Response of bacterial ecological and functional properties to anthropogenic interventions during maturation of mine sand soil.

Soil formation is a complex process that starts from the biological development. The ecological principles and biological function in soil are of great importance, whereas their response to anthropogenic intervention has been poorly understood. In this study, a 150-day microcosmic experiment was conducted with the addition of sludge and/or fermented wood chips (FWC) to promote the soil maturation. The results showed that, compared to the control (natural development without anthropogenic intervention), sludge, FWC, and their combination increased the availability of carbon, nitrogen, and potassium, and promoted the soil aggregation. They also enhanced the cellulase activity, microbial biomass carbon (MBC) and bacterial diversity, indicating that anthropogenic interventions promoted the maturation of sand soil. Molecular ecology network and functional analyses indicated that soil maturation was accomplished with the enhancement of ecosystem functionality and stability. Specifically, sludge promoted a transition in bacterial community function from denitrification to nitrification, facilitated the degradation of easily degradable organic matter, and enhanced the autotrophic nutritional mode. FWC facilitated the transition of bacterial function from denitrification to ammonification, promoted the degradation of recalcitrant organic matter, and simultaneously enhanced both autotrophic and heterotrophic nutritional modes. Although both sludge and FWC promoted the soil functionality, they showed distinct mechanistic actions, with sludge enhancing the physical structure, and FWC altering chemical composition. It is also worth emphasizing that sludge and FWC exhibited a synergistic effect in promoting biological development and ecosystem stability, thereby providing an effective avenue for soil maturation.

Case Report: Perianal infection in children caused by ingested jujube pits: a report of two cases.

Background: The ingestion of jujube pits by children is a rare cause of perianal infection.This article aimed to report two cases of perianal infection in children resulting from the ingestion of jujube pits. Methods: We reviewed the clinical records of perianal infection caused by jujube pits at our hospital. Details of the patients' presentation, imaging studies, complications and treatment were recorded. Results: Both pediatric patients presented with perianal swelling and pain. The caregivers of both patients denied a history of jujube consumption. Magnetic resonance imaging (MRI) indicated the presence of jujube pits, which were subsequently removed during surgery. Postoperatively, both patients recovered well, and follow-up showed no recurrence or the formation of anal fistulas. Conclusion: The ingestion of jujube pits leading to perianal infection is rare and inconspicuous. Early diagnosis and treatment are beneficial in preventing the occurrence of serious complications.

A data-driven epidemic model with human mobility and vaccination protection for COVID-19 prediction.

Epidemiological models allow for quantifying the dynamic characteristics of large-scale outbreaks. However, capturing detailed and accurate epidemiological information often requires consideration of multiple kinetic mechanisms and parameters. Due to the uncertainty of pandemic evolution, such as pathogen variation, host immune response and changes in mitigation strategies, the parameter evaluation and state prediction of complex epidemiological models are challenging. Here, we develop a data-driven epidemic model with a generalized SEIR mechanistic structure that includes new compartments, human mobility and vaccination protection. To address the issue of model complexity, we embed the epidemiological model dynamics into physics-informed neural networks (PINN), taking the observed series of time instances as direct input of the network to simultaneously infer unknown parameters and unobserved dynamics of the underlying model. Using actual data during the COVID-19 outbreak in Australia, Israel, and Switzerland, our model framework demonstrates satisfactory performance in multi-step ahead predictions compared to several benchmark models. Moreover, our model infers time-varying parameters such as transmission rates, hospitalization ratios, and effective reproduction numbers, as well as calculates the latent period and asymptomatic infection count, which are typically unreported in public data. Finally, we employ the proposed data-driven model to analyze the impact of different mitigation strategies on COVID-19.

Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults.

BACKGROUND: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). METHODS: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 µg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. RESULTS: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. CONCLUSION: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.

Kinematic modelling and experimental testing of a particle-jamming soft robot based on a DEM-FEM coupling method.

Particle-jamming soft robots are characterised by high flexibility in motion and high stiffness when executing a task. Regarding particle jamming of soft robots, the discrete element method (DEM)-finite element method (FEM) coupling was used for modelling and control. At first, a real-time particle-jamming soft actuator was proposed by integrating advantages of the driving Pneu-Net and the driven particle-jamming mechanism. Then, DEM and FEM were separately employed to determine the force-chain structure of the particle-jamming mechanism and the bending deformation performance of the pneumatic actuator. Furthermore, the piecewise constant curvature method was adopted for forward and inverse kinematic modelling of the particle-jamming soft robot. Finally, a prototype of the coupled particle-jamming soft robot was prepared, and a visual tracking test platform was established. The adaptive control method was proposed to compensate for the accuracy of motion trajectories. The variable-stiffness performance of the soft robot was verified by conducting stiffness tests and bending tests. The results provide novel theoretical and technical support for the modelling and control of variable-stiffness soft robots.

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers across the world. It has a poor prognosis and lacks effective therapies, especially for patients with advanced-stage cancer, indicating an urgent need for new therapies and novel therapeutic targets. Here, by screening the U.S. Food and Drug Administration drug library against HCC cell lines, we identified that flubendazole, a traditional anthelmintic drug, could prominently suppress HCC cells in vivo and in vitro. RNA sequence analysis and cellular thermal shift assays showed that flubendazole reduced the expression of PCSK9 protein by direct targeting. The increased expression of PCSK9 in HCC tissues was demonstrated to be correlated with poor prognosis, and the inhibitory ability of flubendazole was selectively dependent on PCSK9 expression. PCSK9 knockdown abolished the antitumor effects of flubendazole in HCC. Mechanistically, flubendazole inhibited the Hedgehog signaling pathway induced by PCSK9, resulting in the downregulation of smoothened (SMO) and GLI Family Zinc Finger 1 (Gli1). Moreover, combining flubendazole with lenvatinib was found more effective than administering lenvatinib only for HCC treatment in vivo and in vitro. These findings reveal the therapeutic potential of flubendazole against HCC and provide clues on new repurposed drugs and targets for cancer treatment.

[Expression level and clinical significance of CD44 and CD33 in 77 patients with benign lymphoadenosis of oral mucosa].

PURPOSE: To investigate the expression and clinical significance of CD44 and CD33 in benign lymphoadenosis of oral mucosa(BLOM). METHODS: From January 2017 to March 2020, seventy-seven BLOM wax blocks from the Department of Pathology of Qingdao Traditional Chinese Medicine Hospital were selected as the experimental group, and 63 cases of normal oral mucosal tissue wax blocks during the same period were selected as the control group. Immunohistochemical method was used to detect the positive expression of CD44 and CD33 in the two groups.Spearman correlation analysis was used to analyze the correlation between the positive expression of CD33 and the positive expression of CD44 in the diseased tissues of BLOM patients.The general information about patients were collected.The relationship between the expression of CD33 and CD44 in the diseased tissues of BLOM patients and the clinicopathological characteristics of BLOM patients were analyzed. SPSS 21.0 software package was used for statistical analysis of the data. RESULTS: The positive expression rates of CD33 in the control group and the experimental group were 95.24% and 63.64%, respectively, and the difference was statistically significant(P＜0.05). The positive expression rates of CD44 in the control group and the experimental group were 93.65% and 67.53%, respectively, and the difference was statistically significant(P＜0.05). The results of Spearman correlation analysis showed that the positive expression of CD33 in the diseased tissues of BLOM patients was positively correlated with the positive expression of CD44 (r=0.834, P=0.002). The expression of CD33 and CD44 in the diseased tissues of patients with BLOM were related to clinical type, degree of inflammation, presence or absence of lymphoid follicles, and lymphocyte infiltration(P＜0.05), but not related to age, gender, course of disease, location, and epithelial surface keratinization(P＞0.05). CONCLUSIONS: The positive expression rate of CD33 and CD44 in the BLOM tissues decreased, which was closely related to the clinical type, degree of inflammation, presence or absence of lymphoid follicles, and lymphocyte infiltration.

Reactive-diffusion epidemic model on human mobility networks: Analysis and applications to COVID-19 in China.

The complex dynamics of human mobility, combined with sporadic cases of local outbreaks, make assessing the impact of large-scale social distancing on COVID-19 propagation in China a challenge. In this paper, with the travel big dataset supported by Baidu migration platform, we develop a reactive-diffusion epidemic model on human mobility networks to characterize the spatio-temporal propagation of COVID-19, and a novel time-dependent function is incorporated into the model to describe the effects of human intervention. By applying the system control theory, we discuss both constant and time-varying threshold behavior of proposed model. In the context of population mobility-mediated epidemics in China, we explore the transmission patterns of COVID-19 in city clusters. The results suggest that human intervention significantly inhibits the high correlation between population mobility and infection cases. Furthermore, by simulating different population flow scenarios, we reveal spatial diffusion phenomenon of cases from cities with high infection density to cities with low infection density. Finally, our model exhibits acceptable prediction performance using actual case data. The localized analytical results verify the ability of the PDE model to correctly describe the epidemic propagation and provide new insights for controlling the spread of COVID-19.

Probability Distribution Characteristics of Horizontal and Vertical Mechanical Properties of Rubber Bearings.

Rubber bearings are widely used to protect civil structures from destructive earthquakes. The mechanical properties of the bearings are the key technical parameters that determine the seismic isolation performance of isolated structures. To estimate the probability distribution of the mechanical properties related to rubber bearings (including horizontal stiffness, vertical stiffness, post-yield stiffness and yield force) under seismic events. Typical natural rubber bearings (NRBs) and lead-core rubber bearings (LRBs) were designed and fabricated, and the bearings were subjected to repeated load tests using a compression-shear testing machine. The test results of the horizontal and vertical mechanical properties of the bearings in the tests were basically consistent with the design values, and the rubber bearings showed stable mechanical behavior under repeated cyclic loading. The statistical analysis of the test results revealed that the relevant mechanical properties of the NRB and LRB specimens followed a lognormal or general extreme distribution with coefficients of variation mainly ranging from 0.86% to 5.6%. The dispersion of the yield force of LRB was the largest in the repeated tests of many mechanical parameters of typical rubber bearings.

Primary Hepatoid Adenocarcinoma of the Lung: A Systematic Literature Review.

Background: Hepatoid adenocarcinoma (HAC) of the lung (HAL) is a rare and aggressive extrahepatic adenocarcinoma with an unknown etiology and unfavorable prognosis, which is similar to the pathophysiological characteristics of hepatocellular carcinoma (HCC). Methods: We first presented a 67-year-old patient diagnosed with HAC in the right middle lobe of the lung. Then, a systematic literature search was performed for HAL cases recorded between 1990 and 2020 based on three databases. The clinicopathological features, therapeutic method, and prognosis of this rare disease were reviewed, and corresponding prognostic factors were explored using Kaplan-Meier (K-M) curve and Cox proportional hazards regression model. Additionally, the potential biological mechanisms of HAL were further explored and compared with HCC and lung adenocarcinoma (LUAD) based on online databases. Results: In the present study, we reported an HAL patient who underwent surgical resection combined with chemotherapy and succumbed to disease 13 months after surgery. Additionally, a total of 43 experimental studies with 49 HAL patients, including the present case, met the inclusion criteria and were included in the present review. We found that HAL is characterized by a male-dominated incidence and is more common in the right lung. Patients in the surgical subgroup have a better prognosis than those in the non-surgical subgroup (p = 0.034). Moreover, the Cox proportional hazards regression model demonstrated that surgical resection can significantly improve the prognosis of HAL patients (p = 0.016). HAL is a rare disease associated with gene mutations that has a distinctive cause and unique pathogenesis. Additionally, Afatinib and Gefitinib may be new effective agents to better combat HAL. Conclusion: In conclusion, males may exhibit an increased risk of developing HAL and poorer prognosis than females. Surgical resection combined with chemotherapy may prolong the survival of patients with HAL. HAL has its unique clinicopathological characteristics and biological mechanisms.

Recent Advances on DNAzyme-Based Biosensors for Detection of Uranyl.

Nuclear facilities are widely used in fields such as national defense, industry, scientific research, and medicine, which play a huge role in military and civilian use. However, in the process of widespread application of nuclear technology, uranium and its compounds with high carcinogenic and biologically toxic cause a lot of environmental problems, such as pollutions of water, atmosphere, soil, or ecosystem. Bioensors with sensitivity and specificity for the detection of uranium are highly demand. Nucleic acid enzymes (DNAzyme) with merits of high sensitivity and selectivity for targets as excellent molecular recognition elements are commonly used for uranium sensor development. In this perspective review, we summarize DNAzyme-based biosensors for the quantitative detection of uranyl ions by integrating with diverse signal outputting strategies, such as fluorescent, colorimetry, surface-enhanced Raman scattering, and electrochemistry. Different design methods, limit of detection, and practical applications are fully discussed. Finally, the challenges, potential solutions, and future prospects of such DNAzyme-based sensors are also presented.

Analysis of Esophageal Motility and Reflux Characteristics in Patients with Gastroesophageal Reflux Disease With or Without Extraesophageal Symptoms.

BACKGROUND: The pathogenesis of extraesophageal symptoms of gastroesophageal reflux disease is complex, and esophageal motility and reflux may be involved in it. In this study, we aimed to compare esophageal motility and reflux characteristics in gastroesopha- geal reflux disease patients with and without extraesophageal symptoms by high-resolution manometry and multichannel intraluminal impedance-pH monitoring. METHODS: We retrospectively studied gastroesophageal reflux disease patients between January 2014 and December 2018. All patients had undergone high-resolution manometry and multichannel intraluminal impedance-pH monitoring. The results were compared and analyzed. RESULTS: A total of 59 patients were included in this study. Patients were divided into 3 groups according to their main complaint: only typical symptoms (group A, n = 11), both typical and extraesophageal symptoms (group B, n = 33), and only extraesophageal symp- toms (group C, n = 15). Compared with group A, the lower esophageal sphincter basal pressure, integrated residual pressure, and lower esophageal sphincter length were lower, and the proximal reflux percentages of a weak acid and non-acid reflux were higher in group B and group C (P < .017). The positive rate of esophageal motility disorders was lower in group A than in other groups (P < .05). The propor- tion of patients with multiple rapid swallows/single swallow-distal contractile integral ratio greater than 1-was higher in group A than in other groups (P < .05). CONCLUSIONS: Decreased lower esophageal sphincter pressure and lower esophageal sphincter length, increased proximal esophageal reflux of weak acid and non-acid reflux, esophageal motility disorders, and decreased peristaltic reserve are involved in the pathogenesis of extraesophageal symptoms of gastroesophageal reflux disease.

Consensus-Based Distributed Reduced-Order Observer Design for LTI Systems.

In this article, we refocus on the distributed observer construction of a continuous-time linear time-invariant (LTI) system, which is called the target system, by using a network of observers to measure the output of the target system. Each observer can access only a part of the component information of the output of the target system, but the consensus-based communication among them can make it possible for each observer to estimate the full state vector of the target system asymptotically. The main objective of this article is to simplify the distributed reduced-order observer design for the LTI system on the basis of the consensus communication pattern. For observers interacting on a directed graph, we first address the problem of the distributed reduced-order observer design for the detectable target system and provide sufficient conditions involving the topology information to guarantee the existence of the distributed reduced-order observer. Then, the dependence on the topology information in the sufficient conditions will be eliminated by using the adaptive strategy and so that a completely distributed reduced-order observer can be designed for the target system. Finally, some numerical simulations are proposed to verify the theoretical results.

Consensus of Continuous-Time Linear Multiagent Systems With Discrete Measurements.

This article concerns the robust consensus problem of continuous-time linear multiagent systems (MASs) with uncertainty and discrete-time measurement information, where the output measurement information is in the data-sampled form. Distributed output-feedback protocol with or without controller interaction is proposed for each agent. Specifically, the output-feedback protocol runs in continuous time with an output error correction term mixed with the discrete-time measurement information. The concrete algorithm is given for the construction of the feedback matrices. Then, by using the delay-input approach, sufficient conditions are provided for the robust consensus of this kind of MASs interacting over networks described by the directed graphs. Finally, numerical simulations are given to illustrate the theoretical results.

Observer-Based Multiagent Bipartite Consensus With Deterministic Disturbances and Antagonistic Interactions.

This article studies the multiagent bipartite consensus in networks with deterministic disturbances and antagonistic interactions. An observer-based output-feedback controller design is provided to guarantee the bipartite consensus with deterministic disturbances that satisfy the matching condition. Then, by considering that the bandwidths of communication channels are limited in practical systems, the event-triggered scenario of the proposed output controller for the bipartite consensus is further studied; the node-based broadcast updating fashion is utilized and the Zeno behavior is ruled out. Simulations are also offered to support the theoretical results of protocol designs.

Sulfated polysaccharides from pacific abalone attenuated DSS-induced acute and chronic ulcerative colitis in mice via regulating intestinal micro-ecology and the NF-κB pathway.

Due to potential side effects of current drugs in colitis treatment, polysaccharides with anti-inflammatory activities can be considered as alternative molecules for colitis treatment. Sulfated polysaccharide from pacific abalone (AGSP) reduced the level of lipopolysaccharides (LPS) and increased the production of short chain fatty acids in the colon of mice, and it reduced the levels of interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α and increased the IL-10 level in in vitro cell models, suggesting that it can be used as a probiotic agent to inhibit intestinal inflammation. Furthermore, AGSP reduced the disease activity index and intestinal damage, improved the mucosal immune response, and inhibited oxidative damage in mice with DSS-induced acute and chronic colitis, which can be associated with modulation of the NF-κB signaling pathway and gut microbiota. AGSP regulated the structure of the gut microbiota and reduced the level of Bacteroides that had positive correlation with the colitis symptoms. The in vitro result showed that AGSP may inhibit mucin degradation by Bacteroides via the change of the polysaccharide utilization strategy, which can protect intestinal barrier integrity. This study is useful to understand the mechanism by which AGSP ameliorates colitis and related diseases and promotes further development of AGSP.

A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

Drugs behind the veil of Islam: a view of Saudi youth.

Insufficient research exists on drug trafficking and abuse in Saudi Arabia. This paper aims to uncover how drugs are trafficked to Saudi Arabia, what factors contribute to an ever-growing drug use in the Kingdom, and what the life of illegal drug use looks like in such an Islamic environment. Documentary methods and in-depth interviews were adopted to associate drug problems with social environments. It is discovered that drug trafficking is correlated to economic disparity among regions and social strata in the Kingdom, methods of drug purchase differ regionally, and drug use is an unintended consequence of social changes. The study concludes that drug offenses, countering traditional associations of Saudi society, creates a double life in the Kingdom.