SUMO: A new perspective to decipher fibrosis.

Fibrosis is characterized by excessive extracellular matrix (ECM) deposition resulting from dysregulated wound healing and connective tissue repair mechanisms. Excessive accumulation of ECM leads to fibrous tissue formation, impairing organ function and driving the progression of various fibrotic diseases. Recently, the role of small ubiquitin-like modifiers (SUMO) in fibrotic diseases has attracted significant attention. SUMO-mediated SUMOylation, a highly conserved posttranslational modification, participates in a variety of biological processes, including nuclear-cytosolic transport, cell cycle progression, DNA damage repair, and cellular metabolism. Conversely, SUMO-specific proteases cleave the isopeptide bond of SUMO conjugates, thereby regulating the deSUMOylation process. Mounting evidence indicates that SUMOylation and deSUMOylation regulate the functions of several proteins, such as Smad3, NF-κB, and promyelocytic leukemia protein, which are implicated in fibrotic diseases like liver fibrosis, myocardial fibrosis, and pulmonary fibrosis. This review summarizes the role of SUMO in fibrosis-related pathways and explores its pathological relevance in various fibrotic diseases. All evidence suggest that the SUMO pathway is important targets for the development of treatments for fibrotic diseases.

In Vitro Evaluation of Electrospun PCL Bioscaffold with Zinc-Doped Bioactive Glass Powder Addition.

Preparing electrospun fibers by applying a potential difference between a polymeric solution and a contacting substrate is increasingly attracting attention in tissue engineering applications. Among the numerous polymers, polycaprolactone (PCL) bioscaffold has been widely investigated due to its biocompatibility and biodegradability. Bioactive powder can be added to further improve its performance. In the present study, bioactive glass powder modified by adding 0-6 wt.% antibacterial zinc element (coded as ZBG) was prepared through the sol-gel process. Furthermore, PCL bioscaffolds with various ZBG additions were prepared using the electrospinning technique. The zinc-doped bioactive glass powder and electrospun PCL/ZBG bioscaffolds were evaluated using scanning electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy to determine their structural properties. Additionally, in vitro bioactivity, biocompatibility and antibacterial performance were investigated. Experimental results showed that sol-gelled ZBG powder possessed superior bioactivity and 0.8 g ZBG was the optimal addition to prepare PCL/ZBG bioscaffolds with. All the electrospun PCL/ZBG bioscaffolds were biocompatible and their antibacterial performance against two S. aureus strains (SA133 and Newman) improved with increasing zinc concentration. Electrospun PCL/ZBG bioscaffolds exhibited excellent bioactivity and have great potential for biomedical application.

Achieving Higher Critical Current Density in LGPS-Based Lithium Metal Batteries via a Synergistic Interlayer for Physical Inhibition and Chemical Scavenging of Lithium Dendrites.

Li10.35Ge1.35P1.65S12 (LGPS) electrolyte has garnered attention due to its high ionic conductivity and processability. However, its strong incompatibility with lithium metal hinders its practical application. Conventional interlayer strategy isolates Li from LGPS, avoiding the detrimental side reactions, but lithium dendrite penetration is still a problem. To address the aforementioned challenges, we develop a PVDF-HFP-supported PDOL-based interlayer (PDOL/PVDF-HFP), which stabilizes the LGPS/Li interface by synergistically physically inhibiting and chemically scavenging lithium dendrites. The multifunctional feature of the interlayer comes from the use of a bifunctional initiator, InCl3. On the one hand, InCl3 induces the polymerization of DOL, forming a physical separator and protecting lithium from LGPS; on the other hand, in situ reactions between In3+/Cl- and Li form a LiCl/LiF/LiIn hybrid SEI, homogenizing the surface Li+ flux and suppressing lithium dendrite formation and penetration. In addition, an unexpected dynamic microdendrite scavenging is realized by virtue of the side reactions of LGPS/Li, which converts the undesirable reaction to be an advantage in our design. Benefiting from the comprehensive advantages of such design, the constructed sulfide-based solid-state batteries achieve a super low interfacial impedance of 5.1 Ω, a high critical current density (CCD) value over 5 mA/cm2, and a super long cycling stability over 8000 h. Our synergistic interlayer strategy would open an effective avenue for solving interfacial challenges for practical sulfide-based solid-state batteries.

Predictive factors of response to liraglutide in patients with type 2 diabetes mellitus and metabolic syndrome.

Background: Although liraglutide has established advantages in treating patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), there are still some patients with lower responsiveness to liraglutide. The objective of the study was to identify the predictors of response to liraglutide in patients with T2DM and MS. Methods: This retrospective cohort study included patients diagnosed with T2DM and MS who received liraglutide treatment as a part of their diabetes management for a minimum of six months. The participants were stratified into two groups: responders (HbA1c reduction≥1.0% and weight loss≥3%) and non-responders. The discrepancies in baseline data between the two groups were analyzed, containing comedications, test parameters, and basic profiles. The affecting factors of response to liraglutide by Logistic regression analysis were performed, and the predictive ability of the identified factors was evaluated by plotting a receiver operating characteristic (ROC) curve. Results: A total of 417 patients with T2DM and MS were examined and followed up according to the inclusion criteria, and 206 patients completed the follow-up; 105 (50.97%) were responders and 101 (49.03%) were non-responders to liraglutide. The binary logistic regression analysis identified baseline HbA1c, baseline BMI, and the duration of T2DM as significant predictors of glycemic and weight responses to liraglutide (P <0.05). The area under the curve of the ROC for the three predictors of liraglutide response after 6 months of treatment was 0.851 (95% confidence interval: 0.793 - 0.910). Conclusion: The baseline HbA1c, baseline BMI, and duration of T2DM were shown to be predictive factors of glycemic and weight improvements in patients with T2DM and MS treated with liraglutide, and had good predictive power.

Primary adenocarcinoma of the spermatic cord: a case report and review of the literature.

BACKGROUND: Primary malignant neoplasms of the spermatic cord are extremely rare, with most reported cases being sarcomas or metastatic carcinomas. However, primary adenocarcinoma of the spermatic cord has not been previously reported. CASE PRESENTATION: A 34-year-old male with a solid mass in the right spermatic cord, was eventually diagnosed with primary adenocarcinoma. Histological examination revealed a moderately-to-poorly differentiated adenocarcinoma exhibiting glandular, cribriform, or nested growth patterns, characterized by medium to large-sized cells and focal extracellular mucus. Immunohistochemical analysis demonstrated positive staining for CK (AE1/AE3), CK8/18, CK19, MOC31 (EP-CAM), and Ber-EP4, while negative staining was observed for CK7, D2-40, WT-1, MC, PAX-8, NKX3.1, PSA, CEA, TTF-1, and NapsinA. Furthermore, a complete loss of INI-1 expression and consistent BRG1 expression were noted in all tumor cells. Next-generation sequencing revealed SMARCB1 deletion, low tumor mutation burden (TMB-L), and microsatellite stability (MSS). CONCLUSION: We reported the first case of primary adenocarcinoma of the spermatic cord with SMARCB1 (INI-1) deficiency. This case contributes to the expanding understanding of rare neoplasms and underscores the importance of further research into therapeutic strategies targeting SMARCB1-deficient tumors.

Corrigendum: Traumatic stress produces delayed alterations of synaptic plasticity in basolateral amygdala.

[This corrects the article DOI: 10.3389/fpsyg.2019.02394.].

Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer.

This research aims to investigate the impact of Didang decoction (DD) on the formation of neutrophil extracellular traps (NETs) and cancer-associated thrombosis in lung cancer. BALB/c nude mice were used to establish xenograft models for inducing deep vein thrombosis. Tumor growth and thrombus length were assessed. The impact of DD on NET generation was analyzed using enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR, and western blot analysis, both in vivo and in vitro. CI-amidine, a PAD4 inhibitor, was employed to evaluate the role of PAD4 in the generation of NETs. In vivo studies demonstrated that treatment with DD reduced tumor growth, inhibited thrombus formation, and decreased the levels of NET markers in the serum, tumor tissues, neutrophils, and thrombus tissues of mice. Additional data indicated that DD could suppress neutrophil counts, the release of tissue factor (TF), and the activation of thrombin-activated platelets, all of which contributed to increased formation of NETs in mouse models. In vitro, following incubation with conditioned medium (CM) derived from Lewis lung carcinoma cells, the expression of NET markers in neutrophils was significantly elevated, and an extracellular fibrous network structure was observed. Nevertheless, these NET-associated changes were partially counteracted by DD. Additionally, CI-amidine reduced the expression of NET markers in CM-treated neutrophils, consistent with the effects of DD. Collectively, DD inhibits cancer-associated thrombosis in lung cancer by decreasing PAD4-dependent NET formation through the regulation of TF-mediated thrombin-platelet activation. This presents a promising therapeutic strategy for preventing and treating venous thromboembolism in lung cancer.

Characteristics and temporal evolution of asymptomatic diffusion-weighted imaging lesions in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND AND PURPOSE: The role of asymptomatic diffusion-weighted imaging-positive (aDWI+) lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients remains unclear, and their radiographic features may differ from those of symptomatic diffusion-weighted imaging-positive (sDWI+) lesions. We aimed to investigate the clinicoradiographic characteristics of aDWI+ lesions in CADASIL patients. METHODS: We conducted a retrospective analysis using data from the Taiwan CADASIL Registry. aDWI+ lesions were defined as incidentally detected DWI+ lesions without corresponding acute neurological deficits. We compared the baseline clinical characteristics of patients with and without aDWI+ lesions and analyzed their radiological features and evolution in relation to sDWI+ lesions. RESULTS: Among 154 enrolled patients (mean age 62 ± 10 years), 17 (11%) had aDWI+ lesions. Baseline clinical characteristics were similar in the two groups, but those with aDWI+ lesions had more lacunes (median 8 vs. 2), multiple cerebral microbleeds (CMBs; 85% vs. 40%), and anterior temporal white matter hyperintensity (WMH; 47% vs. 14%). Multivariable analysis showed that aDWI+ lesions were associated with anterior temporal WMH (odds ratio 5.7, 95% confidence interval 1.5-21.0) after adjusting for multiple lacunes, multiple CMBs, and total WMH score. Compared to sDWI+ lesions, aDWI+ lesions were more often small infarcts (<1 cm; 89% vs. 23%) and less likely to involve the corticospinal tract (11% vs. 96%). Among the 11 aDWI+ lesions with follow-up magnetic resonance imaging, seven became microinfarcts, three became lacunes, and one disappeared. CONCLUSIONS: aDWI+ lesions in CADASIL are not uncommon and are associated with higher burdens of small vessel disease and anterior temporal WMH. Further research is needed to assess their long-term impact on CADASIL.

Graded Progressive Home-Based Resistance Combined with Aerobic Exercise in Community-Dwelling Older Adults with Sarcopenia: A Randomized Controlled Trial.

Purpose: This randomized parallel controlled trial aimed to determine the effectiveness of graded progressive home-based resistance combined with aerobic exercise in improving physical fitness in community-dwelling older adults with sarcopenia. Patients and Methods: Community-dwelling older adults (≥60 years) with sarcopenia were randomly assigned to the intervention group (IG), receiving 12 weeks of graded progressive home-based resistance and aerobic exercise training, and the control group (CG), maintaining lifestyle unchanged. The primary outcomes were knee extensor muscle strength and the six-minute walk distance (6MWD). Intention-to-treat analysis was applied to the data from all participants in the CG and IG. Post-intervention differences between the intervention and control groups were determined using a generalized estimated equation model with pre-values adjusted. Results: Data from all the participants in the IG (n=41) and CG (n=45) were analyzed. After the intervention, knee extensor muscle strength (95% CI: 0.140-3.460, P=0.036), 6MWD (95% CI: 35.350-80.010, P<0.001), flexor muscle strength and the results of 30s bicep curls, 30s chair stand, the chair sit and reach test and back stretch test in the IG were larger and value of the timed up-and-go test was smaller than those in the CG (P<0.05). The body composition, quality of life and their changes showed no group differences. The attendance rates were 82.9% and 85.4% for resistance and aerobic exercise, respectively. Conclusion: The 12-week graded progressive home-based resistance and aerobic exercise intervention improved muscle strength, balance, flexibility, and cardiorespiratory fitness in community-dwelling older adults with sarcopenia, whereas body composition and quality of life remained unchanged. The research was approved by the Ethics Committee of Soochow University (ECSU-2019000161) and registered at the Chinese Clinical Trial Registry (ChiCTR1900027960, http://www.chictr.org.cn/showproj.aspx?proj=45968).

MercuryII-mediated construction of DNA capsules for turn-on fluorescence detection of melamine.

Researchers have shown significant interest in three-dimensional DNA building blocks due to their potential applications in biomedicine and biosensing. This study focuses on the synthesis of an HgII ion-stabilized DNA capsule with T-HgII-T pairs for the purpose of detecting melamine (MA). MA reacts with HgII to form a MA-HgII-MA complex, which causes HgII to leave the capsule shell, ultimately leading to capsule collapse and release of fluorescent cargo as output signal. Density functional theory (DFT) calculations and X-ray absorption spectroscopy (XAS) were used to demonstrate the ability of MA to extract HgII from the T-HgII-T adducts. The DNA capsules were characterized using TEM, SEM, DLS, zeta-potential, and melting curve analysis, which indicated the successful construction of the HgII-intercalated DNA shell. The MA-triggered destruction of the DNA capsules was visualized by confocal microscopy, and the dynamics of decapsulation were evaluated through fluorescent cargo release. The HgII-stabilized DNA capsules enable MA detection with a detection limit of 0.037 µM and are insensitive to potential interfering ions and amino acids. The tests conducted using MA spiked milk solution resulted in recoveries ranging from 109 to 113% (0.1 µM) and 94.5 to 96% (0.5 µM). These results suggest that the system is promising for highly accurate and reproducible monitoring of MA adulteration.

Apolipoprotein A-I Mimetic Peptide Restores VEGF-induced Angiogenesis in Hypercholesterolemic Ischemic Heart by Reducing HDL Proinflammatory Properties.

VEGF-induced angiogenesis is impaired in hypercholesterolemia. Previous studies showed that an apolipoprotein A-I(ApoA-I) mimetic peptide, D-4F, is able to reduce HDL proinflammatory index in hypercholesterolemia. Whether D-4F promotes angiogenesis in hypercholesterolemia remains unclear. Low-density lipoprotein receptor null (LDLr-/-) mice and LDLr-/-/ApoA-I-/- mice were fed with high-fat diet with or without D-4F (1mg/kg·d). C57BL/6 mice fed with normal diet served as control. The myocardial infarction was induced by ligation coronary artery, and the VEGFA-AAV 9 was injected in heart. The plasma HDL proinflammatory index, cardiac function, infarct size, and angiogenesis related signaling pathways were examined. The HDL proinflammatory index increases in hypercholesterolemic mice. VEGFA stimulates angiogenesis and improves cardiac function in ischemic heart of C57BL/6 mice, but not in hypercholesterolemic mice. D-4F reduces HDL proinflammatory index. D-4F combined with VEGFA stimulates the expression of CD31 and eNOS, activates ERK1/2, reduces infarct size, and improves cardiac function in ischemic heart in hypercholesterolemic LDLr-/- mice but not in hypercholesterolemic LDLr-/-/ApoA-I-/- mice. D-4F restores the VEGF-induced angiogenesis by reducing HDL proinflammatory properties in hypercholesterolemic ischemic heart.

Application of deep learning reconstruction in abdominal magnetic resonance cholangiopancreatography for image quality improvement and acquisition time reduction.

PURPOSE: To compare deep learning (DL)-based and conventional reconstruction through subjective and objective analysis and ascertain whether DL-based reconstruction improves the quality and acquisition speed of clinical abdominal magnetic resonance imaging (MRI). METHODS: The 124 patients who underwent abdominal MRI between January and July 2021 were retrospectively studied. For each patient, two-dimensional axial T2-weighted single-shot fast spin-echo MRI images with or without fat saturation were reconstructed using DL-based and conventional methods. The subjective image quality scores and objective metrics, including signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of the images were analysed. An explorative analysis was performed to compare 20 patients' MRI images with site routine settings, high-resolution settings and high-speed settings. Paired t tests and Wilcoxon signed-rank tests were used for subjective and objective comparisons. RESULTS: A total of 144 patients were evaluated (mean age, 62.2 ± 14.1 years; 83 men). The MRI images reconstructed using DL-based methods had higher SNRs and CNRs than did those reconstructed using conventional methods (all p < 0.01). The subjective scores of the images reconstructed using DL-based methods were higher than those of the images reconstructed using conventional methods (p < 0.01), with significantly lower variation (p < 0.01). Exploratory analysis revealed that the DL-based reconstructions with thin slice thickness and higher temporal resolution had the highest image quality and were associated with the shortest scan times. CONCLUSIONS: DL-based reconstruction methods can be used to improve the quality with higher stability and accelerate the acquisition of abdominal MRI.

Correlation of White Matter Microstructure MRI and Inflammatory Cytokine Alterations With Symptom Severity in Premenstrual Syndrome.

BACKGROUND: Women with premenstrual syndrome (PMS) are at increased risk for depression throughout their lives. White matter (WM) microstructure and inflammatory cytokine alterations have been proposed in its etiology. PURPOSE: To investigate whether WM, assessed using diffusion tensor imaging (DTI), and inflammatory cytokine levels are altered in PMS, and to examine the relationships between WM microstructure, inflammatory cytokines, and symptom severity. STUDY TYPE: Prospective. SUBJECTS: Forty-two PMS patients and 58 healthy controls (HCs), categorized according to the daily record of severity of problems (DRSP). FIELD STRENGTH/SEQUENCE: 3-T, echo planar imaging DTI. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured by using tract-based spatial statistics (TBSS). Venous blood was collected to measure cytokines, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Symptoms were assessed by using the DRSP. STATISTICAL TESTS: Two-sample t test or Mann-Whitney U test were used to compare the DRSP and cytokines. Abnormal DTI metrics in WM were extracted and the differences between groups were analyzed by using two sample t-tests. Spearman's correlation (r) was used to assess the relationship between DTI metrics, cytokines, and DRSP. A P-value <0.05 with FDR correction was considered statistically significant. RESULTS: Compared with HCs, PMS patients showed significantly lower FA in the corpus callosum and corona radiata, and significantly higher MD, AD, and RD in the corticospinal tract (CST), and significantly higher MD and RD in the anterior thalamic radiation (ATR). These differential metrics were significantly correlated with DRSP. Patients showed significantly higher IL-1ß and TNF-α than HCs. Moreover, TNF-α correlated positively with MD, AD, and RD in both groups (r range, 0.256-0.315). DATA CONCLUSION: Alterations of WM microstructure and IL-1ß and TNF-α may be associated with PMS symptom severity, and TNF-α may correlate with DTI metrics of CST and ATR pathways. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Joint Injection or Aspiration before Total Knee Arthroplasty: Does it Increase the Risk of Periprosthetic Joint Infection?

Background Injections are a common preoperative treatment for patients who eventually undergo total knee arthroplasty (TKA). However, recent studies have shown a relationship between preoperative injections and adverse outcomes following surgery. The purpose of this study was to characterize the type of intra-articular procedure patients receive in the acute period prior to surgery and determine their association with postoperative periprosthetic joint infection (PJI) Methods An observational cohort study was conducted using the Merative MarketScan databases. Patients who underwent primary TKA between April 1, 2019, and July 4, 2021, were included in the study. Patients were grouped according to the type of intra-articular procedure they received in the 90-day period prior to TKA: (i) intra-articular hyaluronic (IA-HA), (ii) intra-articular corticosteroid (IA-CS), (iii) aspiration, and (iv) no drug injections or aspirations. The primary outcome was the postoperative 180-day PJI rate. Results 43,219 patients were included in the study. 11.8% of patients were found to have received at least one injection or aspiration in the 90 days prior to their TKA. The most common injection performed was IA-CS (78.3%), followed by aspiration (13.0%) and IA-HA (8.7%). No image guidance was performed for 92.3% of injections, with most being administered between 61-90 days before surgery (93.6%). 180-day PJI rates were similar between patients with and without injections (OR 1.11, p=.569). Neither drug type nor image guidance had an effect on overall postoperative PJI rate. Conclusion Injections performed prior to TKA do not increase the risk of developing postoperative.

Stephania tetrandra and Its Active Compound Coclaurine Sensitize NSCLC Cells to Cisplatin through EFHD2 Inhibition.

BACKGROUND: Adjuvant chemotherapy, particularly cisplatin, is recommended for non-small cell lung carcinoma (NSCLC) patients at high risk of recurrence. EF-hand domain-containing protein D2 (EFHD2) has been recently shown to increase cisplatin resistance and is significantly associated with recurrence in early-stage NSCLC patients. Natural products, commonly used as phytonutrients, are also recognized for their potential as pharmaceutical anticancer agents. RESULT: In this study, a range of Chinese herbs known for their antitumor or chemotherapy-enhancing properties were evaluated for their ability to inhibit EFHD2 expression in NSCLC cells. Among the herbs tested, Stephania tetrandra (S. tetrandra) exhibited the highest efficacy in inhibiting EFHD2 and sensitizing cells to cisplatin. Through LC-MS identification and functional assays, coclaurine was identified as a key molecule in S. tetrandra responsible for EFHD2 inhibition. Coclaurine not only downregulated EFHD2-related NOX4-ABCC1 signaling and enhanced cisplatin sensitivity, but also suppressed the stemness and metastatic properties of NSCLC cells. Mechanistically, coclaurine disrupted the interaction between the transcription factor FOXG1 and the EFHD2 promoter, leading to a reduction in EFHD2 transcription. Silencing FOXG1 further inhibited EFHD2 expression and sensitized NSCLC cells to cisplatin. CONCLUSIONS: S. tetrandra and its active compound coclaurine may serve as effective adjuvant therapies to improve cisplatin efficacy in the treatment of NSCLC.

Tracheal transplantation: lessons learned that may apply to lung transplantation.

PURPOSE OF REVIEW: The purpose of this review is to explore the lessons learned from experimental and human tracheal transplantation to determine if this information may be applied to lung transplantation. RECENT FINDINGS: Experimental work in animal models and the recent human tracheal transplantation suggests that a robust tracheal vascular supply prevents anastomotic complications. Further, this work demonstrates that tracheal allografts undergo a progressive chimerism as recipient epithelium repopulates the allograft. In contrast to most vascularized composite allografts such as hand and face transplantation that experience high rates of rejection, the tracheal allograft did not demonstrate rejection. This may suggest that tissue chimerism plays a role in evading immune-mediated allograft rejection. SUMMARY: While anastomotic complications and chronic allograft rejection are the most common complications related to lung transplantation, the findings associated with tracheal transplantation may have implications for both reducing complications associated with lung transplantation.

One-Dimensional Red Light-Emissive Organic Manganese(II) Halides as X-Ray Scintillators.

Although metal halide-based X-ray scintillators have obtained significant development with adjustable radioluminescent spectral range, the red light-emitting scintillator has been sparsely reported and remains a great challenge until now. To remedy this research blank, we investigated the scintillating property of red light-emissive one-dimensional (1D) organic manganese halide of (MBIZ)(MnCl3H2O)·H2O (MBIZ = 2-methyl-1H-benzoimidazolium) with a high PLQY of 71% under UV light excitation. Remarkably, this manganese halide single crystal exhibits a compelling X-ray scintillating property in the red light spectral range with a light yield of 19 600 photons MeV-1 and detection limit of 0.204 µGy/s, which is significantly better than the standard dosage for X-ray diagnostics. Furthermore, this manganese halide also exhibits excellent radiation resistance ability toward long-term continuous irradiation of high-dose X-ray with stable radiophotoluminescence intensity. Benefiting from the abovementioned combined merits, (MBIZ)(MnCl3H2O)·H2O demonstrates high-performance X-ray imaging with an outstanding spatial resolution of 11.1 lpmm-1. As far as we know, this is an infrequent red-emissive X-ray scintillator in metal halide materials, which highlights a successful structural design concept to explore new manganese halides as more desirable scintillators and expand the application field in medical diagnosis.

Study on the cross-resistance of Aedes albopictus (Skuse) (Diptera: Culicidae) to deltamethrin and pyriproxyfen.

BACKGROUND: Insecticide resistance poses a significant challenge in the implementation of vector-borne disease control strategies. We have assessed the resistance levels of Aedes albopictus to deltamethrin and pyriproxyfen (PPF) in Fujian Province (China) and investigated the correlation between these resistance levels and mutations in the voltage-gated sodium channel (VGSC). METHODS: The WHO bioassay protocol was used to evaluate the resistance coefficient of Ae. albopictus to deltamethrin and PPF, comparing a susceptible population from the Foshan (FS) area with wild populations from the Sanming (SM), Quanzhou (QZ), Zhangzhou (ZZ), Putian (PT) and Fuzhou (FZ) areas in Fujian Province. Genomic DNA was analyzed by PCR and sequencing to detect knockdown resistance (kdr) in the VGSC, specifically at the pyrethroid resistance alleles V1016V, I1532I and F1534F. Molecular docking was also performed to analyze the binding interactions of PPF and its metabolite 4'-OH-PPF to cytochrome P450 (CYP) 2C19, 2C9 and 3A4 and Ae. albopictus methoprene-tolerant receptors (AeMet), respectively. RESULTS: The analysis of resistance to deltamethrin and PPF among Ae. albopictus populations from the various regions revealed that except for the sensitive population in FS and the SM population, the remaining four regional populations demonstrated resistance levels ranging from 4.31- to 18.87-fold for deltamethrin and from 2.85- to 3.62-fold for PPF. Specifically, the FZ and PT populations exhibited high resistance to deltamethrin, whereas the ZZ and QZ populations approached moderate resistance levels. Also, the resistance of the FZ, PT and ZZ populations to PPF increased slowly but consistently with the increasing trend of deltamethrin resistance. Genomic analysis identified multiple non-synonymous mutations within the VGSC gene; the F1534S and F1534L mutations showed significant resistance to deltamethrin in Ae. albopictus. Molecular docking results revealed that PPF and its metabolite 4'-OH-PPF bind to the Ae. albopictus AeMet receptor and CYP2C19. CONCLUSIONS: The wild Ae. albopictus populations of Fujian Province showed varying degrees of resistance to deltamethrin and PPF and a trend of cross-resistance to deltamethrin and PPF. Increased vigilance is needed for potential higher levels of cross-resistance, especially in the PT and FZ regions.

Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway.

Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion (I/R) injury, and the related mechanisms are unclear. Our previous study has shown that adipose stem cell-derived exosomes (ADSC-Exos) contain high levels of Mir221 and Mir222. The present study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of Mir221 and Mir222 in ADSC-Exos. Wild-type, mir221- and mir222-knockout (KO), and Mir221- and Mir222-overexpressing transgenic (TG) mice were intratracheally injected with PM (10 mg/kg). After 24 h, mice underwent left coronary artery ligation for 30 min, followed by 3 h of reperfusion (I/R). H9c2 cardiomyocytes were cultured under 1% O2 for 6 h, then reoxygenated for 12 h (hypoxia-reoxygenation [H/R]). PM aggravated I/R (or H/R) cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, which increased the expression of mitochondrial fission-related proteins (DNM1L/Drp1 and MFF) and mitophagy-related proteins (BNIP3 and MAP1LC3B/LC3B) in vivo and in vitro. Treatment with ADSC-Exos or Mir221- and Mir222-mimics significantly reduced PM+I/R-induced cardiac injury. Importantly, ADSC-Exos contain Mir221 and Mir222, which directly targets BNIP3, MAP1LC3B/LC3B, and BBC3/PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. The present data showed that ADSC-Exos treatment regulated mitophagy and apoptosis through the Mir221 and Mir222-BNIP3-MAP1LC3B-BBC3/PUMA pathway and significantly reduced the cardiac damage caused by PM+I/R. The present study revealed the novel therapeutic potential of ADSC-Exos in alleviating PM-induced exacerbation of myocardial I/R injury.Abbreviation: ADSC-Exos: adipose-derived stem cell exosomes; AL: autolysosome; ATP: adenosine triphosphate; BBC3/PUMA: BCL2 binding component 3; BNIP3: BCL2/adenovirus E1B interacting protein 3; CASP3: caspase 3; CASP9: caspase 9; CDKN1B/p27: cyclin dependent kinase inhibitor 1B; CVD: cardiovascular disease; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DHE: dihydroethidium; DNM1L/Drp1: dynamin 1-like; EF: ejection fraction; FS: fractional shortening; H/R: hypoxia-reoxygenation; I/R: ischemia-reperfusion; LDH: lactate dehydrogenase; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFF: mitochondrial fission factor; miRNA: microRNA; NAC: N-acetylcysteine; OCR: oxygen consumption rate; PIK3C3/Vps34: phosphatidylinositol 3-kinase catalytic subunit type 3; PM: particulate matter; PRKAA1/AMPK: protein kinase AMP-activated catalytic subunit alpha 1; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TRP53/p53: transformation related protein 53; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.

Prediction of the two-dimensional ferromagnetic semiconductor Janus 2H-ZrTeI monolayer with large valley and piezoelectric polarizations.

Two-dimensional room-temperature Janus ferrovalley semiconductors with valley polarization and piezoelectric polarization offer new perspectives for designing multifunctional nanodevices. Herein, using first-principles calculations, we predict that the Janus 2H-ZrTeI monolayer is an intrinsic ferromagnetic semiconductor with in-plane magnetic anisotropy and a Curie temperature of 111 K. The Janus ZrTeI monolayer possesses a significant valley polarization of 141 meV due to time-reversal and inversion symmetry breaking. Based on the valley-contrasting Berry curvature, the anomalous valley Hall effect can be observed under an in-plane electric field. Meanwhile, the breaking of the inversion symmetry and mirror symmetry results in large longitudinal and transverse piezoelectric coefficients. By applying biaxial strain, the Janus 2H-ZrTeI monolayer can also be transformed into a Weyl nodal line semimetal. Furthermore, bilayers of ZrTeI with AB and BA stacking configurations allow the coexistence of valley polarization and ferroelectricity, enabling the manipulation of magnetism, ferroelectric polarization, and valley polarization through interlayer sliding. Our work provides a platform for studying valley polarization, piezoelectricity, and multiferroic coupling, which is significant for the application of multifunctional devices.