Controlling factors for the global meridional overturning circulation: A lesson from the Paleozoic.

The global meridional overturning circulation (GMOC) is important for redistributing heat and, thus, determining global climate, but what determines its strength over Earth's history remains unclear. On the basis of two sets of climate simulations for the Paleozoic characterized by a stable GMOC direction, our research reveals that GMOC strength primarily depends on continental configuration while climate variations have a minor impact. In the mid- to high latitudes, the volume of continents largely dictates the speed of westerly winds, which in turn controls upwelling and the strength of the GMOC. At low latitudes, open seaways also play an important role in the strength of the GMOC. An open seaway in one hemisphere allows stronger westward ocean currents, which support higher sea surface heights (SSH) in this hemisphere than that in the other. The meridional SSH gradient drives a stronger cross-equatorial flow in the upper ocean, resulting in a stronger GMOC. This latter finding enriches the current theory for GMOC.

Associations of systemic immune-inflammation index with high risk for prostate cancer in middle-aged and older US males: A population-based study.

BACKGROUND: Systemic immune-inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle-aged and elderly males. MATERIALS AND METHODS: Analysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests. RESULTS: Among 3359 participants, those with elevated SII displayed higher total prostate-specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (ß: 0.22, 95% confidence intervals [CI] 0.05-0.38), a 2.22% decline in f/t PSA ratio (ß: -2.22, 95% CI -3.20 to -1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13-2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (ß: 0.55, 95% CI 0.19-0.90), 4.39% reduced f/t PSA ratio (ß: -4.39, 95% CI -6.50 to -2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32-5.46) compared to those in the bottom quartile. CONCLUSION: Systemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle-aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

Channel modeling for NLoS visible light networks with integrated sensing and communication.

Inspired by the advanced integrated sensing and communication (ISAC), in this Letter, we explore the non-line-of-sight (NLoS) optical channels formed by reflections from the ground or objects to establish an integrated channel model for simultaneous communication and sensing. The integrated channel model can, on the one hand, perceive the changes in the surrounding environment and, on the other hand, determine whether these changes positively or negatively affect the quality of communication simultaneously. To validate the effectiveness of the proposed model, from sensing, we analyze the impact of various floor materials and visible light communication (VLC) users on the integrated channel; from communication, we characterize the influence of perceived environmental changes on communication performance by calculating throughput. Experimental results confirm the capability of the derived model, which can support the design and deployment of VL-based ISAC networks.

Combined vaccines against angiotensin II receptor type 1 and alpha 1D-adrenergic receptor for hypertension.

PURPOSE: Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. METHODS: Our team has developed ATRQß-001 and ADRQß-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester ( l -NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQß-001 and ADRQß-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQß-001 and ADRQß-004 combined vaccines in comparison with those of the single vaccine. RESULTS: Both ATRQß-001 and ADRQß-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l -NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. CONCLUSION: Preliminary findings from this investigation suggest that co-administration of the novel ATRQß-001 and ADRQß-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.

Varying ratios of M/G in alginate to modulate macrophages polarization and its application for wound healing in diabetic.

Alginate (SA) comprises repeating unis of ß-1, 4 linked ß-D-mannuronic acid (M) and α-L-guloronic acid (G) in varying proportions. The M/G ratio greatly impacts its anti-inflammatory properties in tissue healing wound, as less knowledge reported. This study examined the performances of both SA and SA hydrogel crosslinked with copper ions (SA-Cu) with different M/G ratios are studied. SA with higher M/G ratios stimulated macrophage migration and shifted from M0 to the pro-inflammatory Ml phenotype, while lower M/G ratios shifted from M1 to the pro-repair M2 phenotype. Furthermore, SA-Cu hydrogels with lower M/G ratios exhibited enhanced cross-linking degree, mechanical and rheological properties, as well Cu releasing rate. The reason may be attributed to a relative easy binding between Cu ions and G unit among Cu ions, M unit and G unit. In vitro cell evaluation showed that SA-Cu hydrogel with M/G ratio of 1:1 activated M2 macrophages and up-regulated anti-inflammatory cytokines expression more effectively than those of SA-Cu ratios (2:1) and (1:2). In vivo, SA-Cu hydrogel with M/G ratio of 1:1 expedited diabetic wound healing, accelerating infiltration and phenotype shift of M2 macrophages, and enhancing anti-inflammatory factors, epithelialization and collagen deposition in healing phases. This research highlights the significant role of M/G ratios in SA materials in influencing macrophage behavior and inflammatory responses, which would benefit its application field.

Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Accuracy of the novel digital non-cross-arch surgical guides with integration of tooth undercut retention and screw-bone support for implant placement in mandibular free-end.

BACKGROUND: Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. MATERIALS AND METHODS: A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide's free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants' insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). RESULTS: GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. CONCLUSION: This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.

Three dimensionally printed template with an interproximal isolation design guide consecutive closure of multiple diastema with injectable resin composite.

OBJECTIVE: This article describes a novel 3D-printed template armed with interproximal matrices to isolate interproximal contact areas and guide injectable resin composite for consecutive closure of multiple diastema. CLINICAL CONSIDERATIONS: Among several treatment options proposed for diastema closure, direct resin composite is noninvasive and easy to repair. The "composite injection technique" has been introduced to improve time efficiency and reduce technique sensitivity for clinicians. However, in the case of multiple diastema, the overflow of excess resin materials onto the adjacent teeth during injection poses challenges for recontouring the interproximal anatomy. A 3D-printed template with special-designed gaps at interproximal areas was designed and fabricated based on a virtual diagnostic wax-up. Flowable resin composite was then consecutively injected through the template to close diastemata at multiple adjacent teeth. CONCLUSION: This technique using a 3D-printed template with interproximal isolation design contributed to an efficient and accurate operation for multiple anterior diastema closure. CLINICAL SIGNIFICANCE: Efficient and accurate freehand buildups of composite restoration for multiple diastema are challenging in operative dentistry. The described noninvasive full digital workflow provides a predictable method to accurately recontour the multiple target restorations and reduce the chair-side time and technical sensitivity.

Impact of sarcopenia on outcomes of bladder cancer undergoing radical cystectomy: A systematic review and meta-analysis.

OBJECTIVE: To provide synthesized evidence on the association between sarcopenia and risk of mortality, recurrence and postoperative complications in patients with bladder cancer and undergoing radical cystectomy (RC). METHODS: Only studies with observational design that investigated the association between sarcopenia and outcomes of interest among patients with bladder cancer undergoing RC were included. The outcomes of interest were mortality, recurrence, and postoperative complications. The systematic search was conducted using three large databases, that is, PubMed, EMBASE, and Scopus. A random effects model was used for the analysis and pooled effect sizes were reported as odds ratio (OR) or hazards ratio (HR) along with 95% confidence intervals (CIs). RESULTS: A total of 21 studies with 4997 patients were included. Compared to non-sarcopenic subjects, those with sarcopenia had increased risk of all-cause mortality (HR 1.45, 95% CI: 1.32, 1.61), cancer-specific mortality (HR 1.74, 95% CI: 1.49, 2.03) and a lower recurrence free survival (HR 1.84, 95% CI: 1.30, 2.62). Patients with sarcopenia also had higher risk of developing complications within 90 days postoperatively (OR 1.77, 95% CI: 1.23, 2.55). CONCLUSION: Sarcopenia among patients with bladder cancer and managed using RC is associated with adverse survival outcomes and an increased risk of postoperative complications.

Stress response membrane protein OsSMP2 negatively regulates rice tolerance to drought.

In a gene chip analysis, rice (Oryza sativa) OsSMP2 gene expression was induced under various abiotic stresses, prompting an investigation into its role in drought resistance and abscisic acid signaling. Subsequent experiments, including qRT-PCR and ß-glucuronidase activity detection, affirmed the OsSMP2 gene's predominant induction by drought stress. Subcellular localization experiments indicated the OsSMP2 protein primarily localizes to the cell membrane system. Overexpressing OsSMP2 increased sensitivity to exogenous abscisic acid, reducing drought resistance and leading to reactive oxygen species accumulation under drought stress. Conversely, in simulated drought experiments, OsSMP2-silenced transgenic plants showed significantly longer roots compared with the wild-type Nipponbare. These results suggest that OsSMP2 overexpression negatively affects rice drought resistance, offering valuable insights into molecular mechanisms, and highlight OsSMP2 as a potential target for enhancing crop resilience to drought stress.

The novel vaccines targeting interleukin-1 receptor type I.

OBJECTIVE: There is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. METHODS: ILRQß-007 and ILRQß-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. RESULTS: ILRQß-007 and ILRQß-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1ß and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. CONCLUSION: The vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction.

Water and Salt Concentration-Dependent Electrochemical Performance of Hydrogel Electrolytes in Zinc-Ion Batteries.

Zinc-ion batteries (ZIBs) are promising energy storage devices with safe, nonflammable electrolytes and abundant, low-cost electrode materials. Their practical applications are hampered by various water-related undesirable reactions, such as the hydrogen evolution reaction (HER), corrosion of zinc metal, and water-induced decay of cathode materials. Polymer hydrogel electrolytes were used to control these reactions. However, salt, water, and polymeric backbones intervene in polymer hydrogels, and currently, there are no systematic studies on how salt and water concentrations synergistically affect polymer hydrogels' electrochemical performance. Here, we used an in situ polymerization method to synthesize polyacrylamide (PAM) hydrogels with varied Zn(ClO4)2 (0.5 to 2.0 mol kg-1) and water (40 to 90 wt %) concentrations. Their electrochemical performances in Zn||Ti half-cells, Zn||Zn symmetrical cells, and Zn||V2O5 full cells have been comprehensively evaluated. Although the ionic conductivity of electrolytes increases with the salt concentration, a high salt concentration of 2.0 mol kg-1 with more Zn2+ solvated H2O would induce more severe HER and Zn corrosion at the electrolyte/electrode interfaces. A narrow window of the water concentration at 70-80 wt % is optimal to balance needs for achieving a high ionic conductivity and restricting water-related undesirable reactions. The chemically more active water counts roughly 64.1-73.1 wt % of the total water in electrolytes. PAM hydrogel electrolyte with 1.0 mol kg-1 Zn(ClO4)2 and 80 wt % water enables 1200 h of stable cycling in a Zn||Zn symmetric cell and 99.24% of Coulombic efficiency in a Zn||Ti half-cell. Due to the water-induced decay of V2O5, the electrolyte with 70 wt % water delivers the best performance in a Zn||V2O5 full cell, which can retain 73.7% of its initial capacity after 400 charge/discharge cycles. Our results show that achieving precise control of salt and water concentrations of hydrogel electrolytes in their optimal windows to reduce the fraction of chemically more active water while retaining high ionic conductivity is essential to enabling high-performance ZIBs.

Dual-Encoded Affinity Microbead Signature Combinatorial Profiling for Acute Myocardial Infarction High-Sensitivity Diagnosis.

The early diagnosis of acute myocardial infarction (AMI) is dependent on the combined feedback of multiple cardiac biomarkers. However, it remains challenging to precisely detect multicardiac biomarkers in complex blood early due to the lack of sensitive and specific diagnostic indicators and the low abundance and small size of associated biomarkers with high specificity (such as microRNAs). To make matters worse, spectral overlap significantly limits the multiplex analysis of cardiac biomarkers by fluorescent probes, leading to bias in the diagnosis of myocardial infarction. Herein, we developed a method for simultaneous detection of miRNAs and protein biomarkers using size- and color-coded microbeads that carry signature for target capture. We also constructed a microfluidic chip with different spacer arrays that segregate these microbeads in different chip regions according to their size to produce signature signals, indicating the level of different biomarkers. The signals on the microbeads were hugely amplified by catalytic hairpin assembly and rolling circle amplification. Notably, this strategy enables the simultaneous and in situ sensitive profiling of six kinds of biomarkers via adding two different fluorescent labels, removing the limitations of spectral overlap. We envision that the strategy has great potential for application in clinical diagnosis for AMI.

1,3-Butadiene Dicarbofunctionalization Enabled by the Dual Role of Diaryl Ketone in Photo-HAT/Chromium Catalysis.

We report a three-component Nozaki-Hiyama-Kishi type reaction of 1,3-dioxolane, 1,3-butadienes, and aldehydes to access masked aldehyde-incorporated homoallylic alcohols, facilitated by photo-hydrogen atom transfer (HAT)/chromium dual catalysis. The diaryl ketone serves dual roles both in the HAT process and in facilitating the turnover of the chromium catalyst. A range of functional groups are tolerated owing to the mild conditions. Both aromatic and aliphatic aldehydes are suitable substrates for coupling with several 1,3-butadienes and 1,3-dioxolane.

EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death.

TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

A digital workflow for tooth-supported complete overdentures with a composite resin injection technique to manage the treatment of a child with ectodermal dysplasia.

This clinical report describes a digital workflow for the rehabilitation of an 8-year-old patient diagnosed with ectodermal dysplasia. Based on the patient's digital primary casts, small custom trays and an arch tracer were designed and 3-dimensionally printed. The mandibular custom tray and retention plate with a tracing screw were assembled with tracing plate, forming an individual assembled mini-arch tracer system to record the jaw relationship together with a conventional facebow and a digital articulator. In addition, composite resin injection guides were designed and fabricated to form the predesigned targeted shape of the abutment teeth and provide a buffer. By following this workflow, complete overdentures with good fit, occlusion, and acceptable esthetics were delivered.

Temporal development and potential interactions between the gut microbiome and resistome in early childhood.

Antimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

Targeting the prostate tumor microenvironment by plant-derived natural products.

Prostate cancer is among the most common malignancies for men, with limited therapy options for last stages of the tumor. There are some different options for treatment and control of prostate tumor growth. However, targeting some specific molecules and cells within tumors has been attracted interests in recent years. The tumor microenvironment (TME) has an important role in the initiation of various malignancies, which can also expand the progression of tumor and facilitate invasion of malignant cells. By regulating immune responses and distinct changes in the metabolism of cells in the tumor, TME has substantial effects in the resistance of cancer cells to therapy. TME in various solid cancers like prostate cancer includes various cells, including cancer cells, supportive stromal cells, immunosuppressive cells, and anticancer inflammatory cells. Natural products including herbal-derived agents and also other natural compounds have been well studied for their anti-tumor potentials. These compounds may modulate various signaling pathways involved in TME, such as immune responses, the metabolism of cells, epigenetics, angiogenesis, and extracellular matrix (ECM). This paper provides a review of the current knowledge of prostate TME and complex interactions in this environment. Additionally, the potential use of natural products and also nanoparticles loaded with natural products as therapeutic adjuvants on different cells and therapeutic targets within prostate TME will be discussed.