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Abstract Hypertension is an important global public health issue because of its high morbidity as well as the increased risk of other diseases. Recent studies have indicated that the development of hypertension is related to the dysbiosis of the gut microbiota in both animals and humans. In this review, we outline the interaction between gut microbiota and hypertension, including gut microbial changes in hypertension, the effect of microbial dysbiosis on blood pressure (BP), indicators of gut microbial dysbiosis in hypertension, and the microbial genera that affect BP at the taxonomic level. For example, increases in Lactobacillus, Roseburia, Coprococcus, Akkermansia, and Bifidobacterium are associated with reduced BP, while increases in Streptococcus, Blautia, and Prevotella are associated with elevated BP. Furthermore, we describe the potential mechanisms involved in the regulation between gut microbiota and hypertension. Finally, we summarize the commonly used treatments of hypertension that are based on gut microbes, including fecal microbiota transfer, probiotics and prebiotics, antibiotics, and dietary supplements. This review aims to find novel potential genera for improving hypertension and give a direction for future studies on gut microbiota in hypertension.

This paper combines the intelligent computer-assisted technology to carry out the architectural design and planning of the agricultural sightseeing area, and mainly plans the electricity consumption system of the agricultural sightseeing area to ensure that the agricultural sightseeing area can provide tourists with a good sightseeing experience at night. Moreover, this paper conducts an end-point analysis of the circuit system and analyzes multiple parameters, and combines the construction power demand of agricultural tourism areas to conduct power model analysis. The computer control system integrates various factor control methods, uses advanced control technology and control strategies, and fully considers the relationship between the control variables to realise the automation, intelligence and energy-saving regulation of the greenhouse environment of the agricultural sightseeing area. Finally, this paper takes the greenhouse system as an example to analyze the architectural planning. From the research point of view, it can be known that the architectural design method of agricultural sightseeing tourism area constructed in this paper has certain effects.

Abstract A low‐cost and feasible method to fabricate three‐dimensional (3D) hierarchical composites composed of CoSe2 nanoparticles embedded in rice‐derived hard carbon (HC) interconnected with carbon nanotubes (CNTs) is devised in this study. The deployment of CoSe2 in the elecrode has provided a very high rate capacity, which is crucial for sodium‐ion commercialization. The deployment of HC with CNTs further provides a 3D hierarchical structure effective in shortening the diffusion paths of both electrons and Na+ ions, offering abundance of active sodium storage sites. Consequently, the CoSe2 acted as an active material with the carbonaceous template, a commonly utilized sodium‐ion battery anode material, which exhibited a superior reversible capacity of 550 mAh g−1 at 0.5 A g−1, outstanding rate performance (451 mAh g−1 at 20 A g−1) and excellent cycling performance (~100% capacity retention over 2500 cycles at 20 A g−1 after electrochemical stabilization).

The carbohydrate binding protein galectin-3 has been linked to diabetes and cancer. Here, authors show that galectin-3 is a sensor of LPS, an important modulator of the mTORC1 signaling, and a critical regulator of glucose metabolism.

Abstract Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects. Graphical Abstract

The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of the Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu3 cell line which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. Competition assay showed that Delta variant outcompeted Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. To confirm the difference in entry pathway between the Omicron and Delta variants, we assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway), and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibited the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, the Omicron variant also showed weaker cell–cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, our results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variants may have an implication on the clinical manifestations or disease severity.

The replication and pathogenicity of SARS-CoV-2 Omicron BA.2 are comparable to that of BA.1 in experimental animal models. However, BA.2 has rapidly emerged to overtake BA.1 to become the predominant circulating SARS-CoV-2 variant worldwide. Here, we compared the replication fitness of BA.1 and BA.2 in cell culture and in the Syrian hamster model of COVID-19. Using a reverse genetics approach, we found that the BA.1-specific spike mutation G496S compromises its replication fitness, which may contribute to BA.1 being outcompeted by BA.2 in the real world. Additionally, the BA.1-unique G496S substitution confers differentiated sensitivity to therapeutic monoclonal antibodies, which partially recapitulates the immunoevasive phenotype of BA.1 and BA.2. In summary, our study identified G496S as an important determinant during the evolutionary trajectory of SARS-CoV-2.

The fast-spreading Omicron variant of SARS-CoV-2 overwhelmed Hong Kong, causing the fifth wave of COVID-19. It remains to be determined what mitigation measures might have played a role in reversing the rising trend of confirmed cases in this major outbreak. The government of Hong Kong has launched the mass rapid antigen tests (RAT) in the population and the StayHomeSafe scheme since February 2022. In this study, we examined the impact of the mass RAT on disease transmission and the case fatality ratio. It was suggested that the implementation of RAT plausibly played a role in the steady decrease of the effective reproduction number, leading to diminished SARS-CoV-2 transmission. In addition, we projected the disease burden of the outbreak in a scenario analysis to highlight the necessity of the StayHomeSafe scheme in Hong Kong. The Omicron outbreak experience in Hong Kong may provide actionable insights for navigating the challenges of COVID-19 surges in other regions and countries.

Abstract Background In the ice-free area of maritime Antarctica, fungi are the essential functioning group in terrestrial and marine ecosystems. Until now, no study has been conducted to comprehensively assess fungal communities in various habitats in Antarctica. We aimed to characterize fungal communities in the eleven habitats (i.e., soil, seawater, vascular plant, dung, moss, marine alga, lichen, green alga, freshwater, feather) in the Fildes Region (maritime Antarctica) using next-generation sequencing. Results A total of 12 known phyla, 37 known classes, 85 known orders, 164 known families, 313 known genera, and 320 known species were detected. Habitat specificity rather than habitat overlap determined the composition of fungal communities, suggesting that, although fungal communities were connected by dispersal at the local scale, the environmental filter is a key factor driving fungal assemblages in the ice-free Antarctica. Furthermore, 20 fungal guilds and 6 growth forms were detected. Many significant differences in the functional guild (e.g., lichenized, algal parasite, litter saprotroph) and growth form (e.g., yeast, filamentous mycelium, thallus photosynthetic) existed among different habitat types. Conclusion The present study reveals the high diversity of fungal communities in the eleven ice-free Antarctic habitats and elucidates the ecological traits of fungal communities in this unique ice-free area of maritime Antarctica. The findings will help advance our understanding of fungal diversity and their ecological roles with respect to habitats on a neighbourhood scale in the ice-free area of maritime Antarctica.

For the purpose of better matching the performance of the organic Rankine cycle (ORC) system concerning the vehicle engine waste heat recovery, this paper studies the output performance of free piston expander-linear generator (FPE-LG). A test bench of FPE-LG is established for small scale ORC system, and timing and displacement control strategy is proposed. Furthermore, the impact of the intake pressure and the torque on motion characteristics and output performance of FPE-LG are analyzed. According to evaluating different learning rates, number of hidden artificial neural networks and training functions, a prediction model of FPE-LG based on artificial neural network is established. Genetic algorithm is used to optimize the key operating parameters, to maximize the power output of FPE-LG. In consideration of the mean square error and determination coefficient, the artificial neural network model is verified and tested by experimental data. Finally, combining genetic algorithm with artificial neural network model, the maximum power output of FPE-LG is optimized and its performance is predicted. The results show that the maximum value of electric current, voltage and power output are 2.8 A, 14.75 V and 28.5 W, respectively. Based on artificial neural network, this method can provide useful guidance for performance prediction and coordinated optimization, with advantages of minimum deviation and high precision.

Abstract Isolated nocturnal hypertension (INH) is a special type of out‐of‐office hypertension. Its determinants and pathophysiology remain unclear. In a nested case‐control study, we intend to investigate the host, environmental, and genetic factors in relation to INH. Among 2030 outpatients screened from December 2008 till June 2015, 128 patients with INH were identified, and then 128 normotensives were matched according to sex and age. INH was an elevated nocturnal blood pressure (BP ≥120/70 mmHg) in the presence of a normal daytime BP (

Abstract Based on the gas–solid two-phase flow theory, numerical simulation of the dust dispersion law of fully mechanized mining work under different inclination angles and comparative analysis of field-measured data show that with the increase of working face inclination, the inclination of airflow into the unmined zone increases from 25° to 50° and the maximum wind speed increases from 2.16 to 2.25 m/s after the mixing of cutting turbulent wind and system ventilation. Meanwhile, the range of high-concentration dust clusters, suspension time, lateral migration intensity, and deposition zone increase to varying degrees; dust clusters increases from 62.02 to 202.46 m3. When X

ABSTRACT Disturbance of commensal intestinal microbiota is related to chronic inflammatory dermatosis. We analyzed the diversity of the gut microbiota to characterize the biological variation of psoriasis (Ps). Significant differences of gut microbiome profiles were revealed in murine model with psoriasis by sequencing 16S rRNA V3-V4 variable region. Group comparisons included the imiquimod cream (IMQ group, n=8), the imiquimod cream and antibiotics (ATB) (PC+IMQ group, n=8) and the healthy control (CTRL group, n=8). The gut microbiota existed in Ps groups including IMQ group and PC+IMQ group encompassed less diversity than controls, which were attributed to decreased presence of several taxa. The two Ps groups were characterized by significant reduction in firmicutes. In this study, microbiota of psoriasis was defined by an increase presence of Bacteroides. After treated with ATB, we found substantial increase of Lactobacillales but significant decrease of Clostridiales and Coriobacteriales. Relative lower abundance of multiple intestinal bacteria was observed in Ps groups. Although part of genera were concomitantly reduced in both IMQ and PC+IMQ conditions, we discovered the specialty of PC+IMQ group samples was that contained lower abundance of beneficial taxa. Characteristics of gut microbiota profiles in Ps mice were comparable to profiles in patients with Ps, which were related to alteration of specific inflammatory proteins in disease groups but were significantly different from control group. Thus, this study emphasizes the role of intestinal microbiota in the pathogenesis of Ps and provides new insight for investigating association between intestinal microbes and immune inflammation.

Abstract Background Dual inhibition of PD-1/PD-L1 and TGF-β pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701. Methods This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR). Results In total, 171 patients were enrolled (dose-escalation: n=17; dose-expansion, n=33; clinical-expansion, n=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4–36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5–73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR. Conclusions SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration. Trial registration ClinicalTrials.gov , NCT03710265