higher‐order planetary boundary layer schemes for numerical weather prediction and climate models. It is most often modeled diagnostically based on the dissipation scaling ɛ ∝ e3/2/L, where e and L are the turbulence kinetic energy (TKE) and the size of the largest turbulent eddies, respectively. Utilizing three‐month‐long vertically‐extended observations accompanied by high resolution large‐eddy simulations, scaling‐based ɛ‐models are evaluated, focusing on their stability dependence under daytime convective conditions. The analysis uncovers biases in the parameterized ɛ profiles that cannot be corrected through tuning of model constants. The biases are attributed to the limited and even opposing stability dependence of the modeled dissipation length. Close examination reveals violation of the dissipation scaling by the inclusion of TKE associated with organized convection. A self‐similar dissipation length is obtained when only the isotropic component of TKE is considered.

Abstract A comprehensive comparison of the trends and drivers of global surface and canopy urban heat islands (termed Is and Ic trends, respectively) is critical for better designing urban heat mitigation strategies. However, such a global comparison remains largely absent. Using spatially continuous land surface temperatures and surface air temperatures (2003–2020), here we find that the magnitude of the global mean Is trend (0.19 ± 0.006°C/decade, mean ± SE) for 5,643 cities worldwide is nearly six‐times the corresponding Ic trend (0.03 ± 0.002°C/decade) during the day, while the former (0.06 ± 0.004°C/decade) is double the latter (0.03 ± 0.002°C/decade) at night. Variable importance scores indicate that global daytime Is trend is slightly more controlled by surface property, while background climate plays a more dominant role in regulating global daytime Ic trend. At night, both global Is and Ic trends are mainly controlled by background climate.

Introduction:Plectropomus leopardus, a commercially significant marine fish, is primarily found in the Western Pacific regions and along the coast of Southeast Asia. A thorough analysis of the molecular mechanisms involved in sex differentiation is crucial for gaining a comprehensive understanding of gonadal development and improving sex control breeding. However, the relevant fundamental studies of P. leopardus are relatively lacking.Methods: In this study, a genome-wide association study (GWAS) was conducted to investigate the genetic basis mechanism of sex differentiation and gonadal developmental traits in P. leopardus utilizing about 6,850,000 high-quality single-nucleotide polymorphisms (SNPs) derived from 168 individuals (including 126 females and 42 males) by the genome-wide efficient mixed-model association (GEMMA) algorithm.Results: The results of these single-trait GWASs showed that 46 SNP loci (-log10p > 7) significantly associated with sex differentiation, and gonadal development traits were distributed in multiple different chromosomes, which suggested the analyzed traits were all complex traits under multi-locus control. A total of 1,838 potential candidate genes were obtained by considering a less-stringent threshold (-log10p > 6) and ±100 kb regions surrounding the significant genomic loci. Moreover, 31 candidate genes were identified through a comprehensive analysis of significant GWAS peaks, gene ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, including taf7, ddx6, apoeb, sgk1, a2m, usf1, hsd3b7, dll4, xbp1, tet3, esr1, and gli3. These trait-associated genes have been shown to be involved in germline development, male sex differentiation, gonad morphogenesis, hormone receptor binding, oocyte development, male gonad development, steroidogenesis, estrogen-synthetic pathway, etc.Discussion: In the present study, multiple genomic loci of P. leopardus associated with sex differentiation and gonadal development traits were identified for the first time by using GWAS, providing a valuable resource for further research on the molecular genetic mechanism and sex control in P. leopardus. Our results also can contribute to understanding the genetic basis of the sex differentiation mechanism and gonadal development process in grouper fish.

Summary: The master transcriptional regulator PU.1/Spi-1 engages DNA sites with affinities spanning multiple orders of magnitude. To elucidate this remarkable plasticity, we have characterized 22 high-resolution co-crystallographic PU.1/DNA complexes across the addressable affinity range in myeloid gene transactivation. Over a purine-rich core (such as 5ʹ-GGAA-3ʹ) flanked by variable sequences, affinity is negotiated by direct readout on the 5ʹ flank via a critical glutamine (Q226) sidechain and by indirect readout on the 3ʹ flank by sequence-dependent helical flexibility. Direct readout by Q226 dynamically specifies PU.1’s characteristic preference for purines and explains the pathogenic mutation Q226E in Waldenström macroglobulinemia. The structures also reveal how disruption of Q226 mediates strand-specific inhibition by DNA methylation and the recognition of non-canonical sites, including the authentic binding sequence at the CD11b promoter. A re-synthesis of phylogenetic and structural data on the ETS family, considering the centrality of Q226 in PU.1, unifies the model of DNA selection by ETS proteins.

Traditionally, the quality grading of distilled Chinese Baijiu is achieved by artificial sensory evaluation along with gas chromatography. The subjective problems, such as poor timeliness and accuracy of grading, become the bottleneck of industry to improve product quality and efficiency. Actually, the quality of Xiaoqu Baijiu is determined by the synergistic effect of all flavoring substances rather than the specific targeted molecules in Baijiu. In this study, the electrochemical measurements were used to characterize the synergistic effect of flavoring substances in-situ, which also served as an untargeted detection for grading of Baijiu. After the abundant characteristic signals of standard samples whose grades have been confirmed via many winetasters were collected, the corresponding relationship between Baijiu grades and electrochemistry signal was received by the index of multi-parameters. Then, the electrochemical recognition model of Baijiu grades was established via mathematical statistics from above characteristic signals of standard samples. Once the testing data of unknow Baijiu were imported to the recognition model, the Baijiu grade value can be obtained quickly and online from the contrast algorithm, and the average accuracy rate of is more than 80%.

The Danxiashan UNESCO Global Geopark (Danxiashan UGGp) is located in Shaoguan, northern Guangdong Province of South China, and was approved as such by the Global Geoparks Network in 2004. It is an ideal site for geodiversity and geoheritage studies as well as a centre for geoeducation owing to its importance in understanding the geodynamics of South China during late Mesozoic and being the most representative danxia landscape (a red beds landscape characterized by well-developed cliffs and developed dominantly on hard conglomerates and sandstones) in the humid subtropical climate of China. The methods of field investigation and literature reviews were applied to document geodiversity characterization of the Danxiashan. The study area is characterized predominately by well-developed Late Cretaceous red beds deposited in alluvial fan and desert environments within a faulted continental basin. The red beds were uplifted during the Himalayan orogenic cycle (ca. 40 Ma to present) and dissected by faulting and jointing to form prominent escarpments and a variety of erosional landforms in tandem with weathering, water erosion and rockfalls. The danxia landscape of Danxiashan is composed of mesas, peaks, cliffs, canyons, rock walls and pillars with dominant bedrock of reddish conglomerates and sandstones. It is designated as the World Heritage ‘China Danxia’ with other five sites in South China owing to its exceptionally beautiful and distinctive landscape as well as diversified geological features and landforms. As one of the earliest and best developed geoparks in China, an assessment and summary of the geodiversity of Danxiashan sets a practical example in formulating long-term strategies in geotourism and geoeducation for geopark development in China and other countries.

The objective of this paper is to explore the characteristics of Mycoplasma pneumoniae (MP) epidemics in Beijing, China. Patients with acute respiratory tract infection (ARTI) were enrolled from 35 sentinel hospitals in Beijing, 2015–2020. Their medical records were reviewed and respiratory specimens were collected for assay for nucleic acids of 24 respiratory pathogens, including MP. The genotypes of MP were analysed using a real-time PCR method. The domain V of 23s rRNA gene was sequenced to identify macrolide-resistant mutations. A total of 41,677 specimens of ARTI patients were included, with an MP positive rate of 6.16%. MP prevalence mainly occurred between August and January, and peaked in October. The increase in the MP detection rate was coincident with the elevation of the reported number of patients with pneumonia in the 35 sentinel hospitals. One or more respiratory pathogens were co-detected in 27.1% of the MP-positive patients. Type 1 MP remained predominant, and the macrolide-resistant rate of MP had exceeded over 90%. A2063G mutation accounted for 99.0% of macrolide-resistant MP infections. MP epidemic in Beijing mainly occurred between August and January with a remarkable high macrolide-resistant rate. MP is one of the important contributors to the pneumonia epidemic in autumn and winter in Beijing.

Abstract Heatwaves detrimentally affect human health and ecosystems. While previous studies focused on either temporal changes or spatial extents of heatwaves, their spatiotemporal contiguity and propagation patterns are unclear. Here, we investigate the climatology, long-term trends, and interannual variations of spatiotemporally contiguous heatwaves across China during 1961 to 2018. Two distinct propagation patterns are identified by introducing a spatiotemporally contiguous events tracking (SCET) method and the k-means clustering. Type 1 contiguous heatwaves mostly generate over eastern China and move southwestward at shorter distances, while Type 2 heatwaves generally initiate over western China and move southeastward at longer distances, with stronger intensity, longer lifetime, and larger coverage. Since the 1960s, both types exhibit significant increases in frequency, intensity, coverage, lifetime, and traveling distances, with relatively larger magnitudes for Type 2, but significant decreases in moving speed only appear for Type 1. On interannual timescale, preceding winter El Niño prolongs the duration and slows down the moving speed of Type 1 through the western North Pacific subtropical high. Type 2 contiguous heatwaves are intensified by the negative spring North Atlantic Oscillation via the upper-atmospheric Rossby wave train.

Abstract The study objective was to observe the treatment effect of the farnesoid X receptor (FXR) agonist GW4064 in a rat model of hilar cholangiocarcinoma to explore a new therapeutic target for gene therapy for hilar cholangiocarcinoma. Eighty male Wistar rats were randomly divided into four groups (treatment group, model group, control group and sham operation group, 20 rats in each group). The four groups were fed a standard diet. The treatment group and the model group were injected with a suspension of cholangiocarcinoma QBC939 cells into the hilar bile duct with a microsyringe, the control group was injected with normal saline, and the sham operation group was not injected with anything. A modified tail suspension test (TST) was used to evaluate the vitality of the rats. At 4 weeks, one rat in the treatment group and model group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma occurred in the treatment group and model group. Then, the treatment group was injected with GW4064 intraperitoneally at a dose of 50 mg/kg/day. One week after injection, the rats in the four groups were euthanized. Pathological examination confirmed that tumours had formed, and hilar bile duct tissues were taken from the four groups. FXR, Bsep, Ntcp and NF-κB expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT–PCR) and immunohistochemistry. After three weeks, the rats in the treatment group and model group ate less, and their weight was significantly reduced. Six weeks later, hilar cholangiocarcinoma was detected in the treatment group and model group. After treatment with GW4064, the ratios of FXR/GAPDH mRNA, Bsep/GAPDH mRNA, Ntcp/GAPDH mRNA and NF-κBp65/GAPDH mRNA were significantly different among the four groups. Under a light microscope, FXR protein reacted with anti-FXR antibody, Bsep protein reacted with anti-Bsep antibody, Ntcp protein reacted with anti-Ntcp antibody and NF-κBp65 protein reacted with anti-NF-κBp65 antibody, and they showed granular expression. Every pathological section included 4,800 cells, and there were different numbers of positive cells in each group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues. GW4064 increased the expression of FXR in tumour tissues. These findings suggest that FXR may be a new therapeutic target and that GW4064 may be helpful in the treatment of hilar cholangiocarcinoma.

The optical transmission system based on all-band is considered to be one of the methods to effectively improve the transmission capacity of optical communication. In addition of the C and L bands, the using of other bands for transmission can fully tap the transmission potential of the existing optical fiber network and solve the bottleneck problem of large capacity communication network. The realization of its key technologies and systems is conducive to promoting the industrialization process of related technologies, which has broad economic benefits. This paper analyzes and discusses the current research status of multi-band optical transmission technology. And then as the focus, the performance difference of S、C and L band is studied by experiments. Based on the devices designed for C and L bands, the experiment of 40 km transmission system covering on S、C and L band is completed by using Polarization Division Multiplexed 16 Quadrature Amplitude Modulation (PDM-16QAM) modulation format, and the transmission capacity can reach 122.4 Tbit/s. The multi-band transmission capability of G. 652.D optical fiber is verified, which provicles an experimental basis for further research on multi-band optical transmission technology.

Zhou and Si et al. used cryogenic electron microscopy and tomography to delineate the molecular interactions among genomic RNA, nucleocapsid protein, matrix protein and glycoprotein in vesicular stomatitis virus and suggest a model of assembly.

Abstract Background We summarize 5 cases of primary gliosarcoma with widespread extracranial metastases including our case. The glial components are eliminated due to the needs of the living environment in the process of parasitism and survival of brain glioma-sarcoma cells in lung metastasis. Methods A PubMed search using the keywords “gliosarcoma” and “extracranial metastases” was performed followed by a review of cited literature. Our case was a 50-year-old female presented with headache and dizziness. MRI examination showed that there was a cystic solid tumor in the right temporal lobe. The tumor was removed totally. Seven months after the operation, the patient suffered recurrent intermittent headache. The resection for the recurrent tumor was performed. Postoperative pathology confirmed the recurrent gliosarcoma. A needle biopsy was performed for the nodular on the right lung. The lung tumor pathology suggested a sarcoma structure. Results There was a female patient in five cases. The age range is 47 to 69 years old. The tumor recurred within a year. A combination of treatment modalities may extend survival; however, the prognosis remains poor. Conclusion Primary gliosarcoma with extracranial metastases is extremely rare. Some findings uncovered an unexpected spatiotemporal morphological variation in the different foci of the same malignancy.

Abstract The Yinggehai Basin (YGH) in the South China Sea is a Cenozoic, high‐temperature, and high‐pressure basin. Exploration and development of natural gas resources in the YGH show that owing to the diapir structures make the formation pressure system is complex, overpressure characteristics are obvious, prediction is difficult, and spatial distribution is irregular, which severely restricts the development of natural gas. To evaluate the influence of diapir structures on the formation and distribution of overpressure, we compared and analyzed the ancient and modern geothermal temperatures, organic matter maturity, clay mineral evolution, burial depth, and pressure coefficient in the diapir and nondiapir zones of the YGH. The results showed that of the diapir structures in the YGH occurred in the following order: Uplift–spiking–piercing–depositing. The Dongfang area is dominated by low‐amplitude turtle‐back diapir structures with weak energy, whereas the Ledong area is dominated by high‐amplitude spiked diapir structures with strong energy, both of which pressurize the upper formation. The Changnan area is dominated by high‐amplitude pierced/depositing diapirs with strong energy, which can relieve pressure. The influence of the diapir and its associated structures on the formation of overpressure can be attributed to the transport of the diapir body and the associated fault‐fracture system and the local thermal effect caused by the upwelling of hot fluids. Under the influence of the diapir structure, the overpressure top surface of the basin was shallower. According to the degree of influence and intensity of the diapir structure, variations in formation pressure coefficient with depth can be divided into four evolution modes: constant pressure, slow pressurization, “Z” pressurization, and “S” pressurization types. This study provides some guidance and references for the identification and accurate prediction of the overpressure formation mechanism in basins containing diapirs, and helps in formulating efficient drilling and production plans.

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host’s inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.

IntroductionGenome-based analysis is crucial in monitoring antibiotic-resistant bacteria (ARB)and antibiotic-resistance genes (ARGs). Short-read sequencing is typically used to obtain incomplete draft genomes, while long-read sequencing can obtain genomes of multidrug resistance (MDR) plasmids and track the transmission of plasmid-borne antimicrobial resistance genes in bacteria. However, long-read sequencing suffers from low-accuracy base calling, and short-read sequencing is often required to improve genome accuracy. This increases costs and turnaround time.MethodsIn this study, a novel ONT sequencing method is described, which uses the latest ONT chemistry with improved accuracy to assemble genomes of MDR strains and plasmids from long-read sequencing data only. Three strains of Salmonella carrying MDR plasmids were sequenced using the ONT SQK-LSK114 kit with flow cell R10.4.1, and de novo genome assembly was performed with average read accuracy (Q > 10) of 98.9%.Results and DiscussionFor a 5-Mb-long bacterial genome, finished genome sequences with accuracy of >99.99% could be obtained at 75× sequencing coverage depth using Flye and Medaka software. Thus, this new ONT method greatly improves base-calling accuracy, allowing for the de novo assembly of high-quality finished bacterial or plasmid genomes without the need for short-read sequencing. This saves both money and time and supports the application of ONT data in critical genome-based epidemiological analyses. The novel ONT approach described in this study can take the place of traditional combination genome assembly based on short- and long-read sequencing, enabling pangenomic analyses based on high-quality complete bacterial and plasmid genomes to monitor the spread of antibiotic-resistant bacteria and antibiotic resistance genes.

Shiga toxin-producing Escherichia coli (STEC) is a foodborne zoonotic pathogen that causes diarrhea, hemorrhagic colitis (HC), and hemolytic uremic syndrome (HUS) worldwide. Since the infection can be asymptomatic, the circulation of STEC in some asymptomatic carriers, especially in healthy-food-related professionals, is not yet well understood. In this study, a total of 3987 anal swab samples from asymptomatic food handlers were collected, and ten swabs recovered STEC strains (0.251%). Of the ten STEC isolates, seven serotypes and eight sequence types (ST) were determined using whole genome sequencing (WGS). Two stx1 subtypes (stx1a and stx1c) and four stx2 subtypes (stx2a, stx2b, stx2d, and stx2e) were detected. Seven different insertion sites were found in fourteen Stx prophages, and the dmsB and yfhL were the newly identified insertion sites. The ten strains showed the variable Stx transcription levels after the mitomycin C induction. The whole-genome phylogeny indicated that the strains from the asymptomatic food handlers were genetically distant from the strains of HUS patients. The STEC isolates circulating in asymptomatic carriers might pose a low potential to cause disease.

The nonlinear Volterra equalizer has been proved to be able to solve the problem of nonlinear distortion, but it has high computational complexity and is difficult to implement. In this paper, a simplified second-order Volterra nonlinear equalizer designed for intensity modulation/direct detection systems based on direct modulated laser is proposed and demonstrated, taking into account the characteristics of the system. It has been proved that the received signal of direct modulation laser/direct detection system can be expressed in Volterra series form, but its form is too complex, and the device parameters should also be considered. We re-derived it and obtained a more concise form. At the same time, we proposed a method to simplify the second-order Volterra nonlinear equalizer without relying on device parameters. The performance of the proposed Volterra nonlinear equalizer is evaluated experimentally on a 56 Gb/s 4-ary pulse amplitude modulation link implemented by using a 1.55 µm direct modulation laser. The results show that, compared with the traditional Volterra nonlinear equalizer, the receiver sensitivity of the equalizer is only reduced by 0.2 dB at most, but the complexity can be reduced by 50%; compared with diagonally pruned Volterra nonlinear equalizers, the complexity of the equalizer is the same, but the reception sensitivity can be improved by 0.5 dB.

The source of oil and gas and the stages of oil and gas accumulation in the “double-Paleo” field of the HZ-A structure in the Pearl River Mouth Basin are analyzed, and the spatiotemporal coupling relationship of the key conditions of oil and gas accumulation are discussed to reconstruct the process of oil and gas accumulation. Based on previous research results, which are based the characteristics of biomarker compounds, the oil and gas in the HZ-A structure double Paleogene field came from the Paleogene Wenchang Formation hydrocarbon source rocks in the HZ26 sub-sag. By means of the casting thin section identification and inclusion homogenization temperature measurement, this paper reveals the three major hydrocarbon accumulation periods and corresponding fluid charging types in the “double-Paleo” field of the HZ-A structure in the Pearl River Mouth Basin. The results show that 13.8–10 Ma is the charging period of low mature crude oil, 10–5.3 Ma is the charging period of mature crude oil, and from 5.3 Ma is the natural gas charging period. Based on actual geological, drilling, logging, and seismic data, the key conditions for hydrocarbon accumulation in the HZ-A structure “double-Paleo” field are sorted out; that is, the source conditions are characterized by high-quality lacustrine source rocks generating early oil and late gas and a near-source continuous hydrocarbon supply. The reservoir conditions are characterized by weathering and superposition of a fracture zone that transforms into a reservoir, and a large-scale sandstone rock mass that transforms into a reservoir. The caprock conditions are characterized by the stacking of several thin mudstones that form a seal and the combination of multiple lithologies that block hydrocarbon migration. The trap conditions are characterized by multistage uplift structure traps and fracture-lithology combination control traps. The transport conditions are characterized by multi-stage cross-bed transport of source-connected faults and lateral differential transport of shallow sand in deep fractures. Finally, oil and gas accumulation models of the HZ-A structure double Paleogene field were established, and the accumulation process was reconstructed. The overall process involved three stages, with the first stage being the localized oil-displacing-water mode, the second being the large-scale oil-displacing-water mode, and the third being the late progressive gas-displacing-oil mode.

Potential geological disasters frequently occur in northwestern Yunnan. Landslide is the main type of geohazard. The identification of landslide in this area is an effective disaster prevention and mitigation measure. The traditional methods of identifying potential geological hazards are relatively single and rely on a large number of manpower and the investigation efficiency are not satisfactory. This paper processes the data from WordView2, Sentinel-1A, and ALOS-2 remote sensing satellite by using the Stacking-InSAR and other technologies, and a variety of optical satellite images and InSAR-processed surface deformation maps were obtained. Optical interpretation signs and InSAR identification signs had undergone multiple visual interpretations and manual interactive interpretations, and based on the interpretation and recognition results, the identification methods are summarized and field investigations were also carried out to verify the results. A total of 806 potential landslides and old landslides were identified, providing new survey ideas and technical references for the future investigation and evaluation of geological disasters in northwestern Yunnan.

Abstract Formation pressure is the most fundamental data in oil and gas drilling and production; it has an important position in the entire cycle of oil and gas extraction. However, most current prediction methods are limited to parametric methods with fixed models; such that the accuracy does not meet requirements. This is especially true for deeper layers of marine sedimentary basins where the safety density window is extremely narrow. In this study, we propose a novel method to predict pore pressure using machine learning techniques. For the first time, the effective stress (direct output variable) was accurately predicted by a combination of four input variables (2900 sets of data, of which 90% is the training subset and 10% is the testing subset), including longitudinal velocity, porosity, mud content, and density. As such, an accurate prediction of the formation pressure was achieved based on the effective stress theorem. The performance of machine learning techniques was verified by comparing and analyzing the prediction results with traditional parametric single and multivariate models; whereby the best algorithm was chosen by structural optimization and comparative analysis of five algorithms (multilayer perceptron neural network, radial basis neural network, support vector machine, random forest, and gradient boosting machine). Compared with the methods based on parametric one‐dimensional and multivariate models, the machine learning‐based method was determined to possess high accuracy, adequate self‐adaptation, and high fault tolerance (D2 = 0.9981, RMSE = 0.00718 g/cm3). Moreover, the multilayer perceptual neural network algorithm outperformed other machine learning algorithms in terms of goodness of fit, generalization, and prediction accuracy, with D2 = 0.9981 and RMSE = 0.00709 g/cm3. The formation pressure prediction model developed in this study is not affected by the mechanical depositional environment and is applicable to sandy mudstone formations, such that it can be a useful and highly accurate alternative to the traditional formation pressure prediction methods with fixed parameter forms.

Abstract The study objective was to detect the expression of farnesoid X receptor (FXR) in a rat model of hilar cholangiocarcinoma to provide a new therapeutic target for gene therapy in hilar cholangiocarcinoma. Sixty male Wistar rats (weighing 190 ± 8 g) were randomly divided into three groups (experimental group, control group and sham operation group, 20 rats in each group). The three groups were fed a standard diet. The QBC939 cell suspension of cholangiocarcinoma was injected into the hilar bile duct in the experimental group with a microsyringe. The control group was injected with normal saline, and the sham operation group was not injected with any drugs. A modified tail suspension test (TST) was used to evaluate the mental state and physical activity of rats every day. At 5 weeks, one rat in the experimental group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at one and half months. After one and half months, hilar cholangiocarcinoma only occurred in the experimental group. Pathological examination confirmed the formation of tumours, and hilar bile duct tissues were taken from the three groups. FXR expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT–PCR) and immunohistochemistry. After two weeks, the rats in the experimental group ate less, and their weight was significantly reduced. One and half months later, hilar cholangiocarcinoma was detected in 16 rats in the experimental group. The levels of alanine aminotransferase and aspartate transaminase in the experimental group were higher than those in the other two groups. The ratio of FXR/GAPDH mRNA was significantly different among the hilar cholangiocarcinoma, control and sham operation groups. Under the light microscope, FXR protein reacted with anti-FXR antibody and showed granular expression. Every pathological section included 4800 cells. A total of 1856 positive cells were in the experimental group, 3279 positive cells were in the control group, and 3371 positive cells were in the sham operation group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues, suggesting that drugs targeting FXR may be a new strategy for the treatment of hilar cholangiocarcinoma.

Abstract Artificial nanomotors are nanoscale machines capable of converting surrounding other energy into mechanical motion and thus entering the tissues and cells of organisms. They hold great potential to revolutionize the diagnosis and treatment of diseases by actively targeting the lesion location, though there are many new challenges that arise with decreasing the size to nanoscale. This review summarizes and comments on the state‐of‐the‐art artificial nanomotors with advantages and limitations. It starts with the fabrication methods, including common physical vapor deposition and colloidal chemistry methods, followed by the locomotion characterization and motion manipulation. Then, the in vitro and in vivo biomedical applications are introduced in detail. The challenges and future prospects are discussed at the end.

PurposeLong-term survival benefit of anthracyclines for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is clear. In the neoadjuvant treatment, compared with the monoclonal antibody such as trastuzumab and pertuzumab, the clinical benefit of pyrotinib, a new small-molecule tyrosine kinase inhibitor (TKI), as the main anti-HER2 strategy currently requires more research to determine. Our real-world study is the first prospective observational study in China to evaluate the efficacy and safety of epirubicin (E) and cyclophosphamide (C) with pyrotinib as anti-HER2 therapy in the neoadjuvant setting of patients with stage II-III HER2-positive breast cancer.MethodsFrom May 2019 to December 2021, 44 untreated patients with HER2-positive nonspecific invasive breast cancer who received 4 cycles of neoadjuvant EC with pyrotinib. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included the overall clinical response, breast pathological complete response rate (bpCR), the rate of axillary lymph nodes pathological negativity and adverse events (AEs). Other objective indicators were the rate of surgical breast-conserving, the negative conversion ratios of tumor markers.ResultsThirty-seven (84.1%) of 44 patients completed this neoadjuvant therapy, and 35 (79.5%) had surgery and were included in the primary endpoint assessment. The objective response rate (ORR) of 37 patients was 97.3%. Two patients reached clinical complete response, 34 obtained clinical partial response, 1 sustained stable disease, and no one had progressive disease. Eleven (31.4%) of 35 patients who had surgery achieved bpCR and the rate of axillary lymph nodes pathological negativity was 61.3%. The tpCR rate was 28.6% (95% CI: 12.8-44.3%). Safety was evaluated in all 44 patients. Thirty-nine (88.6%) had diarrhea, and 2 developed grade 3 diarrhea. Four (9.1%) patients had grade 4 leukopenia. All grade 3-4 AEs could be improved after symptomatic treatment.ConclusionThe regimen of 4 cycles of EC combined with pyrotinib presented some feasibility in the neoadjuvant setting for HER2-positive breast cancer with manageable safety. New regimens with pyrotinib should be evaluated for higher pCR in future.Trial registrationchictr.org Identifier: ChiCTR1900026061.

Abstract Background Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR). Methods The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods. Results We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP. Conclusions In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH. Graphical Abstract

Abstract Background Stomach adenocarcinoma (STAD) is the most common type of gastric cancer (GC), with a high recurrence rate and poor prognosis, but the potential indicators for STAD are insufficient. Methods Herein, we found that MicroRNA-378c (miR-378c) was lowly expressed in STAD, and the low expression of miR-378c was highly correlated with poor overall survival (OS), T stage, Reflux history, DSS events and PFI events of STAD patients. Results In addition, univariate analysis displayed that miR-378c was significantly associated with OS (Hazard ratio 0.735; 95% CI, 0.542–0.995; P = 0.046). Furthermore, it was validated that miR-378c inhibition accelerated STAD cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), while they were suppressed by miR-378c overexpression. Mechanistically, Neuropilin 1 (NRP1) was confirmed as the target of miR-378c, and Lnc-NORAD was identified as its sponger. More importantly, NORAD-mediated miR-378c inhibited malignant behaviors of STAD both in vitro and in vivo. Conclusions Collectively, these results suggest miR-378c as a promising indicator for the treatment of STAD.

Abstract Background The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma is a major factor that limits the benefits of immunotherapy, especially immune checkpoint blockade. One viable strategy for reverting the immunosuppressive conditions is the use of an oncolytic virus (OV) in combination with other immunotherapy approaches. Infection of PDAC cells with a robust OV can change the tumor microenvironment and increase tumor antigen release by its lytic activities. These changes in the tumor may improve responses to immunotherapy, including immune checkpoint blockade. However, a more potent OV may be required for efficiently infecting pancreatic tumors that may be resistant to OV. Methods Vesicular stomatitis virus, a rapid replicating OV, was armed to express the Smac protein during virus infection (VSV-S). Adaptation by limited dilution largely increased the selective infection of pancreatic cancer cells by VSV-S. The engineered OV was propagated to a large quantity and evaluated for their antitumor activities in an animal model. Results In a syngeneic KPC model, intratumoral injection of VSV-S inhibited tumor growth, and induced increasing tumor infiltration of neutrophils and elimination of myeloid derived suppressor cells and macrophages in the tumor. More importantly, M2-like macrophages were eliminated preferentially over those with an M1 phenotype. Reduced levels of arginase 1, TGF-β and IL-10 in the tumor also provided evidence for reversion of the immunosuppressive conditions by VSV-S infection. In several cases, tumors were completely cleared by VSV-S treatment, especially when combined with anti-PD-1 therapy. A long-term survival of 44% was achieved. Conclusions The improved OV, VSV-S, was shown to drastically alter the immune suppressive tumor microenvironment when intratumorally injected. Our results suggest that the combination of potent OV treatment with immune checkpoint blockade may be a promising strategy to treat pancreatic cancer more effectively.

The inter-data center links are meeting the challenge of increasing transmission capacity continuously. Here, the tradeoff between transmission capacity and cost and power consumption especially needs to be considered. The field modulation polarization-division-multiplexed (PDM) four-level pulse amplitude modulation (PAM4) with coherent detection is a potential candidate for 400 Gb/s and beyond inter-data center transmissions, which has several advantages including low-cost, low optical signal to noise ratio (OSNR) requirement and high receiver sensitivity. In this paper, the feasibility and effectiveness of the field PDM-PAM4 coherent system are investigated over multi core fiber (MCF). In order to adapt to the field PAM signals, the signal-phase aid least-mean square (SP-LMS) and training multi-modulus algorithm (TMMA) are modified and analyzed for equalization and polarization demultiplexing. Finally, it is demonstrated that 4×112 Gb/s field PDM-PAM4 is successful transmitted over 16 km MCF and 384 km SSMF in C-band with a BER below 3.8e-3.

Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of −30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm−2) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (−50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm−2) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way.

Abstract Background The oomycete pathogen secretes many effectors into host cells to manipulate host defenses. For the majority of effectors, the mechanisms related to how they alter the expression of host genes and reprogram defenses are not well understood. In order to investigate the molecular mechanisms governing the influence that the Phytophthora infestans RXLR effector Pi04089 has on host immunity, a comparative transcriptome analysis was conducted on Pi04089 stable transgenic and wild-type potato plants. Results Potato plants stably expressing Pi04089 were more susceptible to P. infestans. RNA-seq analysis revealed that 658 upregulated genes and 722 downregulated genes were characterized in Pi04089 transgenic lines. A large number of genes involved in the biological process, including many defense-related genes and certain genes that respond to salicylic acid, were suppressed. Moreover, the comparative transcriptome analysis revealed that Pi04089 significantly inhibited the expression of many flg22 (a microbe-associated molecular pattern, PAMP)-inducible genes, including various Avr9/Cf-9 rapidly elicited (ACRE) genes. Four selected differentially expressed genes (StWAT1, StCEVI57, StKTI1, and StP450) were confirmed to be involved in host resistance against P. infestans when they were transiently expressed in Nicotiana benthamiana. Conclusion The P. infestans effector Pi04089 was shown to suppress the expression of many resistance-related genes in potato plants. Moreover, Pi04089 was found to significantly suppress flg22-triggered defense signaling in potato plants. This research provides new insights into how an oomycete effector perturbs host immune responses at the transcriptome level.

Abstract Background In patients of chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides full haemodynamic support. However, during a rescue treatment of VA-ECMO for patients with difficulty weaning from cardiopulmonary bypass, a significantly increase left ventricular afterload through retrograde infusion of arterialized blood into the descending aorta may occur. Case presentation We report a 70-year-old man who suffered severe residual pulmonary hypertension following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Preoperative echocardiogram showed a dilated and poorly functioning right ventricle, as well as a small left heart with normal function (TAPES9.6 mm, LVEF64%, average E/E′11.94, lateral E′12.1 cm/s, tricuspid regurgitation velocity 2.5 m/s), while postoperative echocardiography revealed a significant decrease of whole ventricular function on postoperative day 1(TAPES4mm, LVEF28%, average E/E′15, lateral E′6.7 cm/s, tricuspid regurgitation velocity 4.1 m/s), indicating the patient developed severe secondary left ventricular dysfunction on the basis of right ventricular dysfunction, during VA-ECMO support. Then comprehensive measures were adopted, such as down-regulating VA-ECMO flow rate, adjusting respiratory parameters, using vasoactive drugs, as well as prostacyclin. Eventually, the pulmonary hypertension decreased to moderate degree, and the heart function improved gradually. Conclusions In the face of severe residual pulmonary hypertension and sencondary left ventricular dysfunction associated with VA-ECMO, comprehensive measures described above may facilitate recovery. ECMO flow titration to maintain relatively low flow rate is very important to not only maintain systemic perfusion, but also reduce left ventricular afterload and ensure pulsatile perfusion of pulmonary artery.

Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with a high incidence and mortality rate. Previous in vitro and in vivo studies have confirmed that liver sinusoidal endothelial cells (LSEC) secrete CXCL16, which acts as a messenger to increase the hepatic accumulation of CXCR6+ natural killer T (NKT) cells and exert potent antitumor effects. However, evidence for this process in humans is lacking and its clinical significance is still unclear. In this study, by dissecting the human HCC single-cell RNA-seq data, we verified this process through cellphoneDB. NKT cells in patients with high expression of CXCL16 exhibited a higher activation state and produced more interferon-γ (IFN-γ) compared with those with low expression. We next investigated the signaling pathways between activated (CD69 high) and unactivated NKT cells (CD69 low) using NKT cell-developmental trajectories and functional enrichment analyses. In vivo experiments, we found that farnesoid X receptor agonist (obeticholic acid) combined with the takeda G protein coupled receptor 5 antagonist (5β-cholanic acid 3) exhibited significant tumor suppressive effects in the orthotopic liver tumor model and this result may be related to the CXCL16/CXCR6 axis. In conclusion, our study provides the basis and potential strategies for HCC immunotherapy based on NKT cells.

PurposeInsomnia is one of the most common diseases in elderly patients, which seriously affect the quality of life and psychological state of patients. The purpose of this study was to investigate the changes in the functional network pattern of the prefrontal cortex in patients with chronic insomnia disorder (CID) after taking drugs, using non-invasive and low-cost functional neuroimaging with multi-channel near-infrared spectroscopy (fNIRS).MethodsAll subjects were assessed using the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and fNIRS. The fNIRS assessment consists of two parts: the verbal fluency test (VFT) task state and the resting state, which assessed the differences in prefrontal activation and functional connectivity, respectively.ResultsA total of 30 patients with chronic insomnia disorder (CID) and 15 healthy peers completed the study. During the VFT task, a significantly lower PFC activation was observed in patients with insomnia compared to the control group (P < 0.05). However, the PFC activation in patients taking medication was higher than in patients who did not receive medication. Functional connectivity analysis showed a weaker mean PFC channel connectivity strength in patients with CID who did not receive drug treatment. Drug treatment resulted in enhanced functional connectivity of the prefrontal lobe, especially the DLPFC and frontal poles.ConclusionA weak prefrontal cortex response was detected in patients with CID when performing the VFT task, which could be enhanced by taking hypnotics. The weakened right prefrontal lobe network may play a role in the development of CID. fNIRS may serve as a potential tool to assess sleep status and guide drug therapy.

BackgroundSpatial transcriptomics (STs) simultaneously obtains the location and amount of gene expression within a tissue section. However, current methods like FindMarkers calculated the differentially expressed genes (DEGs) based on the classical statistics, which should abolish the spatial information.Materials and methodsA new method named spatial analysis of spatial transcriptomics (saSpatial) was developed for both the location and the amount of gene expression. Then saSpatial was applied to detect DEGs in both inter- and intra-cross sections. DEGs detected by saSpatial were compared with those detected by FindMarkers.ResultsSpatial analysis of spatial transcriptomics was founded on the basis of spatial statistics. It was able to detect DEGs in different regions in the normal brain section. As for the brain with ischemic stroke, saSpatial revealed the DEGs for the ischemic core and penumbra. In addition, saSpatial characterized the genetic heterogeneity in the normal and ischemic cortex. Compared to FindMarkers, a larger number of valuable DEGs were found by saSpatial.ConclusionSpatial analysis of spatial transcriptomics was able to effectively detect DEGs in STs data. It was a simple and valuable tool that could help potential researchers to find more valuable genes in the future research.

Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances antitumor immune responses. However, given the reported association of miR-155 with tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, particularly that of cancer cell–derived miR-155, on antitumor immunity in breast cancer. We performed bioinformatic analysis of human breast cancer databases, murine experiments, and human specimen examination. We revealed that higher tumor miR-155 levels correlate with a favorable antitumor immune profile and better patient outcomes. Murine experiments demonstrated that miR-155 overexpression in breast cancer cells enhanced T cell influx, delayed tumor growth, and sensitized the tumors to immune checkpoint blockade (ICB) therapy. Mechanistically, miR-155 overexpression in breast cancer cells upregulated their CXCL9/10/11 production, which was mediated by SOCS1 inhibition and increased phosphorylated STAT1 (p-STAT1)/p-STAT3 ratios. We further found that serum miR-155 levels in breast cancer patients correlated with tumor miR-155 levels and tumor immune status. Our findings suggest that high serum and tumor miR-155 levels may be a favorable prognostic marker for breast cancer patients and that therapeutic elevation of miR-155 in breast tumors may improve the efficacy of ICB therapy via remodeling the antitumor immune landscape.

Aiming at the modulation problem of high energy efficiency and high sensitivity in the space laser communication system, the Differential Pulse Position Modulation (DPPM) format is studied and applied to the coherent optical communication system. The balance point is found in the system considering power consumption, Bit Error Ratio (BER) performance and bandwidth occupation through simulation and experiment. The experimental results show that in the direct modulation direct detection and coherent optical communication transmission systems, the optical power of the signal path required to reach the hard line is-36.5 and-60.0 dBm respectively when the same transmission channel and the same transmission rate of 1.25 Gbit/s DPPM signal is applied. The optical power margin of the coherent transmission system is increased by about 24 dB compared with the direct detection transmission system. In order to achieve the transmission goal of the hard judgment line, the optical power of the receiver for transmitting the DPPM signal at the rate of 3、6、12、24 Gbit/s needs to be about-49、-47、-42、-36 dBm respectively. It is demonstrated that higher sensitivity and lower BER can be obtained by using DPPM format/coherent detection.

BackgroundEpilepsy is one of the leading neurological diseases. Our study is aimed to determine whether there is a focal region of high epilepsy prevalence in China.MethodsAll studies published between 1981 and 2020 investigating the prevalence of epilepsy in China were systematically reviewed. The geographical location, sample size, number of cases, urbanization rate, gross domestic product (GDP) per capita, percentage of

Rabies is an infectious disease of animal origin with a high mortality rate. In the early stages of rabies, the rabies virus (RABV) is usually undetectable in saliva and cerebrospinal fluid (CSF). In addition, there are still no effective drugs and treatments. Here, we present a case in which blood purification alleviated multisystem failures. The patient was a 45-year-old woman who presented with the fear of water and wind, restlessness, and hyperactivity. RABV was detected in her saliva by high-throughput sequencing Next Generation Sequencing (NGS) and polymerase chain reaction (PCR). Based on typical clinical symptoms and the result of NGS and PCR, the patient was diagnosed as a confirmed case of rabies. Hemodialysis combined with antiviral therapy and intensive care unit (ICU) treatment can effectively relieve circulatory failure, respiratory failure, and renal failure. Finally, she died of brain death on the 34th day of admission. The case report showed that blood purification was positive for rabies-induced organ failure. Blood purification combined with antiviral therapy can prolong the lives of patients with rabies to some extent.

Abstract Chinese prickly ash (Zanthoxylum) is extensively used as spice and traditional medicine in eastern Asian countries. Recently, an emergent yellow-flower disease (YFD) break out in green Chinese prickly ash (Zanthoxylum schinifolium, Qinghuajiao in Chinese) at Chongqing municipality, and then leads to a sharp reduction in the yield of Qinghuajiao, and thus results in great economic losses for farmers. To address the molecular response for the emergent YFD of Qinghuajiao, we analyzed the transcriptome of 12 samples including the leaves and inflorescences of asymptomatic and symptomatic plants from three different towns at Chongqing by high-throughput RNA-Seq technique. A total of 126,550 genes and 229,643 transcripts were obtained, and 21,054 unigenes were expressed in all 12 samples. There were 56 and 164 different expressed genes (DEGs) for the AL_vs_SL (asymptomatic leaf vs symptomatic leaf) and AF_vs_SF (asymptomatic flower vs symptomatic flower) groups, respectively. The results of KEGG analysis showed that the “phenylpropanoid biosynthesis” pathway that related to plant–pathogen interaction were found in AL_vs_SL and AF_vs_SF groups, and the “Plant–pathogen interaction” found in AF_vs_SF group, implying that this Qinghuajiao YFD might cause by plant pathogen. Interestingly, we detected 33 common unigenes for the 2 groups, and almost these unigenes were up-regulated in the symptomatic plants. Moreover, most of which were homologs to virus RNA, the components of viruses, implying that this YFD was related to virus. Our results provided a primary molecular basis for the prevention and treatment of YFD of Qinghuajiao trees.

PurposeBiliary drainage is an important modality for extrahepatic obstructive jaundice both in patients with palliative and resectable. Currently, endoscopic biliary drainage is preferred in clinical practice, including endoscopic nasobiliary drainage (ENBD) and endoscopic biliary stenting (EBS), both of which have their own advantages and disadvantages. The purpose of our study was to compare the safety and efficacy of endoscopic biliary stenting (EBS) only vs. EBS plus nasobiliary drain for obstructive jaundice.MethodsWe consecutively reviewed patients with endoscopic biliary drainage in our institution from November 2014 to March 2021. Combined (ENBD plus stent) and single approach (EBS only) were defined as combined approach and single modality, respectively, and all eligible patients were divided into a combined approach group and a single modality group. We compared combined vs. single modality approaches to investigate whether there were statistical differences in liver chemistries, postoperative adverse events, and stent patency time.ResultsIn 271 patients, a total of 356 times endoscopic biliary drainages were performed. All eligible patients were divided into the combined approach group (n = 74) and the single modality group (n = 271). The combined approach was associated with a lower incidence of postoperative cholangitis and bleeding and greater improvement in liver chemistries, although it was not statistically significant. However, it was superior to the single modality group in terms of hospital stay (12.7 ± 5.2 vs. 14.5 ± 7.9 days, p = 0.020 < 0.05) and stent patency time (8.1 ± 3.9 vs. 4.3±2.7 months, p = 0.001 < 0.05).ConclusionEndoscopic combined (ENBD plus stent) drainage is a more advantageous biliary drainage method that is characterized by more adequate biliary drainage, a lower incidence of postoperative adverse events, and longer effective biliary drainage time.