Low levels of supercoiled mitochondrial DNA are involved in heart failure induced by transverse aortic constriction in mice via an inflammatory response mediated by ZBP1.

BACKGROUND: Inflammation in the myocardium plays a critical role in cardiac remodeling and the pathophysiology of heart failure (HF). Previous studies have shown that mitochondrial DNA (mtDNA) can exist in different topological forms. However, the specific influence of the ratio of supercoiled/relaxed mtDNA on the inflammatory response in cardiomyocytes remains poorly understood. The aim of this study was to elucidate the differential effects of different mtDNA types on cardiomyocyte inflammation through regulation of ZBP1. MATERIALS AND METHODS: A mouse model of HF was established by transverse aortic constriction (TAC) or doxorubicin (Doxo) induction. Histopathological changes were assessed by HE staining. ELISA was used to measure cytokine levels (IL-1ß and IL-6). Southern blot analysis was performed to examine the different topology of mtDNA. Pearson correlation analysis was used to determine the correlation between the ratio of supercoiled/relaxed mtDNA and inflammatory cytokines. Reverse transcription quantitative PCR (RT-qPCR) was used to measure the mRNA expression levels of cytokines (IL-1ß, IL-6) and Dloop, as an mtDNA marker. RESULTS: The ratio of supercoiled to relaxed mtDNA was significantly increased in the myocardium of Doxo-induced mice, whereas no significant changes were observed in TAC-induced mice. The levels of IL-1ß and IL-6 were positively correlated with the cytoplasmic mtDNA supercoiled/relaxed circle ratio. Different mtDNA topology has different effects on inflammatory pathways. Low supercoiled mtDNA primarily activates the NF-κB (Ser536) pathway via ZBP1, whereas high supercoiled mtDNA significantly affects the STAT1 and STAT2 pathways. The RIPK3-NF-κB pathway, as a downstream target of ZBP1, mediates the inflammatory response induced by low supercoiled mtDNA. Knockdown of TLR9 enhances the expression of ZBP1, p-NF-κB, and RIPK3 in cardiomyocytes treated with low supercoiled mtDNA, indicating the involvement of TLR9 in the anti-inflammatory role of ZBP1 in low supercoiled mtDNA-induced inflammation. CONCLUSION: Different ratios of supercoiled to relaxed mtDNA influence the inflammatory response of cardiomyocytes and contribute to HF through the involvement of ZBP1. ZBP1, together with its downstream inflammatory mechanisms, mediates the inflammatory response induced by a low ratio of supercoiled mtDNA.

Resolidified Chalcogen-Assisted Growth of Bilayer Semiconductors with Controlled Stacking Orders.

Bilayer semiconductors have attracted much attention due to their stacking-order-dependent properties. However, as both 3R- and 2H-stacking are energetically stable at high temperatures, most of the high-temperature grown bilayer materials have random 3R- or 2H-stacking orders, leading to non-uniformity in optical and electrical properties. Here, a chemical vapor deposition method is developed to grow bilayer semiconductors with controlled stacking order by modulating the resolidified chalcogen precursors supply kinetics. Taking tungsten disulfide (WS2 ) as an example, pure 3R-stacking (100%) and 2H-stacking dominated (87.6%) bilayer WS2 are grown by using this method and both show high structural and optical quality and good uniformity. Importantly, the bilayer 3R-stacking WS2 shows higher field effect mobility than 2H-stacking samples, due to the difference in stacking order-dependent surface potentials. This method is universal for growing other bilayer semiconductors with controlled stacking orders including molybdenum disulfide and tungsten diselenide, paving the way to exploit stacking-order-dependent properties of these family of emerging bilayer materials.

HIO3-HIO2-Driven Three-Component Nucleation: Screening Model and Cluster Formation Mechanism.

Iodine oxoacids (HIO3 and HIO2)-driven nucleation has been suggested to efficiently contribute to new particle formation (NPF) in marine atmospheres. Abundant atmospheric nucleation precursors may further enhance HIO3-HIO2-driven nucleation through various multicomponent nucleation mechanisms. However, the specific enhancing potential (EP) of different precursors remains largely unknown. Herein, the EP-based screening model of precursors and enhancing mechanism of the precursor with the highest EP on HIO3-HIO2 nucleation were investigated. The formation free energies (ΔG), as critical parameters for evaluating EP, were calculated for the dimers of 63 selected precursors with HIO2. Based on the ΔG values, (1) a quantitative structure-activity relationship model was developed for evaluating ΔG of other precursors and (2) atmospheric concentrations of 63 (precursor)1(HIO2)1 dimer clusters were assessed to identify the precursors with the highest EP for HIO3-HIO2-driven nucleation by combining with earlier results for the nucleation with HIO3 as the partner. Methanesulfonic acid (MSA) was found to be one of the precursors with the highest EP. Finally, we found that MSA can effectively enhance HIO3-HIO2 nucleation at atmospheric conditions by studying larger MSA-HIO3-HIO2 clusters. These results augment our current understanding of HIO3-HIO2 and MSA-driven nucleation and may suggest a larger impact of HIO2 in atmospheric aerosol nucleation.

Risk factors for penetrating aortic ulcer progression.

OBJECTIVES: This study aimed to explore risk factors leading to asymptomatic penetrating aortic ulcer (PAU) progression. METHODS: This retrospective study reviewed the clinical data of patients who were diagnosed with asymptomatic PAU through incidental imaging findings and underwent imaging follow-up between August 2018 and July 2022. Patients were grouped according to ulcer progression. The risk factors for PAU progression were also analyzed. RESULTS: Among 60 patients with PAU, 32 (53.33%) experienced PAU progression. The mean follow-up time was 555.72±407.60 days. Although there was no statistically significant difference in cancer incidence between the PAU progression group and non-progression group (24 [75%] vs. 18 [64.28%], p=0.409), the difference in antineoplastic therapy use between the progression and non-progression groups was significant (19 [59.38%] vs. 7 [25.00%], p=0.010). There was no difference in the aortic diameter at the PAU (20.68±4.16 mm vs. 20.70±5.28 mm, p=0.990), PAU width (7.32±2.53 mm vs. 7.11±2.29 mm, p=0.741), and PAU depth (4.13±1.26 mm vs. 4.08±1.41 mm, p=0.880) between the two groups. In the progression group, the progression rates of aortic diameter at PAU, PAU width, and PAU depth were 2.16±4.28 mm/year, 5.91±14.49 mm/year and 2.87±5.87 mm/year, respectively. Binary logistic regression analysis showed that antineoplastic therapy was an independent predictor of PAU progression (p=0.017; OR, 4.144; 95% CI, 1.290-13.316). CONCLUSIONS: Antineoplastic therapy may contribute to the progression of asymptomatic PAU in this retrospective study with small number of patients. Patients with asymptomatic PAU who are receiving or have completed antineoplastic therapy should be more vigilant regarding PAU progression.

Nanoparticles transfected with plasmid-encoded lncRNA-OIP5-AS1 inhibit renal ischemia-reperfusion injury in mice via the miR-410-3p/Nrf2 axis.

Nanostructures composed of liposomes and polydopamine (PDA) have demonstrated efficacy as carriers for delivering plasmids, effectively alleviating renal cell carcinoma. However, their role in acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects of the plasmid-encoded lncRNA-OIP5-AS1@PDA nanoparticles (POP-NPs) on renal ischemia/reperfusion (RI/R) injury and explore the underlying mechanisms. RI/R or OGD/R models were established in mice and HK-2 cells, respectively. In vivo, vector or POP-NPs were administered (10 nmol, IV) 48 h after RI/R treatment. In the RI/R mouse model, the OIP5-AS1 and Nrf2/HO-1 expressions were down-regulated, while miR-410-3p expression was upregulated. POP-NPs treatment effectively reversed RI/R-induced renal tissue injury, restoring altered levels of blood urea nitrogen, creatinine, malondialdehyde, inflammatory factors (IL-8, IL-6, TNF-α), ROS, apoptosis, miR-410-3p, as well as the suppressed expression of SOD and Nrf2/HO-1 in the model mice. Similar results were obtained in cell models treated with POP-NPs. Additionally, miR-410-3p mimics could reverse the effects of POP-NPs on cellular models, partially counteracted by Nrf2 agonists. The binding relationship between OIP5-AS1 and miR-410-3p, alongside miR-410-3p and Nrf2, has been substantiated by dual-luciferase reporter and RNA pull-down assays. The study revealed that POP-NPs can attenuate RI/R-induced injury through miR-410-3p/Nrf2 axis. These findings lay the groundwork for future targeted therapeutic approaches utilizing nanoparticles for RI/R-induced AKI.

Chicken Interferon-Alpha and -Lambda Exhibit Antiviral Effects against Fowl Adenovirus Serotype 4 in Leghorn Male Hepatocellular Cells.

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.

Toward a low carbon path: Do E-commerce reduce CO2 emissions? Evidence from China.

To address global climate change, achieving carbon peak and carbon neutrality has become a global consensus. However, the means to simultaneously achieve carbon reduction and promote green economic development, particularly in developing countries, require further investigation. This study evaluates the impact of e-commerce on CO2 emissions. Through an examination of the effects of the National E-Commerce Demonstration City (NEDC) policy from 2006 to 2017, this paper reveals that e-commerce growth facilitated by the NEDC policy resulted in a 7.89% reduction in total CO2 emissions and a per capita reduction of 1.1146 tons in the pilot cities. Mechanism analysis demonstrates that the upgrading of industrial structure, development of digital finance, and the growth of innovation and entrepreneurship serve as primary pathways for this impact. The robustness of the findings is supported by parallel trend tests, placebo tests, and additional sensitivity analyses. Furthermore, the research reveals that the NEDC policy exhibits a more significant reduction in CO2 emissions in cities with higher levels of economic development and non-resource-based cities. Welfare analyses show that the NEDC policy has significant socio-economic effects. These findings provide new evidence on the environmental effects of the digital economy and offer insights into achieving carbon neutrality.

Enhancement of Atmospheric Nucleation Precursors on Iodic Acid-Induced Nucleation: Predictive Model and Mechanism.

Iodic acid (IA) has recently been recognized as a key driver for new particle formation (NPF) in marine atmospheres. However, the knowledge of which atmospheric vapors can enhance IA-induced NPF remains limited. The unique halogen bond (XB)-forming capacity of IA makes it difficult to evaluate the enhancing potential (EP) of target compounds on IA-induced NPF based on widely studied sulfuric acid systems. Herein, we employed a three-step procedure to evaluate the EP of potential atmospheric nucleation precursors on IA-induced NPF. First, we evaluated the EP of 63 precursors by simulating the formation free energies (ΔG) of the IA-containing dimer clusters. Among all dimer clusters, 44 contained XBs, demonstrating that XBs are frequently formed. Based on the calculated ΔG values, a quantitative structure-activity relationship model was developed for evaluating the EP of other precursors. Second, amines and O/S-atom-containing acids were found to have high EP, with diethylamine (DEA) yielding the highest potential to enhance IA-induced nucleation by combining both the calculated ΔG and atmospheric concentration of considered 63 precursors. Finally, by studying larger (IA)1-3(DEA)1-3 clusters, we found that the IA-DEA system with merely 0.1 ppt (2.5×106 cm-3) DEA yields comparable nucleation rates to that of the IA-iodous acid system.

Predictive value of platelet-related hematological markers in indicating the outcomes after laparoscopic intraperitoneal onlay mesh repair (IPOM).

BACKGROUND: The predictive value of hematological markers in the outcomes after laparoscopic intraperitoneal onlay mesh repair (IPOM) remains to be investigated. We aim to evaluate the role of platelet-related parameters after laparoscopic IPOM in patients with incisional hernias. METHODS: The data of 95 patients who underwent laparoscopic IPOM for appendicectomy-related incisional hernias were retrospectively analyzed. The complete blood count analyses were measured preoperatively, and the outcomes were obtained from hospital records and follow-up calls to patients. Platelet-multiple-lymphocyte index (PLM), neutrophil-leukocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) values were calculated. The patients were grouped based on the recurrence and the postoperative complications after surgery. RESULTS: Using cutoff values acquired by the Youden Index, we found platelet levels < 212.0 × 1000/µl, NLR > 2.33, LMR < 3.17, and PLM < 365.5 were revealed to be statistically significant in the recurrence of hernias based on univariant or multivariant analysis (p = < 0.05). We further divided the patients into two groups based on the cutoff value of PLM and found that a PLM value < 365.5 was significantly associated with the recurrence of incisional hernia (p = 0.018), the occurrence of postoperative seroma (p = 0.044), and there is a tendency that patients with PLM < 365.5 may suffer from other postoperative complications such as cardiopathy, respiratory infection, and hypoproteinemia (p = 0.089). CONCLUSION: The preoperative hematological values, especially PLM, may indicate the outcomes in incisional hernias after laparoscopic IPOM.

Resolidified Chalcogen Precursors for High-Quality 2D Semiconductor Growth.

Two-dimensional (2D) semiconductors including transition metal dichalcogenides (TMDCs) have gained attention in optoelectronics for their extraordinary properties. However, the large amount and locally distributed lattice defects affect the optical properties of 2D TMDCs, and the defects originate from unstable factors in the synthesis process. In this work, we develop a method of pre-melting and resolidification of chalcogen precursors (sulfur and selenium), namely resolidified chalcogen, as precursor for the chemical vapor deposition growth of TMDCs with ultrahigh quality and uniformity. Taking WS2 as an example, the monolayer WS2 shows uniform fluorescence intensity and a small full-width at half-maximum of photoluminescence peak at low temperatures with an average value of 13.6±1.9 meV. The defect densities at the interior and edge region are both low and comparable, i.e., (9±3)×1012  cm-2 and (10±4)×1012  cm-2 , indicating its high structural quality and uniformity. This method is universal in growing high quality monolayer MoS2 , WSe2 , MoSe2 , and will benefit their applications.

Layer-Dependent Raman Spectroscopy and Electronic Applications of Wide-Bandgap 2D Semiconductor ß-ZrNCl.

In recent years, 2D layered semiconductors have received much attention for their potential in next-generation electronics and optoelectronics. Wide-bandgap 2D semiconductors are especially important in the blue and ultraviolet wavelength region, although there are very few 2D materials in this region. Here, monolayer ß-type zirconium nitride chloride (ß-ZrNCl) is isolated for the first time, which is an air-stable layered material with a bandgap of ≈3.0 eV in bulk. Systematical investigation of layer-dependent Raman scattering of ZrNCl from monolayer, bilayer, to bulk reveals a blueshift of its out-of-plane A1g peak at ≈189 cm-1 . Importantly, this A1g peak is absent in the monolayer, suggesting that it is a fingerprint to quickly identify the monolayer and for the thickness determination of 2D ZrNCl. The back gate field-effect transistor based on few-layer ZrNCl shows a high on/off ratio of 108 . These results suggest the potential of 2D ß-ZrNCl for electronic applications.

Critical Role of Iodous Acid in Neutral Iodine Oxoacid Nucleation.

Nucleation of neutral iodine particles has recently been found to involve both iodic acid (HIO3) and iodous acid (HIO2). However, the precise role of HIO2 in iodine oxoacid nucleation remains unclear. Herein, we probe such a role by investigating the cluster formation mechanisms and kinetics of (HIO3)m(HIO2)n (m = 0-4, n = 0-4) clusters with quantum chemical calculations and atmospheric cluster dynamics modeling. When compared with HIO3, we find that HIO2 binds more strongly with HIO3 and also more strongly with HIO2. After accounting for ambient vapor concentrations, the fastest nucleation rate is predicted for mixed HIO3-HIO2 clusters rather than for pure HIO3 or HIO2 ones. Our calculations reveal that the strong binding results from HIO2 exhibiting a base behavior (accepting a proton from HIO3) and forming stronger halogen bonds. Moreover, the binding energies of (HIO3)m(HIO2)n clusters show a far more tolerant choice of growth paths when compared with the strict stoichiometry required for sulfuric acid-base nucleation. Our predicted cluster formation rates and dimer concentrations are acceptably consistent with those measured by the Cosmic Leaving Outdoor Droplets (CLOUD) experiment. This study suggests that HIO2 could facilitate the nucleation of other acids beyond HIO3 in regions where base vapors such as ammonia or amines are scarce.

Endovascular Repair of Penetrating Aortic Ulcers: Indications and Single-Center Mid-Term Results.

BACKGROUND: Although endovascular repair is used to treat penetrating aortic ulcers (PAUs), the indications for endovascular repair in PAUs remain controversial. The current study evaluated the mid-term results of endovascular repair for PAUs and further explored the endovascular indications for PAUs. METHODS: We retrospectively reviewed the clinical data of patients who were diagnosed with PAUs and underwent endovascular repair in our department from October 2018 to August 2020. Endovascular indication included persistent or recurring symptoms, a maximum diameter of the PAU of greater than 20 mm, a maximum depth of the PAU of greater than 10 mm, an increase in the diameter of the aorta at the ulcer of greater than 10 mm annually, and multiple ulcers at the same or adjacent level of the aorta. Patient characteristics, anatomical parameters of the PAU, characteristics of endovascular repair and follow-up data were analyzed. RESULTS: 15 patients were included in the study. 3 patients had PAUs in the aortic arch, 6 PAUs were in the descending thoracic aorta, 4 PAUs were in the abdominal aorta, and 2 PAUs were in the descending thoracic and abdominal aortas. The average age was 70.60±8.27 years. Eight patients were symptomatic. The average depth of the PAUs was 7.32±2.74 mm, and the average diameter was 15.03±6.10 mm. The average operation time was 95.60±33.11 min. Postoperative hospital stay was 3.33±0.61 days. A left subclavian artery chimney stent was implanted in 3 aortic arch cases and 1 occluded case without adverse symptoms during the follow-up period. A bifurcated stent graft was placed in 3 abdominal aorta cases and exhibited good patency during the follow-up period. The duration of follow-up ranged from 3 to 24 months. The follow-up results showed that all PAUs were treated satisfactorily by endovascular repair, and no endoleaks or stent graft-related complications occurred. CONCLUSION: Endovascular repair is a safe and effective treatment for PAUs, and it may be safely performed in elderly patients and patients with comorbidities. The endovascular indications for PAUs must be further studied and optimized.

Flexible gas sensor based on graphene/ethyl cellulose nanocomposite with ultra-low strain response for volatile organic compounds rapid detection.

Minimizing the strain-induced undesirable effects is one of the major efforts to be made for flexible electronics. This work demonstrates a highly sensitive flexible gas sensor with ultra-low strain response, which is potentially suitable for wearable electronics applications. The gas sensing material is a free-standing and flexible thin film made of graphene/ethyl cellulose (EC) nanocomposite, which is then integrated with flexible substrate of polyethylene terephthalate. The sensor exhibits relative resistance change within 0.3% at a minimum bending radius of 3.18 mm and 0.2% at the bending radius of 5 mm after 400 bending cycles. The limited strain response attributes to several applied strategies, including using EC with high Young's modulus as the matrix material, maintaining high graphene concentration and adopting suspended device structure. In contrast to the almost negligible strain sensitivity, the sensor presents large and rapid responses toward volatile organic compounds (VOCs) at room temperature. Specifically, the sensor resistance rapidly increases upon the exposure to VOCs with detection limits ranging from 37 to 167 ppm. A preliminary demo of wearable gas sensing capability is also implemented by wearing the sensor on human hand, which successfully detects several VOCs, instead of normal hand gestures.

Unplanned stents in thoracic endovascular aortic repair for type B aortic dissection: A 16-year single-center report.

Background Unplanned stents in thoracic endovascular aortic repair mean additional stents implantation beyond the preoperative planning to achieve operation success. This study aimed to reveal the prevalence and consequences of unplanned stents in thoracic endovascular aortic repair for type B aortic dissection and explore the reasons, risk factors and solutions for unplanned stents. Methods Retrospectively analysis consecutive patients diagnosed as type B aortic dissection with initial tear originating distal from the left subclavian artery and underwent thoracic endovascular aortic repair from September 1998 to June 2014 in our center. Results Under the criteria, this study enrolled 322 patients, with 83 (25.8%) patients in unplanned group. The incidence rate of unplanned stents in thoracic endovascular aortic repair for type B aortic dissection in each year demonstrates as a bimodal curve. The curve showed that, 2003 and, 2004 was the first and highest peak and 2007 was the second peak. There was no difference in five-year survival rate between planned and unplanned patients (log-rank test, p = 0.994). The unplanned group had higher hospitalization expenses (142,699.08 ± 78,446.75 yuan vs. 175,238.58 ± 34,838.01 yuan; p = 0.019), longer operation time (104.50 ± 93.24 min vs. 179.08 ± 142.47 min; p < 0.001) and hospitalization time (17.07 ± 16.62 d vs. 24.00 ± 15.34 d; p = 0.001). The reasons for unplanned stents were type Ia endoleak (46 patients, 55.4%), bird beak (25 patients, 30.1%), and inappropriate shaping of stent (9 patients, 10.8%). Asymptomatic aortic dissection patients had higher incidence of unplanned stents. Short proximal neck length (2.66 ± 0.59 mm vs. 2.50 ± 0.51 mm; p = 0.016), short stent coverage length (154.62 ± 41.12 mm vs. 133.60 ± 44.33 mm; p = 0.002), and large distal stent oversize (75.44±10.77% vs. 82.68±15.80%; p <0.001) were risk factors for unplanned stents in thoracic endovascular aortic repair. Conclusion There are some special risk factors and reasons for unplanned stents in thoracic endovascular aortic repair for type B aortic dissection. Knowing these can we reduce the utilization of unplanned stents with appropriate methods.

[Influence of oversizing of endovascular stent-graft to prognosis of aortic dissection].

With the increasing application of endovascular stent-graft in the treatment of aortic dissection, there are still some problems and controversies in the selection of the stent-graft oversizing. This review summarized the latest research in the study of the baseline and measurement in stent-graft oversizing selection, the relationship between stent-graft oversizing and prognosis and the selection of stent-graft oversizing in different patients with different conditions, providing a reference for the endovascular stent-graft oversizing selection in the treatment of aortic dissection.

Andrographolide inhibits porcine epidemic diarrhea virus by inhibiting the JAK2-STAT3 pathway and promoting apoptosis.

Porcine epidemic diarrhea (PED) is an acute, virulent, and highly contagious disease caused by the porcine epidemic diarrhea virus (PEDV). The high mutation rate of PEDV makes it difficult to effectively control using traditional vaccines, emphasizing the need for novel anti-PEDV-specific drugs. Therefore, this study aimed to investigate the activity and mechanism of action of andrographolide (AND) against PEDV in vitro and in vivo. In vitro experiments showed that AND treatment significantly inhibited PEDV replication in a cell model. The mechanism is that AND treatment significantly suppressed PEDV-induced activation of the JAK2-STAT3 pathway, which promoted apoptosis and inhibited the proliferation of the virus. Moreover, PEDV-infected 3-day-old piglets were treated with AND, and clinical symptoms, intestinal morphology, and viral load were examined. In vivo experiments showed that AND treatment reduced clinical symptoms, ameliorated intestinal damage, and increased the survival rate of infected piglets by 16.7 %. Conclusively, this study contributes to the field of PEDV antiviral drug development and provides new directions for PED prevention and treatment.

Bushen Formula promotes the decrease of HBsAg levels in patients with CHB by regulating Tfh cells and B-cell subsets.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.

Genetic and molecular characterization of H9N2 avian influenza viruses in Yunnan Province, Southwestern China.

The H9N2 subtype of the avian influenza virus (AIV) is widely prevalent in birds, threatening the poultry industry and providing genetic material for emerging human pathogens. The prevalence and genetic characteristics of H9N2 in Yunnan Province, China, are largely unknown. Samples were collected from live poultry markets (LPMs) and breeding farms in Yunnan Province. H9N2-positive samples were identified by polymerase chain reaction (PCR), with a high positivity rate of 42.86% in tissue samples. The positivity rate of swab samples in the LPMs in Kunming was 3.97% (17/564), but no AIV was detected in samples from poultry farms in Lijiang, Wenshan, and Yuxi. Evolutionary analysis and genotyping were performed for the 17 strains of isolated H9N2 virus. Phylogenetic analysis revealed that all H9N2 viral genes had 91.6%-100% nucleotide homology, belonged to the G57 genotype, and had high homology with H9N2 viruses isolated from Guangdong and Guangxi, suggesting that the H9N2 viruses in Yunnan Province may have been imported by chicks. Using a nucleotide divergence cutoff of 95%, we identified ten distinct H9N2 genotypes that continued to evolve. The surface genes of the H9N2 isolates displayed substantial genetic diversity, highlighting the genetic diversity and complexity of the H9N2-subtype AIVs in Yunnan. Molecular analysis demonstrated that all 17 strains of H9N2 isolates had mutations at H183N, Q226L, L31P, and I268V in hemagglutinin; S31N in matrix protein 2; and no replacements at positions 274 and 292 of the neuraminidase protein. Sixteen strains had the A558V mutation and one strain had the E627V mutation in polymerase basic protein 2. Analysis of these amino acid sites suggests that H9N2 influenza viruses in Yunnan continue to mutate and adapt to mammals and are sensitive to neuraminidase inhibitors but resistant to adamantanes. It is necessary to strengthen surveillance of AIV H9N2 subtypes in poultry and LPMs in Yunnan to further understand their genetic diversity.

An inorganic liquid crystalline dispersion with 2D ferroelectric moieties.

Electro-optical effect-based liquid crystal devices have been extensively used in optical modulation techniques, in which the Kerr coefficient reflects the sensitivity of the liquid crystals and determines the strength of the device's operational electric field. The Peterlin-Stuart theory and the O'Konski model jointly indicate that a giant Kerr coefficient could be obtained in a material with both a large geometrical anisotropy and an intrinsic polarization, but such a material is not yet reported. Here we reveal a ferroelectric effect in a monolayer two-dimensional mineral vermiculite. A large geometrical anisotropy factor and a large inherent electric dipole together raise the record value of Kerr coefficient by an order of magnitude, till 3.0 × 10-4 m V-2. This finding enables an ultra-low operational electric field of 102-104 V m-1 and the fabrication of electro-optical devices with an inch-level electrode separation, which has not previously been practical. Because of its high ultraviolet stability (decay <1% under ultraviolet exposure for 1000 hours), large-scale production, and energy efficiency, prototypical displayable billboards have been fabricated for outdoor interactive scenes. This work provides new insights for both liquid crystal optics and two-dimensional ferroelectrics.