Single-cell transcriptome analysis reveals keratinocyte subpopulations contributing to psoriasis in corneum and granular layer.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease that is common and relapses easily. While the importance of keratinocyte proliferation in psoriasis development is well-documented, the specific functional subpopulations of epidermal keratinocytes associated with this disease remain enigmatic. MATERIALS AND METHODS: Therefore, in our analysis of single-cell transcriptome data from both normal and psoriatic skin tissues, we observed significant increases in certain keratinocytes in the stratum corneum (KC) and stratum granulosum (KG) within psoriatic skin. Furthermore, we identified upregulated expression of specific secreted factors known to promote inflammatory responses. Additionally, we conducted a KEGG pathway enrichment analysis on these identified subsets. RESULTS: In the stratum corneum, the expression of FTL was upregulated in HIST1H1C+ KC. S100P+ KC displayed a significant increase in the expression of both S100P and S100A10, whereas PRR9+ KC showed upregulated expression of DEFB4B, S100A8, and S100A12. SLURP1+ KC was characterized by elevated expression levels of IL-36G, SLURP1, and S100A12. Meanwhile, in the stratum granulosum, KRT1+ KG highly expressed SLURP1, S100A7, S100A8, and S100A9, while DEFB4B expression was upregulated in PI3+ KG. Our findings indicated that subsets within the stratum corneum primarily participate in pathways related to MAPK, NOD-like receptors, HIF-1, cell senescence, and other crucial processes. In contrast, subsets in the stratum granulosum were predominantly associated with pathways involving MAPK, NOD-like receptors, HIF-1, Hippo, mTOR, and IL-17. CONCLUSION: These findings not only uncover the keratinocyte subsets linked to psoriasis but also unveil the molecular mechanisms and related signaling pathways that drive psoriasis development. This knowledge opens new horizons for the development of innovative clinical treatment strategies for psoriasis.

Compact and water flushing resistant mesh biofilms forming at short SRT disappeared naturally under extended SRT in dynamic membrane bioreactor.

Extending the solids retention time (SRT) has been demonstrated to mitigate membrane biofouling. Nevertheless, it remains an intriguing question whether the compact and water flushing resistant mesh biofilms developed at short SRT can undergo biodegradation and be removed with extended SRT. In present study, the bio-fouled mesh filter in the 10d-SRT dynamic membrane bioreactor (DMBR), with mesh surfaces and pores covered by compact and water flushing resistant biofilms exhibiting low water permeability, was reused in the 40d-SRT DMBR without any cleanings. After being reused at 40d-SRT, its flux driven by gravity occurred from the 10th day and recovered to a regular level of 36.7 L m-2·h-1 on the 27th day. Both scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) analyses indicated that the compact mesh biofilms formed at10d-SRT biodegraded and were removed at 40d-SRT, with the residual biofilms becoming removable by water flushing. As a result, the hydraulic resistance of the bio-fouled mesh filter decreased from 4.36 × 108 to 6.97 × 107 m-1, and its flux fully recovered. The protein and polysaccharides densities in mesh-biofilms decreased from 24.4 to 9.7 mg/cm2 and from 10.7 to 0.10 mg/cm2, respectively, which probably have contributed to the disappearance of compact biofilms and the decrease in adhesion. Furthermore, the sludge and mesh-biofilms in the 40d-SRT reactor contained a higher relative abundance of dominant quorum quenching bacteria, such as Rhizobium (3.52% and 1.35%), compared to those in the 10d-SRT sludge (0.096%) and mesh biofilms (0.79%), which might have been linked to a decline in extracellular polymeric substances and, consequently, the biodegradation and disappearance of compact biofilms.

The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata.

BACKGROUND: Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due to its high prevalence and drug resistance in recent years. C. glabrata has developed many strategies to evade the clearance of the host immune system, thereby causing persistent infection. Although coping with the induced DNA damage is widely acknowledged to be important, the underlying mechanisms remain unclear. RESULTS: The present study provides hitherto undocumented evidence of the importance of the regulatory subunits of CgCK2 (CgCkb1 and CgCkb2) in response to DNA damage. Deletion of CgCKB1 or CgCKB2 enhanced cellular apoptosis and DNA breaks and led to cell cycle delay. In addition, deficiencies in survival upon phagocytosis were observed in Δckb1 and Δckb2 strains. Consistently, disruption of CgCKB1 and CgCKB2 attenuated the virulence of C. glabrata in mouse models of invasive candidiasis. Furthermore, global transcriptional profiling analysis revealed that CgCkb1 and CgCkb2 participate in cell cycle resumption and genomic stability. CONCLUSIONS: Overall, our findings suggest that the response to DNA damage stress is crucial for C. glabrata to survive in macrophages, leading to full virulence in vivo. The significance of this work lies in providing a better understanding of pathogenicity in C. glabrata-related candidiasis and expanding ideas for clinical therapies.

Analgesia with reduced incidence of adverse reactions using flurbiprofen axetil in combination with half standard-dose opioids in primary total knee arthroplasty.

OBJECTIVES: To determine the analgesic effect of flurbiprofen axetil (FBA) combined with half standard-dose opioids in patients undergoing primary unilateral total knee arthroplasty (TKA). MATERIALS AND METHODS: A total of 100 patients undergoing primary TKA were randomly divided into two groups, namely a control group and an experimental group, with 50 patients in each group. All patients received the same dose of FBA in the form of a patient-controlled intravenous analgesia but in the control group this was combined with a standard-dose of opioids and in the experimental group with a half standard-dose of opioids. RESULTS: A visual analogue scale, used to assess the level of pain 8 hours, 48 hours, and 5 days after TKA, showed that pain relief in the experimental group was equal to that in the control group (difference non-significant: p > 0.05). The knee flexion and extension activity in both groups reached target levels on the fifth day after TKA where differences were also not significant: p > 0.05. The incidence of nausea and vomiting after TKA in the experimental group was significantly less than in the control group (p < 0.05). CONCLUSION: The analgesic effect of FBA in combination with half standard-dose opioids was similar to that of FBA in combination with conventional standard-dose opioids, but the incidence of adverse effects involving nausea/vomiting in the experimental group were significantly reduced.

Long-Term Low Dissolved Oxygen Operation Decreases N2O Emissions in the Activated Sludge Process.

Nitrous oxide (N2O) is an important greenhouse gas and a dominant ozone-depleting substance. Nitrification in the activated sludge process (ASP) is an important N2O emission source. This study demonstrated that a short-term low dissolved oxygen (DO) increased the N2O emissions by six times, while long-term low DO operation decreased the N2O emissions by 54% (P < 0.01). Under long-term low DO, the ammonia oxidizer abundance in the ASP increased significantly, and thus, complete nitrification was recovered and no NH3 or nitrite accumulated. Moreover, long-term low DO decreased the abundance of ammonia-oxidizing bacteria (AOB) by 28%, while increased the abundance of ammonia-oxidizing archaea (AOA) by 507%, mainly due to their higher oxygen affinity. As a result, AOA outnumbered AOB with the AOA/AOB amoA gene ratio increasing to 19.5 under long-term low DO. The efficient nitrification and decreased AOB abundance might not increase N2O production via AOB under long-term low DO conditions. The enriched AOA could decrease the N2O emissions because they were reported to lack canonical nitric oxide (NO) reductase genes that convert NO to N2O. Probably because of AOA enrichment, the positive and significant (P = 0.02) correlation of N2O emission and nitrite concentration became insignificant (P = 0.332) after 80 days of low DO operation. Therefore, ASPs can be operated with low DO and extended sludge age to synchronously reduce N2O production and carbon dioxide emissions owing to lower aeration energy without compromising the nitrification efficiency.

Effects of Vaccine-Related Conspiracy Theories on Chinese Young Adults' Perceptions of the HPV Vaccine: An Experimental Study.

This online experiment used the Theory of Planned Behavior to examine the impact of exposure to conspiracy social media messages on Chinese young adults' perceptions of the HPV vaccine. Three major findings were identified. First, exposure to anti-vaccine conspiracy theories resulted in less favorable attitudes toward the HPV vaccine, less positive perceived norms regarding getting vaccinated, and weaker vaccination intentions. Second, people who were more knowledgeable about the HPV vaccine had more favorable attitudes, more positive norms, higher perceived behavioral control, and greater behavioral intentions. Finally, vaccine knowledge moderated the effect of exposure to anti-vaccine conspiracy theories. Our results suggest that, among Chinese young adult social media users, preexisting knowledge of the HPV vaccine may have a protective effect against exposure to online conspiracy theories.

Dosimetric impact of using a commercial metal artifact reduction tool in carbon ion therapy in patients with hip prostheses.

The study investigated the dosimetric impact of an iterative metal artifact reduction (iMAR) tool on carbon ion therapy for pelvic cancer patients with hip prostheses. An anthropomorphic pelvic phantom with unilateral and bilateral hip prostheses was used to simulate pelvic cancer patients with metal implants. The raw data obtained from phantom CT scanning were reconstructed with a regular filtered back projection (FBP) algorithm and then corrected with iMAR. The phantom without hip prosthesis was also scanned and used as a reference ground truth (GT). The CT images of three prostate and four sarcoma patients with unilateral hip prosthesis were also reconstructed by FBP and iMAR algorithm and compared. iMAR algorithm reduced the metal artifacts and the maximum WEPL deviation in phantom images from -19.1 to -0.4 mm. However, the CT numbers cannot be retrieved using iMAR for periprosthetic bone materials, eventually leading to a WEPL deviation of -3.6 mm. The use of iMAR improved large discrepancies in DVHs of PTVs and the gamma index between FBP and GT images but increased the difference in the bladder DVH for bilateral hip prostheses due to newly introduced artifacts. In the patient study, the discrepancies of dose distribution were small on iMAR images when compared with FBP images for most cases, except for two sarcoma cases where gamma analysis failed and dose coverage in 98% of the PTV maximally reduced due to large volume of dark metal artifacts. iMAR reduced the metal artifacts and improved dose distribution accuracy in carbon ion radiotherapy for pelvic cancer. However, the residual and newly introduced artifacts, especially with bilateral hip prostheses, may potentially increase WEPL inaccuracy and dose uncertainty. The use of iMAR has the potential to improve carbon ion treatment planning of pelvic cancer but should be used with caution.

A New Inductive Debris Sensor Based on Dual-Excitation Coils and Dual-Sensing Coils for Online Debris Monitoring.

Lubricants are of key importance for mechanical processing, and exist in nearly every mechanical system. When the equipment is in operation, debris particles will be generated in mechanical lubricants. The detection of debris particles can indicate the wear degree of machinery components, and provide prognosis warning for the system before the fault occurs. In this work, a novel type of inductive debris sensor consisting of two excitation coils and two sensing coils is proposed for online debris monitoring. The developed sensor was proven to be of high sensitivity through experimental verification. The testing results show that, using the designed sensor, ferrous metal debris with a size of 115 µm and nonferrous metal debris with a size of 313 µm in a pipe with an inner diameter of 12.7 mm can be effectively detected. Moreover, the proposed inductive debris sensor structure has better sensitivity at higher throughput and its design provides a useful insight into the development of high-quality sensors with superior performances.

Baicalin Inhibits Cell Proliferation and Inflammatory Cytokines Induced by Tumor Necrosis Factor α (TNF-α) in Human Immortalized Keratinocytes (HaCaT) Human Keratinocytes by Inhibiting the STAT3/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BACKGROUND Baicalin is a flavone isolated from the root of Scutellaria baicalensis and is used in traditional Chinese medicine. Psoriasis is a persistent and recurrent chronic inflammatory skin disease that is characterized by inflammation and increased proliferation of keratinocytes. This study aimed to investigate the effects of baicalin on HaCaT immortalized human keratinocytes in vitro and the molecular mechanisms involved. MATERIAL AND METHODS HaCaT keratinocytes were cultured in increasing concentrations of baicalin at 6.25 µM, 12.5 µM, and 25 µM. The in vitro model of psoriasis was established using HaCaT cells treated with tumor necrosis factor-alpha (TNF-alpha). The MTT assay was used to asses cell viability and apoptosis. Western blot was used to measure the expression of Bcl-2, Bax, pro-caspase-3, and cleaved caspase-3, and enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory cytokines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of STAT3 and p65 mRNA. RESULTS Baicalin reduced cell viability and induced apoptosis of HaCaT human keratinocytes in a dose-dependent manner. Increased cell viability and the expression of inflammatory cytokines by HaCaT cells induced by TNF-alpha were significantly inhibited by baicalin. Baicalin significantly inhibited the activation of the STAT3/NF-kappaB pathway in HaCaT cells stimulated by TNF-alpha. CONCLUSIONS Baicalin inhibited the proliferation and expression of inflammatory cytokines in HaCaT immortalized human keratinocytes in vitro through the inhibition of the STAT3/NF-kappaB signaling pathway.

Mitochondrial complex I bridges a connection between regulation of carbon flexibility and gastrointestinal commensalism in the human fungal pathogen Candida albicans.

Efficient assimilation of alternative carbon sources in glucose-limited host niches is critical for colonization of Candida albicans, a commensal yeast that frequently causes opportunistic infection in human. C. albicans evolved mechanistically to regulate alternative carbon assimilation for the promotion of fungal growth and commensalism in mammalian hosts. However, this highly adaptive mechanism that C. albicans employs to cope with alternative carbon assimilation has yet to be clearly understood. Here we identified a novel role of C. albicans mitochondrial complex I (CI) in regulating assimilation of alternative carbon sources such as mannitol. Our data demonstrate that CI dysfunction by deleting the subunit Nuo2 decreases the level of NAD+, downregulates the NAD+-dependent mannitol dehydrogenase activity, and consequently inhibits hyphal growth and biofilm formation in conditions when the carbon source is mannitol, but not fermentative sugars like glucose. Mannitol-dependent morphogenesis is controlled by a ROS-induced signaling pathway involving Hog1 activation and Brg1 repression. In vivo studies show that nuo2Δ/Δ mutant cells are severely compromised in gastrointestinal colonization and the defect can be rescued by a glucose-rich diet. Thus, our findings unravel a mechanism by which C. albicans regulates carbon flexibility and commensalism. Alternative carbon assimilation might represent a fitness advantage for commensal fungi in successful colonization of host niches.

Anti-Inflammatory Effect of Local Anaesthetic Ropivacaine in Lipopolysaccharide-Stimulated RAW264.7 Macrophages.

The present manuscript intended to investigate the anti-inflammatory effect of ropivacaine on lipopolysaccharide-induced inflammation in RAW 264.7 macrophages. Results suggested that ropivacaine causes significant inhibition of generation of nitric oxide (NO), prostaglandin E2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, as well as expression of their synthesizing enzymes, inducible NO synthase, and cyclooxygenase-2. Moreover, ropivacaine causes inhibition of mitogen-activated protein kinases as well as nuclear factor-kappa B signaling pathway and apoptosis in RAW 264.7 cells. Based on the results, it has been suggested that ropivacaine showed beneficial effect against inflammation.

Pretreatment of printing and dyeing wastewater by Fe/C micro-electrolysis combined with H2O2 process.

A novel iron-carbon (Fe/C) micro-electrolysis combined with H2O2 (ICMH) process was proposed to pretreat the printing and dyeing wastewater (PDW), using a micro-electrolysis filling. The effects of H2O2 concentration, reaction time, initial pH, and Fe/C dosage on chemical oxygen demand (COD) removal rate of PDW were optimized by response surface methodology (RSM). The maximum COD removal rate was approximately 77.65% after 186 min treatment, when the concentration of H2O2, initial pH and the dosage of Fe/C were 8.88 g/L, 1.5 and 837 g/L, respectively. Analysis of variance (ANOVA) showed a high coefficient of determination value (R2 = 0.9780). And H2O2 concentration and initial pH were the key factors to improve the treatment effect. UV-Vis spectra indicated that a significant blue shift at 220 nm, attributing that fused aromatic hydrocarbons were degraded effectively. 3D-EEM spectra analysis showed that the water samples of PDW mainly contained three kinds of organic matter: refractory fulvic acid, soluble microbial metabolites and aromatic proteins, and the degradation rate of these was 81.76%, 53.78% and 70.83%, respectively.

[Digital design of internal fixation for distal femoral fractures via 3D printing and standard parts database].

OBJECTIVE: To study the method of internal fixation by the navigation embedded plate from standard parts database for the distal femoral fractures based on digital design by Mimics software with 3D printing technology, and to explore its feasibility and accuracy. METHODS: A total of 21 cases with distal femoral fractures admitted into the Department of Orthopedics, Affiliated Hospital of Putian University were included in this study. Dicom format data of lamellar CT scanning was imported into Mimics software for 3D anatomical modeling and virtual fracture reduction. The steel plates was chose from standard parts database for virtual internal fixation, and to design the navigation module with screw. 3D printing skeleton, steel plates, navigation module, internal fixation implants were simulated based on the printed bones model. Locations of steel plates and screws were determined by the navigation module. Then the sticking effects of navigation module, screws position and postoperative appearance were observed. After second CT scan and 3D reconstruction, 3D registration was performed to obtain the data of the three-dimensional coordinate values of screws entrance points and piercing points to analyze the results. RESULTS: A total of 21 plates and 180 screws were placed with the assistance of navigation module. CT scanning and 3D reconstruction was performed in twenty-one cases of postoperative bone model. The position of plates was in high accordance with the digital design by Mimics software. There were no significant differences between spatial location of screw entrance points and piercing points. The real operation was quite consistent with preoperative design. Navigation module and the corresponding distal femur bony structure jointed closely. The sticking effects and stability of navigation module were good, which was able to guide placement of steel plates and screws. CONCLUSION: These methods can enhance the accuracy of internal fixation of the standard parts database steel plate in distal femur fractures, with the assistance of navigation module.

Technical note: A method to evaluate the effect of scanning beam delivery error on 3D dose and its utilization on carbon ion radiotherapy for prostate cancer.

PURPOSE: To establish a method for evaluating the effect of scanning ion beam delivery error on three-dimensional (3D) dose reconstructed on patients' CT based on log file. MATERIALS AND METHODS: This study used the MATLAB program to reconstruct the 3D dose on the patient's CT based on the log file (Doselog ) for treatment delivery accuracy check. In addition, differences between the parameters in the log file and the treatment plan, such as the spot position, spot size, and particle number, were analyzed, as well as their effects on the dose distribution. The accuracy of the dose reconstruction algorithm was verified by comparing dose from TPS (DoseTPS ) and the dose recalculated based on the treatment plan (Doserec ). Twenty treatment plans of ten prostate cancer patients received carbon ion therapy, and their corresponding 160 log files were selected for analysis and treatment delivery accuracy check. The regions with dose higher than 10% of the maximum dose were selected and 2 mm/2% criteria were used for global gamma analysis. Multiple linear regression was used to evaluate the relation between dose deviation and delivery errors. RESULTS: For the algorithm accuracy verification, the mean relative dose difference is 1.02% ± 0.12%. For prostate cancer patients treated in our facility using carbon ion radiotherapy, the average passing rate of the gamma analysis between the Doselog and the DoseTPS was 95.3%. The dose deviation caused by the difference in the spot position and the number of particles was smaller than that caused by the spot size deviation. CONCLUSION: This study established a 3D dose verification method based on log files to evaluate the accuracy of daily delivered treatment doses. In our facility, the daily delivered dose accuracy of carbon ion therapy for prostate cancer was mainly affected by the spot size deviation in terms of the machine delivery part.

A novel two-level approach to defect detection in braided CFRP using air-coupled ultrasonic testing.

Air-coupled ultrasonic testing and C-scan technique has been increasingly applied to the braided CFRP structures owing to its non-destruction, non-contact and high visualization characteristics. Due to the noise, structural vibration, and airflow in the process of detection, the accuracy of defect identification is easily deteriorated. To address this issue and further determine the relationship between the ultrasonic acoustical pressure attenuation and structural parameters, a novel two-level identification method based on the modified two-dimensional variational mode decomposition (2D-VMD) has been proposed. In the first level, C-scan images have been sparsely decomposed into ensembles of modes by 2D-VMD method. Then, the modes have been screened by mutual information method to realize the reconstruction of new image in the second level. Experimental results have shown that the proposed method has the good ability to identify defects with a minimum detectable diameter of 1-2 mm. It has been noted that the ultrasonic acoustical pressure attenuation has become remarkably higher in the twill weave CFRP than the plain weave CFRP and the ratio of pressure attenuation between two weave types of CFRP has decreased with the defect depth increase. Meanwhile, shadows around defects in C-scan images have been suppressed to a great extent. It has been demonstrated that the capability of denoising has enabled the developed method with the accurate detection in terms of the shape, size, depth and weave type. With these advantages, the proposed method has provided valuable insights into the development of an effective method for defect detection of braided CFRP structures.

On the Investigation of Frequency Characteristics of a Novel Inductive Debris Sensor.

Lubricants have the ability to reduce frictions, prevent wear, convey metal debris particles and increase the efficiency of heat transfer; therefore, they have been widely used in mechanical systems. To assess the safety and reliability of the machine under operational conditions, the development of inductive debris sensors for the online monitoring of debris particles in lubricants has received more attention from researchers. To achieve a high-precision, high-efficiency sensor for accurate prediction on the degree of wear, the equivalent circuit model of the sensor coil has been established, and its equations discovering the relationship between the induced voltage and excitation frequency have been derived. Furthermore, the influence of excitation frequencies and metal debris on the magnetic flux density has been analyzed throughout the simulations to determine the sensor magnetic field. In order to identify a frequency range suitable for detecting both ferrous and non-ferrous materials with a high level of sensitivity, the analytical analysis and experiments have been conducted to investigate the frequency characteristics of the developed inductive debris sensor prototype and its improved inspection capability. Moreover, the developed inductive debris sensor with the noticeable frequency characteristics has been assessed and its theoretical model has been also validated throughout experimental tests. Results have shown that the detection sensitivity of non-ferrous debris by the developed sensor increases with the excitation frequency in the range of 50 kHz to 250 kHz, while more complex results for the detection of ferrous debris have been observed. The detection sensitivity decreases as the excitation frequency increases from 50 kHz to 300 kHz, and then increases with the excitation frequency from 300 kHz to 370 kHz. This leads to the effective selection of the excitation frequency in the process of inspection. In summary, the investigation into the frequency characteristics of the proposed novel inductive debris sensor has enabled its broad applications and also provided a theoretical basis and valuable insights into the development of inductive debris sensors with improved detection sensitivity.

Research on safety early warning of uranium tailings dam based on abnormal radioactive indexes of water leachate.

The radioactive index value of the leachate of the uranium tailings dam is affected by the internal damage of the dam. Therefore, a way of using the deviation of the radioactive index concentration in the leachate to warn the instability of the dam is innovatively proposed in this paper. Firstly, the SSA-BP algorithm is used to predict and analyze the five groups of parameters U, Ra, ∑ α, ∑ ß and Rn. Then, the deviation between the actual value and the predicted value is computed. Finally, an early warning is given based on the entropy weight extension decision-making model. The model is verified by the leachate environment monitoring data of a uranium tailings dam in southern China from 2016 to 2020, which shows that the model can effectively caution of the instability of the uranium tailings dam and provides a reference for the subsequent decommissioning management.

Alpha-Hemolysin from Staphylococcus aureus Obstructs Yeast-Hyphae Switching and Diminishes Pathogenicity in Candida albicans.

The use of antibiotics can disrupt the body's natural balance and increase the susteptibility of patients towards fungal infections. Candida albicans is a dimorphic opportunistic fungal pathogen with niches similar to those of bacteria. Our aim was to study the interaction between this pathogen and bacteria to facilitate the control of C. albicans infection. Alpha-hemolysin (Hla), a protein secreted from Staphylococcus aureus, causes cell wall damage and impedes the yeast-hyphae transition in C. albicans. Mechanistically, Hla stimulation triggered the formation of reactive oxygen species that damaged the cell wall and mitochondria of C. albicans. The cell cycle was arrested in the G0/G1 phase, CDC42 was downregulated, and Ywp1 was upregulated, disrupting yeast hyphae switching. Subsequently, hyphae development was inhibited. In mouse models, C. albicans pretreated with Hla reduced the C. albicans burden in skin and vaginal mucosal infections, suggesting that S. aureus Hla can inhibit hyphal development and reduce the pathogenicity of candidiasis in vivo.

Elucidation of the underlying mechanism of Hua-ban decoction in alleviating acute lung injury by an integrative approach of network pharmacology and experimental verification.

The pathogenic hyper-inflammatory response has been regarded as the major cause of the severity and death related to acute lung injury (ALI). Hua-ban decoction (HBD) is a classical prescription in traditional Chinese medicine (TCM). It has been extensively used to treat inflammatory diseases; however, its bioactive components and therapeutic mechanisms remain unclear. Here, we established a lipopolysaccharide (LPS)-induced ALI model that presents a hyperinflammatory process to explore the pharmaco-dynamic effect and underlying molecular mechanism of HBD on ALI. In vivo, we confirmed that in LPS-induced ALI mice, HBD improved pulmonary injury by via down-regulating the expression of proinflammatory cytokines, including IL-6, TNF-α, and macrophage infiltration, as well as macrophage M1 polarization. Moreover, in vitro experiments in LPS-stimulated macrophages demonstrated that the potential bioactive compounds of HBD inhibited the secretion of IL-6 and TNF-α. Mechanically, the data revealed that HBD treatment of LPS-induced ALI acted via NF-κB pathway, which regulated macrophage M1 polarization. Additionally, two major HBD compounds, i.e., quercetin and kaempferol, showed a high binding affinity with p65 and IkBα. In conclusion, the data obtained in this study demonstrated the therapeutic effects of HBD, which indicates the possibility for the development of HBD as a potential treatment for ALI.

Supplementation of hyaluronic acid injections with vitamin D improve knee function by attenuating synovial fluid oxidative stress in osteoarthritis patients with vitamin D insufficiency.

Objectives: There is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA. Methods: We investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared. Results: The results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = -0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency. Conclusion: We conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.