Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment. AIM: To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model. METHODS: The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1ß, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice. RESULTS: Transforming growth factor (TGF)-ß1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1ß, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF. CONCLUSION: MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

Exploring the potential of isorhapontigenin: attenuating Staphylococcus aureus virulence through MgrA-mediated regulation.

The emerging prevalence of drug-resistant Staphylococcus aureus isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in S. aureus, orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against S. aureus. Isorhapontigenin effectively inhibits the hemolytic activity of S. aureus in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of S. aureus and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating hla and upregulating the MgrA-regulated gene spa. Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the hla promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The in vivo experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating S. aureus infections. IMPORTANCE: The emergence of antibiotic-resistant Staphylococcus aureus strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of S. aureus virulence represents a significant advance in anti-virulence therapy.

Renal protective effects and mechanisms of Astragalus membranaceus for diabetic kidney disease in animal models: An updated systematic review and meta-analysis.

BACKGROUND: Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear. PURPOSE: This systematic review and meta-analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models. METHODS: Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random-effects models. Heterogeneity was presented as I2. Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results' robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis. RESULTS: Forty studies involving 1543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = -19.12 µmol/l, 95 % CI: -25.02 to -13.23), BUN (MD = -6.72 mmol/l, 95 % CI: -9.32 to -4.12), urinary albumin excretion rate (SMD = -2.74, 95 % CI: -3.57, -1.90), histological changes (SMD = -2.25, 95 % CI: -3.19 to -1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95 % CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = -3.58, 95 % CI: -5.21 to -1.95). AM treatment also decreased fibrosis markers (i.e. TGF-ß1, CTGF, collagen IV, Wnt4 and ß-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group. CONCLUSION: AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics.

Oral Chinese Herbal Medicine plus usual care for diabetic kidney disease: study protocol for a randomized, double-blind, placebo-controlled pilot trial.

Background: Diabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD. Methods: A mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant's perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants' benefits, the data's credibility, and the results' validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy. Discussion: Conducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD. Trial registration number: https://www.chictr.org.cn/, identifier ChiCTR2200062786.

Role of HIF-1α in hypercoagulable state of COPD in rats.

OBJECTIVE: To explore the role of HIF-1α in hypercoagulable state of COPD induced by lipopolysaccharide plus smoking in rats. It also has to explore the regulatory mechanism of HIF-1α-EPO/EDN-1/VEGF pathway by using its activator and inhibitor. METHODS: 60 Sprague-Dawley rats (SD rats) were randomly divided into healthy control group, COPD hypercoagulable control group, activator group, and inhibitor group with 15 rats in each group. The healthy control group was fed freely. The other groups were given smoke and lipopolysaccharide by tracheal instillation to establish the experimental animal model of COPD hypercoagulability. After successful modeling, each experimental group was given 0.9 % sodium chloride solution and corresponding drugs by intraperitoneal injection for 7 days. Lung function was detected after drug administration. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay was used to detect serum D-D,F (1 + 2),IL-6,TNF-α. The mRNA expressions of HIF-1α, EPO, EDN-1, and VEGF were detected by RT-PCR. Western-Blot and IHC were used to detect the expression of HIF-1α, EPO, EDN-1, and VEGF in lung tissue of rats. RESULTS: Compared with the healthy control group, rats in COPD hypercoagulable control group had COPD symptoms/signs, decreased lung function, increased the expression of serum D-D and F (1 + 2), increased the expression of inflammatory factors IL-6,TNF-α, and increased the expression of proteins HIF-1α, EPO, EDN-1 and VEGF. Compared with COPD hypercoagulable control group, lung function in activator group and inhibitor group had no obvious changes. The expressions of serum D-D,F (1 + 2),IL-6,TNF-α in activator group have increased noticeably. The expressions of proteins HIF-1α, EPO, EDN-1, and VEGF have further increased. Compared with COPD hypercoagulable control group, the expression of serum D-D, F (1 + 2), HIF-1α, EPO, EDN-1, and VEGF in the inhibitor group decreased. CONCLUSION: HIF-1α-EPO/EDN-1/VEGF pathway plays an important role in the hypercoagulable state of COPD. HIF-1α inhibitor can improve airway inflammation and reduce hypercoagulability in COPD model rats.

Renal-protective effects of Chinese medicinal herbs and compounds for diabetic kidney disease in animal models: protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic kidney disease (DKD) is a common and severe complication of diabetes that can lead to end-stage renal disease with no cure. The first-line drugs recommended by clinical guidelines fail to achieve satisfactory effects for people with DKD. A Chinese herbal medicine Tangshen Qushi Formula (TQF) shows preliminary efficacy and safety in preserving renal function for people with DKD, but the effects on comprehensive renal outcomes remain unclear. We will conduct a systematic review and meta-analysis to evaluate the effects of TQF herbs and their compounds identified from ultra-high performance liquid chromatography-MS/MS in diabetic animal models with renal outcomes. METHODS: This protocol complies with the guideline Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will include studies investigating the effects of TQF herbs and compounds on diabetic rats or mice with renal outcomes. Six electronic databases will be searched from their inception to February 2023. Quality assessment will be conducted using SYRCLE's risk of bias tool. Standardized or weighted mean differences will be estimated for renal outcomes (creatinine, urea, proteinuria, histological changes, oxidative stress, inflammation, and kidney fibrosis). Data will be pooled using random-effects models. Heterogeneity across studies will be expressed as I2. Sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots and Egger's test will be used to explore publication bias. DISCUSSION: The results of this review will provide valuable insights into the potential effects of TQF in managing DKD. The limitation is that the included studies will be animal studies from specific databases, and the interpretation of the findings must be cautious. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023432895. Registered on 19 July 2023 ( https://www.crd.york.ac.uk/PROSPERO/#recordDetails ).

Anti-atherosclerosis mechanisms associated with regulation of non-coding RNAs by active monomers of traditional Chinese medicine.

Atherosclerosis is the leading cause of numerous cardiovascular diseases with a high mortality rate. Non-coding RNAs (ncRNAs), RNA molecules that do not encode proteins in human genome transcripts, are known to play crucial roles in various physiological and pathological processes. Recently, researches on the regulation of atherosclerosis by ncRNAs, mainly including microRNAs, long non-coding RNAs, and circular RNAs, have gradually become a hot topic. Traditional Chinese medicine has been proved to be effective in treating cardiovascular diseases in China for a long time, and its active monomers have been found to target a variety of atherosclerosis-related ncRNAs. These active monomers of traditional Chinese medicine hold great potential as drugs for the treatment of atherosclerosis. Here, we summarized current advancement of the molecular pathways by which ncRNAs regulate atherosclerosis and mainly highlighted the mechanisms of traditional Chinese medicine monomers in regulating atherosclerosis through targeting ncRNAs.

Effects of Career Adaptability and Self-Efficacy on Transition Shock Among Newly Graduated Nurses During the COVID-19 Pandemic: A Survey Conducted in China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has increased the work pressure of nurses worldwide, and managers must provide support and assistance for the transition period of newly graduated nurses. METHOD: A cross-sectional design was adopted to collect a sample of 318 newly graduated nurses from six hospitals in China during the COVID-19 pandemic. Data were collected using a questionnaire that consisted of a demographic questionnaire, the Transition Shock Scale (2015), the Career Adapt-Ability Scale (2012), and the General Self-Efficacy Scale (2001). RESULTS: The transition shock of newly graduated nurses was 3.77 ± 0.48 in China. Regression analysis showed that transition shock among newly graduated nurses was predicted by career adaptability, general self-efficacy, living with one's parents, and education level, which accounted for 37.7% of the variance in transition shock. CONCLUSION: Newly graduated nurses experienced a relatively high level of transition shock in China during the COVID-19 pandemic. Managers may offer continuing education to reduce the transition shock of newly graduated nurses based on the factors that affect their transition shock. [J Contin Educ Nurs. 2023;54(11):524-532.].

A Review on Cu2O-Based Composites in Photocatalysis: Synthesis, Modification, and Applications.

Photocatalysis technology has the advantages of being green, clean, and environmentally friendly, and has been widely used in CO2 reduction, hydrolytic hydrogen production, and the degradation of pollutants in water. Cu2O has the advantages of abundant reserves, a low cost, and environmental friendliness. Based on the narrow bandgap and strong visible light absorption ability of Cu2O, Cu2O-based composite materials show infinite development potential in photocatalysis. However, in practical large-scale applications, Cu2O-based composites still pose some urgent problems that need to be solved, such as the high composite rate of photogenerated carriers, and poor photocatalytic activity. This paper introduces a series of Cu2O-based composites, based on recent reports, including pure Cu2O and Cu2O hybrid materials. The modification strategies of photocatalysts, critical physical and chemical parameters of photocatalytic reactions, and the mechanism for the synergistic improvement of photocatalytic performance are investigated and explored. In addition, the application and photocatalytic performance of Cu2O-based photocatalysts in CO2 photoreduction, hydrogen production, and water pollution treatment are discussed and evaluated. Finally, the current challenges and development prospects are pointed out, to provide guidance in applying Cu2O-based catalysts in renewable energy utilization and environmental protection.

"Lifting Yang to Dredging Du Meridian Manipulation" acupuncture alleviates cerebral ischemia-reperfusion injury by mediating the NF-κB pathway.

BACKGROUND: Ischemic stroke is a permanent neurological impairment resulting from the narrowing or blockage of blood vessels in the brain. The effectiveness of "Lifting Yang to Dredging Du Meridian Manipulation" (LYDD) acupuncture in clinical treatment of ischemic stroke patients has been well-established. Nevertheless, its mechanism is still uncertain. METHODS: MCAO/R rat models at different time points of reperfusion (24, 36, 48 and 72 h) were constructed, and LYDD acupuncture treatment was performed. Zea-Longa score and TTC staining were used for assessing neurological impairment and cerebral infarct in rats, respectively. The pathological changes of cerebral tissue in each group were observed by HE and Nissl's staining. Cerebral tissue from each group was subjected to RNA-seq, and differentially expressed genes (DEGs) were performed for GO and KEGG enrichment analysis, and hub gene was identified based on the String database and MCODE algorithm. RESULTS: LYDD acupuncture treatment significantly reduced Zea-Longa score, dry-wet weight ratio, infarct area, inflammatory factor levels (IL-1ß and TNF-α), cerebral lesions, number of Nissl body and neuronal apoptosis in the MCAO/R model at different time points of reperfusion. A total of 3518 DEGs were identified in the MCAO/R model compared to the control group, and 3461 DEGs were present in the treatment group compared to the MCAO/R model, and they may be implicated in neurotransmitter transmission, synaptic membrane potential, cell junctions, inflammatory response, immune response, cell cycle, and ECM. The expression trends of BIRC3, LTBR, PLCG2, TLR4 and TRADD mRNAs in the Hub gene were consistent with the RNA-seq results, and LYDD acupuncture treatment significantly inhibited MCAO/R-induced p65 nuclear translocation. CONCLUSIONS: LYDD acupuncture ameliorates cerebral ischemia-reperfusion injury by inhibiting NF-κB pathway activity.

Vitamin B ameliorates PM2.5-induced kidney damage by reducing endoplasmic reticulum stress and oxidative stress in pregnant mice and HK-2.

As an air pollutant, particulate matters 2.5 (PM2.5) poses a severe risk to kidney and the mechanism involves oxidative stress and endoplasmic reticulum (ER) stress. As an essential nutrient for human health, Vitamin B performs anti-inflammatory and antioxidant functions. In order to study the effect of Vitamin B on PM2.5-induced kidney damage during pregnancy, the pregnant mice were divided into the four experimental groups randomly: control group, model group, treatment group and VB group. PM2.5 was sprayed on the trachea of pregnant mice once each three days for six times from pregnancy until delivery. The model group was given 30 µL PM2.5 suspension of 3.456 µg/µL and 10 mL/(kg·d) PBS. The treatment group was given 30 µL PM2.5 suspension of 3.456 µg/µL and 10 mL/(kg·d) Vitamin B. The VB group was given 10 mL/(kg·d) Vitamin B and the control group was given the same dose of PBS. Vitamin B was composed of Vitamin B6, Vitamin B12 and folic acid, with final concentrations are 1.14, 0.02 and 0.06 mg/mL, respectively. The results showed Vitamin B ameliorated PM2.5-induced kidney damage such as improving histopathological change, decreasing expressions of Bip and Chop, increasing expressions of Nrf2, HO-1 and Nqo1. In addition, HK-2 cells were used for cell experiments and were divided into the four groups, in which the dosage of PM2.5 was 75 µg/mL for 24 h and Vitamin B was 5 µL/100 µL. The results showed Vitamin B ameliorated PM2.5-induced HK-2 damage, such as decreasing expressions of Bip, Chop, P47phox and ROS, increasing expressions of Nrf2, HO-1, Nqo1 and NO. Our findings showed Vitamin B ameliorated PM2.5-induced kidney damage by reducing ER stress and oxidative stress in pregnant mice and in HK-2.

Molecular detection and identification of Diatrypaceous airborne spores in Australian vineyards revealed high species diversity between regions.

The grapevine trunk disease, Eutypa dieback (ED), causes significant vine decline and yield reduction. For many years, the fungus Eutypa lata was considered the main pathogen causing ED of grapevines in Australia. Recent studies showed other Diatrypaceous fungi were also associated with vines exhibiting dieback symptoms but there is limited information on how these fungal pathogens spread in vineyards. Thus, information on the spore dispersal patterns of Diatrypaceous fungi in different wine regions will assist in identifying high-risk infection periods in vineyards. Using more than 6800 DNA samples from airborne spores collected from eight wine regions in south-eastern Australia over 8 years using a Burkard spore trap, this study investigated the diversity and abundance of Diatrypaceous species, using multi-faceted molecular tools. A multi-target quantitative PCR (qPCR) assay successfully detected and quantified Diatrypaceous spores from 30% of the total samples with spore numbers and frequency of detection varying between regions and years. The high-resolution melting analysis (HRMA) coupled with DNA sequencing identified seven species, with E. lata being present in seven regions and the most prevalent species in the Adelaide Hills, Barossa Valley and McLaren Vale. Cryptovalsa ampelina and Diatrype stigma were the predominant species in the Clare Valley and Coonawarra, respectively while Eutypella citricola and Eu. microtheca dominated in the Hunter Valley and the Riverina regions. This study represents the first report of D. stigma and Cryptosphaeria multicontinentalis in Australian vineyards. This study further showed rainfall as a primary factor that triggers spore release, however, other weather factors that may influence the spore release in different climatic regions of Australia still requires further investigation.

S-Scheme 2D/2D Heterojunction of ZnTiO3 Nanosheets/Bi2WO6 Nanosheets with Enhanced Photoelectrocatalytic Activity for Phenol Wastewater under Visible Light.

The pollution of phenol wastewater is becoming worse. In this paper, a 2D/2D nanosheet-like ZnTiO3/Bi2WO6 S-Scheme heterojunction was synthesized for the first time through a two-step calcination method and a hydrothermal method. In order to improve the separation efficiency of photogenerated carriers, the S-Scheme heterojunction charge-transfer path was designed and constructed, the photoelectrocatalytic effect of the applied electric field was utilized, and the photoelectric coupling catalytic degradation performance was greatly enhanced. When the applied voltage was +0.5 V, the ZnTiO3/Bi2WO6 molar ratio of 1.5:1 had highest degradation rate under visible light: the degradation rate was 93%, and the kinetic rate was 3.6 times higher than that of pure Bi2WO6. Moreover, the stability of the composite photoelectrocatalyst was excellent: the photoelectrocatalytic degradation rate of the photoelectrocatalyst remained above 90% after five cycles. In addition, through electrochemical analysis, XRD, XPS, TEM, radical trapping experiments, and valence band spectroscopy, we found that the S-scheme heterojunction was constructed between the two semiconductors, which effectively retained the redox ability of the two semiconductors. This provides new insights for the construction of a two-component direct S-scheme heterojunction as well as a feasible new solution for the treatment of phenol wastewater pollution.

Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital.

Purpose: Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice. Patients and Methods: In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard. Results: There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9-93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient (P = 0.0003). Importantly, mNGS directly led to a change of treatment regimen in 142 (27.4%) cases, including antibiotic escalation (15.3%), antibiotic de-escalation (9.1%), and early definitive diagnosis to initiate appropriate treatment (3.1%). Conclusion: Our in-house mNGS platform significantly improved the sensitivity for the diagnosis of infectious diseases. mNGS has the potential to improve clinical outcomes by optimizing antimicrobial therapy.

Ciprofloxacin enhances the biofilm formation of Staphylococcus aureus via an agrC-dependent mechanism.

Staphylococcus aureus readily forms biofilms on host tissues and medical devices, enabling its persistence in chronic infections and resistance to antibiotic therapy. The accessory gene regulator (Agr) quorum sensing system plays a key role in regulating S. aureus biofilm formation. This study reveals the widely used fluoroquinolone antibiotic, ciprofloxacin, strongly stimulates biofilm formation in methicillin-resistant S. aureus, methicillin-sensitive S. aureus, and clinical isolates with diverse genetic backgrounds. Crystal violet staining indicated that ciprofloxacin induced a remarkable 12.46- to 15.19-fold increase in biofilm biomass. Confocal laser scanning microscopy revealed that ciprofloxacin induced denser biofilms. Phenotypic assays suggest that ciprofloxacin may enhance polysaccharide intercellular adhesin production, inhibit autolysis, and reduce proteolysis during the biofilm development, thus promoting initial adhesion and enhancing biofilm stability. Mechanistically, ciprofloxacin significantly alters the expression of various biofilm-related genes (icaA, icaD, fnbA, fnbB, eap, emp) and regulators (agrA, saeR). Gene knockout experiments revealed that deletion of agrC, rather than saeRS, abolishes the ciprofloxacin-induced enhancement of biofilm formation, underscoring the key role of agrC. Thermal shift assays showed ciprofloxacin binds purified AgrC protein, thereby inhibiting the Agr system. Molecular docking results further support the potential interaction between ciprofloxacin and AgrC. In summary, subinhibitory concentrations of ciprofloxacin stimulate S. aureus biofilm formation via an agrC-dependent pathway. This inductive effect may facilitate local infection establishment and bacterial persistence, ultimately leading to therapeutic failure.

Immediate neural effects of acupuncture manipulation time for stroke with motor dysfunction: a fMRI pilot study.

Introduction: Acupuncture is widely utilized as a beneficial intervention for the treatment of motor dysfunction after stroke, and its effectiveness depends on the stimulation dose. Manipulation time is an important factor affecting the dose. This trial aimed use fMRI to explore the immediate neural effects in stroke patients with motor dysfunction by different acupuncture manipulation times, to reveal the neural mechanism of acupuncture manipulation. Methods: Thirty participants were divided into three groups according to different acupuncture times. Each group received the same acupoint prescription, although the continuous manipulation time of each acupoint in three groups was 1-min, 2-min, and 3-min, respectively. The NIHSS, FMA and fMRI-BOLD in each participant we obtained before and after acupuncture manipulation. Then, we used the regional homogeneity (ReHo) algorithm to analyze the changes of brain function and to compare the neural effects at different acupuncture manipulation times. Results: There were no significant differences in NIHSS and FMA scores between and within groups. Longitudinal analysis of ReHo values indicated that the right inferior frontal gyrus was activated in the 1-min group, the right insula in the 2-min group, and the right inferior temporal gyrus in the 3-min group. Compared with the 1-min group, the 2-min group showed the ReHo values of the right precentral gyrus was decreased, and the 3-min group showed the left cerebellum posterior lobe was increased, the right posterior cingulate gyrus and the right anterior cingulate gyrus were decreased. Compared with the 2-min group, the 3-min group showed the ReHo values of the right cerebellum anterior lobe was increased. Conclusion: Our findings suggest that acupuncture at different manipulation times caused different changes of the neural effects in stroke patients, and the volume of activated voxel clusters is positively correlated with the manipulation time. Longer acupuncture manipulation could drive SMN and DMN in stroke patients, which may be the potential neurological mechanism of acupuncture manipulation affecting the recovery of motor dysfunction.

Controlled preparation of PAMS hollow core microcapsules with high uniformity and its application in the production of GDP fuel capsules for ICF engineering.

Uniform poly-α-methylstyrene (PAMS) hollow core microcapsules (HCMs) are widely used as templates to fabricate glow discharge polymer (GDP) fuel capsules, which are fundamental devices for inertial confinement fusion (ICF) engineering. The sphericity and surface finish uniformity of PAMS HCMs are critical for achieving high-quality GDP fuel capsules. In this work, millimeter-scale PAMS HCMs were fabricated by a microencapsulation technique. The sphericity and surface finish uniformity were concurrently improved using di-t-butyl peroxide (DTBP). The mechanisms of these effects were also experimentally and theoretically investigated. The results show that DTBP distributes at the O-W2 interface of W1/O/W2 compound droplets, which resists the diffusion of molecules through the O-W2 interface bidirectionally. The resisted diffusion of H2O molecules into the O phase eliminates PAMS HCM surface defects. Additionally, the resistance of fluorobenzene (FB) molecules from diffusing from the O phase into the W2 phase can effectively extend the solidification of W1/O/W2 compound droplets and thus improve the spherical uniformity of the HCMs. Using these improved PAMS HCMs, GDP fuel capsules meeting the stringent requirements for ICF engineering are prepared, and the quality of which is beyond the National Ignition Facility standard.

Revisiting the relationship between complement and ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disorder (IBD) characterized by relapsing chronic inflammation of the colon that causes continuous mucosal inflammation. The global incidence of UC is steadily increasing. Immune mechanisms are involved in the pathogenesis of UC, of which complement is shown to play a critical role by inducing local chronic inflammatory responses that promote tissue damage. However, the function of various complement components in the development of UC is complex and even paradoxical. Some components (e.g. C1q, CD46, CD55, CD59, and C6) are shown to safeguard the intestinal barrier and reduce intestinal inflammation, while others (e.g. C3, C5, C5a) can exacerbate intestinal damage and accelerate the development of UC. The complement system was originally thought to function primarily in an extracellular mode; however, recent evidence indicates that it can also act intracellularly as the complosome. The current study provides an overview of current studies on complement and its role in the development of UC. While there are few studies that describe how intracellular complement contributes to UC, we discuss potential future directions based on related publications. We also highlight novel methods that target complement for IBD treatment.

Efficacy and safety of electric acupuncture in treatment of intractable facial paralysis: A protocol for systematic review and meta-analysis.

BACKGROUND: Facial paralysis is a common clinical disease, it was named intractable facial paralysis when the clinical course more than 2 months. Intractable facial paralysis will produce anxiety and depression, which will seriously affect patients' life and work. Electric acupuncture has been widely used in the treatment of intractable facial paralysis. However, the results of clinical studies on the efficacy and safety have been inconsistent. This study aims to evaluate the efficacy and safety of electric acupuncture for intractable facial paralysis patients by systematic review and meta-analysis, so as to provide clinical decision-making based on evidence-based medicine. METHODS: The following databases will be searched by electronic methods: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, VIP Database, Wan-fang Data and Chinese Biomedical Database. All of them will be retrieved from the establishment date of the electronic database to March 2022, all included studies will be evaluated risk of bias by the Cochrane Handbook. The total effective rate will be the primary outcome. The systematic review will be conducted with the use of the RevMan5.3 software in this study. RESULTS: This study will obtain efficacy and safety of electric acupuncture for the treatment of intractable facial paralysis. DISCUSSION: This study will provide clinical decision-making based on evidence-based medicine that whether electric acupuncture could be used to treat intractable facial paralysis, and when and how it might be more effective and safety. It will help standardize electric acupuncture treatment strategies for intractable facial paralysis. PROSPERO REGISTRATION NUMBER: CRD42021278541.