Incorporation of amylose improves rheological and textural properties of Moringa oleifera seed salt-soluble protein.

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

Suppressing anti-citrullinated protein antibody-induced osteoclastogenesis in rheumatoid arthritis using anti-CD64 and PAD-2 inhibitors.

OBJECTIVES: To evaluate the role of Fcγ receptors (FcγR) and peptidyl arginine deiminase (PAD) in anti-citrullinated protein antibody (ACPA)-induced fibroblast-like synoviocytes (FLSs)-mediated osteoclastogenesis in patients with rheumatoid arthritis (RA). METHODS: FLSs and peripheral blood mononuclear cells were collected from patients with RA. We stimulated RA-FLS with ACPA (100 ng/ml) with and without anti-cluster of differentiation (CD)32a/CD64 (FcγRIIA/FcγRI) antibody and PAD-2/4 inhibitors. Flow cytometry and enzyme-linked immunosorbent assay were also performed. CD14+ monocytes were cultured with receptor activator of nuclear factor kappa beta (RANKL) and macrophage colony-stimulating factor, and ACPA-stimulated RA-FLSs were added. These cells were cultured for 14 days, and osteoclastogenesis was quantified using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: ACPA increased RANKL+ and tumour necrotic factor-alpha (TNF-α+) FLS, which decreased dose-dependently by adding 5 and 10 ug/mL anti-CD64 antibody rather than anti-CD32a antibody. In PAD inhibitor experiments, the proportion of RANKL+ and TNF-α+ FLS decreased in 50 µM condition containing PAD-2 inhibitor rather than PAD-4 inhibitor. The co-culture of ACPA-stimulated RA-FLSs and osteoclast precursors increased the TRAP+ multinucleated osteoclast count, which was decreased by anti-CD64 antibody and PAD2 inhibitor. CONCLUSIONS: The present study showed that ACPA increased RANKL and pro-inflammatory cytokine expression in RA-FLSs, and ACPA-activated RA-FLSs could augment osteoclastogenesis. These processes were inhibited by treatment with anti-CD64 antibody and PAD-2 inhibitors. These results show that CD64 and PAD-2-induced pathways may be involved in ACPA-induced FLS activation and osteoclastogenesis in patients with RA. Therefore, regulating the CD64 and PAD-2 pathways may improve RA treatment.

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry.

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan-Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Discriminant Input Processing Scheme for Self-Assisted Intelligent Healthcare Systems.

Modern technology and analysis of emotions play a crucial role in enabling intelligent healthcare systems to provide diagnostics and self-assistance services based on observation. However, precise data predictions and computational models are critical for these systems to perform their jobs effectively. Traditionally, healthcare monitoring has been the primary emphasis. However, there were a couple of negatives, including the pattern feature generating the method's scalability and reliability, which was tested with different data sources. This paper delves into the Discriminant Input Processing Scheme (DIPS), a crucial instrument for resolving challenges. Data-segmentation-based complex processing techniques allow DIPS to merge many emotion analysis streams. The DIPS recommendation engine uses segmented data characteristics to sift through inputs from the emotion stream for patterns. The recommendation is more accurate and flexible since DIPS uses transfer learning to identify similar data across different streams. With transfer learning, this study can be sure that the previous recommendations and data properties will be available in future data streams, making the most of them. Data utilization ratio, approximation, accuracy, and false rate are some of the metrics used to assess the effectiveness of the advised approach. Self-assisted intelligent healthcare systems that use emotion-based analysis and state-of-the-art technology are crucial when managing healthcare. This study improves healthcare management's accuracy and efficiency using computational models like DIPS to guarantee accurate data forecasts and recommendations.

A local filtering-based energy-aware routing scheme in flying ad hoc networks.

Flying ad hoc network (FANET) is a new technology, which creates a self-organized wireless network containing unmanned aerial vehicles (UAVs). In FANET, routing protocols deal with important challenges due to limited energy, frequent link failures, high mobility of UAVs, and limited communication range of UAVs. Thus, a suitable path is always essential to transmit data between UAVs. In this paper, a local filtering-based energy-aware routing scheme (LFEAR) is proposed for FANETs. LFEAR improves the template of the route request (RREQ) packet by adding three fields, namely the energy, reliable distance, and movement similarity of the relevant route to create stable and energy-efficient paths. In the routing process, LFEAR presents a local filtering construction technique to avoid the broadcasting storm issue. This filter limits the broadcasting range of RREQs in the network. Accordingly, only UAVs inside this local filtered area can rebroadcast RREQs and other UAVs must eliminate these packets. After ending the route discovery process, the destination begins the route selection phase and extracts information about each discovered route, including the number of hops, route energy, reliable distance, and movement similarity. Then, the destination node calculates a score for each path based on the extracted information, selects the route with the highest score, and sends a route reply (RREP) packet to the source node through this route. Finally, the simulation process of LFEAR is performed using the NS2 simulator, and two simulation scenarios, namely change in network density and change in the speed of UAVs, are defined to evaluate network performance. In the first scenario, LFEAR improves energy consumption, packet delivery rate, network lifespan, and delay by 1.33%, 1.77%, 6.74%, and 1.71%, while its routing overhead is about 16.51% more than EARVRT. In the second scenario, LFEAR optimizes energy consumption and network lifetime by 5.55% and 5.67%, respectively. However, its performance in terms of routing overhead, packet delivery rate, and delay is 23%, 2.29%, and 6.67% weaker than EARVRT, respectively.

Interleukin-18 binding protein regulates mast cell activation and mast cell induced osteoclastogenesis of rheumatoid arthritis.

OBJECTIVES: Mast cell activation induces pathological responses, including increased osteoclastogenesis in rheumatoid arthritis (RA). Interleukin (IL)-18 binding protein (IL-18BP) has anti-inflammatory effects. In this study, we evaluated the effect of IL-18BP on mast cell activation and mast cell induced osteoclastogenesis. METHODS: Mast cells were activated by IL-33 (100 ng/mL) and cultured with IL-18BP (10, 50, and 100 ng/mL). The proliferation, apoptosis, and necroptosis of mast cells were measured using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of mast cell enzymes, matrix metalloproteinase (MMP), soluble RANKL (sRANKL), and pro-inflammatory cytokines in the culture media. Monocytes from patients with RA patients (n=5) were cultured with activated mast cells with various concentrations of IL-18BP. TRAP+ multinucleated osteoclasts, bone resorption area, and osteoclast differentiation-related genes were measured. RESULTS: Proliferation of tryptase+chymase+c-kit+FcεR1+ mast cells was suppressed following incubation with IL-18BP (10, 50, and 100 ng/mL). RNA expression levels of tryptase and chymase were reduced by 100 ng/mL IL-18BP. Additionally, the levels of MMP-3/9, IL-17A, IL-6, TNF-α, and sRANKL were significantly inhibited by 100 ng/mL IL-18BP. Annexin V+ and annexin V-PI+ mast cells were reduced following incubation with 100 ng/mL IL-18BP. The addition of IL-33 significantly stimulated mast cell and increased TRAP+ multinucleated cells and bone resorption area, and these effects were suppressed by IL-18BP. The osteoclast-related genes (TRAP, ATP6v0d2, RANK, and cathepsin K) expression were suppressed by IL-18BP. CONCLUSIONS: IL-18BP suppressed mast cell activation and mast cell induced osteoclastogenesis. This suggests a potential anti-arthritic role for IL-18BP in patients with RA.

Structural properties and antioxidant capacity of different aminated starch-phenolic acid conjugates.

Different aminated starch (AS) [EEAS (introducing ethylenediamine into starch using cross-linking-etherification-amination method (CEA)), EPAS (introducing o-phenylenediamine using CEA), OEAS (introducing ethylenediamine using cross-linking-oxidation-amination method (COA)), and OPAS (introducing o-phenylenediamine using COA)] were synthesized. The AS-phenolic acids [gallic acid (GA), syringic acid (SA), and vanillic acid (VA)] conjugates were prepared by laccase-catalyzed reaction. The grafting efficiency of EEAS on GA, SA, and VA was 36.59%, 69.71%, and 68.85%, respectively. SA reduced the maximum depolymerization rate of EEAS. The relative crystallinity of EEAS and EPAS grafted phenolic acid increased, and their particles showed severe breakage in appearance. OEAS-phenolic acid conjugates lost its granular structure and behaved as flakes and lumps, while the surface of OPAS-phenolic acid conjugates remained smooth after grafting phenolic acid. GA increased the DPPH· scavenging efficiency of EEAS from 16.12% to 79.92%. The increased antioxidant capacity of the conjugates suggested that AS-phenolic acids conjugates have high potential for applications.

A Novel Framework for Data Assessment That Uses Edge Technology to Improve the Detection of Communicable Diseases.

Spreading quickly throughout populations, whether animal or human-borne, infectious illnesses provide serious risks and difficulties. Controlling their spread and averting disinformation requires effective risk assessment and epidemic identification. Technology-enabled data analysis on diseases allows for quick solutions to these problems. A Combinational Data Assessment Scheme intended to accelerate disease detection is presented in this paper. The suggested strategy avoids duplicate data replication by sharing data among edge devices. It uses indexed data gathering to improve early detection by using tree classifiers to discern between various kinds of information. Both data similarity and index measurements are considered throughout the data analysis stage to minimize assessment errors. Accurate risk detection and assessment based on information kind and sharing frequency are ensured by comparing non-linear accumulations with accurate shared edge data. The suggested system exhibits high accuracy, low mistakes, and decreased data repetition to improve overall effectiveness in illness detection and risk reduction.

Trivial State Fuzzy Processing for Error Reduction in Healthcare Big Data Analysis towards Precision Diagnosis.

There is a significant public health concern regarding medical diagnosis errors, which are a major cause of mortality. Identifying the root cause of these errors is challenging, and even if one is identified, implementing an effective treatment to prevent their recurrence is difficult. Optimization-based analysis in healthcare data management is a reliable method for improving diagnostic precision. Analyzing healthcare data requires pre-classification and the identification of precise information for precision-oriented outcomes. This article introduces a Cooperative-Trivial State Fuzzy Processing method for significant data analysis with possible derivatives. Trivial State Fuzzy Processing operates on the principle of fuzzy logic-based processing applied to structured healthcare data, focusing on mitigating errors and uncertainties inherent in the data. The derivatives are aided by identifying and grouping diagnosis-related and irrelevant data. The proposed method mitigates invertible derivative analysis issues in similar data grouping and irrelevance estimation. In the grouping and detection process, recent knowledge of the diagnosis progression is exploited to identify the functional data for analysis. Such analysis improves the impact of trivial diagnosis data compared to a voluminous diagnosis history. The cooperative derivative states under different data irrelevance factors reduce trivial state errors in healthcare big data analysis.

Two Undescribed Coumarins from Notopterygium Incisum with Anti-Inflammatory Activity.

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review.

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

Enhancing healthcare IoT systems for diabetic patient monitoring: Integration of Harris Hawks and grasshopper optimization algorithms.

The integration of the Internet of Things (IoT) in healthcare, especially for people with diabetes, allows for constant health monitoring. This means that doctors can watch over patients' health more closely, making sure they catch any issues early on. With this technology, healthcare workers can be more accurate and effective when keeping an eye on how patients are doing. This not only helps in keeping track of patients' health in real-time but also makes the whole process more reliable and efficient.By implementing appropriate routing techniques, the transmission of diabetic patients' data to medical centers will facilitate real-time and timely responses from healthcare professionals. The grasshopper optimization algorithm is employed in the proposed approach to cluster network nodes, resulting in the formation of a network tree that facilitates the establishment of connections between the cluster head and the base station. After identifying the cluster head and establishing the clusters, the second stage of routing is implemented by employing the Harris Hawks optimization algorithm. This algorithm ensures that the data pertaining to diabetic patients is transmitted to the treatment centers and hospitals with minimal delay. For node routing, the optimal next step is selected based on the parameters such as the residual energy of the node, the ratio of delivered data packages, and the number of the neighbors of the node. To continue, first, the MATLAB software is utilized to simulate the proposed method, and then, it is compared with other similar methods. This comparison is conducted based on various parameters, including delay, energy consumption, network throughput, and network lifespan. Compared to other methods, the proposed method demonstrates a significant 33% improvement in the average point-to-point delay parameter in the subsequent iterations or rounds.

Successful secukinumab treatment of generalized pustular psoriasis.

Generalized pustular psoriasis is a rare variant of psoriasis. Evidence recommending generalized pustular psoriasis treatment with secukinumab is limited. This report aims to evaluate the use of secukinumab in two patients with generalized pustular psoriasis. The standard treatment regimen for secukinumab was as follows: 300mg subcutaneously once weekly in weeks 0-4, followed by 300mg every four weeks. The efficacy was evaluated by analyzing the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). One patient had generalized pustular psoriasis, which had developed from palmoplantar pustulosis over 12 years. The second patient was an adolescent with recurrent generalized pustular psoriasis. The first patient achieved PASI-75 response by week 3 and both PASI-90 and a DLQI score of 0 were observed by week 8. The second patient achieved PASI-75 response by week 4 and complete clinical resolution, except for nail changes, and a DLQI of 0 by week 8, without any adverse events.

Costotransverse joint ankylosis and their association with syndesmophyte progression in patients with radiographic axial spondyloarthritis.

Background: Abnormal new bone formation can occur not only in the vertebral body but also can occur in facet, costovertebral, and costotransverse joints in radiographic axial spondyloarthritis (r-axSpA) patients. Little is known about the association between syndesmophyte progression and paravertebral joint ankylosis in r-axSpA. Objectives: Costotransverse joint ankylosis in r-axSpA patients was measured. Furthermore, the association between syndesmophyte progression for 2 years assessed by computed tomography syndesmophyte score (CTSS) and facet, costovertebral, and costotransverse joints ankylosis were evaluated. Design: Single-center, prospective, cohort study. Methods: Whole spine CT images taken at baseline and 2-year follow-up were used to calculate the CTSS of the vertebral body. In addition, ankylosis of the facet/costovertebral/costotransverse joints was scored. CTSS (range, 0-552) and facet joint ankylosis (range, 0-46) were assessed at 23 vertebral units. Costovertebral joints at T1-T12 (range, 0-48) and costotransverse joints at T1-T10 (range, 0-20) were also assessed by independent two readers. Intraclass correlation coefficients (ICC) were calculated to determine inter-reader reliability. Odds ratios (OR) were calculated to identify the associations between syndesmophyte progression and the baseline status of facet, costovertebral, and costotransverse joints. Results: In all, 50 patients with r-axSpA were included. Readers 1 and 2 identified C7-T3 (facet joints), T5-T7 and T12 (costovertebral joints), and T8-T9 (costotransverse joints), as common sites of ankylosis at baseline and at 2-year follow-up. The ICCs for the facet, costovertebral, and costotransverse joints at baseline were 0.876, 0.952, and 0.753, respectively. OR of baseline costovertebral and costotransverse joint ankylosis for predicting syndesmophyte progression of the vertebral body was 4.644 [95% confidence interval (CI), 2.295-9.398] and 1.524 (95% CI, 1.036-2.244), respectively. Conclusion: Costotransverse joint ankylosis in r-axSpA patients can be measured semi-quantitatively on whole spine CT, and ankylosis of the costotransverse and costovertebral joints predicts the progression of syndesmophytes.Trial registration: Not applicable.

Multi-objective and multi constrained task scheduling framework for computational grids.

Grid computing emerged as a powerful computing domain for running large-scale parallel applications. Scheduling computationally intensive parallel applications such as scientific, commercial etc., computational grids is a NP-complete problem. Many researchers have proposed several task scheduling algorithms on grids based on formulating and solving it as an optimization problem with different objective functions such as makespan, cost, energy etc. Further to address the requirements/demands/needs of the users (lesser cost, lower latency etc.) and grid service providers (high utilization and high profitability), a task scheduler needs to be designed based on solving a multi-objective optimization problem due to several trade-offs among the objective functions. In this direction, we propose an efficient multi-objective task scheduling framework to schedule computationally intensive tasks on heterogeneous grid networks. This framework minimizes turnaround time, communication, and execution costs while maximizing grid utilization. We evaluated the performance of our proposed algorithm through experiments conducted on standard, random, and scientific task graphs using the GridSim simulator.

An improved finegrained ciphertext policy based temporary keyword search on encrypted data for secure cloud storage.

We present a temporary keyword search over sensitive and confidential health data in a cloud environment. The cloud constitutes a semi-trusted domain, making it necessary for data owners to secure their data before outsourcing it through techniques like encryption. Attribute-based keyword search techniques tend to perform a search operation using a search token generated by an authorized user. These search tokens can lead to serious privacy threats, as they can extract all ciphertexts that may have been generated along with their keyword. Therefore, restricting search tokens to extract ciphertexts generated within a time interval is a more promising solution. In this paper, we present a novel ciphertext policy fine-grained temporary keyword that prevents the misuse of these search tokens. Further, it mitigates the risk of insider threats within healthcare organizations by limiting the window of opportunity for unauthorized access to minimum. To assess the security, our proposed scheme is formally proven to be secure against Selectively Chosen Keyword Attacks in the generic bilinear group model. Additionally, we demonstrate that the encryption algorithm's complexity is linear in relation to the number of attributes. Our scheme's significance and practicality are revealed by the performance evaluation.

Outcomes of FETD versus UBE in the treatment of L5S1 foraminal stenosis: A comparative study.

Background: The L5S1 level exhibits unique anatomical features compared with other levels. This makes minimally invasive surgery for L5S1 foraminal stenosis (FS) challenging. This study compared the surgical outcomes of full endoscopic transforaminal decompression (FETD) and unilateral biportal endoscopy with the far-lateral approach (UBEFLA) in patients with L5S1FS. Methods: In this retrospective study, 49 patients with L5S1FS were divided into two groups. Of these, 24 patients underwent FETD, 25 patients underwent UBEFLA. The study assessed demographic data, leg pain visual analog scale (VAS) score, back pain VAS score, Oswestry Disability Index (ODI), modified MacNab outcome scale, and radiographic parameters including postoperative lateral facet preservation (POLFP). Results: The Mann-Whitney U test revealed that the UBEFLA group exhibited a higher VAS score for back pain at one week after the operation, whereas the FETD group exhibited a higher leg pain VAS score 6 weeks after the operation. All four undesired MacNab outcomes in the FETD group were attributed to residual leg pain, whereas all five undesired MacNab outcomes in the UBEFLA group were due to recurrent symptoms. Radiographically, the FETD group exhibited greater POLFP. Conclusions: When L5S1FS is performed, there may be challenges in adequately clearing the foraminal space in FETD. On the other hand, UBEFLA allowed for a more comprehensive clearance. However, this advantage of UBEFLA was associated with spinal instability as a future outcome.

Protective effect and mechanism of Hirudo on mice with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease （NAFLD） in mice. METHODS The male ApoE－/－ mice were randomly divided into the model group and Hirudo low- dose and high-dose groups （0.45， 0.9 g/kg）， with 10 mice in each group； another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically， once a day， for 8 consecutive weeks. In the 13th week， the body weight and liver weight of mice in each group were measured after the last medication， and the liver index was calculated； the serum levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF- α）， interleukin-1β （IL-1β）， IL-6， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were detected； the liver pathomorphological changes were observed； the protein expressions of peroxisome proliferator-activated receptor γ（PPARγ） and silence information regulator type 1 （SIRT1） were detected. RESULTS Compared with the control group， the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells， with significant lipid accumulation； the body weight， liver weight and liver index of the mice， and serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C significantly increased， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased （P＜0.01）. Compared with the model group， the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups； the body weight， liver weight and liver index， the serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C decreased significantly， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1， thus having a significant ameliorative effect on NAFLD.

Immune Cells Are DifferentiallyAffected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.