Single-Nucleus Sequencing of Fat Body Reveals Distinct Metabolic and Immune Response Landscapes in Silkworm Larvae after Bombyx mori Nucleopolyhedrovirus Infection.

The fat body plays a central role in the regulation of the life cycle of insects and acts as the major site for detoxification, nutrient storage, energy metabolism, and innate immunity. However, the diversity of cell types in the fat body, as well as how these cell subsets respond to virus infection, remains largely unknown. We used single-nucleus RNA sequencing to identify 23 distinct clusters representing adipocyte, hemocyte, epithelial cell, muscle cell, and glial cell types in the fat body of silkworm larvae. Further, by analysis of viral transcriptomes in each cell subset, we reveal that all fat body cells could be infected by Bombyx mori nucleopolyhedrovirus (BmNPV) at 72 h postinfection, and that the majority of infected cells carried at least a medium viral load, whereas most cells infected by BmNPV at 24 h postinfection had only low levels of infection. Finally, we characterize the responses occurring in the fat body cell clusters on BmNPV infection, which, on one hand, mainly reduce their metabolic functions, involving energy, carbohydrates, lipids, and amino acids, but, on the other hand, initiate a strong antiviral response. Our single-nucleus RNA sequencing analysis reveals the diversity of insect fat body cells and provides a resource of gene expression profiles for a systems-level understanding of their response to virus infection.

The P2X7 receptor mediates NADPH transport across the plasma membrane.

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation.

Establishment and evaluation of a clinical prediction model for cognitive impairment in patients with cerebral small vessel disease.

BACKGROUND: There are currently no effective prediction methods for evaluating the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD). AIMS: To investigate the risk factors for cognitive dysfunction in patients with CSVD and to construct a risk prediction model. METHODS: A retrospective study was conducted on 227 patients with CSVD. All patients were assessed by brain magnetic resonance imaging (MRI), and the Montreal Cognitive Assessment (MoCA) was used to assess cognitive status. In addition, the patient's medical records were also recorded. The clinical data were divided into a normal cognitive function group and a cognitive impairment group. A MoCA score < 26 (an additional 1 point for education < 12 years) is defined as cognitive dysfunction. RESULTS: A total of 227 patients (mean age 66.7 ± 6.99 years) with CSVD were included in this study, of whom 68.7% were male and 100 patients (44.1%) developed cognitive impairment. Age (OR = 1.070; 95% CI = 1.015 ~ 1.128, p < 0.05), hypertension (OR = 2.863; 95% CI = 1.438 ~ 5.699, p < 0.05), homocysteine(HCY) (OR = 1.065; 95% CI = 1.005 ~ 1.127, p < 0.05), lacunar infarct score(Lac_score) (OR = 2.732; 95% CI = 1.094 ~ 6.825, P < 0.05), and CSVD total burden (CSVD_score) (OR = 3.823; 95% CI = 1.496 ~ 9.768, P < 0.05) were found to be independent risk factors for cognitive decline in the present study. The above 5 variables were used to construct a nomogram, and the model was internally validated by using bootstrapping with a C-index of 0.839. The external model validation C-index was 0.867. CONCLUSIONS: The nomogram model based on brain MR images and clinical data helps in individualizing the probability of cognitive impairment progression in patients with CSVD.

Association of blood cadmium concentration with chronic obstructive pulmonary disease progression: a prospective cohort study.

BACKGROUND: Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. METHODS: Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. RESULTS: Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. CONCLUSION: Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling.

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 µg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.

Deep insights into the assembly mechanisms, co-occurrence patterns, and functional roles of microbial community in wastewater treatment plants.

The understanding of activated sludge microbial status and roles is imperative for improving and enhancing the performance of wastewater treatment plants (WWTPs). In this study, we conducted a deep analysis of activated sludge microbial communities across five compartments (inflow, effluent, and aerobic, anoxic, anaerobic tanks) over temporal scales, employing high-throughput sequencing of 16S rRNA amplicons and metagenome data. Clearly discernible seasonal patterns, exhibiting cyclic variations, were observed in microbial diversity, assembly, co-occurrence network, and metabolic functions. Notably, summer samples exhibited higher α-diversity and were distinctly separated from winter samples. Our analysis revealed that microbial community assembly is influenced by both stochastic processes (66%) and deterministic processes (34%), with winter samples demonstrating more random assembly compared to summer. Co-occurrence patterns were predominantly mutualistic, with over 96% positive correlations, and summer networks were more organized than those in winter. These variations were significantly correlated with temperature, total phosphorus and sludge volume index. However, no significant differences were found among microbial community across five compartments in terms of ß diversity. A core community of keystone taxa was identified, playing key roles in eight nitrogen and eleven phosphorus cycling pathways. Understanding the assembly mechanisms, co-occurrence patterns, and functional roles of microbial communities is essential for the design and optimization of biotechnological treatment processes in WWTPs.

Fungal community composition changes and reduced bacterial diversity drive improvements in the soil quality index during arable land restoration.

Arable land is facing the growing challenge of land degradation due to intensive use and this is beginning to affect global food security. However, active and passive restoration can improve soil characteristics and reshape microbial communities. Despite the increasing focus on changes in microbial communities during restoration, the mechanisms underlying how microbes drive the soil quality index (SQI) in arable land restoration remain unclear. In this study, we selected conventional farmland (CF, heavily intensified) and two restoration strategies (AR, artificial restoration; NR, natural restoration), with the same context (including soil texture, climate, etc.), and measured the microbial indicators over 2 years to investigate the mechanisms driving SQI improvement on restored arable land. The AR and NR treatments resulted in a 50% and 58% increase in SQI, respectively, compared to CF as soil nutrient levels increased, resulting in higher microbial biomasses and enzyme activities. Microbial abundance on the AR land was approximately two times greater than on the NR land due to the introduction of legumes. Bacterial diversity declined, while fungi developed in a more diverse direction under the restoration strategies. The AR and NR areas were mainly enriched with rhizobium (Microvirga, Bradyrhizobium), which contribute to healthy plant growth. The pathogenic fungi (Gibberella, Fusarium, Volutella) were more abundant in the CF area and the plant pathogen guild was about five times higher in the restored areas. Following arable land restoration, microbial life history strategies shifted from r-to K-strategists due to the higher proportion of recalcitrant SOC (DOC/SOC decreased by 18%-30%). The altered microbial community in the restored areas created new levels of functionality, with a 2.6%-4.3% decrease in bacterial energy metabolism (oxidative phosphorylation, C fixation, and N metabolism decreased by 7%, 4%, and 6%, respectively). Structural equation modelling suggested that restoration strategy affected SQI either directly by increasing total soil nutrient levels or indirectly by altering the microbial community and that fungal community composition and bacterial diversity made the largest contributions to SQI. These results provided new insights into soil quality improvement from a microbial perspective and can help guide future arable land restoration.

Blood cadmium concentration and pulmonary function injury: potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients.

BACKGROUND: Exposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown. METHODS: The cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models. RESULTS: Each 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively. CONCLUSION: Blood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

Clinical Performance of Immunonephelometric Assay and Chemiluminescent Immunoassay for Detection of IgG Subclasses in Chinese.

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.

Toxic effect and mechanism of ß-cypermethrin and its chiral isomers on HTR-8/SVneo cells.

Beta-cypermethrin (ß-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of ß-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17ß-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of ß-CYP and its specific isomers. Our results showed that ß-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 µM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and ß-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 µM 1R-trans-αS. Scratch assays revealed that ß-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor ß (ERß), ß-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of ß-CYP, its isomers, and E2 for PDE3A than for ERα or ERß. Consequently, ß-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2, and down-regulation of Myo7a and Pdgfrb, suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms.

Long-term residue returning increased subsoil carbon quality in a rice-wheat cropping system.

Residue returning (RR) was widely implemented to increase soil organic carbon (SOC) in farmland. Extensive studies concentrated on the effects of RR on SOC quantity instead of SOC fractions at aggregate scales. This study investigated the effects of 20-year RR on the distribution of labile (e.g., dissolved, microbial biomass, and permanganate oxidizable organic) and stable (e.g., microbial necromass) carbon fractions at aggregate scales, as well as their contribution to SOC accumulation and mineralization. The findings indicated a synchronized variation in the carbon content of bacterial and fungal necromass. Residue retention (RR) notably elevated the concentration of bacterial and fungal necromass carbon, while it did not amplify the microbial necromass carbon (MNC) contribution to SOC when compared to residue removal (R0) in the topsoil (0-5 cm). In the subsoil (5-15 cm), RR increased the MNC contribution to SOC concentration by 21.2%-33.4% and mitigated SOC mineralization by 12.6% in micro-aggregates (P < 0.05). Besides, RR increased soil ß-glucosidase and peroxidase activities but decreased soil phenol oxidase activity in micro-aggregates (P < 0.05). These indicated that RR might accelerate cellulose degradation and conversion to stable microbial necromass C, and thus RR improved SOC stability because SOC occluded in micro-aggregates were more stable. Interestingly, SOC concentration was mainly regulated by MNC, while SOC mineralization was by dissolved organic carbon under RR, both of which were affected by soil carbon, nitrogen, and phosphorus associated nutrients and enzyme activities. The findings of this study emphasize that the paths of RR-induced SOC accumulation and mineralization were different, and depended on stable and labile C, respectively. Overall, long-term RR increased topsoil carbon quantity and subsoil carbon quality.

Effects of straw biochar on microbial-derived carbon: A global meta-analysis.

Pyrolyzing biomass (e.g., crop straw) to produce biochar is a sustainable strategy in agricultural farmlands. Straw-derived biochar could increase soil organic carbon (SOC) and microbial-derived carbon (C) compared to no addition, while it is imperative to understand the effects of straw-derived biochar compared to its feedstock (e.g., straw). We retrieved 321 and 387 observations to investigate the effects of straw-derived biochar on microbial-derived C (e.g., microbial biomass C (MBC) and microbial necromass C (MNC)) taking no addition and straw as control, respectively. Notably, straw-derived biochar significantly increased dissolved organic C (DOC) by 24.9% and provided available substrates for microbial utilization, thus improving MBC by 16.7% and MNC by 19.7% compared to no addition. Nevertheless, compared to its feedstock (crop straw), straw-derived biochar significantly decreased MBC by 26.1% and MNC by 18.0% attributed to lower DOC, supported by a positive correlation between MBC and DOC (R2 = 0.53). A negative correlation between changes in MBC and SOC indicated the adverse of microbial activity for C accrual under conversion from straw to biochar. Moreover, soil layer, experiment duration, and initial C/N ratio are the crucial factors affecting MBC under the conversion from straw to biochar. Specifically, with significant variations among subgroups, when compared to straw addition, straw-derived biochar had lower reduction in MBC observed on 0-5 cm layers, mean annual precipitation ≥550 mm, mean annual temperature ≥10 °C, clay loam soil, experiment duration≥1 yr, initial SOC≥14 g kg-1, pH≥8, and bulk density ≥1.28 g cm-3. Straw-derived biochar even increased MBC by 32.8% in an anaerobic environment, associated with biochar produced under limited oxygen and anaerobic microorganisms dominating the microbial community. This study concludes that the conversion from crop straw to biochar increases SOC but constrains microbial-derived C, which may disturb the microbial-mediated C-cycling process.

Ratiometric Afterglow Luminescent Imaging of Matrix Metalloproteinase-2 Activity via an Energy Diversion Process.

Ratiometric afterglow luminescent (AGL) probes are attractive for in vivo imaging due to their high sensitivity and signal self-calibration function. However, there are currently few ratiometric AGL probes available for imaging enzymatic activity in living organisms. Here, we present an energy diversion (ED) strategy that enables the design of an enzyme-activated ratiometric AGL probe (RAG-RGD) for in vivo afterglow imaging. The ED process provides RAG-RGD with a radiative transition for an 'always on' 520-nm AGL signal (AGL520) and a cascade three-step energy transfer (ET) process for an 'off-on' 710-nm AGL signal (AGL710) in response to a specific enzyme. Using matrix metalloproteinase-2 (MMP-2) as an example, RAG-RGD shows a significant ~11-fold increase in AGL710/AGL520 toward MMP-2. This can sensitively detect U87MG brain tumors through ratiometric afterglow imaging of MMP-2 activity, with a high signal-to-background ratio and deep imaging depth. Furthermore, by utilizing the self-calibration effect of ratiometric imaging, RAG-RGD demonstrated a strong negative correlation between the AGL710/AGL520 value and the size of orthotopic U87MG tumor, enabling accurate monitoring of orthotopic glioma growth in vivo. This ED process may be applied for the design of other enzyme-activated ratiometric afterglow probes for sensitive afterglow imaging.

Encapsulating Ni Nanoparticles into Interlayers of Nitrogen-Doped Nb2 CTx MXene to Boost Hydrogen Evolution Reaction in Acid.

Design and development of low-cost and highly efficient non-precious metal electrocatalysts for hydrogen evolution reaction (HER) in an acidic medium are key issues to realize the commercialization of proton exchange membrane water electrolyzers. Ni is regarded as an ideal alternative to substitute Pt for HER based on the similar electronic structure and low price as well. However, low intrinsic activity and poor stability in acid restrict its practical applications. Herein, a new approach is reported to encapsulate Ni nanoparticles (NPs) into interlayer edges of N-doped Nb2 CTx MXene (Ni NPs@N-Nb2 CTx ) by an electrochemical process. The as-prepared Ni NPs@N-Nb2 CTx possesses Pt-like onset potentials and can reach 500 mA cm-2 at overpotentials of only 383 mV, which is much higher than that of N-Nb2 CTx supported Ni NPs synthesized by a wet-chemical method (w- Ni NPs/N-Nb2 CTx ). Furthermore, it shows high durability toward HER with a large current density of 300 mA cm-2 for 24 h because of the encapsulated structure against corrosion, oxidation as well as aggregation of Ni NPs in an acidic medium. Detailed structural characterization and density functional theory calculations reveal that the stronger interaction boosts the HER.

Internal moisture barrier layer for improving high-humidity reliability of miniature light emitting diode die without encapsulation.

Atomic layer deposited Al2O3 films are incorporated into miniature light emitting diodes (mini-LEDs) as an internal moisture barrier layer. The experimental results show that the water vapor transmission rate reaches ≤10-4 g/m2/day when the Al2O3 thickness is ≥40 nm. The mini-LED with a 40 nm-thick Al2O3 layer shows negligible degradation after 1000 h of 85°C/85% relative humidity testing, whereas the device without an Al2O3 layer fails after only 500 h due to delamination occurring at the GaN surface. Current-voltage characteristics of the device without an Al2O3 moisture barrier layer indicate an increase in series resistance and ideality factor. This study provides a simple, light-weighting method to have a satisfactory encapsulation function for miniature LEDs.

High power, broad tuning quantum cascade laser at λ ∼ 8.9 µm.

Many molecules have broad fingerprint absorption spectra in mid-wave infrared range which requires broadly tunable lasers to cover the interested spectrum in one scan. We report a strain-balanced, InAlAs/InGaAs/InP quantum cascade laser structure based on diagonal transition active region with high output power and and wide tuning range at λ ∼ 8.9 µm. The maximum pulsed optical power and the wall-plug efficiency at room temperature are 4 W and 11.7%, respectively. Maximum continuous wave double-facet power is 1.2 W at 25 °C for a 4 mm by 9 µm laser mounted epi-side down on a diamond/copper composite submount. The maximum pulsed and continuous wave external-cavity tuning range are from 7.71 µm to 9.15 µm and from 8 µm to 8.9 µm, respectively. The continuous wave power of the external cavity mode exceeds 200 mW across the entire spectrum.

Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Unsaturated Fatty Acid Liposomes Selectively Regulate Glutathione Peroxidase 4 to Exacerbate Lipid Peroxidation as an Adaptable Liposome Platform for Anti-Tumor Therapy.

Regulating non-apoptotic cell death of cancer cells provides a promising strategy to overcome apoptosis resistance during cancer treatment. Lipids are essential components to exacerbate several non-apoptotic cell death pathways. In the present study, unsaturated fatty acid (UFA) liposomes prepared with linoleic acid, oleic acid, or α-linolenic acid have the potential to affect lipid metabolism. Notably, UFA liposomes markedly increased cellular reactive oxygen species (ROS) and down-regulated the expression of glutathione peroxidase 4 (GPX4) in tumor cells, resulting in lipid peroxidation, which in turn caused rapid membrane rupture and induced non-apoptotic cell death of tumor cells. Concomitantly, UFA liposomes induced ROS-mediated tumor-associated macrophages toward a tumoricidal phenotype to reverse the immunosuppressive tumor microenvironment. Consequently, UFA liposomes substantially inhibited tumor growth in a melanoma model by promoting lipid peroxidation, inducing non-apoptotic cell death of tumor cells, and increasing infiltration of anti-tumor immune cells at tumor sites. Therefore, UFA liposomes regulate GXP4 to exacerbate lipid peroxidation and provide a versatile liposome platform for enhancing anti-tumor therapy which could be readily extended to the delivery of anticancer agents.

The Potential Value of Ki-67 in Prognostic Classification in Early Low-Risk Endometrial Cancer.

PURPOSE: This study aims to determine the optimal cut-off value of Ki-67 to better predict the recurrence of early low-risk endometrial cancer (EC). METHODS: Seven hundred and forty-eight patients diagnosed with low-risk EC from West China Second Hospital of Sichuan University and the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The receiver operating characteristic curve (ROC) and Youden index were used to calculate the optimal cut-off value of Ki-67 expression. The clinicopathological indexes between two groups divided by cut-off value of Ki-67 were compared. The univariate and multivariate regression analyses were performed to investigate risk factors connected to the recurrence of early low-risk EC. The survival analysis was shown in Kaplan-Meier curve. RESULT: Thirty-three patients were detected with tumor recurrence after primary surgery (4.4%); 33% was the optimal cut-off value of the Ki-67 index. A high Ki-67 was significantly associated with age (P = .002), myometrial invasion (P < .001), and the expression of P53 (P = .007). The multivariate regression analysis verified that Ki67 ≥ 33% was an independent prognostic factor for predicting recurrence. The recurrence-free survival (RFS) and the overall survival (OS) in high Ki-67 group was significantly lower than that in low Ki-67 group (P < .001 and P = .029, respectively). The prognostic values of ER, PR, and P53 in combination with Ki-67 were superior to each single predictor. CONCLUSIONS: The optimal cut-off value of Ki-67 for predicting recurrence is 33%, which quantitatively defines the specific value of Ki-67 that causes high-risk recurrence in early low-risk EC.