Exposure of benzo[a]pyrene induces HCC exosome-circular RNA to activate lung fibroblasts and trigger organotropic metastasis.

BACKGROUND: Benzo[a]pyrene (B[a]P), a carcinogen pollutant produced by combustion processes, is present in the western diet with grilled meats. Chronic exposure of B[a]P in hepatocellular carcinoma (HCC) cells promotes metastasis rather than primary proliferation, implying an unknown mechanism of B[a]P-induced malignancy. Given that exosomes carry bioactive molecules to distant sites, we investigated whether and how exosomes mediate cancer-stroma communications for a toxicologically associated microenvironment. METHOD: Exosomes were isolated from B[a]P stimulated BEL7404 HCC cells (7404-100Bap Exo) at an environmental relevant dose (100 nmol/L). Lung pre-education animal model was prepared via injection of exosomes and cytokines. The inflammatory genes of educated lungs were evaluated using quantitative reverse transcription PCR array. HCC LM3 cells transfected with firefly luciferase were next injected to monitor tumor burdens and organotropic metastasis. Profile of B[a]P-exposed exosomes were determined by ceRNA microarray. Interactions between circular RNA (circRNA) and microRNAs (miRNAs) were detected using RNA pull-down in target lung fibroblasts. Fluorescence in situ hybridization and RNA immunoprecipitation assay was used to evaluate the "on-off" interaction of circRNA-miRNA pairs. We further developed an adeno-associated virus inhalation model to examine mRNA expression specific in lung, thereby exploring the mRNA targets of B[a]P induced circRNA-miRNA cascade. RESULTS: Lung fibroblasts exert activation phenotypes, including focal adhesion and motility were altered by 7404-100Bap Exo. In the exosome-educated in vivo model, fibrosis factors and pro-inflammatory molecules of are up-regulated when injected with exosomes. Compared to non-exposed 7404 cells, circ_0011496 was up-regulated following B[a]P treatment and was mainly packaged into 7404-100Bap Exo. Exosomal circ_0011496 were delivered and competitively bound to miR-486-5p in recipient fibroblasts. The down-regulation of miR-486-5p converted fibroblast to cancer-associated fibroblast via regulating the downstream of Twinfilin-1 (TWF1) and matrix metalloproteinase-9 (MMP9) cascade. Additionally, increased TWF1, specifically in exosomal circ_0011496 educated lungs, could promote cancer-stroma crosstalk via activating vascular endothelial growth factor (VEGF). These modulated fibroblasts promoted endothelial cells angiogenesis and recruited primary HCC cells invasion, as a consequence of a pre-metastatic niche formation. CONCLUSION: We demonstrated that B[a]P-induced tumor exosomes can deliver circ_0011496 to activate miR-486-5p/TWF1/MMP9 cascade in the lung fibroblasts, generating a feedback loop that promoted HCC metastasis.

Downregulation of MYBL1 in endothelial cells contributes to atherosclerosis by repressing PLEKHM1-inducing autophagy.

MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of this study is to elucidate the role and mechanism of MYBL1 in atherosclerosis. GSE28829, GSE43292 and GSE41571 were downloaded from NCBI for differentially expressed analysis. The expression levels of MYBL1 in atherosclerotic plaque tissue and normal vessels were detected by qRT-PCR, Western blot and Immunohistochemistry. Transwell and CCK-8 were used to detect the migration and proliferation of HUVECs after silencing MYBL1. RNA-seq, Western blot, qRT-PCR, Luciferase reporter system, Immunofluorescence, Flow cytometry, ChIP and CO-IP were used to study the role and mechanism of MYBL1 in atherosclerosis. The microarray data of GSE28829, GSE43292, and GSE41571 were analyzed and intersected, and then MYBL1 were verified. MYBL1 was down-regulated in atherosclerotic plaque tissue. After silencing of MYBL1, HUVECs were damaged, and their migration and proliferation abilities were weakened. Overexpression of MYBL1 significantly enhanced the migration and proliferation of HUVECs. MYBL1 knockdown induced abnormal autophagy in HUVEC cells, suggesting that MYBL1 was involved in the regulation of HUVECs through autophagy. Mechanistic studies showed that MYBL1 knockdown inhibited autophagosome and lysosomal fusion in HUVECs by inhibiting PLEKHM1, thereby exacerbating atherosclerosis. Furthermore, MYBL1 was found to repress lipid accumulation in HUVECs after oxLDL treatment. MYBL1 knockdown in HUVECs was involved in atherosclerosis by inhibiting PLEKHM1-induced autophagy, which provided a novel target of therapy for atherosclerosis.

Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

Association of preoperative elevated lipoprotein (a) with poor survival in patients with biliary tract cancers.

BACKGROUND: Biliary tract cancers have garnered significant attention due to their highly malignant nature. The relationship between abnormal lipid metabolism and tumor occurrence and development is a research hotspot. However, its correlation with biliary tract cancers is unclear. METHODS: We enrolled 78 patients with biliary tract cancers and obtained data on clinical characteristics, pathological findings, and preoperative blood lipid indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and lipoprotein (a) [Lp(a)]. Receiver operating characteristic (ROC) curves were used to determine the optimal predictive cutoff values of lipid indicators among the participants. Independent risk factors were determined using Cox regression, and survival was predicted using the Kaplan-Meier method. Statistical analyses were performed using SPSS software. RESULTS: Univariate Cox regression analysis revealed that the body mass index (BMI), tumor location, surgical margin, N stage, and abnormally increased LDL-C, TG, and Lp(a) levels were significantly associated with poor prognosis of biliary tract cancers (p < 0.05). Multifactor Cox regression demonstrated that only N stage (HR = 3.393, p < 0.001) and abnormally increased Lp(a) levels (HR = 2.814, p = 0.004) were significantly associated with shorter survival. N stage and Lp(a) were identified as independent prognostic risk factors for patients with biliary tract cancers. CONCLUSION: This study presents Lp(a) as a novel biochemical marker that can guide clinical treatment strategies for patients with biliary tract cancers. More effective treatment options and intensive postoperative testing should be considered to prolong the survival of these patients with preoperative abnormal lipid metabolism.

GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration.

PURPOSE: The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS: We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by  Multiplex immunohistochemistry (mIHC). RESULTS: Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS: Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.

External Electrons Directly Stimulate Escherichia coli for Enhancing Biological Hydrogen Production.

External electric field has the potential to influence metabolic processes such as biological hydrogen production in microorganisms. Based on this concept, we designed and constructed an electroactive hybrid system for microbial biohydrogen production under an electric field comprised of polydopamine (PDA)-modified Escherichia coli (E. coli) and Ni foam (NF). In this system, electrons generated from NF directly migrate into E. coli cells to promote highly efficient biocatalytic hydrogen production. Compared to that generated in the absence of electric field stimulation, biohydrogen production by the PDA-modified E. coli-based system is significantly enhanced. This investigation has demonstrated the mechanism for electron transfer in a biohybrid system and gives insight into precise basis for the enhancement of hydrogen production by using the multifield coupling technology.

Low-temperature plasma jet suppresses bacterial colonisation and affects wound healing through reactive species.

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.

Sporoderm-broken spores of Ganoderma lucidum modulate hepatoblastoma malignancy by regulating RACK1-mediated autophagy and tumour immunity.

Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.

Development of a Serum-Based MicroRNA Signature for Early Detection of Pancreatic Cancer: A Multicenter Cohort Study.

BACKGROUND: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. AIMS: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. METHODS: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. RESULTS: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. CONCLUSIONS: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.

Single-Ended Eddy Current Micro-Displacement Sensor with High Precision Based on Temperature Compensation.

To measure the micro-displacement reliably with high precision, a single-ended eddy current sensor based on temperature compensation was studied in detail. At first, the principle of the eddy current sensor was introduced, and the manufacturing method of the probe was given. The overall design plan for the processing circuit was induced by analyzing the characteristics of the probe output signal. The variation in the probe output signal was converted to pulses with different widths, and then it was introduced to the digital phase discriminator along with a reference signal. The output from the digital phase discriminator was processed by a low-pass filter to obtain the DC component. At last, the signal was amplified and compensated to reduce the influence of temperature. The selection criteria of the frequency of the exciting signal and the design of the signal conditioning circuit were described in detail, as well as the design of the temperature-compensating circuit based on the digital potentiometer with an embedded temperature sensor. Finally, an experimental setup was constructed to test the sensor, and the results were given. The results show that nonlinearity exists in the single-ended eddy current sensor with a large range. When the range is 500 µm, the resolution can reach 46 nm, and the repeatability error is ±0.70% FR. Within the temperature range from +2 °C to +58 °C, the voltage fluctuation in the sensor is reduced to 44 mV after temperature compensation compared to the value of 586 mV before compensation. The proposed plan is verified to be feasible, and the measuring range, precision, and target material should be considered in real-world applications.

The relevance of the superior cervical ganglion for cardiac autonomic innervation in health and disease: a systematic review.

PURPOSE: The heart receives cervical and thoracic sympathetic contributions. Although the stellate ganglion is considered the main contributor to cardiac sympathetic innervation, the superior cervical ganglia (SCG) is used in many experimental studies. The clinical relevance of the SCG to cardiac innervation is controversial. We investigated current morphological and functional evidence as well as controversies on the contribution of the SCG to cardiac innervation. METHODS: A systematic literature review was conducted in PubMed, Embase, Web of Science, and COCHRANE Library. Included studies received a full/text review and quality appraisal. RESULTS: Seventy-six eligible studies performed between 1976 and 2023 were identified. In all species studied, morphological evidence of direct or indirect SCG contribution to cardiac innervation was found, but its contribution was limited. Morphologically, SCG sidedness may be relevant. There is indirect functional evidence that the SCG contributes to cardiac innervation as shown by its involvement in sympathetic overdrive reactions in cardiac disease states. A direct functional contribution was not found. Functional data on SCG sidedness was largely unavailable. Information about sex differences and pre- and postnatal differences was lacking. CONCLUSION: Current literature mainly supports an indirect involvement of the SCG in cardiac innervation, via other structures and plexuses or via sympathetic overdrive in response to cardiac diseases. Morphological evidence of a direct involvement was found, but its contribution seems limited. The relevance of SCG sidedness, sex, and developmental stage in health and disease remains unclear and warrants further exploration.

Ternary Eutectic Electrolyte-Assisted Formation and Dynamic Breathing Effect of the Solid-Electrolyte Interphase for High-Stability Aqueous Magnesium-Ion Full Batteries.

Aqueous rechargeable magnesium batteries hold immense potential for intrinsically safe, cost-effective, and sustainable energy storage. However, their viability is constrained by a narrow voltage range and suboptimal compatibility between the electrolyte and electrodes. Herein, we introduce an innovative ternary deep eutectic Mg-ion electrolyte composed of MgCl2·6H2O, acetamide, and urea in a precisely balanced 1:1:7 molar ratio. This formulation was optimized by leveraging competitive solvation effects between Mg2+ ions and two organic components. The full batteries based on this ternary eutectic electrolyte, Mn-doped sodium vanadate (Mn-NVO) anode, and copper hexacyanoferrate cathode exhibited an elevated voltage plateau and high rate capability and showcased stable cycling performance. Ex-situ characterizations unveiled the Mg2+ storage mechanism of Mn-NVO involving initial extraction of Na+ followed by subsequent Mg2+ intercalation/deintercalation. Detailed spectroscopic analyses illuminated the formation of a pivotal solid-electrolyte interphase on the anode surface. Moreover, the solid-electrolyte interphase demonstrated a dynamic adsorption/desorption behavior, referred to as the "breathing effect", which substantially mitigated undesired dissolution and side reactions of electrode materials. These findings underscore the crucial role of rational electrolyte design in fostering the development of a favorable solid-electrolyte interphase that can significantly enhance compatibility between electrode materials and electrolytes, thus propelling advancements in aqueous multivalent-ion batteries.

The Seasonal Influenza Vaccine Cannot Trigger a Titer Increase Among Some Elderly Individuals.

Many elderlies exhibited absent responses to influenza vaccines. Our exploration of this heterogeneity revealed associations with vaccine dose (HD vs. SD, OR: 0.59 (95%CrI, 0.4 to 0.87)), pre-vaccination titer levels (OR: 1.57 (95%CrI, 1.38 to 1.8), and gender (Male vs. Female OR: 2.12 (95%CrI, 1.38 to 3.25)).

High-Voltage Electrostatic Field Hydrogel Microsphere 3D Culture System Improves Viability and Liver-like Properties of HepG2 Cells.

Three-dimensional (3D) hepatocyte models have become a research hotspot for evaluating drug metabolism and hepatotoxicity. Compared to two-dimensional (2D) cultures, 3D cultures are better at mimicking the morphology and microenvironment of hepatocytes in vivo. However, commonly used 3D culture techniques are not suitable for high-throughput drug screening (HTS) due to their high cost, complex handling, and inability to simulate cell-extracellular matrix (ECM) interactions. This article describes a method for rapid and reproducible 3D cell cultures with ECM-cell interactions based on 3D culture instrumentation to provide more efficient HTS. We developed a microsphere preparation based on a high-voltage electrostatic (HVE) field and used sodium alginate- and collagen-based hydrogels as scaffolds for 3D cultures of HepG2 cells. The microsphere-generating device enables the rapid and reproducible preparation of bioactive hydrogel microspheres. This 3D culture system exhibited better cell viability, heterogeneity, and drug-metabolizing activity than 2D and other 3D culture models, and the long-term culture characteristics of this system make it suitable for predicting long-term liver toxicity. This system improves the overall applicability of HepG2 spheroids in safety assessment studies, and this simple and controllable high-throughput-compatible method shows potential for use in drug toxicity screening assays and mechanistic studies.

Magneto-Mechanical Coupling Study of Magnetorheological Elastomer Thin Films for Sensitivity Enhancement.

Magnetorheological elastomer thin films (MREFs) exhibit remarkable deformability and an adjustable modulus under magnetic fields, rendering them promising in fields such as robotics, flexible sensors, and biomedical engineering. Here, we fabricated MREF by introducing magnetostrictive particles (MSPs) and evaluated the magneto-mechanical coupling effect on the enhancement of sensitivity. The saturation magnetization (Ms) in a parallel anisotropic TbDyFe-PDMS MREF was 5.8 emu/g, and the initial tensile modulus was 55% greater than that of an Iso MREF. We propose a nonlinear magnetorheological formula on the magnetostriction effect, incorporating magnetic dipole interactions and the nonlinear prestress of magnetic particles. This formula highlights the complex nonlinear relationship between the external magnetic field (H) and the key parameters that affect the enhanced MR effect of MSPs-MREF, such as saturation magnetization, remanence (Mr), magnetostriction constant (λs) and stress deviator in ferromagnetic particles (Sed) in the magnetic chain structure. Furthermore, we validate the influence of the key parameters of the rectified magnetorheological formula on a nonlinear magneto-mechanical behavior of MSPs-MREF in PDMS-based MSPs-MREF models by using finite-element simulations. Finally, we developed a biosensor based on MSPs-MREF to detect human serum albumin at low concentrations in human urine samples. There is a 4-fold increase in sensitivity, a lower detection of limit (0.442 µg/mL), and a faster response time (15 min) than traditional biosensors, which in the future might provide an effective way of detecting biomolecules of low concentrations.

Off the Shelf Multibranched Endograft for Thoraco-Abdominal and Pararenal Abdominal Aortic Aneurysms: a Prospective, Single Centre Study of the G-Branch Endograft.

OBJECTIVE: To investigate outcomes of a novel, off the shelf multibranched endovascular stent graft for the treatment of thoraco-abdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PAAA). METHODS: A prospective, single centre study including 15 patients (mean age, 63.4 ± 10.7 years; 13 male) with TAAA or PAAA treated from October 2019 to March 2021 with a G-Branch endograft (Lifetech Scientific, Shenzhen, China) featuring a mixed multibranch design with two inner and two outer branches for reconstruction of the visceral and bilateral renal arteries, respectively. Follow up assessments were scheduled before discharge and at 30 days, six and 12 months after the index procedure. Annual telephone interviews were performed beyond the initial 12 months. The Kaplan-Meier method was used to estimate cumulative mortality and morbidity rates after endovascular repair. RESULTS: Technical success was achieved in all 15 patients. Nine patients (60%) had TAAA and six (40%) had PAAA (mean maximum aneurysm diameter, 73.7 ± 15.8 mm). The median follow up was 31.4 months (range, 10.1 - 44.0 months). At 30 days, there was no death and 7% morbidity (one case of temporary spinal cord ischaemia on Day 4). At one year, the mortality rate was 7% (one death from stroke at 10 months) and morbidity was 13% (one other case of renal function decline at six months). There were no aneurysm dilatations, re-interventions, or access related complications, and two (13%) persistent type II endoleaks. The one year primary branch patency rate was 100% for the four renovisceral arteries in all 13 patients who underwent computed tomography examinations. One patient died of hepatocellular carcinoma 29 months post-operatively, resulting in an estimated three year mortality rate of 13%. CONCLUSION: The G-Branch endograft yielded high technical success with good early and midterm outcomes for the treatment of TAAA and PAAA. A large multicentre study is warranted.

If Long-Term Suppression is not Possible, how do we Minimize Mortality for Infectious Disease Outbreaks?

OBJECTIVE: For any emerging pathogen, the preferred approach is to drive it to extinction with non-pharmaceutical interventions (NPI) or suppress its spread until effective drugs or vaccines are available. However, this might not always be possible. If containment is infeasible, the best people can hope for is pathogen transmission until population level immunity is achieved, with as little morbidity and mortality as possible. METHODS: A simple computational model was used to explore how people should choose NPI in a non-containment scenario to minimize mortality if mortality risk differs by age. RESULTS: Results show that strong NPI might be worse overall if they cannot be sustained compared to weaker NPI of the same duration. It was also shown that targeting NPI at different age groups can lead to similar reductions in the total number of infected, but can have strong differences regarding the reduction in mortality. CONCLUSIONS: Strong NPI that can be sustained until drugs or vaccines become available are always preferred for preventing infection and mortality. However, if people encounter a worst-case scenario where interventions cannot be sustained, allowing some infections to occur in lower-risk groups might lead to an overall greater reduction in mortality than trying to protect everyone equally.

A Novel Endovascular Double-Disc Implant for Sealing Intimal Tears in Aortic Dissection.

Postdissection thoracoabdominal aortic aneurysm incidence after thoracic endovascular aortic repair for type B aortic dissection is high, with residual distal tears being a major reason for persistent blood flow in the false lumen. The EndoPatch is an endovascular double-disc implant for sealing re-entry tears in aortic dissection, isolating blood flow in the false lumen and promoting thrombosis formation. Compared with conventional endovascular treatment techniques, this endovascular double-disc implant's small size and minimal working space requirements may reduce the risk of spinal ischemia and offer flexible vascular access. Although several barriers still impede this endovascular device's broad application, its innovative design, flexible vascular access, and streamlined surgical process make it a promising alternative for managing intimal tears in aortic dissection, either alone or as a supplementary method combined with conventional endovascular techniques. (Guo's Entry Tear Repair: The First in Man Study of Endopatch System; NCT04745039).

Direct Capturing and Regulating Key Intermediates for High-Efficiency Oxygen Evolution Reactions.

Developing efficient oxygen evolution reaction (OER) electrocatalysts can greatly advance the commercialization of proton exchange membrane (PEM) water electrolysis. However, the unclear and disputed reaction mechanism and structure-activity relationship of OER pose significant obstacles. Herein, the active site and intermediate for OER on AuIr nanoalloys are simultaneously identified and correlated with the activity, through the integration of in situ shell-isolated nanoparticle-enhanced Raman spectroscopy and X-ray absorption spectroscopy. The AuIr nanoalloys display excellent OER performance with an overpotential of only 246 mV to achieve 10 mA cm-2 and long-term stability under strong acidic conditions. Direct spectroscopic evidence demonstrates that * OO adsorbed on IrOx sites is the key intermediate for OER, and it is generated through the O-O coupling of adsorbed oxygen species directly from water, providing clear support for the adsorbate evolution mechanism. Moreover, the Raman information of the * OO intermediate can serve as a universal "in situ descriptor" that can be obtained both experimentally and theoretically to accelerate the catalyst design. It unveils that weakening the interactions of * OO on the catalysts and facilitating its desorption would boost the OER performance. This work deepens the mechanistic understandings on OER and provides insightful guidance for the design of more efficient OER catalysts.

Similarities and differences in the microbial structure of surface soils of different vegetation types.

Background: Soil microbial community diversity serves as a highly sensitive indicator for assessing the response of terrestrial ecosystems to various changes, and it holds significant ecological relevance in terms of indicating ecological alterations. At the global scale, vegetation type acts as a major driving force behind the diversity of soil microbial communities, encompassing both bacterial and fungal components. Modifications in vegetation type not only induce transformations in the visual appearance of land, but also influence the soil ecosystem's material cycle and energy flow, resulting in substantial impacts on the composition and performance of soil microbes. Methods: In order to examine the disparities in the structure and diversity of soil microbial communities across distinct vegetation types, we opted to utilize sample plots representing four specific vegetation types. These included a woodland with the dominant tree species Drypetes perreticulata, a woodland with the dominant tree species Horsfieldia hainanensis, a Zea mays farmland and a Citrus reticulata fields. Through the application of high-throughput sequencing, the 16S V3_V4 region of soil bacteria and the ITS region of fungi were sequenced in this experiment. Subsequently, a comparative analysis was conducted to explore and assess the structure and dissimilarities of soil bacterial and fungal communities of the four vegetation types were analyzed comparatively. Results: Our findings indicated that woodland soil exhibit a higher richness of microbial diversity compared to farmland soils. There were significant differences between woodland and farmland soil microbial community composition. However, all four dominant phyla of soil fungi were Ascomycota across the four vegetation types, but the bacterial dominant phyla were different in the two-farmland soil microbial communities with the highest similarity. Furthermore, we established a significant correlation between the nutrient content of different vegetation types and the relative abundance of soil microorganisms at both phyla and genus levels. This experiment serves as a crucial step towards unraveling the intricate relationships between plants, soil microbes, and soil, as well as understanding the underlying driving mechanism.