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The perishable of fresh agricultural products and the improvement of people's requirements for food quality have put forward higher requirements for the distribution efficiency. This article for the cold chain of fresh agricultural products logistics distribution path optimization problem, in Chengdu shuangliu district A company agricultural products co., LTD., as A research object, using the particle swarm algorithm of the original raw agricultural products distribution path optimization design, calculate more reasonable distribution scheme, effectively improve the distribution efficiency, vehicle rate, and reduce the use of the vehicle, reasonable to reduce the logistics costs, ultimately improve the economic benefit of the enterprise and customer satisfaction, realize enterprise scientific logistics management.

A next-generation probiotic Lactobacillus plantarum-pMG36e-GLP-1 was constructed to express GLP-1 in vivo, which may affect the gut-pancreas-liver axis, thereby relieving the symptoms of HFD/STZ-induced T2DM mice and db/db mice.

Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon-like peptide-1 receptor (GLP-1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP-1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP-1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum-pMTL007-GLP-1 (CB-GLP-1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB-GLP-1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, β-MHC, α-SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high-throughput sequencing further demonstrated that CB-GLP-1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB-GLP-1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.

Fat grafting is an efficient and safe procedure for the correction of upper eyelid sulcus deepening. Stromal vascular fraction (SVF) gel has been proven to be an ideal fat derivative and can be widely used for facial augmentation. We aimed to determine the efficacy of SVF gel for the correction of a mild-to-moderate sunken superior sulcus among Asian patients.Patients with a mild-to-moderate sunken superior sulcus underwent SVF gel grafting of the sunken upper periorbital area. The primary result was the quantitative volume difference in the superior sulcus region before and after grafting. This was evaluated through three-dimensional VECTRAThirty-one patients with mild-to-moderate sunken upper eyelids were included in this study. The average unilateral injected amount was 1.235 mL (± 0.171 mL). The 1-year delta volume was 0.801 ± 0.086 mL, and the effective survival volume was 65.3% (± 6.1%). The median preoperative pretarsal space and upper lid area ratio was 1.010 (± 0.150). The median postoperative pretarsal space and upper lid area ratio at 1 year was 0.159 (± 0.031) (n = 62; P 0.0001), indicating a significantly reduced sunken appearance. The average GAIS score was 2.174 (± 0.391). All patients were satisfied with their surgical outcomes. The reoperation rate was 12.9%.SVF gel is safe and effective for the treatment of a mild-to-moderate sunken superior sulcus and is associated with satisfactory clinical outcomes and short recovery times.

Importance: Coleman fat, nanofat, and stromal vascular fraction-gel (SVF-gel) are three widely used fat derivatives. However, their rheological properties and structure remain unknown. Objectives: ...

Hazardous weather has become a major cause of flight delays in recent years. With the development of satellite navigation systems, the study of flight-path optimization under hazardous weather conditions has become especially important. In this study, radar data were used as the basis for the initial flight-restricted area under hazardous weather conditions, and the Graham algorithm was used to delineate the dynamic flight-restricted area by comprehensively considering the hazardous weather boundary changes along with the speed and direction. Then, under the grid environment model, the range of influence, size, and distribution characteristics of the flight-restricted area was examined, and the path optimization model was created according to constraints related to the path distance, corner size, and number of turning points. An improved F-RRT ∗ algorithm was developed to solve the model. The algorithm can overcome the problems of traditional path planning algorithms, such as strong randomness, poor guidance, slow convergence speed, unsmooth paths, and poor tracing smoothness. Finally, a simulation analysis was conducted on the Guiyang–Guangzhou route in China as an example. This study can address the drawbacks of existing research on route change and provide sufficient theoretical support and reference for the implementation of specific route change plans in the future.

The influence of gastric acid inhibitors (GAIs) on nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is controversial. Herein, the influences of different GAIs on NSAID-induced intestinal injury and the underlying mechanisms are clarified.Indomethacin (IND; 10 mg/kg/day) was administered to mice to induce small intestinal injury. Disease activity was examined macroscopically and histologically. The permeability of small intestine was evaluated by measuring plasma lipopolysaccharide levels. 16S rDNA sequencing was performed to determine the composition of intestinal flora.Among the four GAIs, ilaprazole (IPZ) significantly attenuated IND-induced small intestinal injury and maintained the integrity of the mucosal barrier. Omeprazole (OPZ) and vonoprazan (VPZ) ameliorated ulceration without significant differences, while rabeprazole (RPZ) failed to protect against the injury. To explore the potential mechanism, we investigated changes in the gut microbiota mediated by GAIs. After 5-day administration, GAIs significantly altered the composition of the gut microbiota. The IND group had a significant decrease in alpha diversity compared with the control group, and this decrease was reversed by OPZ and IPZ treatment, respectively. After IPZ treatment, the community membership was more assembled in the control group than the IND group. Further, we found that Lactobacillus was significantly increased in the groups of OPZ, IPZ, and VPZ, while Bacteroides was significantly increased in the RPZ group.Our results indicated that GAIs have different influences on the mucosal barrier, possibly by altering the composition of intestinal microbiota, and the impacts mediated by various GAIs in the IND-induced intestinal damage model seem different.

In the present study, via a 180-day field trial, the indicators of soil total cadmium, DTPA-Cd, organic matter, and plant cadmium extraction were tested after the application of chelate tetrasodium glutamate diacetate (GLDA) to investigate the potential of GLDA combined with Tagetes patula L. to remediate cadmium-contaminated soil. To do so, five GLDA treatments (e.g., 0, 292.5, 585, 1170, and 2340 kg hm

Diabetic wounds severely influence life, facing grand challenges in clinical treatments. The demand for better treatment is growing dramatically. Diabetic wound healing is challenging because of inflammation, angiogenesis disruptions, and tissue remodeling. Based on sequencing results of diabetic patients' skins and artificial intelligence (AI)-assisted bioinformatics, we excavate a potential therapeutic agent Trichostatin A (TSA) and a potential target histone deacetylase 4 (HDAC4) for diabetic wound healing. The molecular docking simulation reveals the favorable interaction between TSA and HDAC4. Taking advantage of the microneedle (MN) minimally invasive way to pierce the skin barrier for drug administration, we develop a swelling modified MN-mediated patch loaded with TSA to reduce the probability of injection-caused iatrogenic secondary damage. The MN-mediated TSA patch has been demonstrated to reduce inflammation, promote tissue regeneration, and inhibit HDAC4, which provides superior results in diabetic wound healing. We envisage that our explored specific drug TSA and the related MN-mediated drug delivery system can provide an innovative approach for diabetic wound treatment with simple, effective, and safe features and find a broad spectrum of applications in related biomedical fields.

Users enjoy the convenience of watching videos on smart devices. However, video watching records can be exposed without users' knowledge and be exploited to infer private information. In this paper, we design and implement a new side-channel attack system, named video aficionado, which can identify video watching information without violating any access control policies on Android. Our system only needs to collect power consumption data of a video playing app, which does not require explicit user permission. The collected data is sent to a remote server, where noise is cleaned and identified by a Multi-Layer Perceptron (MLP) trained classifier. We evaluate our proposed system through a set of carefully designed experiments. Experimental results demonstrate that our system can make an identification with 74.5% accuracy on average for each 20-second power measurement segment out of 3918 segments collected from 20 videos. To the best of our knowledge, video aficionado is the first real-time power consumption-based video identification system on smart devices.

Background Time-location information (time spent on commuting, indoors and outdoors around residential and work places and physical activity) and infiltrated outdoor pollution was less considered estimating individual exposure to ambient air pollution. Studies investigating the association between individual exposure to particulate matter (PM) with aerodynamic diameter 10) and 2.5) and carotid atherosclerosis presented inconsistent results. Moreover, combined effect of pollutants on carotid atherosclerosis was not fully explored. We aimed to investigate the association between long-term individual time-weighted average exposure to PM2.5 and PM10 and the risk of carotid atherosclerosis, and further explore the overall effect of co-exposure to pollutants on carotid atherosclerosis. Methods The study population included 3069 participants derived from the Beijing Health Management Cohort (BHMC) study. Daily concentration of ambient air pollutants was estimated by land-use regression model at both residential and work addresses, and one- and two-year time-weighted average individual exposure was calculated by further considering personal activity pattern and infiltration of ambient air pollution indoors. We explored the association of PM2.5 and PM10 with carotid atherosclerosis and pooled the overall effect of co-exposure to ambient air pollutants by quantile g-computation. Results A significant association between time-weighted average exposure to PM2.5 and PM10 and carotid atherosclerosis was observed. Per interquartile range increase in two-year exposure to PM2.5 (Hazard ratio (HR): 1.322, 95% confidence interval (CI): 1.219–1.434) and PM10 (HR:1.213, 95% CI: 1.116–1.319) showed the strongest association with carotid atherosclerosis, respectively. Individuals in higher quartiles of pollutants were at higher risk for carotid atherosclerosis compared with those in the lowest quartile group. Concentration response functions documented the nearly linear and nonlinear relationship and interpreted the upward trends of the risk for carotid atherosclerosis with increasing level of pollutant concentrations. Moreover, effect estimates for the mixture of pollutants and carotid atherosclerosis were larger than any of the individual pollutants (HR (95% CI) was 1.510 (1.338–1.704) and 1.613 (1.428–1.822) per quartile increase for one-year and two-year time-weighted average exposure, respectively). Conclusions Individual time-weighted average exposure to PM2.5 and PM10 was associated with carotid atherosclerosis. Co-exposure to ambient air pollution was also positively associated with carotid atherosclerosis.

PurposeIn this study, the aim was to comprehensively analyze the current status, hotspots, and trends of trans-oral endoscopic thyroidectomy (TOET) through bibliometric analysis and by presenting the field atlas.MethodsWeb of Science Core Collection database was adopted to screen studies regarding TOET published between January 1, 2008 and August 1, 2022. The evaluation covered the criteria total number of studies, keywords, and contributions from countries/regions, institutions, journals, and authors.ResultsA total of 229 studies were covered. SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES is the largest publication in the field of TOET. The three countries that contributed the most studies were Korea, China, and the USA. The most frequently occurring core keywords in the field of TOET are vestibular approach, outcomes, experience, safety, robotic thyroidectomy, scar, video-assisted thyroidectomy and quality-of-life. The seven clusters were generated in this study: intraoperative monitoring of the laryngeal return nerve (# 0), learning curve (# 1), postoperative quality of life (# 2), central lymph node dissection and safety (# 3), complications (# 4), minimally invasive surgery (# 5), and robotic surgery (# 6).ConclusionThe main research topics in the field of TOET place focuses on learning curves, laryngeal nerve monitoring, carbon dioxide gas bolus, chin nerve injury, surgical complications, and surgical safety. In the future, more academics will focus on the safety of the procedure and reducing complications..

This supporting information includes five movies, providing theraw observation of hydrate slurry vertical upflow patterns in the flow loop. The five movies correspond to fiveflow patterns. Movies S1(LL=0.5, WCF=0.06) is uploaded with file nameMovies S1(LL=0.5, WCF=0.06).mp4. Detailed information includes the raw observation of "rapid conversion slug flow" in low liquid loading conditions. Movies S2(LL=0.5, WCF=0.13) is uploaded with file nameMovies S2.1(LL=0.5, WCF=0.13).mp4. Detailed information includes the raw observation of "depositionslug flow" in low liquid loading conditions. Movies S3(LL=0.5, WCF=0.2) is uploaded with file nameMovies S2.2(LL=0.5, WCF=0.2).mp4. Detailed information includes the raw observation of "hydrate wisp annular flow" in low liquid loading conditions. Movies S4(LL=0.8, WCF=0.15) is uploaded with file nameMovies S3(LL=0.8, WCF=0.15).mp4. Detailed information includes the raw observation of "rapid conversion slug flow" in highliquid loading conditions. Movies S5(LL=0.8, WCF=0.25) is uploaded with file nameMovies S4(LL=0.8, WCF=0.25).mp4. Detailed information includes the raw observation of "depositionslug flow" in highliquid loading conditions.

Supplemental Figures and Tables

Supplementary Table 1. List of primers and oligos used in this investigation; Supplementary Table 2 Primary antibodies used in this investigation; Supplementary Figure S1. HJC0152 exerts antitumor effect against HNSCC cell lines via regulating STAT3; Supplementary Figure S2. HJC0152 blocks nuclear translocation of p-STAT3 and β-catenin; Supplementary Figure S3. HJC0152 suppresses invasion and migration in HNSCC cell lines; Supplementary Figure S4. HJC0152 regulates the activity of miR-21/β-catenin axis; Supplementary Figure S5. VHL abrogation dramatically counteracts the impact of HJC0152 in vitro.

Supplementary Figures and Tables

Liver kinase B1 (LKB1)–inactivated tumors are vulnerable to the disruption of pyrimidine metabolism, and leflunomide emerges as a therapeutic candidate because its active metabolite, A77–1726, inhibits dihydroorotate dehydrogenase, which is essential for de novo pyrimidine biosynthesis. However, it is unclear whether leflunomide inhibits LKB1-inactivated tumors in vivo, and whether its inhibitory effect on the immune system will promote tumor growth. Here, we carried out a comprehensive analysis of leflunomide treatment in various LKB1-inactivated murine xenografts, patient-derived xenografts, and genetically engineered mouse models. We also generated a mouse tumor–derived cancer cell line, WRJ388, that could metastasize to the lung within a month after subcutaneous implantation in all animals. This model was used to assess the ability of leflunomide to control distant metastasis. Leflunomide treatment shrank a HeLa xenograft and attenuated the growth of an H460 xenograft, a patient-derived xenograft, and lung adenocarcinoma in the immune-competent genetically engineered mouse models. Interestingly, leflunomide suppressed tumor growth through at least three different mechanisms. It caused apoptosis in HeLa cells, induced G1 cell-cycle arrest in H460 cells, and promoted S-phase cell-cycle arrest in WRJ388 cells. Finally, leflunomide treatment prevented lung metastasis in 78% of the animals in our novel lung cancer metastasis model. In combination, these results demonstrated that leflunomide utilizes different pathways to suppress the growth of LKB1-inactivated tumors, and it also prevents cancer metastasis at distant sites. Therefore, leflunomide should be evaluated as a therapeutic agent for tumors with LKB1 inactivation.

Previous studies focused on the intense TCs in the central-southeastern western North Pacific (WNP), whose variability is intimately linked to El Niño–Southern Oscillation and the extratropical sea surface temperature anomaly (SSTA) in the Pacific. Compared with them, weak TCs (WTCs) are more numerous and form farther northwestward. The great number of WTCs and thereby the landfall cases may also cause huge damage to countries in Southeast Asia. However, their modulators are far from fully understood. Our research emphasizes the delayed impact of the early spring North Atlantic tripole SSTA (NAT) on the WTC formation frequency through the “capacitor” effect of sea ice (SIC) and SST in the Barents Sea. Detailed analysis indicates that a positive NAT may modulate an anomalous high in the Barents Sea–North Europe and decrease the local low cloud cover. Thus, more downward solar radiation tends to heat the local SST and decrease the SIC. This warmer Barents Sea could maintain through the typhoon season and excite a significant southeastward wave train, with several centers in the Arctic, central Asia, and East Asia. The abnormal easterly wind to the south of the anticyclone in East Asia facilitates the cyclonic anomaly in the South China Sea, the Philippines, and the subtropical WNP, which reinforces the local monsoon trough and favors the WTC formation there. A physical-based empirical model is developed for the WTC frequency, and hindcast is performed from 1979 to 2018. It shows the early spring NAT effectively improves the prediction skill for the WTC frequency, which can be considered as a crucial source of predictability for WTCs. Significance Statement Previous studies have focused on the western North Pacific intense TCs. The great number of weak TCs (WTCs) and thereby the landfall cases may also cause huge damage. However, modulators for WTCs have not been fully understood. This research emphasizes the potential impact of the early spring North Atlantic tripole SSTA (NAT) pattern on the WTC frequency through the persistent sea ice and sea surface temperature in the Barents Sea. By considering the NAT signal, the seasonal forecasting skill for WTC frequency is effectively improved. Therefore, the NAT signal may help better understand the WTC variability about 1–2 seasons in advance.

Metabolic-associated fatty liver disease (MAFLD) is a series of liver diseases based on liver steatosis and metabolic disorders. Steatosis, as the core factor in MAFLD diagnosis, and fibrosis, as the major determinant of adverse outcomes of MAFLD, need to be assessed simply and accurately. In this study, we explored the significance of mid-upper arm circumference (MUAC) in evaluating liver steatosis and fibrosis in patients with MAFLD. We included 2397 cases with MAFLD from the 2017-2018 National Health and Nutrition Examination Surveys (NHANES) database. Liver steatosis and fibrosis were measured by vibration controlled transient elastography. Anthropometric parameters and demographic and serological data were obtained from the NHANES database. The association between MUAC and liver steatosis and fibrosis were evaluated by a multivariable linear regression model, a weighted generalized additive model, and smooth curve fitting using R. MUAC was positively associated with liver steatosis in every multivariate linear regression model (model 1: β = 3.3513; 95% confidence interval [CI], 2.7722-3.9304; model 2: β = 3.8492; 95% CI, 3.2441-4.4542; model 3: β = 2.4987; 95% CI, 1.8371-3.1604), and this positive association was consistent in both men and women and among different race groups (Mexican American, other Hispanic, non-Hispanic White, Black, Asian, and other race). On the other hand, MUAC was positively associated with liver fibrosis in every multivariate linear regression model, and this positive association also was consistent in both men and women and among non-Hispanic White and Black populations. Increased MUAC was positively associated with liver steatosis and fibrosis in patients with MAFLD. This was particularly true for MUAC ≥ 42.0 cm. MUAC might be a simple and convenient evaluation tool for MAFLD.

To evaluate the obstetrical and oncological progression of twin pregnancies with hydatidiform mole coexisting fetus (HMCF).Using a retrospective method based on patients from the Women's Hospital, Zhejiang University School of Medicine database between January 1990 and October 2020, 17 patients were histologically confirmed as having HMCF, and the patients' prenatal diagnosis, outcomes and development of gestational trophoblastic neoplasia (GTN) were reviewed.Among these 17 cases, 11 (64.71%) cases were complete hydatidiform mole coexisting fetus (CHMCF), and 6 (35.29%) cases were partial hydatidiform mole coexisting fetus (PHMCF). The gestational age at diagnosis of CHMCF was significantly earlier than that of PHMCF [9 (8-24) vs. 18 (11-32) weeks, respectively, P 0.05]. The live birth rate of PHMCF was slightly higher than that of CHMCF (33.33%; 18.18%), but this difference was not statistically significant. The overall rate of GTN incidence of HMCF was 47.06% (8/17), and the GTN rates of PHMCF and CHMCF were 33.33% (2/6) and 54.55% (6/11), respectively. There was no significant difference in the GTN rate between patients who chose to continue pregnancy and those who terminated pregnancy before 24 weeks of gestation. The GTN rate of patients with term delivery was not significantly higher than that of preterm delivery.In HMCF cases, the incidence rate of CHMCF was higher than that of PHMCF, and PHMCF is more difficult to diagnose in the early stage. Continuing pregnancy does not increase the risk of GTN compared to terminating pregnancy. In cases of HMCF, when the fetal karyotype is normal and maternal complications are controlled, it is safe to continue the pregnancy and extend it to term.

Polyacrylamide hydrogel (PAAG) has been used globally for breast augmentation, leading to long-term clinical complications. However, whether the infiltrated fibrotic capsule should be removed with PAAG to alleviate the complications remains unclear. This study aimed to ascertain different causes of complications and proper management strategies for PAAG removal in augmented breasts.From July 2015 to December 2019, patients who underwent breast augmentation with PAAG and in whom surgical intervention was undertaken for PAAG-associated adverse events at Shanghai Ninth People's Hospital were retrospectively reviewed. Patients were categorized into two groups according to whether the fibrotic capsule was removed (RFC) or not (NRFC). Aesthetic outcomes, PAAG residues, and adverse events were evaluated post-operatively to assess whether important issues pertaining to these arose following fibrotic capsule removal. Tissue histology and PAAG degradation analysis were implemented to investigate immune response, degradability, and toxicity of PAAG.Altogether, 257 patients (88 RFC and 169 NRFC patients) were enrolled. 73.4% and 79.5% of the RFC and NRFC groups showed fairly good outcomes, with no significant difference, respectively. (XBoth treatment strategies showed good results in our study. Removal of the fibrotic capsule from infiltration of PAAG largely depends on the individual psychological condition, aesthetic expectations, complications, and magnetic resonance imaging results. While PAAG does not degrade in the host's body over time, it may elicit immune reactions and chronic inflammation in the long term.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Supplementary Figure 2 from Silencing PinX1 Compromises Telomere Length Maintenance As Well As Tumorigenicity in Telomerase-Positive Human Cancer Cells

The nucleolar protein PinX1 has been proposed to be a putative tumor suppressor due to its binding to and inhibition of the catalytic activity of telomerase, an enzyme that is highly expressed in most human cancers in which it counteracts telomere shortening–induced senescence to confer cancer cell immortalization. However, the role of PinX1 in telomere regulation, as well as in cancer, is still poorly understood. In this study, we showed that the PinX1 protein is constitutively expressed in various human cells regardless of their telomerase activity and malignant status. Most interestingly, we found that silencing PinX1 expression by a potent short hairpin RNA construct led to a robust telomere length shortening and growth inhibition in telomerase-positive but not in telomerase-negative human cancer cells. We further showed that silencing PinX1 significantly reduced the endogenous association of telomerase with the Pot1-containing telomeric protein complex, and therefore, could account for the phenotypic telomere shortening in the affected telomerase-positive cancer cells. Our results thus reveal a novel positive role for PinX1 in telomerase/telomere regulations and suggest that the constitutive expression of PinX1 attributes to telomere maintenance by telomerase and tumorigenicity in cancer cells. [Cancer Res 2009;69(1):75–83]

Supplementary Figure 1 from Silencing PinX1 Compromises Telomere Length Maintenance As Well As Tumorigenicity in Telomerase-Positive Human Cancer Cells

Protein phosphatase 2A (PP2A) is usually a heterotrimeric enzyme, consisting of a catalytic subunit (C) and a scaffolding subunit (A) associated with a third, variable regulatory subunit (B). Fungi usually carry a single gene for A and C subunits, and three genes for the B subunit. In addition, fungi contain a conserved atypical C subunit named Ppg1, which is essential to the pathogenicity of the rice blast fungus Magnaporthe oryzae. However, it remains largely unknown how the B subunit combinatorically assembles with the A and C subunits or Ppg1 to regulate fungal growth, development and pathogenicity. Here we report and functionally characterize one regulatory subunit of PP2A, named MoB56, in M. oryzae. We generated a MoB56 deletion mutant Δmob56, which was severely defective in vegetative growth, conidiation and septum formation, and had lost pathogenicity. The defects of Δmob56 could be rescued by introducing MoB56 fused with GFP (MoB56-GFP) at its C terminus. Fluorescence microscopic observations revealed that the MoB56-GFP signals were widely distributed in the cytoplasm and formed a dot-like structure at the center of the septum in conidia, appressoria and infection hyphae, supporting its function in septation. Further, we performed co-immunoprecipitation and pull-down assays, indicating that MoB56 forms a protein complex with the A subunit and Ppg1 in mycelial cells. The yeast two-hybrid assay showed that MoB56 could interact with the A subunit of PP2A but not with Ppg1, while Ppg1 could interact with the A subunit, suggesting that the A subunit ties MoB56 with Ppg1 for the protein complex formation. In addition, we revealed that MoB56 has multiple isoforms, which are likely originated from alternative splicing and sumoylation. This is the first report revealing that the regulatory subunit B56 is associated with the PP2A-like phosphatase Ppg1 in fungi. Importantly, this study showed that B56, like Ppg1, is essential to the pathogenicity of M. oryzae, offering a potential new lead to control this devastating fungal pathogen by targeting specific PP2A-like phosphatase. Together, this study provides important information for understanding how the regulatory subunit B56 of PP2A regulates fungal pathogenicity and for the control of rice blast disease.

BackgroundThe disease burden caused by chronic hepatitis B virus (HBV) infection is still heavy, and the current treatment scheme has not achieved a complete cure. Changes in natural and adaptive immunity usually accompany chronic HBV infection. As a marker expressed on dendritic cells (DCs), whether lysosome-associated membrane glycoprotein 3 (LAMP3) participates in chronic HBV infection deserves further analysis.MethodsWe retrieved chronic HBV infection transcriptional information from the Gene Expression Omnibus (GEO) database. The LAMP3 expression in the liver of patients with chronic hepatitis B (CHB) was analyzed in three GEO datasets and confirmed in our validation cohort (27 patients with CHB). Differentially expressed genes were obtained from one CHB cohort by comparing LAMP3high and LAMP3low expression subgroups. These genes underwent Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis to decipher the influence of LAMP3 on the biological process and immunity changes in HBV infection. Furthermore, we investigated the potential relationship between LAMP3 levels, the abundance of infiltrating immune cells, and liver dysfunction.ResultsCompared to healthy controls, LAMP3 expression was upregulated in the transcriptional profiles of the liver in patients with CHB. The high LAMP3 expression was related to T cell activation and the chemokine signaling pathway. The LAMP3 gene was positively linked to marker sets of infiltrating activated regulatory T cells (Treg), T cell exhaustion, monocytes, and DCs. Moreover, CHB patients with high LAMP3 expression had unfavorable liver dysfunction.ConclusionsLAMP3 is a gene related to HBV infection, which might be involved in HBV infection by regulating T cell activation and adaptive immune response.

Background and aimHepatitis C virus infection can lead to an enormous health burden worldwide. Investigating the changes in HCV-related burden between different countries could provide inferences for disease management. Hence, we aim to explore the temporal tendency of the disease burden associated with HCV infection in China, India, the United States, and the world.MethodsDetailed data on the total burden of disease related to HCV infection were collected from the Global Burden of Disease (GBD) 2019 database. Joinpoint regression models were used to simulate the optimal joinpoints of annual percent changes (APCs). Further analysis of the age composition of each index over time and the relationship between ASRs and the socio-demographic Index (SDI) were explored. Finally, three factors (population growth, population aging, and age-specific changes) were deconstructed for the changes in the number of incidences, deaths, and DALYs.ResultsIt was estimated that 6.2 million new HCV infections, 0.54 million HCV-related deaths, and 15.3 million DALYs worldwide in 2019, with an increase of 25.4, 59.1, and 43.6%, respectively, from 1990, are mainly due to population growth and aging. China experienced a sharp drop in age-standardized rates in 2019, the United States showed an upward trend, and India exhibited a fluctuating tendency in the burden of disease. The incidence was increasing in all locations recently.ConclusionHCV remains a global health concern despite tremendous progress being made. The disease burden in China improved significantly, while the burden in the United States was deteriorating, with new infections increasing recently, suggesting more targeted interventions to be established to realize the 2030 elimination goals.

Backgroud With the reform of medical system in China, Beijing municipal hospitals explored a new pharmaceutical care model and set up medication therapy management services (MTMs) in ambulatory care since 2019. We were one of the first hospitals to set up this service in China. At the present, there were relatively few reports about the effect of MTMs in China. In this study, we summarized the implementation of MTMs in our hospital, explore the feasibility of pharmacist-led MTMs in ambulatory care and the impact of MTMs on patients’ medical costs. Methods A retrospective study was conducted in a university-affiliated, tertiary comprehensive hospital in Beijing, China. The patients who received at least one MTMs and with complete medical records and pharmaceutical documents from May 2019 to February 2020 were included. Pharmacists provided pharmaceutical care for patients according to the MTMs standards issued by the American Pharmacists Association, identified the numbers and classification of the patients’ perceived medication-related demands, identified medication-related problems (MRPs), and developed the medication-related action plans (MAPs). All MRPs found by pharmacists, pharmaceutical interventions, and resolving recommendations were documented, and calculate the cost of treatment drugs that patients can reduce. Results A total of 112 patients received MTMs in ambulatory care, among them 81 cases with the completed record were included in this study. 67.9% of patients had five or more diseases, 83% of them co-took over 5 drugs. While performing MTMs, 128 patients’ perceived medication-related demands were recorded in all, monitoring and judgment of adverse drug reaction (ADR) (17.19%) was the most common demand. 181 MRPs were found, with an average of 2.55 MPRs per patient. Nonadherence (38%), excessive drug treatment (20%), and adverse drug events (17.12%) were the top three MRPs. Pharmaceutical care (29.77%), adjustment of drug treatment plan (29.10%) and referral to the clinical department (23.41%) were the top three MAPs. Whereby the MTMs provided by pharmacists, the cost-saving of each patient was about $ 43.2 monthly. Conclusion By participating in the MTMs of outpatients, the pharmacists could identify more MRPs and develop personalized MAPs timely for patients, thereby promoting rational drug use and reducing medical expenses.

This supporting information includes five movies, providing theraw observation of hydrate slurry vertical upflow patterns in the flow loop. The five movies correspond to four flow patterns, of which two related videos (S2.1-S2.2)were uploaded to understand the characteristics of flow pattern 2 better. Movies S1(LL=0.5, WCF=0.06) is uploaded with file nameMovies S1(LL=0.5, WCF=0.06).mp4. Detailed information includes the raw observation of "rapid conversion slug flow" in low liquid loading conditions. Movies S2.1(LL=0.5, WCF=0.13) is uploaded with file nameMovies S2.1(LL=0.5, WCF=0.13).mp4. Detailed information includes the raw observation of "depositionslug flow" in low liquid loading conditions. Movies S2.2(LL=0.5, WCF=0.2) is uploaded with file nameMovies S2.2(LL=0.5, WCF=0.2).mp4. Detailed information includes the raw observation of "depositionslug flow" in low liquid loading conditions. Movies S3(LL=0.8, WCF=0.15) is uploaded with file nameMovies S3(LL=0.8, WCF=0.15).mp4. Detailed information includes the raw observation of "rapid conversion slug flow" in highliquid loading conditions. Movies S4(LL=0.8, WCF=0.25) is uploaded with file nameMovies S4(LL=0.8, WCF=0.25).mp4. Detailed information includes the raw observation of "depositionslug flow" in highliquid loading conditions.

Non-alcoholic fatty liver disease (NAFLD) is a commonly occurring liver disease; however, its exact pathogenesis is not fully understood. The purpose of this study was to quantitatively evaluate the progression of steatosis and fibrosis by examining their distribution, morphology, and co-localisation in NAFLD animal models. qSteatosis showed a good correlation with steatosis grade (R:0.823–0.953,P